Actavis Pharma, Inc.

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Actavis Pharma, Inc. Drugs

Viberzi

Viberzi

The recommended dosage of VIBERZI is 100 mg taken orally twice daily with food.

The recommended dosage of VIBERZI is 75 mg taken orally twice daily with food in patients who:
do not have a gallbladder [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. are unable to tolerate the 100 mg dose of VIBERZI [see Adverse Reactions (6.1)]. are receiving concomitant OATP1B1 inhibitors [see Drug Interactions (7)]. have mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment [see Use in Specific Population (8.6), Clinical Pharmacology (12.3)].
Discontinue VIBERZI in patients who develop severe constipation for more than 4 days.

Instruct patients if they miss a dose, take the next dose at the regular time and not to take 2 doses at the same time to make up for a missed dose.
Tilia Fe

Tilia Fe

The tablet dispenser has been designed to make oral contraceptive dosing as easy and as convenient as possible. The tablets are arranged in four rows of seven tablets each, with the days of the week appearing on the tablet dispenser above the first row of tablets.

Note: Each tablet dispenser has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen. Six different day label strips have been provided with the Detailed Patient & Brief Summary Patient Package Insert in order to accommodate a Day-1 Start regimen. If the patient is using the Day-1 Start regimen, she should place the self-adhesive day label strip that corresponds to her starting day over the preprinted days.

Important: The patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle when utilizing the Sunday-Start regimen.

The possibility of ovulation and conception prior to initiation of use should be considered.

Dosage and Administration for 28-Day Dosage Regimen

To achieve maximum contraceptive effectiveness, TILIA Fe should be taken exactly as directed and at intervals not exceeding 24 hours.

TILIA Fe provides a continuous administration regimen consisting of 21 white oral contraceptive tablets and seven brown non-hormone containing tablets of ferrous fumarate. The ferrous fumarate tablets are present to facilitate ease of drug administration via a 28-day regimen and do not serve any therapeutic purpose. There is no need for the patient to count days between cycles because there are no “off-tablet days”.

A. Sunday-Start Regimen: The patient begins taking the first white tablet from the top row of the dispenser (labeled Sunday) on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first white tablet is taken on the same day. The patient takes one white tablet daily for 21 days. The last white tablet in the dispenser will be taken on a Saturday. Upon completion of all 21 white tablets, and without interruption, the patient takes one brown tablet daily for 7 days. Upon completion of this first course of tablets, the patient begins a second course of 28-day tablets, without interruption, the next day (Sunday), starting with the Sunday white tablet in the top row. Adhering to this regimen of one white tablet daily for 21 days, followed without interruption by one brown tablet daily for 7 days, the patient will start all subsequent cycles on a Sunday.

B. Day-1 Start Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive day label strip that corresponds to her starting day over the preprinted days on the tablet dispenser. She starts taking one white tablet daily, beginning with the first white tablet in the top row. After the last white tablet (at the end of the third row) has been taken, the patient will then take the brown tablets for a week (7 days). For all subsequent cycles, the patient begins a new 28 tablet regimen on the eighth day after taking her last white tablet, again starting with the first tablet in the top row after placing the appropriate day label strip over the preprinted days on the tablet dispenser. Following this regimen of 21 white tablets and 7 brown tablets, the patient will start all subsequent cycles on the same day of the week as the first course.

Tablets should be taken regularly at the same time each day and can be taken without regard to meals. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule.

Special Notes on Administration

Menstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after the brown tablets have been started. In any event, the next course of tablets should be started without interruption. If spotting occurs while the patient is taking white tablets, continue medication without interruption.

If the patient forgets to take one or more white tablets, the following is suggested:

One tablet is missed
take tablet as soon as remembered take next tablet at the regular time
Two consecutive tablets are missed (Week 1 or Week 2)
take two tablets as soon as remembered take two tablets the next day use another birth control method for seven days following the missed tablets
Two consecutive tablets are missed (Week 3)Sunday-Start Regimen:
take one tablet daily until Sunday discard remaining tablets start new pack of tablets immediately (Sunday) use another birth control method for seven days following the missed tablets
Day-1 Start Regimen:
discard remaining tablets start new pack of tablets that same day use another birth control method for seven days following the missed tablets
Three (or more) consecutive tablets are missedSunday-Start Regimen:
take one tablet daily until Sunday discard remaining tablets start new pack of tablets immediately (Sunday) use another birth control method for seven days following the missed tablets
Day-1 Start Regimen:
discard remaining tablets start new pack of tablets that same day use another birth control method for seven days following the missed tablets
The possibility of ovulation occurring increases with each successive day that scheduled white tablets are missed. While there is little likelihood of ovulation occurring if only one white tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive white tablets are missed.

If the patient forgets to take any of the seven brown tablets in week four, those brown tablets that were missed are discarded and one brown tablet is taken each day until the pack is empty. A back-up birth control method is not required during this time. A new pack of tablets should be started no later than the eighth day after the last white tablet was taken.

In the rare case of bleeding which resembles menstruation, the patient should be advised to discontinue medication and then begin taking tablets from a new tablet dispenser on the next Sunday or the first day (Day 1) depending on her regimen. Persistent bleeding which is not controlled by this method indicates the need for reexamination of the patient, at which time nonfunctional causes should be considered.

Use of Oral Contraceptives in the Event of a Missed Menstrual Period

1. If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and oral contraceptives should be withheld until pregnancy has been ruled out.

2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

After several months on treatment, bleeding may be reduced to a point of virtual absence. This reduced flow may occur as a result of medication, in which event it is not indicative of pregnancy.

Acne

The timing of initiation of dosing with TILIA Fe for acne should follow the guidelines for use of TILIA Fe as an oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section for oral contraceptives.
Provence Water Drop Pac...

Provence Water Drop Pact 23 Natural Beige

To achieve maximum contraceptive effectiveness, NECON 7/7/7® Tablets must be taken exactly as directed and at intervals not exceeding 24 hours. NECON 7/7/7® Tablets are available in a blister card with a tablet dispenser which is preset for a Sunday Start. Day 1 Start is also available.

Sunday Start

When taking NECON 7/7/7®, the first white "active" tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first white "active" tablet should be taken that day. Take one active tablet daily for 21 days followed by one green "reminder" tablet daily for 7 days. After 28 tablets have been taken, a new course is started the next day (Sunday). For the first cycle of a Sunday Start regimen, another method of contraception, such as a condom or spermicide, should be used until after the first 7 consecutive days of administration.

If the patient misses one (1) active tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) active tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control, such as a condom or spermicide, if she has sex in the seven (7) days after missing pills. If the patient misses two (2) active tablets in the third week or misses three (3) or more active tablets in a row, the patient should continue taking one tablet every day until Sunday. On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills.

Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling ("How to Take the Pill" section).

Day 1 Start

The dosage of NECON 7/7/7® for the initial cycle of therapy is one active tablet administered daily from the 1st through the 21st day of the menstrual cycle, counting the first day of menstrual flow as "Day 1" followed by one green "reminder" tablet daily for 7 days. Tablets are taken without interruption for 28 days. After 28 tablets have been taken, a new course is started the next day.

If the patient misses one (1) active tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) active tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control, such as a condom or spermicide, if she has sex in the seven (7) days after missing pills. If the patient misses two (2) active tablets in the third week or misses three (3) or more active tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills.

Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling ("How to Take the Pill" section).

The use of NECON 7/7/7® for contraception may be initiated 4 weeks postpartum in women who elect not to breastfeed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS: Nursing Mothers.) The possibility of ovulation and conception prior to initiation of medication should be considered.

(See Discussion of Dose-Related Risk of Vascular Disease from Oral Contraceptives.)
Clobetasol Propionate S...

Clobetasol Propionate Spray

Clobetasol Propionate Spray, 0.05% is for topical use only, and not for ophthalmic, oral or intravaginal use. Clobetasol Propionate Spray, 0.05% should be sprayed directly onto the affected skin areas twice daily and rubbed in gently and completely.

The total dosage should not exceed 50 g (59 mL or 2 fluid ounces) per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Do not use more than 26 sprays per application or 52 sprays per day.

Clobetasol Propionate Spray, 0.05% contains a topical corticosteroid; therefore treatment should be limited to 4 weeks. Therapy should be discontinued when control has been achieved. Treatment beyond 2 weeks should be limited to localized lesions of moderate to severe plaque psoriasis that have not sufficiently improved after the initial 2 weeks of treatment with Clobetasol Propionate Spray, 0.05%. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Before prescribing for more than 2 weeks, any additional benefits of extending treatment to 4 weeks should be weighed against the risk of HPA axis suppression. Use in pediatric patients younger than 18 years is not recommended because of the potential for HPA axis suppression [see Use in Specific Populations (8.4)].

Unless directed by physician, Clobetasol Propionate Spray, 0.05% should not be used with occlusive dressings.
Lidocaine

Lidocaine

When Lidocaine HCI 2% Jelly is used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind.

The dosage varies and depends upon the area to be anesthetized, vascularity of the tissues, individual tolerance, and the technique of anesthesia. The lowest dosage needed to provide effective anesthesia should be administered. Dosages should be reduced for children and for elderly and debilitated patients. Although the incidence of adverse effects with Lidocaine HCI 2% Jelly is quite low, caution should be exercised, particularly when employing large amounts, since the incidence of adverse effects is directly proportional to the total dose of local anesthetic agent administered.

For Surface Anesthesia of the Male Adult Urethra: When using Lidocaine 2% Jelly 30 mL tubes, sterilize the plastic cone for 5 minutes in boiling water, cool, and attach to the tube. The cone may be gas sterilized or cold sterilized, as preferred. Slowly instill approximately 15 mL (300 mg of lidocaine HCI) into the urethra or until the patient has a feeling of tension. A penile clamp is then applied for several minutes at the corona. An additional dose of not more than 15 mL (300 mg) can be instilled for adequate anesthesia.

Prior to sounding or cystoscopy, a penile clamp should be applied for 5 to 10 minutes to obtain adequate anesthesia. A total dose of 30 mL (600 mg) is usually required to fill and dilate the male urethra.

Prior to catheterization, smaller volumes of 5 to 10 mL (100 to 200 mg) are usually adequate for lubrication.

For Surface Anesthesia of the Female Adult Urethra: When using Lidocaine 2% Jelly 30 mL tubes, sterilize the plastic cone for 5 minutes in boiling water, cool, and attach to the tube. The cone may be gas sterilized or cold sterilized, as preferred. Slowly instill 3 to 5 mL (60 to 100 mg of lidocaine HCI) of the jelly into the urethra. If desired, some jelly may be deposited on a cotton swab and introduced into the urethra. In order to obtain adequate anesthesia, several minutes should be allowed prior to performing urological procedures.

Lubrication for Endotracheal Intubation: Apply a moderate amount of jelly to the external surface of the endotracheal tube shortly before use. Care should be taken to avoid introducing the product into the lumen of the tube. Do not use the jelly to lubricate endotracheal stylettes. See WARNINGS and ADVERSE REACTIONS concerning rare reports of inner lumen occlusion. It is also recommended that use of endotracheal tubes with dried jelly on the external surface be avoided for lack of lubricating effect.
Dermasilkrx Sdspak

Dermasilkrx Sdspak

2.1 General Dosing Information

VRAYLAR is given orally once daily and can be taken with or without food.

Because of the long half-life of cariprazine and its active metabolites, changes in dose will not be fully reflected in plasma for several weeks. Prescribers should monitor patients for adverse reactions and treatment response for several weeks after starting VRAYLAR and after each dosage change [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)].

The maximum recommended dose is 6 mg daily. In short-term controlled trials, dosages above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions [see Adverse Reactions (6.1), Clinical Studies (14)].

2.2 Schizophrenia

The recommended dose range is 1.5 mg to 6 mg once daily. The starting dose of VRAYLAR is 1.5 mg. The dosage can be increased to 3 mg on Day 2. Depending upon clinical response and tolerability, further dose adjustments can be made in 1.5 mg or 3 mg increments.

2.3 Manic or Mixed Episodes Associated with Bipolar I Disorder

The recommended dose range is 3 mg to 6 mg once daily. The starting dose of VRAYLAR is 1.5 mg and should be increased to 3 mg on Day 2. Depending upon clinical response and tolerability, further dose adjustments can be made in 1.5 mg or 3 mg increments.

2.4 Dosage Adjustments for CYP3A4 Inhibitors and Inducers

CYP3A4 is responsible for the formation and elimination of the major active metabolites of cariprazine.

Dosage recommendation for patients initiating a strong CYP3A4 inhibitor while on a stable dose of VRAYLAR: If a strong CYP3A4 inhibitor is initiated, reduce the current dosage of VRAYLAR by half. For patients taking 4.5 mg daily, the dosage should be reduced to 1.5 mg or 3 mg daily. For patients taking 1.5 mg daily, the dosing regimen should be adjusted to every other day. When the CYP3A4 inhibitor is withdrawn, VRAYLAR dosage may need to be increased [see Drug Interactions (7.1)].

Dosage recommendation for patients initiating VRAYLAR therapy while already on a strong CYP3A4 inhibitor: Patients should be administered 1.5 mg of VRAYLAR on Day 1 and on Day 3 with no dose administered on Day 2. From Day 4 onward, the dose should be administered at 1.5 mg daily, then increased to a maximum dose of 3 mg daily. When the CYP3A4 inhibitor is withdrawn, VRAYLAR dosage may need to be increased [see Drug Interactions (7.1)].

Dosage recommendation for patients concomitantly taking VRAYLAR with CYP3A4 inducers:

Concomitant use of VRAYLAR and a CYP3A4 inducer has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear [see Dosage and Administration (2.1), Warnings and Precautions (5.5), Drug Interactions (7.1), Clinical Pharmacology (12.3)].

2.5 Treatment Discontinuation

Following discontinuation of VRAYLAR, the decline in plasma concentrations of active drug and metabolites may not be immediately reflected in patients' clinical symptoms; the plasma concentration of cariprazine and its active metabolites will decline by 50% in ~1 week [see Clinical Pharmacology (12.3)]. There are no systematically collected data to specifically address switching patients from VRAYLAR to other antipsychotics or concerning concomitant administration with other antipsychotics.
Memantine Hydrochloride...

Memantine Hydrochloride

The recommended starting dose of Memantine HCl is 5 mg once daily. The dose should be increased in 5 mg increments to 10 mg/day (5 mg twice daily), 15 mg/day (5 mg and 10 mg as separate doses), and 20 mg/day (10 mg twice daily). The minimum recommended interval between dose increases is one week. The dosage shown to be effective in controlled clinical trials is 20 mg/day.

Memantine HCl can be taken with or without food. If a patient misses a single dose of Memantine HCl, that patient should not double up on the next dose. The next dose should be taken as scheduled.

If a patient fails to take Memantine HCl for several days, dosing may need to be resumed at lower doses and retitrated as described above.

Do not mix Memantine HCl oral solution with any other liquid. The oral solution is administered with a dosing device that comes with the drug and consists of a syringe, syringe adaptor cap, tubing and other supplies a patient needs to administer the drug. The supplied syringe should be used to withdraw the correct volume of oral solution and the oral solution should be slowly squirted into the corner of the patient's mouth.

Special Populations

Renal Impairment

A target dose of 5 mg twice daily is recommended in patients with severe renal impairment (creatinine clearance of 5 – 29 mL/min based on the Cockroft-Gault equation).

Hepatic Impairment

Memantine HCl should be administered with caution to patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].
Escitalopram Oxalate So...

Escitalopram Oxalate Solution

Escitalopram oxalate should be administered once daily, in the morning or evening, with or without food.

2.1 Major Depressive Disorder

Initial Treatment

Adolescents

The recommended dose of escitalopram oxalate is 10 mg (10 mL) once daily. A flexible-dose trial of escitalopram oxalate (10 to 20 mg/day) (10 to 20 mL/day) demonstrated the effectiveness of escitalopram oxalate [see Clinical Studies (14.1)]. If the dose is increased to 20 mg (20 mL), this should occur after a minimum of three weeks.

Adults

The recommended dose of escitalopram oxalate is 10 mg (10 mL) once daily. A fixed-dose trial of escitalopram oxalate demonstrated the effectiveness of both 10 mg (10 mL) and 20 mg (20 mL) of escitalopram oxalate, but failed to demonstrate a greater benefit of 20 mg (20 mL) over 10 mg (10 mL) [see Clinical Studies (14.1)]. If the dose is increased to 20 mg (20 mL), this should occur after a minimum of one week.

Maintenance Treatment

It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of continuing escitalopram oxalate 10 or 20 mg/day (10 or 20 mL/day) in adult patients with major depressive disorder who responded while taking escitalopram oxalate during an 8-week, acute-treatment phase demonstrated a benefit of such maintenance treatment [see Clinical Studies (14.1)]. Nevertheless, the physician who elects to use escitalopram oxalate for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient. Patients should be periodically reassessed to determine the need for maintenance treatment.

2.2 Generalized Anxiety Disorder

Initial Treatment

Adults

The recommended starting dose of escitalopram oxalate is 10 mg (10 mL) once daily. If the dose is increased to 20 mg (20 mL), this should occur after a minimum of one week.

Maintenance Treatment

Generalized anxiety disorder is recognized as a chronic condition. The efficacy of escitalopram oxalate in the treatment of GAD beyond 8 weeks has not been systematically studied. The physician who elects to use escitalopram oxalate for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

2.3 Special Populations

10 mg/day (10 mL/day) is the recommended dose for most elderly patients and patients with hepatic impairment.

No dosage adjustment is necessary for patients with mild or moderate renal impairment. Escitalopram oxalate should be used with caution in patients with severe renal impairment.

2.4 Discontinuation of Treatment with Escitalopram Oxalate

Symptoms associated with discontinuation of escitalopram oxalate and other SSRIs and SNRIs have been reported [see Warnings and Precautions (5.3)]. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

2.5 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with escitalopram oxalate. Conversely, at least 14 days should be allowed after stopping escitalopram oxalate before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.1)].

2.6 Use of Escitalopram Oxalate with Other MAOIs such as Linezolid or Methylene Blue

Do not start escitalopram oxalate in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4.1)].

In some cases, a patient already receiving escitalopram oxalate therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, escitalopram oxalate should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with escitalopram oxalate may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with escitalopram oxalate is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.2)].
Risedronate Sodium

Risedronate Sodium

2.1       Treatment of Postmenopausal Osteoporosis

[see Indications and Usage (1.1)]

The recommended regimen is:
one 35 mg delayed-release tablet orally, taken once-a-week
2.2       Important Administration Instructions

Instruct patients to do the following:
Take Risedronate sodium in the morning immediately following breakfast. Risedronate sodium should be taken immediately following breakfast and not under fasting conditions because of a higher risk of abdominal pain if taken before breakfast when fasting. Swallow Risedronate sodium whole while in an upright position and with at least 4 ounces of plain water to facilitate delivery to the stomach. Avoid lying down for 30 minutes after taking the medication [see Warnings and Precautions (5.2)]. Do not chew, cut, or crush Risedronate sodium tablets.
2.3       Recommendations for Calcium and Vitamin D Supplementation

Instruct patients to take supplemental calcium and vitamin D if dietary intake is inadequate [see Warnings and Precautions (5.3)] and to take calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations at a different time of the day as they interfere with the absorption of Risedronate sodium.

2.4 Administration Instructions for Missed Doses

If the once-weekly dose is missed, instruct patients to take one tablet on the morning after they remember and return to taking one tablet once-a-week, as originally scheduled on their chosen day. Patients should not take two tablets on the same day.
Hydrochlorothiazide

Hydrochlorothiazide

Matzim® LA extended-release tablets are an extended release formulation intended for once-a-day administration.

Patients controlled on diltiazem alone or in combination with other medications may be switched to Matzim® LA extended-release tablets once-a-day at the nearest equivalent total daily dose. Higher doses of Matzim® LA extended-release tablets once-a-day dosage may be needed in some patients. Patients should be closely monitored. Subsequent titration to higher or lower doses may be necessary and should be initiated as clinically warranted. There is limited general clinical experience with doses above 360 mg, but the safety and efficacy of doses as high as 540 mg have been studied in clinical trials. The incidence of side effects increases as the dose increases with first-degree AV block, dizziness, and sinus bradycardia bearing the strongest relationship to dose.

The tablet should be swallowed whole and not chewed or crushed.

Hypertension

Dosage needs to be adjusted by titration to individual patient needs. When used as monotherapy, reasonable starting doses are 180 to 240 mg once daily, although some patients may respond to lower doses. Maximum antihypertensive effect is usually observed by 14 days of chronic therapy; therefore, dosage adjustments should be scheduled accordingly. The dosage range studied in clinical trials was 120 to 540 mg once daily. The dosage may be titrated to a maximum of 540 mg daily.

Matzim® LA extended-release tablets should be taken about the same time once each day either in the morning or at bedtime. The time of dosing should be considered when making dose adjustments based on trough effects.

Angina

Dosage for the treatment of angina should be individualized based on response. The initial dose of 180 mg once daily may be increased at intervals of 7 to 14 days if adequate response is not obtained. Matzim® LA doses above 360 mg appear to confer no additional benefit.

Matzim® LA can be given once daily, either in the evening or in the morning.

Concomitant Use with Other Cardiovascular Agents
Sublingual NTG. May be taken as required to abort acute anginal attacks during diltiazem hydrochloride extended-release therapy. Prophylactic Nitrate Therapy. Diltiazem hydrochloride extended-release tablets may be safely coadministered with short-and long-acting nitrates. Beta-blockers. (See WARNINGS and PRECAUTIONS.) Antihypertensives. Matzim® LA has an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of diltiazem hydrochloride extended-release tablets or the concomitant antihypertensives may need to be adjusted when adding one to the other.
Trisdent

Trisdent

Buprenorphine sublingual tablet is administered sublingually as a single daily dose. Buprenorphine sublingual tablet contains no naloxone HCl and is preferred for use only during induction. Following induction, buprenorphine and naloxone sublingual film or buprenorphine and naloxone sublingual tablet is preferred due to the presence of naloxone when clinical use includes unsupervised administration. The use of buprenorphine sublingual tablet for unsupervised administration should be limited to those patients who cannot tolerate buprenorphine and naloxone sublingual film or buprenorphine and naloxone sublingual tablet; for example, those patients who have been shown to be hypersensitive to naloxone.

Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits.

2.1 Induction

Prior to induction, consideration should be given to the type of opioid dependence (i.e., long- or short-acting opioid), the time since last opioid use, and the degree or level of opioid dependence. To avoid precipitating withdrawal, induction with buprenorphine sublingual tablet should be undertaken when objective and clear signs of withdrawal are evident.

It is recommended that an adequate treatment dose, titrated to clinical effectiveness, should be achieved as rapidly as possible. In a one-month study, patients received 8 mg of buprenorphine sublingual tablet on Day 1 and 16 mg buprenorphine sublingual tablet on Day 2. From Day 3 onward, patients received either buprenorphine and naloxone sublingual tablet or buprenorphine sublingual tablet at the same buprenorphine dose as Day 2 based on their assigned treatment. Induction in the studies of buprenorphine solution was accomplished over 3 to 4 days, depending on the target dose. In some studies, gradual induction over several days led to a high rate of drop-out of buprenorphine patients during the induction period.

Patients taking heroin or other short-acting opioids: At treatment initiation, the dose of buprenorphine sublingual tablet should be administered at least 4 hours after the patient last used opioids or preferably when moderate objective signs of opioid withdrawal appear.

Patients on methadone or other long-acting opioids: There is little controlled experience with the transfer of methadone-maintained patients to buprenorphine. Available evidence suggests that withdrawal signs and symptoms are possible during induction onto buprenorphine. Withdrawal appears more likely in patients maintained on higher doses of methadone (greater than 30 mg) and when the first buprenorphine dose is administered shortly after the last methadone dose. Buprenorphine sublingual tablet dosing should be initiated preferably when moderate objective signs of opioid withdrawal appear.

2.2 Maintenance
Buprenorphine and naloxone is preferred for maintenance treatment. Where buprenorphine is used in maintenance in patients who cannot tolerate the presence of naloxone, the dosage of buprenorphine should be progressively adjusted in increments / decrements of 2 mg or 4 mg buprenorphine to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms. The maintenance dose is generally in the range of 4 mg to 24 mg buprenorphine per day depending on the individual patient. Doses higher than this have not been demonstrated to provide any clinical advantage.
2.3 Method of Administration

Buprenorphine sublingual tablet should be placed under the tongue until it is dissolved. For doses requiring the use of more than two tablets, patients are advised to either place all the tablets at once or alternatively (if they cannot fit in more than two tablets comfortably), place two tablets at a time under the tongue. Either way, the patients should continue to hold the tablets under the tongue until they dissolve; swallowing the tablets reduces the bioavailability of the drug. To ensure consistency in bioavailability, patients should follow the same manner of dosing with continued use of the product.

Proper administration technique should be demonstrated to the patient.

2.4 Clinical Supervision

Treatment should be initiated with supervised administration, progressing to unsupervised administration as the patient’s clinical stability permits. The use of buprenorphine for unsupervised administration should be limited to those patients who cannot tolerate buprenorphine and naloxone, for example those patients with known hypersensitivity to naloxone. Buprenorphine and naloxone and buprenorphine are both subject to diversion and abuse. When determining the size of the prescription quantity for unsupervised administration, consider the patient’s level of stability, the security of his or her home situation, and other factors likely to affect the ability of the patient to manage supplies of take-home medication.

Ideally, patients should be seen at reasonable intervals (e.g., at least weekly during the first month of treatment) based upon the individual circumstances of the patient. Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits. Periodic assessment is necessary to determine compliance with the dosing regimen, effectiveness of the treatment plan, and overall patient progress.

Once a stable dosage has been achieved and patient assessment (e.g., urine drug screening) does not indicate illicit drug use, less frequent follow-up visits may be appropriate. A once-monthly visit schedule may be reasonable for patients on a stable dosage of medication who are making progress toward their treatment objectives. Continuation or modification of pharmacotherapy should be based on the physician’s evaluation of treatment outcomes and objectives such as:
Absence of medication toxicity. Absence of medical or behavioral adverse effects. Responsible handling of medications by the patient. Patient’s compliance with all elements of the treatment plan (including recovery-oriented activities, psychotherapy, and/or other psychosocial modalities). Abstinence from illicit drug use (including problematic alcohol and/or benzodiazepine use).
If treatment goals are not being achieved, the physician should re-evaluate the appropriateness of continuing the current treatment.

2.5 Patients With Hepatic Impairment

Severe hepatic impairment: Consider reducing the starting and titration incremental dose by half compared to patients with normal liver function, and monitor for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine.

Moderate hepatic impairment: Although no dose adjustment is necessary for patients with moderate hepatic impairment, buprenorphine sublingual tablets should be used with caution in these patients and prescribers should monitor patients for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine.

Mild hepatic impairment: No clinically significant differences in pharmacokinetic parameters were observed in subjects with mild hepatic impairment. No dose adjustment is needed in patients with mild hepatic impairment [see Warnings and Precautions (5.11)].

2.6 Unstable Patients

Physicians will need to decide when they cannot appropriately provide further management for particular patients. For example, some patients may be abusing or dependent on various drugs, or unresponsive to psychosocial intervention such that the physician does not feel that he/she has the expertise to manage the patient. In such cases, the physician may want to assess whether to refer the patient to a specialist or more intensive behavioral treatment environment. Decisions should be based on a treatment plan established and agreed upon with the patient at the beginning of treatment.

Patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided with, or referred to, more intensive and structured treatment.

2.7 Stopping Treatment

The decision to discontinue therapy with buprenorphine and naloxone or buprenorphine after a period of maintenance should be made as part of a comprehensive treatment plan. Both gradual and abrupt discontinuation of buprenorphine has been used, but the data are insufficient to determine the best method of dose taper at the end of treatment.
Emla

Emla

Adult Patients-Intact Skin

A thick layer of EMLA Cream is applied to intact skin and covered with an occlusive dressing (see INSTRUCTIONS FOR APPLICATION).

Minor Dermal Procedures: For minor procedures such as intravenous cannulation and venipuncture, apply 2.5 grams of EMLA Cream (1/2 the 5 g tube) over 20 to 25 cm2 of skin surface for at least 1 hour. In controlled clinical trials using EMLA Cream, two sites were usually prepared in case there was a technical problem with cannulation or venipuncture at the first site.

Major Dermal Procedures: For more painful dermatological procedures involving a larger skin area such as split thickness skin graft harvesting, apply 2 grams of EMLA Cream per 10 cm2 of skin and allow to remain in contact with the skin for at least 2 hours.

Adult Male Genital Skin: As an adjunct prior to local anesthetic infiltration, apply a thick layer of EMLA Cream (1 g/10 cm2) to the skin surface for 15 minutes. Local anesthetic infiltration should be performed immediately after removal of EMLA Cream.

Dermal analgesia can be expected to increase for up to 3 hours under occlusive dressing and persist for 1 to 2 hours after removal of the cream. The amount of lidocaine and prilocaine absorbed during the period of application can be estimated from the information in Table 2, ** footnote, in Individualization of Dose.

Adult Female Patients-Genital Mucous Membranes

For minor procedures on the female external genitalia, such as removal of condylomata acuminata, as well as for use as pretreatment for anesthetic infiltration, apply a thick layer (5 to 10 grams) of EMLA Cream for 5 to 10 minutes.

Occlusion is not necessary for absorption, but may be helpful to keep the cream in place. Patients should be lying down during the EMLA Cream application, especially if no occlusion is used. The procedure or the local anesthetic infiltration should be performed immediately after the removal of EMLA Cream.

Pediatric Patients-Intact Skin

The following are the maximum recommended doses, application areas and application times for EMLA Cream based on a child's age and weight:

Please note: If a patient greater than 3 months old does not meet the minimum weight requirement, the maximum total dose of EMLA Cream should be restricted to that which corresponds to the patient's weight (see INSTRUCTIONS FOR APPLICATION).

Practitioners should carefully instruct caregivers to avoid application of excessive amounts of EMLA Cream (see PRECAUTIONS).

When applying EMLA Cream to the skin of young children, care must be taken to maintain careful observation of the child to prevent accidental ingestion of EMLA Cream or the occlusive dressing. A secondary protective covering to prevent inadvertent disruption of the application site may be useful.

EMLA Cream should not be used in neonates with a gestational age less than 37 weeks nor in infants under the age of 12 months who are receiving treatment with methemoglobin-inducing agents (see Methemoglobinemia subsection of WARNINGS).

When EMLA Cream (lidocaine 2.5% and prilocaine 2.5%) is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered (see Individualization of Dose). The amount absorbed in the case of EMLA Cream is determined by the area over which it is applied and the duration of application under occlusion (see Table 2, ** footnote, in Individualization of Dose).

Although the incidence of systemic adverse reactions with EMLA Cream is very low, caution should be exercised, particularly when applying it over large areas and leaving it on for longer than 2 hours. The incidence of systemic adverse reactions can be expected to be directly proportional to the area and time of exposure (see Individualization of Dose).
Docetaxel

Docetaxel

Apply a thin film of Clindamycin Phosphate Topical Solution USP, 1% twice daily to affected area. Keep container tightly closed.
Hydroxychloroquine Sulf...

Hydroxychloroquine Sulfate

Regardless of the indication, the starting dose in patients with moderate hepatic impairment should be 5 mg twice daily, followed by adjustment based on therapeutic response and tolerability. Patients with mild hepatic insufficiency do not require dosage reductions. The use of pilocarpine in patients with severe hepatic insufficiency is not recommended. If needed, refer to the Hepatic Insufficiency subsection of the Precautions section of this label for definitions of mild, moderate and severe hepatic impairment.

Head & Neck Cancer Patients: The recommended initial dose of Pilocarpine Hydrochloride Tablets is 5 mg taken three times a day. Dosage should be titrated according to therapeutic response and tolerance. The usual dosage range is up to 15-30 mg per day. (Not to exceed 10 mg per dose). Although early improvement may be realized, at least 12 weeks of uninterrupted therapy with Pilocarpine Hydrochloride Tablets may be necessary to assess whether a beneficial response will be achieved. The incidence of the most common adverse events increases with dose. The lowest dose that is tolerated and effective should be used for maintenance.

Sjogren's Syndrome Patients: The recommended dose of Pilocarpine Hydrochloride Tablets is 5 mg taken four times a day. Efficacy was established by 6 weeks of use.
Celecoxib

Celecoxib

Use lowest effective dose for the shortest duration consistent with treatment goals for the individual patient.

These doses can be given without regard to timing of meals.

2.1 Osteoarthritis

For relief of the signs and symptoms of OA the recommended oral dose is 200 mg per day administered as a single dose or as 100 mg twice daily.

2.2 Rheumatoid Arthritis

For relief of the signs and symptoms of RA the recommended oral dose is 100 to 200 mg twice daily.

2.3 Juvenile Rheumatoid Arthritis

For the relief of the signs and symptoms of JRA the recommended oral dose for pediatric patients (age 2 years and older) is based on weight. For patients ≥10 kg to ≤25 kg the recommended dose is 50 mg twice daily. For patients >25 kg the recommended dose is 100 mg twice daily.

For patients who have difficulty swallowing capsules, the contents of a celecoxib capsule can be added to applesauce. The entire capsule contents are carefully emptied onto a level teaspoon of cool or room temperature applesauce and ingested immediately with water. The sprinkled capsule contents on applesauce are stable for up to 6 hours under refrigerated conditions (2–8° C/ 35–45° F).

2.4 Ankylosing Spondylitis

For the management of the signs and symptoms of AS, the recommended dose of celecoxib is 200 mg daily in single (once per day) or divided (twice per day) doses. If no effect is observed after 6 weeks, a trial of 400 mg daily may be worthwhile. If no effect is observed after 6 weeks on 400 mg daily, a response is not likely and consideration should be given to alternate treatment options.

2.5 Management of Acute Pain and Treatment of Primary Dysmenorrhea

The recommended dose of celecoxib is 400 mg initially, followed by an additional 200 mg dose if needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily as needed.

2.6 Special Populations

Hepatic insufficiency: The daily recommended dose of celecoxib capsules in patients with moderate hepatic impairment (Child-Pugh Class B) should be reduced by 50%. The use of celecoxib in patients with severe hepatic impairment is not recommended [see Warnings and Precautions (5.5), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Poor Metabolizers of CYP2C9 Substrates: Patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin) should be administered celecoxib with caution. Consider starting treatment at half the lowest recommended dose in poor metabolizers (i.e. CYP2C9*3/*3). Consider using alternative management in JRA patients who are poor metabolizers. [see Use in Specific populations (8.8), and Clinical Pharmacology (12.5)].
Ursodiol

Ursodiol

2.1 General Dosing Information

The recommended adult dosage for ursodiol tablets, USP 250 mg and 500 mg in the treatment of PBC is 13-15 mg/kg/day administered in two to four divided doses with food. Dosing regimen should be adjusted according to each patient’s need at the discretion of the physician.

2.2 Liver Function Tests

Liver function tests (γ-GT, alkaline phosphatase, AST, ALT) and bilirubin levels should be monitored every month for three months after start of therapy, and every six months thereafter [see Warnings and Precautions (5.1)].

2.3 Scoring the Ursodiol Tablets, USP 500 mg

The ursodiol tablets, USP 500 mg scored tablet can be broken in halves to provide recommended dosage.

To break ursodiol tablets, USP 500 mg scored tablet easily, place the tablet on a flat surface with the scored section on top. Hold the tablet with your thumbs placed close to the scored part of the tablet (groove). Then apply gentle pressure and snap the tablet segments apart (segments breaking incorrectly should not be used). The segments should be washed down unchewed, with water, keeping the segments in the mouth can reveal a bitter taste. Due to the bitter taste, segments should be stored separately from whole tablets. [see How Supplied/Storage and Handling (16.2)].

2.1 General Dosing Information

The recommended adult dosage for ursodiol tablets, USP 250 mg and 500 mg in the treatment of PBC is 13-15 mg/kg/day administered in two to four divided doses with food. Dosing regimen should be adjusted according to each patient’s need at the discretion of the physician.

2.2 Liver Function Tests

Liver function tests (γ-GT, alkaline phosphatase, AST, ALT) and bilirubin levels should be monitored every month for three months after start of therapy, and every six months thereafter [see Warnings and Precautions (5.1)].

2.3 Scoring the Ursodiol Tablets, USP 500 mg

The ursodiol tablets, USP 500 mg scored tablet can be broken in halves to provide recommended dosage.

To break ursodiol tablets, USP 500 mg scored tablet easily, place the tablet on a flat surface with the scored section on top. Hold the tablet with your thumbs placed close to the scored part of the tablet (groove). Then apply gentle pressure and snap the tablet segments apart (segments breaking incorrectly should not be used). The segments should be washed down unchewed, with water, keeping the segments in the mouth can reveal a bitter taste. Due to the bitter taste, segments should be stored separately from whole tablets. [see How Supplied/Storage and Handling (16.2)].
Gabapentin Capsule Gaba...

Gabapentin Capsule Gabapentin

2.1 Ovarian Cancer

Recommended Dose and Schedule

The recommended dose of Gemcitabine for Injection USP is 1000 mg/m2 as an intravenous infusion over 30 minutes on Days 1 and 8 of each 21-day cycle, in combination with carboplatin AUC 4 intravenously after Gemcitabine for Injection USP administration on Day 1 of each 21-day cycle. Refer to carboplatin prescribing information for additional information.

Dose Modifications

Recommended Gemcitabine for Injection USP dose modifications for myelosuppression are described Table 1 and Table 2 [see Warnings and Precautions (5.2)]. Refer to Dosage and Administration (2.5) for recommendations for non-hematologic adverse reactions.
Table 1: Dosage Reduction Guidelines for Gemcitabine for Injection USP for Myelosuppression on Day of Treatment in Ovarian Cancer Treatment Absolute granulocyte count Platelet count % of full dose Day (x 106/L) (x 106/L) Day 1 ≥1500 and ≥100,000 100% <1500 or <100,000 Delay Treatment Cycle Day 8 ≥1500 and ≥100,000 100 1000 to 1499 or 75,000 to 99,999 50 <1000 or <75,000 Hold Table 2: Gemcitabine for Injection USP Dose Modification for Myelosuppression in Previous Cycle In Ovarian Cancer Occurrence Myelosuppression During Treatment Cycle Dose Modification Initial Occurrence Absolute granulocyte count less than 500 x 106/L for more than 5 days Absolute granulocyte count less than 100 x 106/L for more than 3 days Febrile neutropenia Platelets less than 25,000x106/L Cycle delay of more than one week due to toxicity Permanently reduce Gemcitabine for Injection USP to 800 mg/m2 on Days 1 and 8 Subsequent Occurrence If any of the above toxicities occur after the initial dose reduction Permanently reduce Gemcitabine for Injection USP dose to 800 mg/m2 on Day 1 only
2.2 Breast Cancer

Recommended Dose and Schedule

The recommended dose of Gemcitabine for Injection USP is 1250 mg/m2 intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle that includes paclitaxel. Paclitaxel should be administered at 175 mg/m2 on Day 1 as a 3 hour intravenous infusion before Gemcitabine for Injection USP administration.

Dose Modifications

Recommended dose modifications for Gemcitabine for Injection USP for myelosuppression are described in Table 3 [see Warnings and Precautions (5.2)]. Refer to Dosage and Administration (2.5) for recommendations for non-hematologic adverse reactions.
Table 3: Recommended Dose Reductions for Gemcitabine for Injection USP for Myelosuppression on Day of Treatment in Breast Cancer Treatment Day Absolute granulocyte count Platelet count % of full dose (x 106/L) (x 106/L) Day 1 ≥1500 and ≥100,000 100% less than 1500 or less than 100,000 Hold Day 8 ≥1200 and >75,000 100% 1000 to 1199 or 50,000 to 75,000 75% 700 to 999 and ≥50,000 50% <700 or <50,000 Hold
2.3 Non-Small Cell Lung Cancer

Recommended Dose and Schedule

Every 4-week schedule

The recommended dose of Gemcitabine for Injection USP is 1000 mg/m2 intravenously over 30 minutes on Days 1, 8, and 15 in combination with cisplatin therapy. Administer cisplatin intravenously at 100 mg/m2 on Day 1 after the infusion of Gemcitabine for Injection USP.

Every 3-week schedule

The recommended dose of Gemcitabine for Injection USP is 1250 mg/m2 intravenously over 30 minutes on Days 1 and 8 in combination with cisplatin therapy. Administer cisplatin intravenously at 100 mg/m2 on Day 1 after the infusion of Gemcitabine for Injection USP.

Dose Modifications

Recommended dose modifications for Gemcitabine for Injection USP myelosuppression are described in Table 4 [see Warnings and Precautions (5.2)]. Refer to Dosage and Administration (2.5) for Gemcitabine for Injection USP recommendations for non-hematologic adverse reactions.

2.4 Pancreatic Cancer

Recommended Dose and Schedule

The recommended dose of Gemcitabine for Injection USP is 1000 mg/m2 over 30 minutes intravenously. The recommended treatment schedule
Weeks 1 to 8: weekly dosing for the first 7 weeks followed by one week rest. After week 8: weekly dosing on Days 1, 8, and 15 of 28-day cycles.
Dose Modifications

Recommended dose modifications for Gemcitabine for Injection USP for myelosuppression are described in Table 4 [see Warnings and Precautions (5.2)]. Refer to Dosage and Administration (2.5) for recommendations for non-hematologic adverse reactions.

Patients receiving Gemcitabine for Injection USP should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet count. If marrow suppression is detected, therapy should be modified or suspended according to the guidelines in Table 4.
Table 4: Recommended Dose Reductions for Gemcitabine for Injection USP for Myelosuppression in Pancreatic Cancer and Non-Small Cell Lung Cancer Absolute granulocyte count Platelet count % of full dose (x 106/L) (x 106/L) ≥1000 And ≥100,000 100 500 to 999 Or 50,000 to 99,999 75 <500 Or <50,000 Hold
2.5 Dose Modifications for Non-Hematologic Adverse Reactions

Permanently discontinue Gemcitabine for Injection USP for any of the following
Unexplained dyspnea or other evidence of severe pulmonary toxicity Severe hepatic toxicity Hemolytic-Uremic Syndrome Capillary Leak Syndrome Posterior reversible encephalopathy syndrome
Withhold Gemcitabine for Injection USP or reduce dose by 50% for other severe (Grade 3 or 4) non-hematological toxicity until resolved. No dose modifications are recommended for alopecia, nausea, or vomiting.

2.6 Preparation and Administration Precautions

Exercise caution and wear gloves when preparing Gemcitabine for Injection USP solutions. Immediately wash the skin thoroughly or rinse the mucosa with copious amounts of water if Gemcitabine for Injection USP contacts the skin or mucus membranes. Death has occurred in animal studies due to dermal absorption. For further guidance on handling Gemcitabine for Injection USP go to “OSHA Hazardous Drugs” (refer to antineoplastic weblinks including OSHA Technical Manual) at OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

2.7 Preparation for Intravenous Infusion Administration

Reconstitute the vials with 0.9% Sodium Chloride Injection without preservatives.

Add 5 mL to the 200-mg vial or 25 mL to the 1-g vial. These dilutions each yield a Gemcitabine for Injection USP concentration of 38 mg/mL. Complete withdrawal of the vial contents will provide 200 mg or 1 g of Gemcitabine for Injection USP. Prior to administration the appropriate amount of drug must be diluted with 0.9% Sodium Chloride Injection. Final concentrations may be as low as 0.1 mg/mL.

Reconstituted Gemcitabine for Injection USP is a clear, colorless to light straw-colored solution. Inspect visually prior to administration and discard for particulate matter or discoloration. Gemcitabine for Injection USP solutions are stable for 24 hours at controlled room temperature of 20° to 25°C (68° to 77°F). Do not refrigerate as crystallization can occur.

No incompatibilities have been observed with infusion bottles or polyvinyl chloride bags and administration sets.
Fesi

Fesi

For safety reasons, only prescribers who enroll in the Prometheus Prescribing Program for LOTRONEX which includes its authorized generic alosetron hydrochloride should prescribe alosetron hydrochloride [see Warnings and Precautions (5.3)].

2.1 Adult Patients

To lower the risk of constipation, alosetron hydrochloride should be started at a dosage of 0.5 mg twice a day. Patients who become constipated at this dosage should stop taking alosetron hydrochloride until the constipation resolves. They may be restarted at 0.5 mg once a day. If constipation recurs at the lower dose, alosetron hydrochloride should be discontinued immediately.

Patients well controlled on 0.5 mg once or twice a day may be maintained on this regimen. If after 4 weeks the dosage is well tolerated but does not adequately control IBS symptoms, then the dosage can be increased to up to 1 mg twice a day. Alosetron hydrochloride should be discontinued in patients who have not had adequate control of IBS symptoms after 4 weeks of treatment with 1 mg twice a day.

Alosetron hydrochloride can be taken with or without food [see Clinical Pharmacology (12.3)].

Alosetron hydrochloride should be discontinued immediately in patients who develop constipation or signs of ischemic colitis. Alosetron hydrochloride should not be restarted in patients who develop ischemic colitis.

Clinical trial and postmarketing experience suggest that debilitated patients or patients taking additional medications that decrease gastrointestinal motility may be at greater risk of serious complications of constipation. Therefore, appropriate caution and follow-up should be exercised if alosetron hydrochloride is prescribed for these patients.

Postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation; therefore, appropriate caution and follow-up should be exercised if alosetron hydrochloride is prescribed for these patients [see Warnings and Precautions (5.1)].

2.2 Patients With Hepatic Impairment

Alosetron hydrochloride is extensively metabolized by the liver, and increased exposure to alosetron hydrochloride is likely to occur in patients with hepatic impairment. Increased drug exposure may increase the risk of serious adverse reactions. Alosetron hydrochloride should be used with caution in patients with mild or moderate hepatic impairment and is contraindicated in patients with severe hepatic impairment [see Contraindications (4), Use in Specific Populations (8.6)].

2.3 Information for Pharmacists

Alosetron hydrochloride may be dispensed only on presentation of a prescription for alosetron hydrochloride with a sticker for the Prescribing Program for LOTRONEX attached. A Medication Guide for alosetron hydrochloride must be given to the patient each time alosetron hydrochloride is dispensed as required by law. No telephone, facsimile, or computerized prescriptions are permitted with this program. Refills are permitted to be written on prescriptions.
Rapaflo

Rapaflo

One or 2 capsules every 4 hours. Total daily dosage should not exceed 6 capsules.

Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Clobetasol Propionate

Clobetasol Propionate

Apply a thin layer of clobetasol propionate cream to the affected skin areas twice daily and rub in gently and completely. Clobetasol propionate cream is a super-high potency topical corticosteroid; therefore, treatment should be limited to 2 consecutive weeks, and amounts greater than 50 g per week should not be used. As with other highly active corticosteroids, therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Clobetasol propionate cream should not be used with occlusive dressings.
Nystatin And Triamcinol...

Nystatin And Triamcinolone Acetonide

Nystatin and Triamcinolone Acetonide Cream is usually applied to the affected areas twice daily in the morning and the evening by gently and thoroughly massaging the preparation into the skin. The cream should be discontinued if symptoms persist after 25 days of therapy (see PRECAUTIONS, Laboratory Tests).Nystatin and Triamcinolone Acetonide Cream should not be used with occlusive dressings.
Bimectin Pour-on

Bimectin Pour-on

Note: Contact of the undiluted concentrate with plasticized PVC equipment or devices used to prepare solutions for infusion is not recommended. In order to minimize patient exposure to the plasticizer DEHP [di-(2-ethylhexyl)phthalate], which may be leached from PVC infusion bags or sets, diluted Paclitaxel Injection USP solutions should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.

All patients should be premedicated prior to Paclitaxel Injection USP administration in order to prevent severe hypersensitivity reactions. Such premedication may consist of dexamethasone 20 mg PO administered approximately 12 and 6 hours before Paclitaxel Injection USP, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to Paclitaxel Injection USP, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before Paclitaxel Injection USP.

For patients with carcinoma of the ovary, the following regimens are recommended (see CLINICAL STUDIES: Ovarian Carcinoma):

1) For previously untreated patients with carcinoma of the ovary, one of the following recommended regimens may be given every 3 weeks. In selecting the appropriate regimen, differences in toxicities should be considered (see TABLE 11 in ADVERSE REACTIONS: Disease-Specific Adverse Event Experiences).
Paclitaxel administered intravenously over 3 hours at a dose of 175 mg/m2 followed by cisplatin at a dose of 75 mg/m2; or Paclitaxel administered intravenously over 24 hours at a dose of 135 mg/m2 followed by cisplatin at a dose of 75 mg/m2.
2) In patients previously treated with chemotherapy for carcinoma of the ovary, paclitaxel has been used at several doses and schedules; however, the optimal regimen is not yet clear. The recommended regimen is paclitaxel 135 mg/m2 or 175 mg/m2 administered intravenously over 3 hours every 3 weeks.

For patients with carcinoma of the breast, the following regimens are recommended (see CLINICAL STUDIES: Breast Carcinoma):

1) For the adjuvant treatment of node-positive breast cancer, the recommended regimen is paclitaxel, at a dose of 175 mg/m2 intravenously over 3 hours every 3 weeks for 4 courses administered sequentially to doxorubicin-containing combination chemotherapy. The clinical trial used 4 courses of doxorubicin and cyclophosphamide (see CLINICAL STUDIES: Breast Carcinoma).

2) After failure of initial chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy, paclitaxel at a dose of 175 mg/m2 administered intravenously over 3 hours every 3 weeks has been shown to be effective.

For patients with non-small cell lung carcinoma, the recommended regimen, given every 3 weeks, is paclitaxel administered intravenously over 24 hours at a dose of 135 mg/m2 followed by cisplatin, 75 mg/m2.

For patients with AIDS-related Kaposi’s sarcoma, paclitaxel administered at a dose of 135 mg/m2 given intravenously over 3 hours every 3 weeks or at a dose of 100 mg/m2 given intravenously over 3 hours every 2 weeks is recommended (dose intensity 45 to 50 mg/m2/week). In the 2 clinical trials evaluating these schedules (see CLINICAL STUDIES: AIDS-Related Kaposi’s Sarcoma), the former schedule (135 mg/m2 every 3 weeks) was more toxic than the latter. In addition, all patients with low performance status were treated with the latter schedule (100 mg/m2 every 2 weeks).

Based upon the immunosuppression in patients with advanced HIV disease, the following modifications are recommended in these patients:

1) Reduce the dose of dexamethasone as 1 of the 3 premedication drugs to 10 mg PO (instead of 20 mg PO);

2) Initiate or repeat treatment with Paclitaxel Injection USP only if the neutrophil count is at least 1000 cells/mm3;

3) Reduce the dose of subsequent courses of Paclitaxel Injection USP by 20% for patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer); and

4) Initiate concomitant hematopoietic growth factor (G-CSF) as clinically indicated.

For the therapy of patients with solid tumors (ovary, breast, and NSCLC), courses of Paclitaxel Injection USP should not be repeated until the neutrophil count is at least 1500 cells/mm3 and the platelet count is at least 100,000 cells/mm3. Paclitaxel Injection USP should not be given to patients with AIDS-related Kaposi’s sarcoma if the baseline or subsequent neutrophil count is less than 1000 cells/mm3. Patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer) or severe peripheral neuropathy during Paclitaxel Injection USP therapy should have dosage reduced by 20% for subsequent courses of Paclitaxel Injection USP. The incidence of neurotoxicity and the severity of neutropenia increase with dose.

Hepatic Impairment: Patients with hepatic impairment may be at increased risk of toxicity, particularly grade III–IV myelosuppression (see CLINICAL PHARMACOLOGY and PRECAUTIONS: Hepatic). Recommendations for dosage adjustment for the first course of therapy are shown in TABLE 17 for both 3- and 24-hour infusions. Further dose reduction in subsequent courses should be based on individual tolerance. Patients should be monitored closely for the development of profound myelosuppression.
TABLE 17 RECOMMENDATIONS FOR DOSING IN PATIENTS WITH HEPATIC IMPAIRMENT BASED ON CLINICAL TRIAL DATAa Degree of Hepatic Impairment Transaminase Levels Bilirubin Levelsb Recommended PACLITAXEL Dosec a These recommendations are based on dosages for patients without hepatic impairment of 135 mg/m2 over 24 hours or 175 mg/m2 over 3 hours; data are not available to make dose adjustment recommendations for other regimens (eg, for AIDS-related Kaposi’s sarcoma). b Differences in criteria for bilirubin levels between the 3- and 24-hour infusion are due to differences in clinical trial design. c Dosage recommendations are for the first course of therapy; further dose reduction in subsequent courses should be based on individual tolerance. 24-hour infusion <2 x ULN and ≤1.5 mg/dL 135 mg/m2 2 to <10 x ULN and ≤1.5 mg/dL 100 mg/m2 <10 x ULN and 1.6 to 7.5 mg/dL 50 mg/m2 ≥10 x ULN or >7.5 mg/dL Not recommended 3-hour infusion <10 x ULN and ≤1.25 x ULN 175 mg/m2 <10 x ULN and 1.26 to 2.0 x ULN 135 mg/m2 <10 x ULN and 2.01 to 5.0 x ULN 90 mg/m2 ≥10 x ULN or >5.0 x ULN Not recommended
Preparation and Administration Precautions

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1-4To minimize the risk of dermal exposure, always wear impervious gloves when handling vials containing Paclitaxel Injection USP. If Paclitaxel Injection USP solution contacts the skin, wash the skin immediately and thoroughly with soap and water. Following topical exposure, events have included tingling, burning, and redness. If Paclitaxel Injection USP contacts mucous membranes, the membranes should be flushed thoroughly with water. Upon inhalation, dyspnea, chest pain, burning eyes, sore throat, and nausea have been reported.

Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration (see PRECAUTION: Injection Site Reaction).

Preparation for Intravenous Administration

Paclitaxel Injection USP must be diluted prior to infusion. Paclitaxel Injection USP should be diluted in 0.9% Sodium Chloride Injection, USP, 5% Dextrose Injection, USP, 5% Dextrose and 0.9% Sodium Chloride Injection, USP, or 5% Dextrose in Ringer’s Injection to a final concentration of 0.3 to 1.2 mg/mL. The solutions are physically and chemically stable for up to 27 hours at ambient temperature (approximately 25° C) and room lighting conditions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Upon preparation, solutions may show haziness, which is attributed to the formulation vehicle. No significant losses in potency have been noted following simulated delivery of the solution through IV tubing containing an in-line (0.22 micron) filter.

Data collected for the presence of the extractable plasticizer DEHP [di-(2-ethylhexyl)phthalate] show that levels increase with time and concentration when dilutions are prepared in PVC containers. Consequently, the use of plasticized PVC containers and administration sets is not recommended. Paclitaxel Injection USP solutions should be prepared and stored in glass, polypropylene, or polyolefin containers. Non-PVC containing administration sets, such as those which are polyethylene-lined, should be used.

Paclitaxel Injection USP should be administered through an in-line filter with a microporous membrane not greater than 0.22 microns. Use of filter devices such as IVEX-2® filters which incorporate short inlet and outlet PVC-coated tubing has not resulted in significant leaching of DEHP.

The Chemo Dispensing Pin™ device or similar devices with spikes should not be used with vials of Paclitaxel Injection USP since they can cause the stopper to collapse resulting in loss of sterile integrity of the Paclitaxel Injection USP solution.

Parenteral products should be visually inspected for particulate matter.

Stability

Unopened vials of Paclitaxel Injection USP are stable until the date indicated on the package when stored between 20°–25° C (68°–77° F), in the original package. Neither freezing nor refrigeration adversely affects the stability of the product. Upon refrigeration, components in the Paclitaxel Injection USP vial may precipitate, but will redissolve upon reaching room temperature with little or no agitation. There is no impact on product quality under these circumstances. If the solution remains cloudy or if an insoluble precipitate is noted, the vial should be discarded. Solutions for infusion prepared as recommended are stable at ambient temperature (approximately 25° C) and lighting conditions for up to 27 hours.
Fiorinal

Fiorinal

One or 2 capsules every 4 hours. Total daily dose should not exceed 6 capsules. Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Actigall

Actigall

Gallstone Dissolution

The recommended dose for Actigall treatment of radiolucent gallbladder stones is 8-10 mg/kg/day given in 2 or 3 divided doses.

Ultrasound images of the gallbladder should be obtained at 6-month intervals for the first year of Actigall therapy to monitor gallstone response. If gallstones appear to have dissolved, Actigall therapy should be continued and dissolution confirmed on a repeat ultrasound examination within 1-3 months. Most patients who eventually achieve complete stone dissolution will show partial or complete dissolution at the first on-treatment reevaluation. If partial stone dissolution is not seen by 12 months of Actigall therapy, the likelihood of success is greatly reduced.

Gallstone Prevention

The recommended dosage of Actigall for gallstone prevention in patients undergoing rapid weight loss is 600 mg/day (300 mg b.i.d.).
Disopyramide Phosphate

Disopyramide Phosphate

The dosage of disopyramide (as the phosphate) must be individualized for each patient on the basis of response and tolerance. The usual adult dosage of disopyramide is 400 to 800 mg (calculated as the disopyramide base) per day given in divided doses. The recommended dosage for most adults is 600 mg/day given in divided doses (150 mg every 6 hours). For patients whose body weight is less than 110 pounds (50 kg), the recommended dosage is 400 mg/day given in divided doses (100 mg every 6 hours). In the event of increased anticholinergic side effects, plasma levels of disopyramide should be monitored and the dose of the drug adjusted accordingly. A reduction of the dose by one third, from the recommended 600 mg/day to 400 mg/day, would be reasonable, without changing the dosing interval.

For patients with cardiomyopathy or possible cardiac decompensation, a loading dose, as discussed below, should not be given, and initial dosage should be limited to 100 mg every 6 to 8 hours. Subsequent dosage adjustments should be made gradually, with close monitoring for the possible development of hypotension and/or congestive heart failure (see WARNINGS).

For patients with moderate renal insufficiency (creatinine clearance greater than 40 mL/min) or hepatic insufficiency, the recommended dosage is 400 mg/day given in divided doses (100 mg every 6 hours).

For patients with severe renal insufficiency (Ccr 40 mL/min or less), the recommended dosage regimen of disopyramide is 100 mg at intervals shown in the table below, with or without an initial loading dose of 150 mg.
DISOPYRAMIDE PHOSPHATE DOSAGE INTERVAL FOR PATIENTS WITH RENAL INSUFFICIENCY Creatinine clearance (mL/min) 40-30 30-15 less than 15 Approximate Maintenance- dosing interval q 8 hr q 12 hr q 24 hr
For patients in whom rapid control of ventricular arrhythmia is essential, an initial loading dose of 300 mg disopyramide (200 mg for patients whose body weight is less than 110 pounds) is recommended, followed by the appropriate maintenance dosage. Therapeutic effects are usually attained 30 minutes to 3 hours after administration of a 300 mg loading dose. If there is no response or evidence of toxicity within 6 hours of the loading dose, 200 mg of disopyramide every 6 hours may be prescribed instead of the usual 150 mg. If there is no response to this dosage within 48 hours, either disopyramide should then be discontinued or the physician should consider hospitalizing the patient for careful monitoring while subsequent disopyramide doses of 250 mg or 300 mg every 6 hours are given. A limited number of patients with severe refractory ventricular tachycardia have tolerated daily doses of disopyramide up to 1600 mg per day (400 mg every 6 hours), resulting in disopyramide plasma levels up to 9 mcg/mL. If such treatment is warranted, it is essential that patients be hospitalized for close evaluation and continuous monitoring.

Transferring to Disopyramide Phosphate

The following dosage schedule based on theoretical considerations rather than experimental data is suggested for transferring patients with normal renal function from either quinidine sulfate or procainamide therapy (Type 1 antiarrhythmic agents) to disopyramide therapy:

Disopyramide should be started using the regular maintenance schedule without a loading dose 6 to 12 hours after the last dose of quinidine sulfate or 3 to 6 hours after the last dose of procainamide.

In patients in whom withdrawal of quinidine sulfate or procainamide is likely to produce life-threatening arrhythmias, the physician should consider hospitalization of the patient.

Pediatric Dosage

Controlled clinical studies have not been conducted in pediatric patients; however, the following suggested dosage table is based on published clinical experience.

Total daily dosage should be divided and equal doses administered orally every 6 hours or at intervals according to individual patient needs. Disopyramide plasma levels and therapeutic response must be monitored closely. Patients should be hospitalized during the initial treatment period, and dose titration should start at the lower end of the ranges provided below.
SUGGESTED TOTAL DAILY DOSAGE* Age (years) Disopyramide (mg/kg body weight/day) *Dosage is expressed in milligrams of disopyramide base. Under 1 10 to 30 1 to 4 10 to 20 4 to 12 10 to 15 12 to 18 6 to 15
Since disopyramide phosphate 100 mg capsules contain 100 mg of disopyramide base, the pharmacist can readily prepare a 1 mg/mL to 10 mg/mL liquid suspension by adding the entire contents of disopyramide phosphate capsules to cherry syrup, (Prepare cherry syrup as follows: cherry juice, 475 mL; sucrose 800 g; alcohol, 20 mL; purified water, a sufficient quantity to make 1000 mL). The resulting suspension, when refrigerated, is stable for one month and should be thoroughly shaken before measurement of each dose. The suspension should be dispensed in an amber glass bottle with a child-resistant closure.
Naproxen

Naproxen

Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance.

Lower dosages are recommended for elderly patients and adolescents. Lower dosages are also recommended for outpatients as compared to hospitalized patients who will be under close supervision. It is not possible to prescribe a single dosage schedule of trimipramine maleate that will be therapeutically effective in all patients. The physical psychodynamic factors contributing to depressive symptomatology are very complex; spontaneous remissions or exacerbations of depressive symptoms may occur with or without drug therapy. Consequently, the recommended dosage regimens are furnished as a guide which may be modified by factors such as the age of the patient, chronicity and severity of the disease, medical condition of the patient, and degree of psychotherapeutic support.

Most antidepressant drugs have a lag period of ten days to four weeks before a therapeutic response is noted. Increasing the dose will not shorten this period but rather increase the incidence of adverse reactions.

Usual Adult Dose

Outpatients and Office Patients—Initially, 75 mg/day in divided doses, increased to 150 mg/day. Dosages over 200 mg/day are not recommended. Maintenance therapy is in the range of 50 to 150 mg/day. For convenient therapy and to facilitate patient compliance, the total dosage requirement may be given at bedtime.

Hospitalized Patients—Initially, 100 mg/day in divided doses. This may be increased gradually in a few days to 200 mg/day, depending upon individual response and tolerance. If improvement does not occur in 2 to 3 weeks, the dose may be increased to the maximum recommended dose of 250 to 300 mg/day.

Adolescent and Geriatric Patients—Initially, a dose of 50 mg/day is recommended, with gradual increments up to 100 mg/day, depending upon patient response and tolerance.

Maintenance—Following remission, maintenance medication may be required for a longer period of time, at the lowest dose that will maintain remission. Maintenance therapy is preferably administered as a single dose at bedtime. To minimize relapse, maintenance therapy should be continued for about three months.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders: At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with trimipramine maleate. Conversely, at least 14 days should be allowed after stopping trimipramine maleate before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).

Use of Trimipramine Maleate With Other MAOIs, Such as Linezolid or Methylene Blue: Do not start trimipramine maleate in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).

In some cases, a patient already receiving therapy with trimipramine maleate may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, trimipramine maleate should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with trimipramine maleate may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with trimipramine maleate is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).
Methylphenidate Hcl

Methylphenidate Hcl

There is currently no dosage information available for this product. We apologize for any inconvenience.
Famciclovir

Famciclovir

Famciclovir tablets may be taken with or without food.

2.1 Dosing Recommendation in Immunocompetent Adult Patients

Herpes labialis (cold sores): The recommended dosage of famciclovir tablets for the treatment of recurrent herpes labialis is 1500 mg as a single dose. Therapy should be initiated at the first sign or symptom of herpes labialis (e.g., tingling, itching, burning, pain, or lesion).

Genital herpes:

Recurrent episodes: The recommended dosage of famciclovir tablets for the treatment of recurrent episodes of genital herpes is 1000 mg twice daily for 1 day. Therapy should be initiated at the first sign or symptom of a recurrent episode (e.g., tingling, itching, burning, pain, or lesion).

Suppressive therapy: The recommended dosage of famciclovir tablets for chronic suppressive therapy of recurrent episodes of genital herpes is 250 mg twice daily.

2.2 Dosing Recommendation in HIV-Infected Adult Patients

Recurrent orolabial or genital herpes: The recommended dosage of famciclovir tablets for the treatment of recurrent orolabial or genital herpes in HIV-infected patients is 500 mg twice daily for 7 days. Therapy should be initiated at the first sign or symptom of a recurrent episode (e.g., tingling, itching, burning, pain, or lesion).

2.3 Dosing Recommendation in Patients with Renal Impairment

Dosage recommendations for adult patients with renal impairment are provided in Table 1 [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Table 1 Dosage Recommendations for Adult Patients with Renal Impairment * Hemodialysis Indication and Normal Dosage Regimen Creatinine Clearance (mL/min.) Adjusted Dosage Regimen Dose (mg) Dosing Interval Single-Day Dosing Regimens Recurrent Genital Herpes1000 mg every 12 hours for 1 day ≥60 1000 every 12 hours for 1 day 40-59 500 every 12 hours for 1 day 20-39 500 single dose <20 250 single dose HD* 250 single dose following dialysis Recurrent Herpes Labialis1500 mg single dose ≥60 1500 single dose 40-59 750 single dose 20-39 500 single dose <20 250 single dose HD* 250 single dose following dialysis Multiple-Day Dosing Regimens Suppression of RecurrentGenital Herpes250 mg every 12 hours ≥40 250 every 12 hours 20-39 125 every 12 hours <20 125 every 24 hours HD* 125 following each dialysis Recurrent Orolabialor Genital Herpesin HIV-Infected Patients500 mg every 12 hours ≥40 500 every 12 hours 20-39 500 every 24 hours <20 250 every 24 hours HD* 250 following each dialysis
Acetylcysteine Inhalant...

Acetylcysteine Inhalant

LILETTA contains 52 mg of levonorgestrel (LNG). Initially, LNG is released at a rate of 18.6 mcg/day. This rate decreases progressively to approximately 16.3 mcg/day at 1 year, 14.3 mcg/day at 2 years, and 12.6 mcg/day at 3 years after insertion. The average in vivo release rate of LNG is approximately 15.6 mcg/day over a period of 3 years.

LILETTA can be removed at any time but must be removed by the end of the third year. LILETTA can be replaced at the time of removal with a new LILETTA if continued contraceptive protection is desired.

2.1 Insertion Instructions

LILETTA (Figure 1) is provided in a sterile pouch [see Description (11)] and is inserted into the uterine cavity with the provided inserter (Figure 2) by carefully following the insertion instructions. Use strict aseptic techniques throughout the insertion procedure [see Warnings and Precautions (5.3)].

2.1. Insertion

Figure 1  LILETTA Intrauterine Contraceptive System (IUS)

Figure 2: LILETTA IUS with Inserter

LILETTA should only be inserted by a trained healthcare provider. Healthcare providers should become thoroughly familiar with the product, product educational materials, product insertion instructions, prescribing information, and patient labeling before attempting insertion of LILETTA.
Obtain a complete medical and social history to determine conditions that might influence the selection of a levonorgestrel-releasing intrauterine system (LILETTA) for contraception. If indicated, perform a physical examination and appropriate tests for genital or sexually transmitted infections. [See Contraindications (4) and Warnings and Precautions (5.4, 5.10).] Check the expiration date on the box before opening it. Do not insert LILETTA after the expiration date. Visually inspect the packaging (sealed pouch) containing LILETTA to verify that the packaging has not been damaged (e.g., torn, punctured, etc.). If the packaging has any visual damage that could compromise sterility, do not use the unit for insertion [see Warnings and Precautions (5.3)]. Ensure that the patient understands the contents of the Patient Information Booklet and obtain consent. A sample consent form that includes the lot number is on the last page of the Patient Information Booklet. Complete the pelvic examination, speculum placement, tenaculum placement, and sounding of the uterus before opening the LILETTA pouch. Do not open the pouch to insert LILETTA if the cervix is unable to be properly visualized, if the uterus cannot be adequately instrumented (during sounding), or if the uterus sounds to less than 5.5 cm.
Timing of Insertion

Refer to Table 1 for instructions on when to start use of LILETTA.
Table 1: When to Insert LILETTA Starting LILETTA in women not currently using hormonal or intrauterine contraception       LILETTA can be inserted any time the provider can be reasonably certain the woman is not pregnant. Consider the possibility of ovulation and conception prior to initiation of this product. If LILETTA is not inserted during the first 7 days of the menstrual cycle, a barrier method of contraception (such as condoms and spermicide) should be used or the patient should abstain from vaginal intercourse for 7 days to prevent pregnancy. Switching to LILETTA from an oral, transdermal or vaginal hormonal contraceptive              LILETTA may be inserted at any time.•    May be inserted during the hormone-free interval of the previous method•    If inserted during active use of the previous method, continue the previous method after LILETTA insertion for seven days or until the end of the current cycle. If using continuous hormonal contraception, discontinue the method seven days after LILETTA insertion. Switching to LILETTA from an injectable progestin contraceptive                                            LILETTA may be inserted at any time; a barrier method of contraception (such as condoms and spermicide) should also be used for 7 days if LILETTA is inserted as instructed more than 3 months (13 weeks) after the last injection. Switching to LILETTA from a contraceptive implant or another IUS                                           Insert LILETTA on the same day the implant or IUS is removed. LILETTA may be inserted at any time during the menstrual cycle. Inserting LILETTA after abortion or miscarriage First-trimester LILETTA may be inserted immediately after a first-trimester abortion or miscarriage. Second-trimester Do not insert LILETTA until a minimum of 6 weeks after second trimester abortion or miscarriage, or until the uterus is fully involuted. If involution is delayed, wait until involution is complete before insertion [see Warnings and Precautions (5.5, 5.6)]. If the woman has not yet had a period, consider the possibility of ovulation and conception occurring prior to insertion of LILETTA. [See Contraindications (4), Warnings and Precautions (5.2), and FDA-Approved Patient Labeling.] LILETTA can be inserted any time the provider can be reasonably certain the woman is not pregnant. If LILETTA is not inserted during the first 7 days of the menstrual cycle, a barrier method of contraception should be used or the patient should abstain from vaginal intercourse for 7 days to prevent pregnancy. Inserting LILETTA after Childbirth Do not insert LILETTA until a minimum of 6 weeks after delivery, or until the uterus is fully involuted. If involution is delayed, wait until involution is complete before insertion [see Warnings and Precautions (5.5, 5.6)]. If the woman has not yet had a period, consider the possibility of ovulation and conception occurring prior to insertion of LILETTA. [See Contraindications (4), Warnings and Precautions (5.2), and FDA-Approved Patient Labeling.] LILETTA can be inserted any time the provider can be reasonably certain the woman is not pregnant. If LILETTA is not inserted during the first 7 days of the menstrual cycle, a barrier method of contraception should be used or the patient should abstain from vaginal intercourse for 7 days to prevent pregnancy. There appears to be an increased risk of perforation in lactating women. [See Warnings and Precautions (5.5).]
Planning for Insertion
Ensure all needed items for LILETTA insertion are readily available:○ Gloves○ Speculum○ Sterile uterine sound○ Sterile tenaculum○ Antiseptic solution○ LILETTA with inserter in sealed pouch ○ Sterile, blunt-tipped scissors ○ Additional items that may be useful could include:     •   Local anesthesia, needle, and syringe     •   Os finder and/or cervical dilators     •   Ultrasound with abdominal probe Exclude pregnancy and confirm that there are no other contraindications to the insertion and use of LILETTA. Follow the insertion instructions exactly as described in order to ensure proper insertion. If you encounter cervical stenosis at any time during uterine sounding or LILETTA insertion, use cervical dilators, not force, to overcome resistance. If necessary, dilation, sounding, and insertion may be performed with ultrasound guidance. Insertion may be associated with some pain and/or bleeding or vasovagal reactions (e.g., diaphoresis, syncope, bradycardia, or seizure), especially in patients with a predisposition to these conditions. Consider administering analgesics prior to insertion.
Use aseptic technique during the entire insertion procedure. Loading and inserting LILETTA does not require sterile gloves. If not using sterile gloves, complete all steps for loading the IUS (Steps 1-7) inside the pouch. Maintain sterility during LILETTA insertion; do not touch LILETTA or parts of any sterile instrument that will pierce tissue (e.g., a tenaculum on the cervix) or go into the uterine cavity.

Preparation for Insertion
With the patient comfortably in lithotomy position, do a bimanual exam to establish the size, shape, and position of the uterus and to evaluate any signs of uterine infection. Gently insert a speculum to visualize the cervix. Thoroughly cleanse the cervix and vagina with antiseptic solution. Administer cervical anesthetic, if needed. Apply a tenaculum to the cervix and use gentle traction to align the cervical canal with the uterine cavity. If the uterus is retroverted, it may be more appropriate to grasp the lower lip of the cervix. Keep the tenaculum in position and maintain gentle traction on the cervix throughout the insertion procedure. Carefully sound the uterus to measure its depth. The uterus should sound to a depth of at least 5.5 cm. Insertion of LILETTA into a uterine cavity that sounds to less than 5.5 cm may increase the incidence of expulsion, bleeding, pain, perforation, and possibly pregnancy. LILETTA should not be inserted if the uterus sounds to less than 5.5 cm. After ascertaining that the patient is appropriate for LILETTA, open the pouch containing LILETTA.
Insertion Procedure

Loading the IUS into the Inserter

Step 1
Place the LILETTA pouch on a flat surface with the clear side of the pouch facing up (Figure 3).
Figure 3:  Place the LILETTA pouch on a flat surface.

Open the sterile LILETTA pouch from the bottom (end with the rod ring) approximately 1/3 of the way until the lower ends of the IUS threads, the rod, and the insertion tube are exposed (Figure 4).
If using sterile gloves, you can open the pouch completely before putting on the sterile gloves.

Figure 4:  Release the threads from the flange and insert the rod.

Step 2
Pull back the blue threads to dislodge them from the flange. Be careful to not pull the IUS down at the same time (Figure 4).
Step 3
Hold the exposed end of the insertion tube containing the IUS (Figure 4) while keeping the end of the insertion tube with the IUS inside the packaging. Remove the rod from the pouch. Do not touch the end of the rod that will go into the insertion tube. Place the rod into the insertion tube (alongside the IUS threads) to about the 5 cm marking (Figure 4).
Step 4
While holding the insertion tube and the rod firmly between the fingers and thumb of one hand, pull downward on both blue threads with the other hand to draw the IUS into the insertion tube (Figure 5). The arms of the IUS should be kept in a horizontal plane, parallel to the flat side of the flange (refer to Figure 4). Do not pull the IUS all of the way through the insertion tube; only pull the threads until the IUS is loaded at the top of the insertion tube. Note: If you accidentally remove the IUS completely out of the insertion tube, do not use or attempt to re-load. Figure 5: Pull on the threads to pull the IUS into the tube. Figure 6: Adjust the Flange.
Step 5
Hold the insertion tube and the rod firmly with one hand. With the other hand, adjust the position of the flange (through the sterile packaging if not using sterile gloves) by moving the tube to correspond to the sound measurement (Figure 6). The top end of the flange should be at the measurement corresponding to the sounded depth of the uterus.
Step 6
Final IUS positioning: position the IUS in the tube so that the knobs of the lateral arms are opposed to each other and protrude slightly above the tip of the insertion tube to form a hemispherical dome (Figure 7). Hold the tube at its proximal end between your fingers and thumb of one hand. With the other hand, while pulling on the blue threads, slowly advance the rod forward to adjust the position of the IUS. When the IUS tips are in the correct position (slightly protruding), pinch and hold the proximal end of the tube firmly to maintain rod position. The proximal end of the insertion tube will be approximately at the top of the first indent on the rod (Figure 7).
Figure 7:  Final IUS Positioning
ENSURE A HEMISPHERICAL DOME IS ACHIEVED. When the IUS is in the correct position, the lower end of the tube will be aligned approximately at the upper edge of the upper indent on the rod.
Step 7

Check to make sure the IUS is correctly loaded. You should note the following:
The IUS is completely within the insertion tube with the knobs of the arms forming a hemispherical dome at the top of the tube. The top of the rod is touching the bottom of the IUS. The blue threads are hanging through the end of the insertion tube. The flange is marking the depth of the uterus based on pre-insertion sounding.
Step 8

Remove the loaded IUS insertion tube from the pouch while holding the lower end of the tube firmly between your fingers and thumb.

If not using sterile gloves, do not touch the flange and any part of the insertion tube above the flange during this step and through the IUS insertion procedure.

IUS Insertion into the Uterus

Step 1
Apply gentle traction on the tenaculum to straighten the alignment of the cervical canal and uterine cavity. While still firmly pinching the proximal end of the insertion tube to maintain the IUS in the correct position (Hand A), slide the loaded IUS insertion tube through the cervical canal until the upper edge of the flange is approximately 1.5 – 2.0 cm from the cervix (Figure 8). DO NOT advance flange to the cervix at this step. DO NOT force the inserter. If necessary, dilate the cervical canal. Figure 8:  While holding the rod and the tube, advance into the uterine cavity. Advance to 1.5 – 2.0 cm from the cervix. Figure 9: Hold the rod still and pull back the tube until the second indent on the rod.
Step 2
Release hold on the tenaculum. Hold the insertion tube with the fingers of one hand (Hand A) and the rod with the fingers of the other hand (Hand B). Hold the rod still (Hand B), relax the firmness of the pinch on the tube, and pull the insertion tube back with Hand A to the edge of the second indent of the rod (Figure 9). This will allow the IUS arms to open in the lower uterine segment.
Step 3
Wait 10 – 15 seconds for the arms of the IUS to fully open.
Step 4
Apply gentle traction with the tenaculum before advancing the IUS. With Hand A still holding the proximal end of the tube, advance both the insertion tube and rod simultaneously up to the uterine fundus (Figure 10). You will feel slight resistance when the IUS is at the fundus. The flange should be touching the cervix when the IUS reaches the uterine fundus.
Note: Fundal positioning is important to prevent expulsion.

Figure 10:  After 10 – 15 seconds, advance to the fundus while holding both the rod and the tube.

Step 5
Hold the rod still (Hand B) while pulling the insertion tube back with Hand A to the ring of the rod (Figure 11).
Figure 11:  Hold the rod still and pull back the tube to the ring on the rod.

Step 6
While holding the inserter tube with Hand A, withdraw the rod from the insertion tube all of the way out to prevent the rod from catching on the knot at the lower end of the IUS.
Note: Ensure the tube is held firmly in place until the rod is completely pulled outside of the tube as there will be some slight resistance while removing the rod from the tube.

Step 7
Completely remove the insertion tube.
Step 8
Use blunt-tipped sharp scissors to cut the IUS threads perpendicular to the thread length, leaving about 3 cm outside of the cervix (Figure 12). Note: Cutting threads at an angle may leave sharp ends. Do not apply tension or pull on the threads when cutting to prevent displacing the IUS.
Figure 12: Cut the threads about 3 cm from the cervix.

Insertion of LILETTA is now complete.

Important information to consider during or after insertion:
If you suspect the IUS is not in the correct position: Check insertion with an ultrasound or other appropriate radiologic test. If incorrect insertion is suspected, remove LILETTA. A removed LILETTA must not be re-inserted.
Difficult insertion
If insertion is difficult because the uterus cannot be appropriately instrumented, the following measures can be considered: Use of cervical anesthesia to make sounding and manipulation more tolerable. Use of dilators to dilate the cervix if needed to allow passage of the sound. Abdominal ultrasound guidance during dilation and/or insertion. If there is clinical concern, exceptional pain, or bleeding during or after insertion, take appropriate steps, such as physical examination and ultrasound, immediately to exclude perforation.
2.2 Patient Counseling and Record-Keeping
Keep a copy of the consent form and LILETTA lot number for your records. Counsel the patient on what to expect following LILETTA insertion. Give her the Patient Information Booklet, which includes the website address (www.LILETTA.com). Discuss expected bleeding patterns with LILETTA use. Review the signs and symptoms of LILETTA expulsion. [See Patient Counseling Information (17).] Prescribe analgesics, if indicated.
2.3 Patient Follow-Up

Re-examine and evaluate patients 4 to 6 weeks after insertion and once a year thereafter, or more frequently if clinically indicated.

2.4 Removal of LILETTA

Timing of Removal
If pregnancy is desired, LILETTA can be removed at any time. If pregnancy is not desired, LILETTA can be removed at any time; however, a contraception method should be started prior to removal of LILETTA [see Dosage and Administration (2.5)]. Counsel your patient that if she has intercourse in the week prior to removal without use of a backup contraceptive method, she is at risk of pregnancy. LILETTA should be removed after 3 years. LILETTA can be replaced at the time of removal with a new LILETTA if continued contraceptive protection is desired.
Planning for Removal
Ensure all needed items for LILETTA removal are readily available:○ Gloves○ Speculum○ Sterile forceps○ Additional items that may be required could include:      •     Local anesthetic, needle, and syringe      •     Os finder and/or cervical dilators      •     Ultrasound with abdominal probe      •     Sterile tenaculum      •     Antiseptic solution      •     Long, narrow forceps Removal may be associated with some pain and/or bleeding or vasovagal reactions (e.g., syncope, bradycardia, or seizure), especially in patients with a predisposition to these conditions. After removal of LILETTA, examine the system to ensure that it is intact.
Removal Instructions
With the patient comfortably in lithotomy position, place a speculum and visualize the cervix. When the threads of LILETTA are visible:○ Remove the IUS by applying gentle traction on the threads with forceps (Figure 13).○ The arms of the device will fold upward as it is withdrawn from the uterus.○ If the IUS cannot be removed with traction on the threads, perform an ultrasound examination to confirm location of the IUS, including assessment for partial or total perforation. If the IUS is in the uterus, use a long, narrow forceps to grasp LILETTA. Consider use of a tenaculum, cervical anesthesia, cervical dilators, and/or ultrasound guidance as needed. If the threads of LILETTA are not visible:○ Determine location of the IUS by ultrasound examination.○ If the IUS is in the uterine cavity, use a long, narrow forceps (e.g., Alligator forceps) to grasp LILETTA. Consider use of a tenaculum, cervical anesthesia, cervical dilators, and/or ultrasound guidance as needed. If LILETTA cannot be removed using the above techniques, consider hysteroscopic evaluation for removal.○ If the IUS is not in the uterine cavity, consider an abdominal x-ray or CT scan to evaluate if the IUS is in the abdominal cavity. Consider laparoscopic evaluation for removal, as clinically indicated.
Figure 13:  Removal of LILETTA

2.5 Continuation of Contraception After Removal
If pregnancy is not desired and if a woman wishes to continue using LILETTA, a new system can be inserted immediately after removal any time during the cycle. If a patient with regular cycles wants to start a different birth control method, time the removal and initiation of a new method to ensure continuous contraception. Either remove LILETTA during the first 7 days of the menstrual cycle and start the new method or start the new method at least 7 days prior to removing LILETTA if removal is to occur at other times during the cycle. If a patient with irregular cycles or amenorrhea wants to start a different birth control method, start the new method at least 7 days before LILETTA removal. If LILETTA is removed but no other contraceptive method has already been started, the new contraceptive method can be started on the day LILETTA is removed. The patient should use a backup barrier method of contraception (e.g., condoms and spermicide) or abstain from vaginal intercourse for 7 days to prevent pregnancy.
Condylox

Condylox

The prescriber should ensure that the patient is fully aware of the correct method of therapy and identify which specific warts should be treated.

Apply twice daily for 3 consecutive days, then discontinue for 4 consecutive days. This one week cycle of treatment may be repeated until there is no visible wart tissue or for a maximum of four cycles. If there is incomplete response after four treatment cycles, discontinue treatment and consider alternative treatment. Safety and effectiveness of more than four treatment cycles has not been established. There is no evidence to suggest that more frequent application will increase efficacy, but additional applications would be expected to increase the rate of local adverse reactions and systemic absorption.

Condylox Gel 0.5% should be applied to the warts with the applicator tip or finger. Application on the surrounding normal tissue should be minimized. Treatment should be limited to 10 cm2 or less of wart tissue and to no more than 0.5 g of the gel per day.

Care should be taken to allow the gel to dry before allowing the return of opposing skin surfaces to their normal positions. Patients should be instructed to wash their hands thoroughly before and after each application.
Condylox

Condylox

In order to ensure that the patient is fully aware of the correct method of therapy and to identify which specific warts should be treated, the technique for initial application of the medication should be demonstrated by the prescriber.

Apply twice daily morning and evening (every 12 hours), for 3 consecutive days, then withhold use for 4 consecutive days. This one week cycle of treatment may be repeated up to four times until there is no visible wart tissue. If there is incomplete response after four treatment weeks, alternative treatment should be considered. Safety and effectiveness of more than four treatment weeks have not been established.

Condylox 0.5% Solution is applied to the warts with a cotton-tipped applicator supplied with the drug. The drug-dampened applicator should be touched to the wart to be treated, applying the minimum amount of solution necessary to cover the lesion. Treatment should be limited to less than 10 cm2 of wart tissue and to no more than 0.5 mL of the solution per day. There is no evidence to suggest that more frequent application will increase efficacy, but additional applications would be expected to increase the rate of local adverse reactions and systemic absorption.

Care should be taken to allow the solution to dry before allowing the return of opposing skin surfaces to their normal positions. After each treatment, the used applicator should be carefully disposed of and the patient should wash his or her hands.
Levetiracetam

Levetiracetam

2.1 Recommended Dosing

Levetiracetam extended-release tablets are administered once daily.

Initiate treatment with a dose of 1000 mg once daily. The once daily dosage may be adjusted in increments of 1000 mg every 2 weeks to a maximum recommended daily dose of 3000 mg/day.

2.2 Dosage Adjustment in Adult Patients with Renal Impairment

Levetiracetam extended-release tablets dosing must be individualized according to the patient's renal function status. Recommended dosage adjustments for adults are shown in Table 1. In order to calculate the dose recommended for patients with renal impairment, creatinine clearance adjusted for body surface area must be calculated. To do this, an estimate of the patient's creatinine clearance (CLcr) in mL/min must first be calculated using the following formula:

CLcr= [140-age (years)] x weight (kg) (x 0.85 for female patients) 72 x serum creatinine (mg/dL)

Then CLcr is adjusted for body surface area (BSA) as follows:

CLcr (mL/min)CLcr (mL/min/1.73m2)= ---------------------------- x 1.73 BSA subject (m2)
Table 1: Dosage Adjustment Regimen For Adult Patients With Renal Impairment Group CreatinineClearance(mL/min/1.73m2) Dosage(mg) Frequency Normal > 80 1000 to 3000 Every 24 hours Mild 50 – 80 1000 to 2000 Every 24 hours Moderate 30 – 50 500 to 1500 Every 24 hours Severe < 30 500 to 1000 Every 24 hours
Chlorzoxazone

Chlorzoxazone

Usual Adult Dosage

One tablet three or four times daily. If adequate response is not obtained with this dose, it may be increased to one and one-half tablets (750 mg) three or four times daily. As improvement occurs dosage can usually be reduced.
Benefit Boo Boo Zap Med...

Benefit Boo Boo Zap Medicated Acne Treatment

Apply sufficient quantity to adequately cover all lesions every 3 hours, 6 times per day for 7 days. The dose size per application will vary depending upon the total lesion area but should approximate a one-half inch ribbon of ointment per 4 square inches of surface area. A finger cot or rubber glove should be used when applying acyclovir to prevent autoinoculation of other body sites and transmission of infection to other persons. Therapy should be initiated as early as possible following onset of signs and symptoms.
Nitrofurantoin Suspensi...

Nitrofurantoin Suspension

Use lowest effective dose for the shortest duration consistent with treatment goals for the individual patient. These doses can be given without regard to timing of meals.

2.1 Osteoarthritis

For relief of the signs and symptoms of OA the recommended oral dose is 200 mg per day administered as a single dose or as 100 mg twice daily.

2.2 Rheumatoid Arthritis

For relief of the signs and symptoms of RA the recommended oral dose is 100 to 200 mg twice daily.

2.3 Juvenile Rheumatoid Arthritis

For the relief of the signs and symptoms of JRA the recommended oral dose for pediatric patients (age 2 years and older) is based on weight. For patients >10 kg to <25 kg the recommended dose is 50 mg twice daily. For patients >25 kg the recommended dose is 100 mg twice daily.

For patients who have difficulty swallowing capsules, the contents of a celecoxib capsule can be added to applesauce. The entire capsule contents are carefully emptied onto a level teaspoon of cool or room temperature applesauce and ingested immediately with water. The sprinkled capsule contents on applesauce are stable for up to 6 hours under refrigerated conditions (2-8° C/ 35-45° F).

2.4 Ankylosing Spondylitis

For the management of the signs and symptoms of AS, the recommended dose of celecoxib capsules is 200 mg daily in single (once per day) or divided (twice per day) doses. If no effect is observed after 6 weeks, a trial of 400 mg daily may be worthwhile. If no effect is observed after 6 weeks on 400 mg daily, a response is not likely and consideration should be given to alternate treatment options.

2.5 Management of Acute Pain and Treatment of Primary Dysmenorrhea

The recommended dose of celecoxib capsules is 400 mg initially, followed by an additional 200 mg dose if needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily as needed.

2.6 Special Populations Hepatic insufficiency:

The daily recommended dose of celecoxib capsules in patients with moderate hepatic impairment (Child-Pugh Class B) should be reduced by 50%. The use of celecoxib in patients with severe hepatic impairment is not recommended [see Warnings and Precautions (5.5), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Poor Metabolizers of CYP2C9 Substrates:

Patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin) should be administered celecoxib with caution. Consider starting treatment at half the lowest recommended dose in poor metabolizers (i.e. CYP2C9*3/*3). Consider using alternative management in JRA patients who are poor metabolizers. [see Use in Specific populations (8.8), and Clinical Pharmacology (12.5)].
Tri-norinyl

Tri-norinyl

To achieve maximum contraceptive effectiveness, oral contraceptives must be taken exactly as directed and at intervals not exceeding 24 hours.

For a DAY 1 START, count the first day of menstrual flow as Day 1 and the first blue tablet is then taken on Day 1. For a SUNDAY START when menstrual flow begins on or before Sunday, the first blue tablet is taken on that day. With either a DAY 1 START or SUNDAY START, 1 blue tablet is taken for 7 days, then 1 yellow-green tablet for 9 days, then 1 blue tablet for 5 days, then 1 orange tablet (inert) for 7 days, whether bleeding has stopped or not. With either a DAY 1 START or SUNDAY START 1 tablet is taken each day at the same time for 28 days. After all 28 tablets are taken, whether bleeding has stopped or not, the same dosage schedule is repeated beginning on the following day.
Oxaliplatin

Oxaliplatin

The usual dietary intake of potassium by the average adult is 50 to 100 mEq per day. Potassium depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of potassium from the total body store.

Dosage must be adjusted to the individual needs of each patients. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40 to 100 mEq per day or more are used for the treatment of potassium depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose. Because of the potential for gastric irritation (see WARNINGS), Potassium Chloride Extended-release Capsules, USP, 8 mEq and 10 mEq should be taken with meals and with a full glass of water or other liquid.

Patients who have difficulty swallowing capsules may sprinkle the contents of the capsule onto a spoonful of soft food. The soft food, such as applesauce or pudding, should be swallowed immediately without chewing and followed with a glass of cool water or juice to ensure complete swallowing of the microcapsules. The food used should not be hot and should be soft enough to be swallowed without chewing. Any microcapsule/food mixture should be used immediately and not stored for future use.
Acarbose

Acarbose

There is no fixed dosage regimen for the management of diabetes mellitus with acarbose tablets or any other pharmacologic agent. Dosage of acarbose tablets must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dose of 100 mg t.i.d. Acarbose tablets should be taken three times daily at the start (with the first bite) of each main meal. Acarbose tablets should be started at a low dose, with gradual dose escalation as described below, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.

During treatment initiation and dose titration (see below), one-hour postprandial plasma glucose may be used to determine the therapeutic response to acarbose tablets and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months.

The therapeutic goal should be to decrease both postprandial plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of acarbose tablets, either as monotherapy or in combination with sulfonylureas, insulin or metformin.

Initial Dosage

The recommended starting dosage of acarbose tablets is 25 mg given orally three times daily at the start (with the first bite) of each main meal. However, some patients may benefit from more gradual dose titration to minimize gastrointestinal side effects. This may be achieved by initiating treatment at 25 mg once per day and subsequently increasing the frequency of administration to achieve 25 mg t.i.d.

Maintenance Dosage

Once a 25 mg t.i.d. dosage regimen is reached, dosage of acarbose tablets should be adjusted at 4-8 week intervals based on one-hour postprandial glucose or glycosylated hemoglobin levels, and on tolerance. The dosage can be increased from 25 mg t.i.d. to 50 mg t.i.d. Some patients may benefit from further increasing the dosage to 100 mg t.i.d. The maintenance dose ranges from 50 mg t.i.d. to 100 mg t.i.d. However, since patients with low body weight may be at increased risk for elevated serum transaminases, only patients with body weight > 60 kg should be considered for dose titration above 50 mg t.i.d. (see PRECAUTIONS). If no further reduction in postprandial glucose or glycosylated hemoglobin levels is observed with titration to 100 mg t.i.d., consideration should be given to lowering the dose. Once an effective and tolerated dosage is established, it should be maintained.

Maximum Dosage

The maximum recommended dose for patients ≤ 60 kg is 50 mg t.i.d. The maximum recommended dose for patients > 60 kg is 100 mg t.i.d.

Patients Receiving Sulfonylureas or Insulin

Sulfonylurea agents or insulin may cause hypoglycemia. Acarbose tablets given in combination with a sulfonylurea or insulin will cause a further lowering of blood glucose and may increase the potential for hypoglycemia. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made.
Cyclosporine

Cyclosporine

CYCLOSPORINE CAPSULES [MODIFIED] (SOFT GELATIN) and CYCLOSPORINE ORAL SOLUTION [MODIFIED]

Cyclosporine capsules [MODIFIED] and cyclosporine oral solution [MODIFIED] have increased bioavailability in comparison to Sandimmune®* (cyclosporine capsules and cyclosporine oral solution). Cyclosporine [MODIFIED] and Sandimmune®* are not bioequivalent and cannot be used interchangeably without physician supervision.

The daily dose of cyclosporine [MODIFIED] should always be given in two divided doses (b.i.d.). It is recommended that cyclosporine [MODIFIED] be administered on a consistent schedule with regard to time of day and relation to meals. Grapefruit and grapefruit juice affect metabolism, increasing blood concentration of cyclosporine, thus should be avoided.

Specific PopulationsRenal Impairment in Kidney, Liver and Heart Transplantation Cyclosporine undergoes minimal renal elimination and its pharmacokinetics do not appear to be significantly altered in patients with end-stage renal disease who receive routine hemodialysis treatments (See CLINICAL PHARMACOLOGY). However, due to its nephrotoxic potential (See WARNINGS), careful monitoring of renal function is recommended; cyclosporine dosage should be reduced if indicated. (See WARNINGS and PRECAUTIONS)

Renal Impairment in Rheumatoid Arthritis and Psoriasis Patients with impaired renal function should not receive cyclosporine (see CONTRAINDICATIONS, WARNINGS and PRECAUTIONS).

Hepatic Impairment

The clearance of cyclosporine may be significantly reduced in severe liver disease patients (See CLINICAL PHARMACOLOGY). Dose reduction may be necessary in patients with severe liver impairment to maintain blood concentrations within the recommended target range. (See WARNINGS and PRECAUTIONS)

Newly Transplanted Patients:

The initial oral dose of cyclosporine [MODIFIED] can be given 4 to 12 hours prior to transplantation or be given postoperatively. The initial dose of cyclosporine [MODIFIED] varies depending on the transplanted organ and the other immunosuppressive agents included in the immunosuppressive protocol. In newly transplanted patients, the initial oral dose of cyclosporine [MODIFIED] is the same as the initial oral dose of Sandimmune®*. Suggested initial doses are available from the results of a 1994 survey of the use of Sandimmune®* in U.S. transplant centers. The mean ± SD initial doses were 9±3 mg/kg/day for renal transplant patients (75 centers), 8±4 mg/kg/day for liver transplant patients (30 centers), and 7±3 mg/kg/day for heart transplant patients (24 centers). Total daily doses were divided into two equal daily doses. The cyclosporine [MODIFIED] dose is subsequently adjusted to achieve a pre-defined cyclosporine blood concentration. (See Blood Concentration Monitoring in Transplant Patients, below.)

If cyclosporine trough blood concentrations are used, the target range is the same for cyclosporine [MODIFIED] as for Sandimmune®*. Using the same trough concentration target range for cyclosporine [MODIFIED] as for Sandimmune®* results in greater cyclosporine exposure when cyclosporine [MODIFIED] is administered. (See Pharmacokinetics, Absorption.) Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower cyclosporine [MODIFIED] doses may be sufficient as maintenance therapy.

Adjunct therapy with adrenal corticosteroids is recommended initially. Different tapering dosage schedules of prednisone appear to achieve similar results. A representative dosage schedule based on the patient’s weight started with 2 mg/kg/day for the first 4 days tapered to 1 mg/kg/day by 1 week, 0.6 mg/kg/day by 2 weeks, 0.3 mg/kg/day by 1 month, and 0.15 mg/kg/day by 2 months and thereafter as a maintenance dose. Steroid doses may be further tapered on an individualized basis depending on status of patient and function of graft. Adjustments in dosage of prednisone must be made according to the clinical situation.

Conversion from Sandimmune®* (cyclosporine to cyclosporine [MODIFIED] in Transplant Patients:

In transplanted patients who are considered for conversion to cyclosporine [MODIFIED] from Sandimmune®*, cyclosporine [MODIFIED] should be started with the same daily dose as was previously used with Sandimmune®* (1:1 dose conversion). The cyclosporine [MODIFIED] dose should subsequently be adjusted to attain the pre-conversion cyclosporine blood trough concentration. Using the same trough concentration target range for cyclosporine [MODIFIED] as for Sandimmune®* results in greater cyclosporine exposure when cyclosporine [MODIFIED] is administered. (See Pharmacokinetics, Absorption.) Patients with suspected poor absorption of Sandimmune®* require different dosing strategies. (See Transplant Patients with Poor Absorption of Sandimmune®*). In some patients, the increase in blood trough concentration is more pronounced and may be of clinical significance.

Until the blood trough concentration attains the pre-conversion value, it is strongly recommended that the cyclosporine blood trough concentration be monitored every 4 to 7 days after conversion to cyclosporine [MODIFIED]. In addition, clinical safety parameters such as serum creatinine and blood pressure should be monitored every two weeks during the first two months after conversion. If the blood trough concentrations are outside the desired range and/or if the clinical safety parameters worsen, the dosage of cyclosporine [MODIFIED] must be adjusted accordingly.

Transplant Patients with Poor Absorption of Sandimmune®*:

Patients with lower than expected cyclosporine blood trough concentrations in relation to the oral dose of Sandimmune®* may have poor or inconsistent absorption of cyclosporine from Sandimmune®*. After conversion to cyclosporine [MODIFIED], patients tend to have higher cyclosporine concentrations. Due to the increase in bioavailability of cyclosporine following conversion to cyclosporine [MODIFIED], the cyclosporine blood trough concentration may exceed the target range. Particular caution should be exercised when converting patients to cyclosporine [MODIFIED] at doses greater than 10 mg/kg/day. The dose of cyclosporine [MODIFIED] should be titrated individually based on cyclosporine trough concentrations, tolerability, and clinical response. In this population the cyclosporine blood trough concentration should be measured more frequently, at least twice a week (daily, if initial dose exceeds 10 mg/kg/day) until the concentration stabilizes within the desired range.

Rheumatoid Arthritis:

The initial dose of cyclosporine [MODIFIED] is 2.5 mg/kg/day, taken twice daily as a divided (b.i.d.) oral dose. Salicylates, nonsteroidal anti-inflammatory agents, and oral corticosteroids may be continued. (See WARNINGS and PRECAUTIONS: Drug Interactions.) Onset of action generally occurs between 4 and 8 weeks. If insufficient clinical benefit is seen and tolerability is good (including serum creatinine less than 30% above baseline), the dose may be increased by 0.5 to 0.75 mg/kg/day after 8 weeks and again after 12 weeks to a maximum of 4 mg/kg/day. If no benefit is seen by 16 weeks of therapy, cyclosporine [MODIFIED] therapy should be discontinued.

Dose decreases by 25% to 50% should be made at any time to control adverse events, e.g., hypertension, elevations in serum creatinine (>30% above patient’s pretreatment level) or clinically significant laboratory abnormalities. (See WARNINGS and PRECAUTIONS.)

If dose reduction is not effective in controlling abnormalities or if the adverse event or abnormality is severe, cyclosporine [MODIFIED] should be discontinued. The same initial dose and dosage range should be used if cyclosporine [MODIFIED] is combined with the recommended dose of methotrexate. Most patients can be treated with cyclosporine [MODIFIED] doses of 3 mg/kg/day or below when combined with methotrexate doses of up to 15 mg/week. (See CLINICAL PHARMACOLOGY, CLINICAL TRIALS.)

There is limited long-term treatment data. Recurrence of rheumatoid arthritis disease activity is generally apparent within 4 weeks after stopping cyclosporine.

Psoriasis:

The initial dose of cyclosporine [MODIFIED] should be 2.5 mg/kg/day. Cyclosporine [MODIFIED] should be taken twice daily, as a divided (1.25 mg/kg b.i.d.) oral dose. Patients should be kept at that dose for at least 4 weeks, barring adverse events. If significant clinical improvement has not occurred in patients by that time, the patient’s dosage should be increased at 2 week intervals. Based on patient response, dose increases of approximately 0.5 mg/kg/day should be made to a maximum of 4 mg/kg/day.

Dose decreases by 25% to 50% should be made at any time to control adverse events, e.g., hypertension, elevations in serum creatinine (> 25% above the patient’s pretreatment level), or clinically significant laboratory abnormalities. If dose reduction is not effective in controlling abnormalities, or if the adverse event or abnormality is severe, cyclosporine [MODIFIED] should be discontinued. (See Special Monitoring of Psoriasis Patients.)

Patients generally show some improvement in the clinical manifestations of psoriasis in 2-weeks. Satisfactory control and stabilization of the disease may take 12 to 16 weeks to achieve. Results of a dose-titration clinical trial with cyclosporine [MODIFIED] indicate that an improvement of psoriasis by 75% or more (based on PASI) was achieved in 51% of the patients after 8 weeks and in 79% of the patients after 16 weeks. Treatment should be discontinued if satisfactory response cannot be achieved after 6 weeks at 4 mg/kg/day or the patient’s maximum tolerated dose. Once a patient is adequately controlled and appears stable the dose of cyclosporine [MODIFIED] should be lowered, and the patient treated with the lowest dose that maintains an adequate response (this should not necessarily be total clearing of the patient). In clinical trials, cyclosporine doses at the lower end of the recommended dosage range were effective in maintaining a satisfactory response in 60% of the patients. Doses below 2.5 mg/kg/day may also be equally effective.

Upon stopping treatment with cyclosporine, relapse will occur in approximately 6 weeks (50% of the patients) to 16 weeks (75% of the patients). In the majority of patients rebound does not occur after cessation of treatment with cyclosporine. Thirteen cases of transformation of chronic plaque psoriasis to more severe forms of psoriasis have been reported. There were 9 cases of pustular and 4 cases of erythrodermic psoriasis. Long-term experience with cyclosporine [MODIFIED] in psoriasis patients is limited and continuous treatment for extended periods greater than one year is not recommended. Alternation with other forms of treatment should be considered in the long-term management of patients with this life long disease.

Cyclosporine oral solution [MODIFIED] — Recommendations for Administration:

To make cyclosporine oral solution [MODIFIED] more palatable, it should be diluted with orange or apple juice that is at room temperature. Patients should avoid switching diluents frequently. Grapefruit juice affects metabolism of cyclosporine and should be avoided. The combination of cyclosporine oral solution [MODIFIED] with milk can be unpalatable. The effect of milk on the bioavailability of cyclosporine when administered as cyclosporine oral solution [MODIFIED] has not been evaluated.

Take the prescribed amount of cyclosporine oral solution [MODIFIED] from the container using the dosing syringe supplied, after removal of the protective cover, and transfer the solution to a glass of orange or apple juice. Stir well and drink at once. Do not allow diluted oral solution to stand before drinking. Use a glass container (not plastic). Rinse the glass with more diluent to ensure that the total dose is consumed. After use, dry the outside of the dosing syringe with a clean towel and replace the protective cover. Do not rinse the dosing syringe with water or other cleaning agents. If the syringe requires cleaning, it must be completely dry before resuming use.

Blood Concentration Monitoring in Transplant Patients:

Transplant centers have found blood concentration monitoring of cyclosporine to be an essential component of patient management. Of importance to blood concentration analysis are the type of assay used, the transplanted organ, and other immunosuppressant agents being administered. While no fixed relationship has been established, blood concentration monitoring may assist in the clinical evaluation of rejection and toxicity, dose adjustments, and the assessment of compliance.

Various assays have been used to measure blood concentrations of cyclosporine. Older studies using a nonspecific assay often cited concentrations that were roughly twice those of the specific assays. Therefore, comparison between concentrations in the published literature and an individual patient concentration using current assays must be made with detailed knowledge of the assay methods employed. Current assay results are also not interchangeable and their use should be guided by their approved labeling. A discussion of the different assay methods is contained in Annals of Clinical Biochemistry 1994;31:420-446. While several assays and assay matrices are available, there is a consensus that parent-compound-specific assays correlate best with clinical events. Of these, HPLC is the standard reference, but the monoclonal antibody RIAs and the monoclonal antibody FPIA offer sensitivity, reproducibility, and convenience. Most clinicians base their monitoring on trough cyclosporine concentrations. Applied Pharmacokinetics, Principles of Therapeutic Drug Monitoring (1992) contains a broad discussion of cyclosporine pharmacokinetics and drug monitoring techniques. Blood concentration monitoring is not a replacement for renal function monitoring or tissue biopsies.
Verapamil Hydrochloride...

Verapamil Hydrochloride

Essential Hypertension

The dose of Verapamil Hydrochloride Sustained-Release Capsules should be individualized by titration. The usual daily dose of sustained-release verapamil, Verapamil Hydrochloride Sustained-Release Capsules, in clinical trials has been 240 mg given by mouth once daily in the morning. However, initial doses of 120 mg a day may be warranted in patients who may have an increased response to verapamil (e.g., elderly, small people, etc.). Upward titration should be based on therapeutic efficacy and safety evaluated approximately 24 hours after dosing. The antihypertensive effects of Verapamil Hydrochloride Sustained-Release Capsules are evident within the first week of therapy.

If adequate response is not obtained with 120 mg of Verapamil Hydrochloride Sustained-Release Capsules, the dose may be titrated upward in the following manner:

(a) 180 mg in the morning.

(b) 240 mg in the morning.

(c) 360 mg in the morning.

(d) 480 mg in the morning.

Verapamil Hydrochloride Sustained-Release Capsules are for once-a-day administration. When switching from immediate-release verapamil to Verapamil Hydrochloride Sustained-Release Capsules, the same total daily dose of Verapamil Hydrochloride Sustained-Release Capsules can be used.

As with immediate-release verapamil, dosages of Verapamil Hydrochloride Sustained-Release Capsules should be individualized and titration may be needed in some patients.

Sprinkling the Capsule Contents on Food

Verapamil Hydrochloride Sustained-Release Capsules may also be administered by carefully opening the capsule and sprinkling the pellets on a spoonful of applesauce. The applesauce should be swallowed immediately without chewing and followed with a glass of cool water to ensure complete swallowing of the pellets. The applesauce used should not be hot, and it should be soft enough to be swallowed without chewing. Any pellet/applesauce mixture should be used immediately and not stored for future use. Subdividing the contents of a Verapamil Hydrochloride Sustained-Release Capsule is not recommended.
Diclofenac Sodium

Diclofenac Sodium

Carefully consider the potential benefits and risks of diclofenac sodium extended-release tablets, USP and other treatment options before deciding to use diclofenac sodium extended-release tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with diclofenac sodium extended-release tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.

For the relief of osteoarthritis, the recommended dosage is 100 mg q.d.

For the relief of rheumatoid arthritis, the recommended dosage is 100 mg q.d. In the rare patient where diclofenac sodium extended-release tablets 100 mg/day are unsatisfactory, the dose may be increased to 100 mg b.i.d. if the benefits outweigh the clinical risks of increased side effects.

Different formulations of diclofenac (diclofenac sodium enteric-coated tablets; diclofenac sodium extended-release tablets, USP, diclofenac potassium immediate-release tablets) are not necessarily bioequivalent even if the milligram strength is the same.
Triple Antibiotic

Triple Antibiotic

The optimum daily dosage of carbidopa and levodopa must be determined by careful titration in each patient. Carbidopa and levodopa tablets are available in a 1:4 ratio of carbidopa to levodopa (25 mg/100 mg) as well as 1:10 ratio (25 mg/250 mg and 10 mg/100 mg). Tablets of the two ratios may be given separately or combined as needed to provide the optimum dosage.

Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg a day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.

Usual Initial Dosage: Dosage is best initiated with one tablet of carbidopa and levodopa

25 mg/100 mg three times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by one tablet every day or every other day, as necessary, until a dosage of eight tablets of carbidopa and levodopa 25 mg/100 mg a day is reached.

If carbidopa and levodopa 10 mg/100 mg is used, dosage may be initiated with one tablet three or four times a day. However, this will not provide an adequate amount of carbidopa for many patients. Dosage may be increased by one tablet every day or every other day until a total of eight tablets (2 tablets four times a day) is reached.

How to Transfer Patients from Levodopa: Levodopa must be discontinued at least twelve hours before starting this combination product. A daily dosage of carbidopa and levodopa should be chosen that will provide approximately 25% of the previous levodopa dosage. Patients who are taking less than 1500 mg of levodopa a day should be started on one tablet of carbidopa and levodopa 25 mg/100 mg three or four times a day. The suggested starting dosage for most patients taking more than 1500 mg of levodopa is one tablet of carbidopa and levodopa 25 mg/250 mg three or four times a day.

Maintenance: Therapy should be individualized and adjusted according to the desired therapeutic response. At least 70 to 100 mg of carbidopa per day should be provided. When a greater proportion of carbidopa is required, one 25 mg/100 mg tablet may be substituted for each 10 mg/100 mg tablet. When more levodopa is required, each 25 mg/250 mg tablet should be substituted for a 25 mg/100 mg tablet or a 10 mg/100 mg tablet. If necessary, the dosage of carbidopa levodopa 25 mg/250 mg may be increased by one-half or one tablet every day or every other day to a maximum of eight tablets a day. Experience with total daily dosages of carbidopa greater than 200 mg is limited.

Because both therapeutic and adverse responses occur more rapidly with this combination product than with levodopa alone, patients should be monitored closely during the dose adjustment period. Specifically, involuntary movements will occur more rapidly with carbidopa and levodopa than with levodopa. The occurrence of involuntary movements may require dosage reduction. Blepharospasm may be a useful early sign of excess dosage in some patients.

Addition of Other Antiparkinsonian Medications: Standard drugs for Parkinson's disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly while carbidopa and levodopa is being administered, although dosage adjustments may be required.

Interruption of Therapy: Sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of carbidopa and levodopa. Patients should be observed carefully if abrupt reduction or discontinuation of carbidopa and levodopa is required, especially if the patient is receiving neuroleptics. (See WARNINGS.)

If general anesthesia is required, carbidopa and levodopa may be continued as long as the patient is permitted to take fluids and medication by mouth. If therapy is interrupted temporarily, the patient should be observed for symptoms resembling NMS, and the usual daily dosage may be administered as soon as the patient is able to take oral medication.
Doxycycline Hyclate Cap...

Doxycycline Hyclate Capsule Doxycycline Hyclate

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS. Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg/day.

In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

For children above eight years of age: The recommended dosage schedule for children weighing 100 pounds or less is 2 mg/lb of body weight divided into two doses on the first day of treatment, followed by 1 mg/lb of body weight given as a single daily dose or divided into two doses, on subsequent days. For more severe infections, up to 2 mg/lb of body weight may be used. For children over 100 lb the usual adult dose should be used.

The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage.

When used in streptococcal infections, therapy should be continued for 10 days.

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS.)

If gastric irritation occurs, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.

Studies to date have indicated that administration of doxycycline at the usual recommended doses does not lead to excessive accumulation of doxycycline in patients with renal impairment.

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose. The dose may be administered with food, including milk or carbonated beverage, as required.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis: 100 mg, by mouth, twice a day for 7 days.

Nongonococcal urethritis (NGU) caused by C. trachomatis or U. urealyticum: 100 mg, by mouth, twice a day for 7 days.

Syphilis–early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks.

Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 4 weeks.

Acute epididymo-orchitis caused by N. gonorrhoeae: 100 mg, by mouth, twice a day for at least 10 days.

Acute epididymo-orchitis caused by C. trachomatis: 100 mg, by mouth, twice a day for at least 10 days.

For prophylaxis of malaria: For adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up to the adult dose. Prophylaxis should begin 1 to 2 days before travel to the malarious area.

Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area.

Inhalational anthrax (post-exposure): ADULTS: 100 mg of doxycycline, by mouth, twice a day for 60 days. CHILDREN: weighing less than 100 lb (45 kg); 1 mg/lb (2.2 mg/kg) of body weight, by mouth, twice a day for 60 days. Children weighing 100 lb or more should receive the adult dose.
Bacitracin Zinc Ointmen...

Bacitracin Zinc Ointment

clean affected area apply a small amount (equal to the surface area of the tip of a finger) on the area 1 to 3 times daily may be covered with a sterile bandage
Haloperidol

Haloperidol

2.1 General Dosing Information

Clonidine hydrochloride extended-release is an extended-release tablet to be taken orally with or without food. Swallow tablets whole. Do not crush, chew, or break tablets because this will increase the rate of clonidine release.

Due to the lack of controlled clinical trial data and differing pharmacokinetic profiles, substitution of clonidine hydrochloride extended-release tablets for other clonidine products on a mg-per-mg basis is not recommended [see Clinical Pharmacology (12.3)].

2.2 Dose Selection

The dose of clonidine hydrochloride extended-release tablets administered either as monotherapy or as adjunctive therapy to a psychostimulant, should be individualized according to the therapeutic needs and response of the patient. Dosing should be initiated with one 0.1 mg tablet at bedtime, and the daily dosage should be adjusted in increments of 0.1 mg/day at weekly intervals until the desired response is achieved. Doses should be taken twice a day, with either an equal or higher split dosage being given at bedtime (see Table 1).
Table 1 Clonidine Hydrochloride Extended-Release Tablets Dosing Guidance Total Daily Dose Morning Dose Bedtime Dose 0.1 mg/day 0.1 mg 0.2 mg/day 0.1 mg 0.1 mg 0.3 mg/day 0.1 mg 0.2 mg 0.4 mg/day 0.2 mg 0.2 mg
Doses of clonidine hydrochloride extended-release tablets higher than 0.4 mg/day (0.2 mg twice daily) were not evaluated in clinical trials for ADHD and are not recommended.

When a clonidine hydrochloride extended-release tablet is being added-on to a psychostimulant, the dose of the psychostimulant can be adjusted depending on the patient's response to clonidine hydrochloride extended-release tablets.

2.3 Discontinuation

When discontinuing clonidine hydrochloride extended-release tablets, the total daily dose should be tapered in decrements of no more than 0.1 mg every 3 to 7 days to avoid rebound hypertension [see Warnings and Precautions (5.3)].

2.4 Missed Doses

If patients miss a dose of clonidine hydrochloride extended-release tablets, they should skip that dose and take the next dose as scheduled. Do not take more than the prescribed total daily amount of clonidine hydrochloride extended-release tablets in any 24-hour period.
Metoprolol Succinate

Metoprolol Succinate

Metoprolol succinate extended-release tablets are intended for once daily administration. For treatment of hypertension and angina, when switching from immediate-release metoprolol to metoprolol succinate extended-release tablets, use the same total daily dose of metoprolol succinate extended-release tablets. Individualize the dosage of metoprolol succinate extended-release tablets. Titration may be needed in some patients.

Metoprolol succinate extended-release tablets are scored and can be divided; however, do not crush or chew the whole or half tablet.

2.1 Hypertension

Adults: The usual initial dosage is 25 to 100 mg daily in a single dose. The dosage may be increased at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after 1 week of therapy. Dosages above 400 mg per day have not been studied.

Due to AstraZeneca’s marketing exclusivity rights, this generic drug product is not labeled for pediatric use. Dosage and administration information in pediatric patients 6 years and older is approved for AstraZeneca’s metoprolol succinate extended-release tablets.

Metoprolol succinate extended-release is not recommended in pediatric patients < 6 years of age [see Use in Specific Population (8.4)]

2.2 Angina Pectoris

Individualize the dosage of metoprolol succinate extended-release tablets. The usual initial dosage is 100 mg daily, given in a single dose. Gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is a pronounced slowing of the heart rate. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, reduce the dosage gradually over a period of 1 - 2 weeks [see Warnings and Precautions (5)].

2.3 Heart Failure

Dosage must be individualized and closely monitored during up-titration. Prior to initiation of metoprolol succinate extended-release tablets, stabilize the dose of other heart failure drug therapy. The recommended starting dose of metoprolol succinate extended-release tablets is 25 mg once daily for two weeks in patients with NYHA Class II heart failure and 12.5 mg once daily in patients with more severe heart failure. Double the dose every two weeks to the highest dosage level tolerated by the patient or up to 200 mg of metoprolol succinate extended-release tablets. Initial difficulty with titration should not preclude later attempts to introduce metoprolol succinate extended-release tablets. If patients experience symptomatic bradycardia, reduce the dose of metoprolol succinate extended-release tablets. If transient worsening of heart failure occurs, consider treating with increased doses of diuretics, lowering the dose of metoprolol succinate extended-release tablets or temporarily discontinuing it. The dose of metoprolol succinate extended-release tablets should not be increased until symptoms of worsening heart failure have been stabilized.
Ifosfamide

Ifosfamide

2.1 General Instructions

For the relief of the signs and symptoms of osteoarthritis of the knee(s), the recommended dose is 40 drops per knee, 4 times a day.

Apply diclofenac sodium topical solution to clean, dry skin.

To avoid spillage, dispense diclofenac sodium topical solution 10 drops at a time either directly onto the knee or first into the hand and then onto the knee. Spread diclofenac sodium topical solution evenly around front, back and sides of the knee. Repeat this procedure until 40 drops have been applied and the knee is completely covered with solution.

To treat the other knee, if symptomatic, repeat the procedure.

Application of diclofenac sodium topical solution in an amount exceeding or less than the recommended dose has not been studied and is therefore not recommended.

2.2 Special Precautions

Avoid showering/bathing for at least 30 minutes after the application of diclofenac sodium topical solution to the treated knee.

Wash and dry hands after use.

Do not apply diclofenac sodium topical solution to open wounds.

Avoid contact of diclofenac sodium topical solution with eyes and mucous membranes.

Do not apply external heat and/or occlusive dressings to treated knees.

Avoid wearing clothing over the diclofenac sodium topical solution-treated knee(s) until the treated knee is dry.

Protect the treated knee(s) from sunlight.

Wait until the treated area is dry before applying sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medication to the same knee you have just treated with diclofenac sodium topical solution.

Until the treated knee(s) is completely dry, avoid skin-to-skin contact between other people and the treated knee(s).
Exparel

Exparel

shake well before using use only with enclosed dosing cup adults and children 12 years of age and over take 2 teaspoonfuls (10 mL) every 12 hours; do not take more than 4 teaspoonfuls (20 mL) in 24 hours children 2 to under 12 years of age take 1 teaspoonful (5 mL) every 12 hours; do not take more than 2 teaspoonfuls (10 mL) in 24 hours children under 2 years of age ask a doctor adults 65 years of age and older ask a doctor consumers with kidney disease ask a doctor
Primor

Primor

Carefully consider the potential benefits and risks of ibuprofen oral suspension and other treatment options before deciding to use ibuprofen oral suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with ibuprofen oral suspension, the dose and frequency should be adjusted to suit an individual patient’s needs.

Pediatric PatientsFever Reduction: For reduction of fever in children, 6 months up to 2 years of age, the dosage should be adjusted on the basis of the initial temperature level (see CLINICAL PHARMACOLOGY). The recommended dose is 5 mg/kg if the baseline temperature is less than 102.5ºF, or 10 mg/kg if the baseline temperature is 102.5ºF or greater. The duration of fever reduction is generally 6 to 8 hours. The recommended maximum daily dose is 40 mg/kg.

Analgesia: For relief of mild to moderate pain in children 6 months up to 2 years of age, the recommended dosage is 10 mg/kg, every 6 to 8 hours. The recommended maximum daily dose is 40 mg/kg. Doses should be given so as not to disturb the child's sleep pattern.

Juvenile Arthritis: The recommended dose is 30 to 40 mg/kg/day divided into three to four doses (see Individualization of Dosage). Patients with milder disease may be adequately treated with 20 mg/kg/day.

In patients with juvenile arthritis, doses above 50 mg/kg/day are not recommended because they have not been studied and doses exceeding the upper recommended dose of 40 mg/kg/day may increase the risk of causing serious adverse events. The therapeutic response may require from a few days to several weeks to be achieved. Once a clinical effect is obtained, the dosage should be lowered to the smallest dose of ibuprofen oral suspension needed to maintain adequate control of symptoms.

Pediatric patients receiving doses above 30 mg/kg/day or if abnormal liver function tests have occurred with previous NSAID treatments should be carefully followed for signs and symptoms of early liver dysfunction.

Adults Primary Dysmenorrhea: For the treatment of primary dysmenorrhea, beginning with the earliest onset of such pain, ibuprofen oral suspension should be given in a dose of 400 mg every 4 hours, as necessary, for the relief of pain.

Rheumatoid Arthritis and Osteoarthritis: Suggested dosage: 1200-3200 mg daily (300 mg q.i.d. or 400 mg, 600 mg or 800 mg t.i.d. or q.i.d.). Individual patients may show a better response to 3200 mg daily, as compared with 2400 mg, although in well-controlled clinical trials patients on 3200 mg did not show a better mean response in terms of efficacy. Therefore, when treating patients with 3200 mg/day, the physician should observe sufficient increased clinical benefits to offset potential increased risk.

Individualization of Dosage

The dose of ibuprofen oral suspension should be tailored to each patient, and may be lowered or raised from the suggested doses depending on the severity of symptoms either at time of initiating drug therapy or as the patient responds or fails to respond.

One fever study showed that, after the initial dose of ibuprofen oral suspension, subsequent doses may be lowered and still provide adequate fever control.

In a situation when low fever would require the ibuprofen oral suspension 5 mg/kg dose in a child with pain, the dose that will effectively treat the predominant symptom should be chosen.

In chronic conditions, a therapeutic response to ibuprofen therapy is sometimes seen in a few days to a week, but most often is observed by two weeks. After a satisfactory response has been achieved, the patient's dose should be reviewed and adjusted as required.

Patients with rheumatoid arthritis seem to require higher doses than do patients with osteoarthritis. The smallest dose of ibuprofen oral suspension that yields acceptable control should be employed.

Ibuprofen oral suspension may be used in combination with gold salts and/or corticosteroids.
Oxytrol

Oxytrol

OXYTROL 3.9 mg/day should be applied to dry, intact skin on the abdomen, hip, or buttock twice weekly (every 3 or 4 days). A new application site should be selected with each new system to avoid re-application to the same site within 7 days.
Tranexamic Acid

Tranexamic Acid

2.1 Recommended Dosage

The recommended dose of tranexamic acid tablets for women with normal renal function is two 650 mg tablets taken three times daily (3900 mg/day) for a maximum of 5 days during monthly menstruation. Tranexamic acid tablets may be administered without regard to meals. Tablets should be swallowed whole and not chewed or broken apart.

2.2 Renal Impairment

In patients with renal impairment, the plasma concentration of tranexamic acid increased as serum creatinine concentration increased [see Clinical Pharmacology (12.3)]. Dosage adjustment is needed in patients with serum creatinine concentration higher than 1.4 mg/dL (Table 1).
Table 1. Dosage of Tranexamic Acid Tablets in Patients with Renal Impairment Tranexamic Acid Tablets Serum Creatinine (mg/dL) Adjusted Dose Total Daily Dose Cr above 1.4 and≤ 2.8 1300 mg (two 650 mg tablets) two times a day for a maximum of 5 days during menstruation 2600 mg Cr above 2.8 and≤ 5.7 1300 mg (two 650 mg tablets) once a day for a maximum of 5 days during menstruation 1300 mg Cr above 5.7 650 mg (one 650 mg tablet) once a day for a maximum of 5 days during menstruation 650 mg
Oxycodone Hydrochloride...

Oxycodone Hydrochloride

Oxycodone hydrochloride tablets are intended for the management of moderate to severe pain in patients who require treatment with an oral opioid analgesic. The dose should be individually adjusted according to severity of pain, patient response and patient size. If the pain increases in severity, if analgesia is not adequate, or if tolerance occurs, a gradual increase in dosage may be required.

Patients who have not been receiving opioid analgesics should be started on oxycodone hydrochloride tablets in a dosing range of 5 to 15 mg every 4 to 6 hours as needed for pain. The dose should be titrated based upon the individual patient's response to their initial dose of oxycodone hydrochloride tablets. Patients with chronic pain should have their dosage given on an around-the-clock basis to prevent the reoccurrence of pain rather than treating the pain after it has occurred. This dose can then be adjusted to an acceptable level of analgesia taking into account side effects experienced by the patient.

For control of severe chronic pain, oxycodone hydrochloride tablets should be administered on a regularly scheduled basis, every 4 to 6 hours, at the lowest dosage level that will achieve adequate analgesia.

As with any potent opioid, it is critical to adjust the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience. Although it is not possible to list every condition that is important to the selection of the initial dose of oxycodone hydrochloride tablets, attention should be given to: 1) the daily dose, potency, and characteristics of a pure agonist or mixed agonist/antagonist the patient has been taking previously, 2) the reliability of the relative potency estimate to calculate the dose of oxycodone needed, 3) the degree of opioid tolerance, 4) the general condition and medical status of the patient, and 5) the balance between pain control and adverse experiences.

Conversion From Fixed-Ratio Opioid/Acetaminophen, Opioid/Aspirin, or Opioid/Nonsteroidal Combination Drugs:

When converting patients from fixed ratio opioid/non-opioid drug regimens a decision should be made whether or not to continue the non-opioid analgesic. If a decision is made to discontinue the use of non-opioid analgesic, it may be necessary to titrate the dose of oxycodone hydrochloride tablets in response to the level of analgesia and adverse effects afforded by the dosing regimen. If the non-opioid regimen is continued as a separate single entity agent, the starting dose of oxycodone hydrochloride tablets should be based upon the most recent dose of opioid as a baseline for further titration of oxycodone. Incremental increases should be gauged according to side effects to an acceptable level of analgesia.

Patients Currently on Opioid Therapy:

If a patient has been receiving opioid-containing medications prior to taking oxycodone hydrochloride tablets, the potency of the prior opioid relative to oxycodone should be factored into the selection of the total daily dose (TDD) of oxycodone.

In converting patients from other opioids to oxycodone hydrochloride tablets close observation and adjustment of dosage based upon the patient's response to oxycodone hydrochloride tablets is imperative. Administration of supplemental analgesia for breakthrough or incident pain and titration of the total daily dose of oxycodone hydrochloride tablets may be necessary, especially in patients who have disease states that are changing rapidly.

Maintenance of Therapy:

Continual re-evaluation of the patient receiving oxycodone hydrochloride tablets is important, with special attention to the maintenance of pain control and the relative incidence of side effects associated with therapy. If the level of pain increases, effort should be made to identify the source of increased pain, while adjusting the dose as described above to decrease the level of pain.

During chronic therapy, especially for non-cancer-related pain (or pain associated with other terminal illnesses), the continued need for the use of opioid analgesics should be re-assessed as appropriate.

Cessation of Therapy:

When a patient no longer requires therapy with oxycodone hydrochloride tablets or other opioid analgesics for the treatment of their pain, it is important that therapy be gradually discontinued over time to prevent the development of an opioid abstinence syndrome (narcotic withdrawal). In general, therapy can be decreased by 25% to 50% per day with careful monitoring for signs and symptoms of withdrawal (see Drug Abuse and Dependence section for description of the signs and symptoms of withdrawal). If the patient develops these signs or symptoms, the dose should be raised to the previous level and titrated down more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. It is not known at what dose of oxycodone hydrochloride tablets that treatment may be discontinued without risk of the opioid abstinence syndrome.
Sildenafil

Sildenafil

2.1 Sildenafil Tablets

The recommended dose of sildenafil tablets is 20 mg three times a day. Administer sildenafil doses 4 to 6 hours apart.

In the clinical trial no greater efficacy was achieved with the use of higher doses. Treatment with doses higher than 20 mg three times a day is not recommended.
Meclizine Hydrochloride...

Meclizine Hydrochloride

Motion Sickness

The initial dose of 25 to 50 mg of Meclizine Hydrochloride Tablets should be taken one hour prior to travel for protection against motion sickness. Thereafter, the dose may be repeated every 24 hours for the duration of the journey.
Diclofenac Sodium And M...

Diclofenac Sodium And Misoprostol

Carefully consider the potential benefits and risks of diclofenac sodium and misoprostol delayed-release tablets and other treatment options before deciding to use diclofenac sodium and misoprostol delayed-release tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with diclofenac sodium and misoprostol delayed-release tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.

For the relief of rheumatoid arthritis and osteoarthritis, the recommended dose is given below.

Diclofenac sodium and misoprostol delayed-release tablets are administered as diclofenac sodium and misoprostol delayed-release tablets (50 mg diclofenac sodium/0.2 mg misoprostol) or as diclofenac sodium and misoprostol delayed-release tablets (75 mg diclofenac sodium/0.2 mg misoprostol).

Note: See SPECIAL DOSING CONSIDERATIONS section below.

Osteoarthritis: The recommended dosage for maximal GI mucosal protection is diclofenac sodium and misoprostol delayed-release tablets 50 mg/0.2 mg tid. For patients who experience intolerance, diclofenac sodium and misoprostol delayed-release tablets 75 mg/0.2 mg bid or diclofenac sodium and misoprostol delayed-release tablets 50 mg/0.2 mg bid can be used, but are less effective in preventing ulcers. This fixed combination product, diclofenac sodium and misoprostol delayed-release tablets, is not recommended for patients who would not receive the appropriate dose of both ingredients. Doses of the components delivered with these regimens are as follows:
OA regimen Diclofenac sodium (mg/day) Misoprostol (mcg/day) Diclofenac Sodium and Misoprostol Delayed-Release Tablets 50 mg/0.2 mg tidbid 150100 600400 Diclofenac Sodium and Misoprostol Delayed-Release Tablets 75 mg/0.2 mg bid 150 400
Rheumatoid Arthritis: The recommended dosage is diclofenac sodium and misoprostol delayed-release tablets 50 mg/0.2 mg tid or qid. For patients who experience intolerance, diclofenac sodium and misoprostol delayed-release tablets 75 mg/0.2 mg bid or diclofenac sodium and misoprostol delayed-release tablets 50 mg/0.2 mg bid can be used, but are less effective in preventing ulcers. This fixed combination product, diclofenac sodium and misoprostol delayed-release tablets, is not recommended for patients who would not receive the appropriate dose of both ingredients. Doses of the components delivered with these regimens are as follows:
RA regimen Diclofenac sodium (mg/day) Misoprostol (mcg/day) Diclofenac Sodium and Misoprostol Delayed-Release Tablets 50 mg/0.2 mg qidtidbid 200150100 800600400 Diclofenac Sodium and Misoprostol Delayed-Release Tablets 75 mg/0.2 mg bid 150 400
SPECIAL DOSING CONSIDERATIONS: Diclofenac sodium and misoprostol delayed-release tablets contain misoprostol, which provides protection against gastric and duodenal ulcers (see CLINICAL STUDIES). For gastric ulcer prevention, the0.2 mg qid and tid regimens are therapeutically equivalent, but more protective than the bid regimen. For duodenal ulcer prevention, the qid regimen is more protective than the tid or bid regimens. However, the qid regimen is less well tolerated than the tid regimen because of usually self-limited diarrhea related to the misoprostol dose (see ADVERSE REACTIONS — Gastrointestinal), and the bid regimen may be better tolerated than tid in some patients.

Dosages may be individualized using the separate products (misoprostol and diclofenac), after which the patient may be changed to the appropriate dose of diclofenac sodium and misoprostol delayed-release tablets. If clinically indicated, misoprostol co-therapy with diclofenac sodium and misoprostol delayed-release tablets, or use of the individual components to optimize the misoprostol dose and/or frequency of administration, may be appropriate. The total dose of misoprostol should not exceed 800 mcg/day, and no more than 200 mcg of misoprostol should be administered at any one time. Doses of diclofenac higher than 150 mg/day in osteoarthritis or higher than 225 mg/day in rheumatoid arthritis are not recommended.

For additional information, it may be helpful to refer to the package inserts for Cytotec® tablets and Voltaren® tablets.
Doxycycline Hyclate

Doxycycline Hyclate

2.1 Dosing Information

Prior to initiating ANDRODERM, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.

The recommended starting dose is one ANDRODERM 4 mg/day system (not two 2 mg/day systems) applied nightly for 24 hours, delivering approximately 4 mg of testosterone per day. To ensure proper dosing, approximately 2 weeks after starting therapy, the early morning serum testosterone concentration should be measured following system application the previous evening. Serum concentrations outside the range of 400 - 930 ng/dL require increasing the daily dose to 6 mg (i.e., one 4 mg/day and one 2 mg/day system) or decreasing the daily dose to 2 mg (i.e., one 2 mg/day system), maintaining nightly application.

Patients currently maintained on ANDRODERM 2.5 mg/day, 5 mg/day, and 7.5 mg/day may be switched to the 2 mg/day, 4 mg/day, and 6 mg/day dosage using the following schema:
Patients using 2.5 mg daily may be switched to 2 mg/day systems at the next scheduled dose. Patients using 5 mg daily may be switched to 4 mg/day systems at the next scheduled dose. Patients using 7.5 mg daily may be switched to 6 mg (2 mg/day and 4 mg/day systems) at the next scheduled dose.
To ensure proper dosing, approximately 2 weeks after switching therapy, the early morning serum testosterone concentration should be measured following system application the previous evening.

The adhesive side of the ANDRODERM system should be applied to a clean, dry area of the skin on the back, abdomen, upper arms, or thighs. Avoid application over bony prominences or on a part of the body that may be subject to prolonged pressure during sleep or sitting (e.g., the deltoid region of the upper arm, the greater trochanter of the femur, and the ischial tuberosity). DO NOT APPLY TO THE SCROTUM. The sites of application should be rotated, with an interval of 7 days between applications to the same site. The area selected should not be oily, damaged, or irritated.

The system should be applied immediately after opening the pouch and removing the protective release liner. The system should be pressed firmly in place, making sure there is good contact with the skin, especially around the edges.

The patient should avoid swimming, showering, or washing the administration site for a minimum of 3 hours after application [see Clinical Pharmacology (12.3)].

Mild skin irritation may be ameliorated by treatment of the affected skin with over-the-counter topical hydrocortisone cream applied after system removal. Applying a small amount of 0.1% triamcinolone acetonide cream to the skin under the central drug reservoir of the ANDRODERM system has been shown to reduce the incidence and severity of skin irritation.
Family Care Tolnaftate

Family Care Tolnaftate

2.1 General Instruction for Use

Swallow tablets whole. Do not crush, chew, or break tablets because this will increase the rate of guanfacine release. Do not administer with high fat meals, due to increased exposure.

2.2 Dose Selection

Guanfacine extended-release tablets should be taken once daily, either in the morning or evening, at approximately same time each day. Begin at a dose of 1 mg/day, and adjust in increments of no more than 1 mg/week. Maintain the dose within the range of 1 mg to 4 mg once daily, depending on clinical response and tolerability, for both monotherapy and adjunctive therapy to a psychostimulant. Doses above 4 mg/day have not been systematically studied in controlled clinical studies [see Clinical Studies (14.1)].

Clinically relevant improvements were observed beginning at doses in the range 0.05 to 0.08 mg/kg once daily in both mono- and adjunctive therapy. Efficacy increased with increasing weight-adjusted dose (mg/kg). If well tolerated, doses up to 0.12 mg/kg once daily may provide additional benefit.

In clinical trials, there were dose-related and exposure-related risks for several clinically significant adverse reactions (hypotension, bradycardia, sedative events). Thus, consideration should be given to dosing guanfacine extended-release on a mg/kg basis, in order to balance the exposure-related potential benefits and risks of treatment.

2.3 Switching from Immediate-Release Guanfacine to Guanfacine Extended-Release

If switching from immediate-release guanfacine, discontinue that treatment, and titrate with guanfacine extended-release following above recommended schedule.

Do not substitute for immediate-release guanfacine tablets on a milligram-per-milligram basis, because of differing pharmacokinetic profiles. Guanfacine extended-release has a delayed Tmax, reduced Cmax and lower bioavailability compared to those of the same dose of immediate-release guanfacine [see Clinical Pharmacology (12.3)].

2.4 Maintenance Treatment

It is generally agreed that pharmacological treatment of ADHD may be needed for extended period. The effectiveness of guanfacine extended-release for longer-term use (more than 9 weeks) has not been systematically evaluated in controlled trials. Therefore the physician electing to use guanfacine extended-release for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

2.5 Discontinuation

Infrequent, transient elevations in blood pressure above original baseline (i.e., rebound) have been reported to occur upon abrupt discontinuation of guanfacine. To minimize these effects, the dose should generally be tapered in decrements of no more than 1 mg every 3 to 7 days.

2.6 Missed Doses

When reinitiating patients to the previous maintenance dose after two or more missed consecutive doses, physicians should consider titration based on patient tolerability.

2.7 Dose Adjustment with Concomitant Use of Strong CYP3A4 Inhibitors or Inducers

Dosage adjustments for guanfacine extended-release are recommended with concomitant use of strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and voriconazole), or CYP3A4 inducers (e.g., avasimibe, carbamazepine, phenytoin, rifampin, and St. John’s wort) (Table 1) [see Drug Interactions (7)].
Table 1: Dose Adjustments in Patients Taking Concomitant CYP3A4 Inhibitors or Inducers Scenarios Comedications Initiate guanfacine extended-release when taking comedications Continue guanfacine extended-release when adding a comedication Stop a comedication when continuing guanfacine extended-release Strong CYP3A4 Inhibitors Guanfacine extended-release dose should be limited to 2 mg/day Guanfacine extended-release dose should be decreased by half. Guanfacine extended-release dose should be doubled based on patient tolerability. The maximum dose should not exceed 4 mg/day Strong CYP3A4 Inducers Guanfacine extended-release dose may be titrated up to 8 mg/day. Consider faster titration (e.g. in increments of 2 mg/week) Consider increase guanfacine extended-release dose gradually in 1 to 2 weeks to 2 fold of the original dose based on patient tolerability. Guanfacine extended-release dose should be decreased by half in 1 to 2 weeks based on patient tolerability. The maximum dose should not exceed 4 mg/day
Ammonia N 13

Ammonia N 13

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

2.1 Hypercalcemia of Malignancy

The maximum recommended dose of Zoledronic Acid Injection in hypercalcemia of malignancy (albumin-corrected serum calcium greater than or equal to 12 mg/dL [3.0 mmol/L]) is 4 mg. The 4-mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes. Patients who receive Zoledronic Acid Injection should have serum creatinine assessed prior to each treatment.

Dose adjustments of Zoledronic Acid Injection are not necessary in treating patients for hypercalcemia of malignancy presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine less than 400 µmol/L or less than 4.5 mg/dL).

Patients should be adequately rehydrated prior to administration of Zoledronic Acid Injection [see Warnings and Precautions (5.2)].

Consideration should be given to the severity of, as well as the symptoms of, tumor-induced hypercalcemia when considering use of Zoledronic Acid Injection. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated adequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia.

Retreatment with Zoledronic Acid Injection 4 mg may be considered if serum calcium does not return to normal or remain normal after initial treatment. It is recommended that a minimum of 7 days elapse before retreatment, to allow for full response to the initial dose. Renal function must be carefully monitored in all patients receiving Zoledronic Acid Injection and serum creatinine must be assessed prior to retreatment with Zoledronic Acid Injection [see Warnings and Precautions (5.2)].

2.2 Multiple Myeloma and Metastatic Bone Lesions of Solid Tumors

The recommended dose of Zoledronic Acid Injection in patients with multiple myeloma and metastatic bone lesions from solid tumors for patients with creatinine clearance (CrCl) greater than 60 mL/min is 4 mg infused over no less than 15 minutes every 3 to 4 weeks. The optimal duration of therapy is not known.

Upon treatment initiation, the recommended Zoledronic Acid Injection doses for patients with reduced renal function (mild and moderate renal impairment) are listed in Table 1. These doses are calculated to achieve the same area under the curve (AUC) as that achieved in patients with creatinine clearance of 75 mL/min. CrCl is calculated using the Cockcroft-Gault formula [see Warnings and Precautions (5.2)].
Table 1: Reduced Doses for Patients with Baseline CrCl Less than or Equal to 60 mL/min Baseline Creatinine Clearance (mL/min) Zoledronic Acid Injection Recommended Dose* *Doses calculated assuming target AUC of 0.66(mg•hr/L) (CrCl = 75 mL/min) greater than 60 4 mg 50 to 60 3.5 mg 40 to 49 3.3 mg 30 to 39 3 mg
During treatment, serum creatinine should be measured before each Zoledronic Acid Injection dose and treatment should be withheld for renal deterioration. In the clinical studies, renal deterioration was defined as follows:

For patients with normal baseline creatinine, increase of 0.5 mg/dL

For patients with abnormal baseline creatinine, increase of 1.0 mg/dL

In the clinical studies, Zoledronic Acid Injection treatment was resumed only when the creatinine returned to within 10% of the baseline value. Zoledronic Acid Injection should be reinitiated at the same dose as that prior to treatment interruption.

Patients should also be administered an oral calcium supplement of 500 mg and a multiple vitamin containing 400 international units of vitamin D daily.

2.3 Preparation of Solution

Zoledronic Acid Injection must not be mixed with calcium or other divalent cation-containing infusion solutions, such as Lactated Ringer’s solution, and should be administered as a single intravenous solution in a line separate from all other drugs.

4 mg/5 mL Single-Use Vial

Vials of Zoledronic Acid Injection concentrate for infusion contain overfill allowing for the withdrawal of 5 mL of concentrate (equivalent to 4 mg zoledronic acid). This concentrate should immediately be diluted in 100 mL of sterile 0.9% Sodium Chloride, USP, or 5% Dextrose Injection, USP, following proper aseptic technique, and administered to the patient by infusion. Do not store undiluted concentrate in a syringe, to avoid inadvertent injection.

To prepare reduced doses for patients with baseline CrCl less than or equal to 60 mL/min, withdraw the specified volume of the Zoledronic Acid Injection concentrate from the vial for the dose required (see Table 3).
Table 3: Preparation of Reduced Doses – Zoledronic Acid Injection Concentrate Remove and Use Zoledronic Acid Injection Volume (mL) Dose (mg) 4.4 3.5 4.1 3.3 3.8 3.0
The withdrawn concentrate must be diluted in 100 mL of sterile 0.9% Sodium Chloride, USP, or 5% Dextrose Injection, USP.

If not used immediately after dilution with infusion media, for microbiological integrity, the solution should be refrigerated at 2°C to 8°C (36°F to 46°F). The refrigerated solution should then be equilibrated to room temperature prior to administration. The total time between dilution, storage in the refrigerator, and end of administration must not exceed 24 hours.

2.4 Method of Administration

Due to the risk of clinically significant deterioration in renal function, which may progress to renal failure, single doses of Zoledronic Acid Injection should not exceed 4 mg and the duration of infusion should be no less than 15 minutes [see Warnings and Precautions (5.3)]. In the trials and in postmarketing experience, renal deterioration, progression to renal failure and dialysis, have occurred in patients, including those treated with the approved dose of 4 mg infused over 15 minutes. There have been instances of this occurring after the initial Zoledronic Acid Injection dose.
Alprazolam

Alprazolam

Dosage should be individualized for maximum beneficial effect. While the usual daily dosages given below will meet the needs of most patients, there will be some who require doses greater than 4 mg/day. In such cases, dosage should be increased cautiously to avoid adverse effects.

Anxiety Disorders and Transient Symptoms of Anxiety

Treatment for patients with anxiety should be initiated with a dose of 0.25 to 0.5 mg given three times daily. The dose may be increased to achieve a maximum therapeutic effect, at intervals of 3 to 4 days, to a maximum daily dose of 4 mg, given in divided doses. The lowest possible effective dose should be employed and the need for continued treatment reassessed frequently. The risk of dependence may increase with dose and duration of treatment.

In all patients, dosage should be reduced gradually when discontinuing therapy or when decreasing the daily dosage. Although there are no systematically collected data to support a specific discontinuation schedule, it is suggested that the daily dosage be decreased by no more than 0.5 mg every 3 days. Some patients may require an even slower dosage reduction.

Panic Disorder

The successful treatment of many panic disorder patients has required the use of alprazolam at doses greater than 4 mg daily. In controlled trials conducted to establish the efficacy of alprazolam in panic disorder, doses in the range of 1 to 10 mg daily were used. The mean dosage employed was approximately 5 to 6 mg daily. Among the approximately 1700 patients participating in the panic disorder development program, about 300 received alprazolam in dosages of greater than 7 mg/day, including approximately 100 patients who received maximum dosages of greater than 9 mg/day. Occasional patients required as much as 10 mg a day to achieve a successful response.

Dose Titration

Treatment may be initiated with a dose of 0.5 mg three times daily. Depending on the response, the dose may be increased at intervals of 3 to 4 days in increments of no more than 1 mg per day. Slower titration to the dose levels greater than 4 mg/day may be advisable to allow full expression of the pharmacodynamic effect of alprazolam. To lessen the possibility of interdose symptoms, the times of administration should be distributed as evenly as possible throughout the waking hours, that is, on a three or four times per day schedule.

Generally, therapy should be initiated at a low dose to minimize the risk of adverse responses in patients especially sensitive to the drug. Dose should be advanced until an acceptable therapeutic response (ie, a substantial reduction in or total elimination of panic attacks) is achieved, intolerance occurs, or the maximum recommended dose is attained.

Dose Maintenance

For patients receiving doses greater than 4 mg/day, periodic reassessment and consideration of dosage reduction is advised. In a controlled postmarketing dose-response study, patients treated with doses of alprazolam greater than 4 mg/day for 3 months were able to taper to 50% of their total maintenance dose without apparent loss of clinical benefit. Because of the danger of withdrawal, abrupt discontinuation of treatment should be avoided. (See WARNINGS, PRECAUTIONS, DRUG ABUSE AND DEPENDENCE).

The necessary duration of treatment for panic disorder patients responding to alprazolam is unknown. After a period of extended freedom from attacks, a carefully supervised tapered discontinuation may be attempted, but there is evidence that this may often be difficult to accomplish without recurrence of symptoms and/or the manifestation of withdrawal phenomena.

Dose Reduction

Because of the danger of withdrawal, abrupt discontinuation of treatment should be avoided (see WARNINGS, PRECAUTIONS, DRUG ABUSE AND DEPENDENCE).

In all patients, dosage should be reduced gradually when discontinuing therapy or when decreasing the daily dosage. Although there are no systematically collected data to support a specific discontinuation schedule, it is suggested that the daily dosage be decreased by no more than 0.5 mg every three days. Some patients may require an even slower dosage reduction.

In any case, reduction of dose must be undertaken under close supervision and must be gradual. If significant withdrawal symptoms develop, the previous dosing schedule should be reinstituted and, only after stabilization, should a less rapid schedule of discontinuation be attempted. In a controlled postmarketing discontinuation study of panic disorder patients which compared this recommended taper schedule with a slower taper schedule, no difference was observed between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome. It is suggested that the dose be reduced by no more than 0.5 mg every 3 days, with the understanding that some patients may benefit from an even more gradual discontinuation. Some patients may prove resistant to all discontinuation regimens.

Dosing in Special Populations

In elderly patients, in patients with advanced liver disease or in patients with debilitating disease, the usual starting dose is 0.25 mg, given two or three times daily. This may be gradually increased if needed and tolerated. The elderly may be especially sensitive to the effects of benzodiazepines. If side effects occur at the recommended starting dose, the dose may be lowered.
Progesterone

Progesterone

Progesterone is administered by intramuscular injection. It differs from other commonly used steroids in that it is irritating at the place of injection.

Amenorrhea: Five to 10 mg are given for six to eight consecutive days. If there has been sufficient ovarian activity to produce a proliferative endometrium, one can expect withdrawal bleeding forty-eight to seventy-two hours after the last injection. This may be followed by spontaneous normal cycles.

Functional Uterine Bleeding: Five to 10 mg are given daily for six doses. Bleeding may be expected to cease within six days. When estrogen is given as well, the administration of progesterone is begun after two weeks of estrogen therapy. If menstrual flow begins during the course of injections of progesterone, they are discontinued.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit.
Metoprolol Tartrate

Metoprolol Tartrate

Hypertension

Individualize the dosage of metoprolol tartrate tablets. Metoprolol tartrate tablets should be taken with or immediately following meals.

The usual initial dosage of metoprolol tartrate tablets is 100 mg daily in single or divided doses, whether used alone or added to a diuretic. Increase the dosage at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after 1 week of therapy. The effective dosage range of metoprolol tartrate tablets is 100 mg to 450 mg per day. Dosages above 450 mg per day have not been studied. While once-daily dosing is effective and can maintain a reduction in blood pressure throughout the day, lower doses (especially 100 mg) may not maintain a full effect at the end of the 24-hour period, and larger or more frequent daily doses may be required. This can be evaluated by measuring blood pressure near the end of the dosing interval to determine whether satisfactory control is being maintained throughout the day. Beta1 selectivity diminishes as the dose of metoprolol tartrate is increased.

Angina Pectoris

The dosage of metoprolol tartrate tablets should be individualized. Metoprolol tartrate tablets should be taken with or immediately following meals.

The usual initial dosage of metoprolol tartrate tablets is 100 mg daily, given in two divided doses. Gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is pronounced slowing of the heart rate. The effective dosage range of metoprolol tartrate tablets is 100 mg to 400 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, gradually decrease the dosage over a period of 1 to 2 weeks (see WARNINGS).

Myocardial Infarction

Early Treatment:

During the early phase of definite or suspected acute myocardial infarction, initiate treatment with metoprolol as soon as possible after the patient’s arrival in the hospital. Such treatment should be initiated in a coronary care or similar unit immediately after the patient’s hemodynamic condition has stabilized.

Begin treatment in this early phase with the intravenous administration of three bolus injections of 5 mg of metoprolol tartrate each; give the injections at approximately 2-minute intervals. During the intravenous administration of metoprolol, monitor blood pressure, heart rate, and electrocardiogram.

In patients who tolerate the full intravenous dose (15 mg), initiate metoprolol tartrate tablets, 50 mg every 6 hours, 15 minutes after the last intravenous dose and continue for 48 hours. Thereafter, the maintenance dosage is 100 mg twice daily (see Late Treatment below).

Start patients who appear not to tolerate the full intravenous dose on metoprolol tartrate tablets either 25 mg or 50 mg every 6 hours (depending on the degree of intolerance) 15 minutes after the last intravenous dose or as soon as their clinical condition allows.

In patients with severe intolerance, discontinue metoprolol (See WARNINGS).

Late Treatment:

Start patients with contraindications to treatment during the early phase of suspected or definite myocardial infarction, patients who appear not to tolerate the full early treatment, and patients in whom the physician wishes to delay therapy for any other reason on metoprolol tartrate tablets, 100 mg twice daily, as soon as their clinical condition allows. Continue therapy for at least 3 months. Although the efficacy of metoprolol beyond 3 months has not been conclusively established, data from studies with other beta blockers suggest that treatment should be continued for 1 to 3 years.

Special populationsPediatric patients: No pediatric studies have been performed. The safety and efficacy of metoprolol in pediatric patients have not been established.

Renal impairment: No dose adjustment of metoprolol is required in patients with renal impairment.

Hepatic impairment: Metoprolol blood levels are likely to increase substantially in patients with hepatic impairment. Therefore, metoprolol should be initiated at low doses with cautious gradual dose titration according to clinical response.

Geriatric patients (>65 years): In general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Method of administration:For oral treatment, the tablets should be swallowed un-chewed with a glass of water. Metoprolol should always be taken in standardized relation with meals. If the physician asks the patient to take metoprolol either before breakfast or with breakfast, then the patient should continue taking metoprolol with the same schedule during the course of therapy.
Fiorinal With Codeine

Fiorinal With Codeine

One or 2 capsules every 4 hours. Total daily dosage should not exceed 6 capsules.

Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Fioricet With Codeine

Fioricet With Codeine

1 or 2 capsules every 4 hours as needed. Total daily dosage should not exceed 6 capsules.

Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Kazano

Kazano

Verify dose using body surface area prior to dispensing. Recommended dosage should generally not exceed 4 mg intravenously [see Overdosage (10)].

2.1 Ovarian Cancer

Recommended Dose and Schedule

The recommended dose of Topotecan Hydrochloride for Injection is 1.5 mg/m2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day course.

2.2 Small Cell Lung Cancer

Recommended Dose and Schedule

The recommended dose of Topotecan Hydrochloride for Injection is 1.5 mg/m2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day course.

2.3 Cervical Cancer

Recommended Dose and Schedule

The recommended dose of Topotecan Hydrochloride for Injection is 0.75 mg/m2 by intravenous infusion over 30 minutes daily on Days 1, 2, and 3 in combination with cisplatin 50 mg/m2 on Day 1, repeated every 21 days.

2.4 Dose Modifications

Hematologic Toxicities

For single-agent use, dose reduce Topotecan Hydrochloride for Injection to 1.25 mg/m2 for:
neutrophil counts of less than 500 cells/mm3, or administer granulocyte-colony stimulating factor (G-CSF) starting no sooner than 24 hours following the last dose of Topotecan Hydrochloride for Injection. platelet counts less than 25,000 cells/mm3 during previous cycle.
For combination use with cisplatin, dose reduce Topotecan Hydrochloride for Injection to 0.60 mg/m2 (and further to 0.45 mg/m2 if necessary) for:
febrile neutropenia (defined as neutrophil counts less than 1,000 cells/mm3 with temperature of greater than or equal to 38.0°C (100.4°F), or administer G-CSF starting no sooner than 24 hours following the last dose of Topotecan Hydrochloride for Injection. platelet counts less than 25,000 cells/mm3 during previous cycle.
Renal Impairment

For single-agent use, dose reduce Topotecan Hydrochloride for Injection to 0.75 mg/m2 in patients with moderate renal impairment (creatinine clearance [Clcr] = 20 to 39 mL/min). Insufficient data are available in patients with severe renal impairment (Clcr less than 20 mL/min) to provide a dosage recommendation for Topotecan Hydrochloride for Injection [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.5 Preparation and Intravenous Administration

Topotecan Hydrochloride for Injection is a cytotoxic drug. Follow applicable special handling and disposable procedures.1

Preparation and Administration

Reconstitute each 4-mg vial of Topotecan Hydrochloride for Injection with 4 mL Sterile Water for Injection, USP. Dilute the appropriate volume of the reconstituted solution in either 0.9% Sodium Chloride Intravenous Infusion, USP or 5% Dextrose in Water Injection, USP prior to administration.

Stability

Unopened vials of Topotecan Hydrochloride for Injection are stable until the date indicated on the package when stored between 20°C and 25°C (68°F and 77°F) [see USP] and protected from light in the original carton. Because the vials contain no preservative, contents should be used immediately after reconstitution.

Reconstituted vials of Topotecan Hydrochloride for Injection diluted for infusion are stable at approximately 20°C to 25°C (68°F to 77°F) and ambient lighting conditions for 24 hours.
Diclofenac Sodium

Diclofenac Sodium

Carefully consider the potential benefits and risks of diclofenac sodium delayed-release tablets, USP and other treatment options before deciding to use diclofenac sodium delayed-release. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with diclofenac sodium delayed-release, the dose and frequency should be adjusted to suit an individual patient’s needs.

For the relief of osteoarthritis, the recommended dosage is 100 to 150 mg/day in divided doses (50 mg b.i.d. or t.i.d., or 75 mg b.i.d.).

For the relief of rheumatoid arthritis, the recommended dosage is 150 to 200 mg/day in divided doses (50 mg t.i.d. or q.i.d., or 75 mg b.i.d.).

For the relief of ankylosing spondylitis, the recommended dosage is 100 to 125 mg/day, administered as 25 mg q.i.d., with an extra 25 mg dose at bedtime if necessary.

Different formulations of diclofenac (diclofenac sodium delayed-release tablets; diclofenac sodium extended-release tablets, USP; diclofenac potassium immediate-release tablets) are not necessarily bioequivalent even if the milligram strength is the same.
Carbidopa And Levodopa

Carbidopa And Levodopa

Nitrofurantoin capsules (macrocrystals) should be given with food to improve drug absorption and, in some patients, tolerance.

Adults:

50 mg to 100 mg four times a day -- the lower dosage level is recommended for uncomplicated urinary tract infections.

Pediatric Patients:

5 to 7 mg/kg of body weight per 24 hours, given in four divided doses (contraindicated under one month of age).

Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained. Continued infection indicates the need for reevaluation.

For long-term suppressive therapy in adults, a reduction of dosage to 50-100 mg at bedtime may be adequate. For long-term suppressive therapy in pediatric patients, doses as low as 1 mg/kg per 24 hours, given in a single dose or in two divided doses, may be adequate. SEE WARNINGS SECTION REGARDING RISKS ASSOCIATED WITH LONG-TERM THERAPY.
Bupropion Hydrochloride...

Bupropion Hydrochloride Xl

General Dosing Considerations

It is particularly important to administer bupropion hydrochloride extended-release tablets (XL) in a manner most likely to minimize the risk of seizure (see WARNINGS). Gradual escalation in dosage is also important if agitation, motor restlessness, and insomnia, often seen during the initial days of treatment, are to be minimized. If necessary, these effects may be managed by temporary reduction of dose or the short-term administration of an intermediate to long-acting sedative hypnotic. A sedative hypnotic usually is not required beyond the first week of treatment. Insomnia may also be minimized by avoiding bedtime doses. If distressing, untoward effects supervene, dose escalation should be stopped. Bupropion hydrochloride extended-release tablets (XL) should be swallowed whole and not crushed, divided, or chewed, as this may lead to an increased risk of adverse effects including seizures. Bupropion hydrochloride extended-release tablets (XL) may be taken without regard to meals.

Major Depressive Disorder:

Initial Treatment:

The usual adult target dose for bupropion hydrochloride extended-release tablets (XL) is 300 mg/day, given once daily in the morning. Dosing with bupropion hydrochloride extended-release tablets (XL) should begin at 150 mg/day given as a single daily dose in the morning. If the 150 mg initial dose is adequately tolerated, an increase to the 300 mg/day target dose, given as once daily, may be made as early as day 4 of dosing. There should be an interval of at least 24 hours between successive doses.

Increasing the Dosage Above 300 mg/day:

As with other antidepressants, the full antidepressant effect of bupropion hydrochloride extended-release tablets (XL) may not be evident until 4 weeks of treatment or longer. An increase in dosage to the maximum of 450 mg/day, given as a single dose, may be considered for patients in whom no clinical improvement is noted after several weeks of treatment at 300 mg/day.

Maintenance Treatment:

It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacological therapy beyond response to the acute episode. It is unknown whether or not the dose of bupropion hydrochloride extended-release tablets (XL) needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Seasonal Affective Disorder:

For the prevention of seasonal major depressive episodes associated with seasonal affective disorder, bupropion hydrochloride extended-release tablets (XL) should generally be initiated in the autumn prior to the onset of depressive symptoms. Treatment should continue through the winter season and should be tapered and discontinued in early spring. The timing of initiation and duration of treatment should be individualized based on the patient's historical pattern of seasonal major depressive episodes. Patients whose seasonal depressive episodes are infrequent or not associated with significant impairment should not generally be treated prophylactically.

Dosing with bupropion hydrochloride extended-release tablets (XL) should begin at 150 mg/day given as a single daily dose in the morning. If the 150-mg initial dose is adequately tolerated, the dose of bupropion hydrochloride extended-release tablets (XL) should be increased to the 300-mg/day dose after 1 week. If the 300-mg dose is not adequately tolerated, the dose can be reduced to 150 mg/day. The usual adult target dose for bupropion hydrochloride extended-release tablets (XL) is 300 mg/day, given once daily in the morning.

For patients taking 300 mg/day during the autumn-winter season, the dose should be tapered to 150 mg/day for 2 weeks prior to discontinuation.

Doses of bupropion hydrochloride extended-release tablets (XL) above 300 mg/day have not been studied for the prevention of seasonal major depressive episodes.

Switching Patients from WELLBUTRIN Tablets or from WELLBUTRIN SR Sustained-Release Tablets:

When switching patients from WELLBUTRIN Tablets to bupropion hydrochloride extended-release tablets (XL) or from WELLBUTRIN SR Sustained-ReleaseTablets to bupropion hydrochloride extended-release tablets (XL), give the same total daily dose when possible. Patients who are currently being treated with WELLBUTRIN Tablets) at 300 mg/day (for example, 100 mg 3 times a day) may be switched to bupropion hydrochloride extended-release tablets (XL) 300 mg once daily. Patients who are currently being treated with WELLBUTRIN SR Sustained-ReleaseTablets at 300 mg/day (for example, 150 mg twice daily) may be switched to bupropion hydrochloride extended-release tablets (XL) 300 mg once daily.

Dosage Adjustment for Patients With Impaired Hepatic Function:

Bupropion hydrochloride extended-release tablets (XL) should be used with extreme caution in patients with severe hepatic cirrhosis. The dose should not exceed 150 mg every other day in these patients. Bupropion hydrochloride extended-release tablets (XL) should be used with caution in patients with hepatic impairment (including mild-to-moderate hepatic cirrhosis) and a reduced frequency and/or dose should be considered in patients with mild-to-moderate hepatic cirrhosis (see CLINICAL PHARMACOLOGY, WARNINGS, and PRECAUTIONS).

Dosage Adjustment for Patients With Impaired Renal Function:

Bupropion hydrochloride extended-release tablets (XL) should be used with caution in patients with renal impairment and a reduced frequency and/or dose should be considered (see CLINICAL PHARMACOLOGY and PRECAUTIONS).
Gabapentin

Gabapentin

Gabapentin capsules are given orally with or without food.

Gabapentin capsules should be swallowed whole with plenty of water.

If gabapentin dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).

2.1 Postherpetic Neuralgia

In adults with postherpetic neuralgia, gabapentin therapy may be initiated on Day 1 as a single 300 mg dose, on Day 2 as 600 mg/day (300 mg two times a day), and on Day 3 as 900 mg/day (300 mg three times a day). The dose can subsequently be titrated up as needed for pain relief to a dose of 1800 mg/day (600 mg three times a day). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range; however, in these clinical studies, the additional benefit of using doses greater than 1800 mg/day was not demonstrated.

2.2 Epilepsy with Partial Onset Seizures

Gabapentin is recommended for add-on therapy in patients 3 years of age and older. Effectiveness in pediatric patients below the age of 3 years has not been established.

Patients 12 years of age and above: The starting dose is 300 mg three times a day. The effective dose of gabapentin is 300 mg to 600 mg three times a day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. Gabapentin should be administered three times a day using 300 mg or 400 mg capsules. The maximum time between doses should not exceed 12 hours.

Pediatric Patients Age 3 to 11 years: The starting dose range is 10 mg/kg/day to 15 mg/kg/day, given in three divided doses, and the effective dose reached by upward titration over a period of approximately 3 days. The effective dose of gabapentin in patients 3 to 4 years of age is 40 mg/kg/day, given in three divided doses. The effective dose of gabapentin in patients 5 to 11 years of age is 25 mg/kg/day to 35 mg/kg/day, given in three divided doses. Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.

It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further, because there are no significant pharmacokinetic interactions among gabapentin and other commonly used antiepileptic drugs, the addition of gabapentin does not alter the plasma levels of these drugs appreciably.

If gabapentin is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.

2.3 Patients with Renal Impairment

Dosage adjustment in patients 12 years of age and older with compromised renal function or undergoing hemodialysis is recommended, as follows (see dosing recommendations above for effective doses in each indication):
TABLE 1. Gabapentin Dosage Based on Renal Function
Renal Function

Total Daily

Dose Regimen

Creatinine Clearance (mL/min)

Dose Range(mg/day)

(mg)

≥60

900 to 3600

300 TID

400 TID

600 TID

800 TID

1200 TID

>30 to 59

400 to 1400

200 BID

300 BID

400 BID

500 BID

700 BID

>15 to 29

200 to 700

200 QD

300 QD

400 QD

500 QD

700 QD

15a

100 to 300

100 QD

125 QD

150 QD

200 QD

300 QD
.
Post-Hemodialysis Supplemental Dose (mg)b

Hemodialysis

125b

150b

200b

250b

350b

TID = Three times a day; BID = Two times a day; QD = Single daily dose

a For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table.

Creatinine clearance (CLCr) is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance can be reasonably well estimated using the equation of Cockcroft and Gault:

The use of gabapentin in patients less than 12 years of age with compromised renal function has not been studied.

2.4 Dosage in Elderly

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.
Ibuprofen

Ibuprofen

2.1 OCD (Obsessive Compulsive Disorder)

The recommended starting dose is 100 mg at bedtime, with weekly increases of 50 mg as tolerated to maximum therapeutic benefit, not to exceed 300 mg per day.

Capsules should not be crushed or chewed.

2.2 Pediatric Patients Naïve to Fluvoxamine Maleate

Physicians should consider that the lowest available dose of fluvoxamine maleate extended-release capsules may not be appropriate for pediatric patients naïve to fluvoxamine maleate.

2.3 Dosage for Elderly or Hepatically Impaired Patients

Elderly patients and those with hepatic impairment have been observed to have a decreased clearance of fluvoxamine maleate. Consequently, it may be appropriate to titrate slowly following the initial dose of 100 mg in these patient groups.

2.4 Maintenance/Continuation of Extended Treatment

Although the efficacy of fluvoxamine maleate extended-release capsules beyond 12 weeks of dosing has not been documented in controlled trials, OCD is a chronic condition, and it is reasonable to consider continuation for a responding patient. The benefit of maintaining patients with OCD on immediate-release fluvoxamine maleate tablets after achieving a response for an average duration of about 4 weeks in a 10-week single-blind phase during which patients were titrated to effect was demonstrated in a controlled trial (see CLINICAL TRIALS [14.2]). Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

2.5 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with fluvoxamine maleate extended-release capsules. Conversely, at least 14 days should be allowed after stopping fluvoxamine maleate extended-release capsules before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS [4.1]).

2.6 Use of Fluvoxamine Maleate Extended-Release Capsules with Other MAOIs such as Linezolid or Methylene Blue

Do not start fluvoxamine maleate extended-release capsules in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS [4.1]).

In some cases, a patient already receiving fluvoxamine maleate extended-release capsules therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, fluvoxamine maleate extended-release capsules should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with fluvoxamine maleate extended-release capsules may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS AND PRECAUTIONS [5.2]).

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with fluvoxamine maleate extended-release capsules is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS AND PRECAUTIONS [5.2]).

2.7 Discontinuation of Treatment with Fluvoxamine Maleate Extended-Release Capsules

Symptoms associated with discontinuation of other SSRIs or SNRIs have been reported (see WARNINGS AND PRECAUTIONS [5.10]). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the health care provider may continue decreasing the dose but at a more gradual rate.
Lisinopril

Lisinopril

2.1 General Instructions for Use

To minimize the risk of seizure, increase the dose gradually [see Warnings and Precautions (5.3)].

Bupropion hydrochloride extended-release tablets (XL) should be swallowed whole and not crushed, divided, or chewed. Bupropion hydrochloride extended-release tablets (XL) should be administered in the morning and may be taken with or without food.

2.2 Dosage for Major Depressive Disorder (MDD)

The recommended starting dose for MDD is 150 mg once daily in the morning. After 4 days of dosing, the dose may be increased to the target dose of 300 mg once daily in the morning.

It is generally agreed that acute episodes of depression require several months or longer of antidepressant treatment beyond the response in the acute episode. It is unknown whether the bupropion hydrochloride extended-release tablets (XL) dose needed for maintenance treatment is identical to the dose that provided an initial response. Periodically reassess the need for maintenance treatment and the appropriate dose for such treatment.

2.3 Dosage for Seasonal Affective Disorder (SAD)

The recommended starting dose for SAD is 150 mg once daily. After 7 days of dosing, the dose may be increased to the target dose of 300 mg once daily in the morning. Doses above 300 mg of bupropion HCl extended-release were not assessed in the SAD trials.

For the prevention of seasonal MDD episodes associated with SAD, initiate bupropion hydrochloride extended-release tablets (XL) in the autumn, prior to the onset of depressive symptoms. Continue treatment through the winter season. Taper and discontinue bupropion hydrochloride extended-release tablets (XL) in early spring. For patients treated with 300 mg per day, decrease the dose to 150 mg once daily before discontinuing bupropion hydrochloride extended-release tablets (XL). Individualize the timing of initiation and duration of treatment should be individualized, based on the patient’s historical pattern of seasonal MDD episodes.

2.4 Switching Patients from Bupropion Hydrochloride Tablets or from Bupropion Hydrochloride Sustained-Release Tablets

When switching patients from bupropion hydrochloride tablets to bupropion hydrochloride extended-release tablets (XL) or from bupropion hydrochloride sustained-release tablets to bupropion hydrochloride extended-release tablets (XL), give the same total daily dose when possible.

2.5 To Discontinue Bupropion Hydrochloride Extended-Release Tablets (XL), Taper the Dose

When discontinuing treatment in patients treated with bupropion hydrochloride extended-release tablets (XL) 300 mg once daily, decrease the dose to 150 mg once daily prior to discontinuation.

2.6 Dosage Adjustment in Patients with Hepatic Impairment

In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose is 150 mg every other day. In patients with mild hepatic impairment (Child- Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.7 Dose Adjustment in Patients with Renal Impairment

Consider reducing the dose and/or frequency of bupropion hydrochloride in patients with renal impairment (Glomerular Filtration Rate less than 90 mL/min) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.8 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Antidepressant

At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with bupropion hydrochloride extended-release tablets (XL). Conversely, at least 14 days should be allowed after stopping bupropion hydrochloride extended-release tablets (XL) before starting an MAOI antidepressant [see Contraindications (4) and Drug Interactions (7.6)].

2.9 Use of Bupropion Hydrochloride Extended-Release Tablets (XL) with Reversible MAOIs Such as Linezolid or Methylene Blue

Do not start bupropion hydrochloride extended-release tablets (XL) in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase risk of hypertensive reactions. In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered [see Contraindications (4)].

In some cases, a patient already receiving therapy with bupropion hydrochloride extended-release tablets (XL) may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of hypertensive reactions in a particular patient, bupropion hydrochloride extended-release tablets (XL) should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with bupropion hydrochloride extended-release tablets (XL) may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with bupropion hydrochloride extended-release tablets (XL) is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use [see Contraindications (4) and Drug Interactions (7.6)].
Afeditab Cr

Afeditab Cr

Dosage should be adjusted according to each patient’s needs. It is recommended that nifedipine extended-release tablets be administered orally once daily on an empty stomach. Afeditab® CR is an extended release dosage form and tablets should be swallowed whole, not bitten or divided. In general, titration should proceed over a 7 to 14 day period starting with 30 mg once daily. Upward titration should be based on therapeutic efficacy and safety. The usual maintenance dose is 30 mg to 60 mg once daily. Titration to doses above 90 mg daily is not recommended.

If discontinuation of Afeditab® CR is necessary, sound clinical practice suggests that the dosage should be decreased gradually with close physician supervision. Co-administration of nifedipine with grapefruit juice is to be avoided (See CLINICAL PHARMACOLOGY and PRECAUTIONS).

Care should be taken when dispensing Afeditab® CR to assure that the extended-release dosage form has been prescribed.
Tizanidine Hydrochlorid...

Tizanidine Hydrochloride

2.1       Dosing Information

Tizanidine hydrochloride capsules may be prescribed with or without food. Once the formulation has been selected and the decision to take with or without food has been made, this regimen should not be altered.

Food has complex effects on tizanidine pharmacokinetics, which differ with the different formulations. Tizanidine hydrochloride capsules and tizanidine hydrochloride tablets are bioequivalent to each other under fasting conditions (more than 3 hours after a meal), but not under fed conditions (within 30 minutes of a meal). These pharmacokinetic differences may result in clinically significant differences when switching administration of tablet and capsules and when switching administration between the fed or fasted state. These changes may result in increased adverse events, or delayed or more rapid onset of activity, depending upon the nature of the switch. For this reason, the prescriber should be thoroughly familiar with the changes in kinetics associated with these different conditions [see Clinical Pharmacology (12.3)].

The recommended starting dose is 2 mg. Because the effect of tizanidine hydrochloride peaks at approximately 1 to 2 hours post-dose and dissipates between 3 to 6 hours post-dose, treatment can be repeated at 6 to 8 hour intervals, as needed, to a maximum of three doses in 24 hours.

Dosage can be gradually increased by 2 mg to 4 mg at each dose, with 1 to 4 days between dosage increases, until a satisfactory reduction of muscle tone is achieved. The total daily dose should not exceed 36 mg. Single doses greater than 16 mg have not been studied.

2.2       Dosing in Patients with Renal Impairment

Tizanidine hydrochloride should be used with caution in patients with renal insufficiency (creatinine clearance < 25 mL/min), as clearance is reduced by more than 50%. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased [see Warnings and Precautions (5.7)].

2.3       Dosing in Patients with Hepatic Impairment

Tizanidine hydrochloride should be used with caution in patients with any hepatic impairment. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. Monitoring of aminotransferase levels is recommended for baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected. [see Use in Specific Populations (8.7)]

2.4       Drug Discontinuation

If therapy needs to be discontinued, particularly in patients who have been receiving high doses (20 mg to 36 mg daily) for long periods (9 weeks or more) or who may be on concomitant treatment with narcotics, the dose should be decreased slowly (2 mg to 4 mg per day) to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia [see Drug Abuse and Dependence (9.3)].
Neomycin And Polymyxin ...

Neomycin And Polymyxin B Sulfates And Hydrocortisone

CAUTION: Methoxsalen Capsules, USP (Soft Gelatin Capsules) represent a new dose form of methoxsalen. This new dosage form of methoxsalen exhibits significantly greater bioavailability and earlier photosensitization onset time than previous methoxsalen dosage forms. Each patient should be evaluated by determining the minimum phototoxic dose (MPD) and phototoxic peak time after drug administration prior to onset of photochemotherapy with this dosage form. Human bioavailability studies have indicated the following drug dosage and administration directions are to be used as a guideline only.

Psoriasis Therapy

Drug Dosage – Initial Therapy

The Methoxsalen Capsules, USP (Soft Gelatin Capsules) should be taken 1 1/2 to 2 hours before UVA exposure with some low fat food or milk according to the following table:
Patient’s Weight Dose (kg) (lbs) (mg) <30 <66 10 30 to 50 66 to 110 20 51 to 65 112 to 143 30 66 to 80 146 to 176 40 81 to 90 179 to 198 50 91 to 115 201 to 254 60 >115 >254 70
Elderly patients should generally be started at the low end of the dose recommended according to body weight and closely monitored during PUVA therapy. Although clinical experience has not identified differences in response between elderly and younger patients, the use of methoxsalen in older individuals may be affected by the presence of pre-existing medical conditions.

Initial Exposure

The initial UVA exposure energy level and corresponding time of exposure is determined by the patient’s skin characteristics for sun burning and tanning as follows:
Skin Type History Recommended (*Patients with natural pigmentation of these types should be classified into a lower skin type category if the sun burning history so indicates.) I Always burn, never tan (patients with erythrodermic psoriasis are to Joules/cm2 be classed as Type I for determination of UVA dosage.) 0.5 J/cm2 II Always burn, but sometimes tan 1.0 J/cm2 III Sometimes burn, but always tan 1.5 J/cm2 IV Never burn, always tan 2.0 J/cm2 Skin Type Physician Examination Joules/cm2 V* Moderately pigmented 2.5 J/cm2 VI* Blacks 3.0 J/cm2
If the MPD is done, start at 1/2 MPD.

Additional drug dosage directions are as follows:

Weight Change

In the event that the weight of a patient changes during treatment such that he/she falls into an adjacent weight range/dose category, no change in the dose of methoxsalen is usually required. If, in the physician’s opinion, however, a weight change is sufficiently great to modify the drug dose, then an adjustment in the time of exposure to UVA should be made.

Dose/Week

The number of doses per week of Methoxsalen Capsules, USP (Soft Gelatin Capsules) will be determined by the patient’s schedule of UVA exposures. In no case should treatments be given more often than once every other day because the full extent of phototoxic reactions may not be evident until 48 hours after each exposure.

Dosage Increase

Dosage may be increased by 10 mg after the fifteenth treatment under the conditions outlined in section PUVA TREATMENT PROTOCOL, Clearing Phase, Miscellaneous Situations.

UVA RADIATION SOURCE SPECIFICATIONS & INFORMATION

Irradiance Uniformity

The following specifications should be met with the window of the detector held in a vertical plane:

Vertical Variation

For readings taken at any point along the vertical center axis of the chamber (to within 15 cm from the top and bottom), the lowest reading should not be less than 70 percent of the highest reading.

Horizontal Variation

Throughout any specific horizontal plane, the lowest reading must be at least 80 percent of the highest reading, excluding the peripheral 3 cm of the patient treatment space.

Patient Safety Features

The following safety features should be present:
Protection from electrical hazard: All units should be grounded and conform to applicable electrical codes. The patient or operator should not be able to touch any live electrical parts. There should be ground fault protection. Protective shielding of lamps: The patient should not be able to come in contact with the bare lamps. In the event of lamp breakage, the patient should not be exposed to broken lamp components. Hand rails and hand holds: Appropriate supports should be available to the patient. Patient viewing window: A window which blocks UV should be provided for viewing the patient during treatment. Door and latches: Patients should be able to open the door from the inside with only slight pressure to the door. Non-skid floor: The floor should be of a non-skid nature. Thermoregulation: Sufficient air flow should be provided for patient safety and comfort, limiting temperature within the UVA radiator cabinet to approximately less than 100°F. Timer: The irradiator should be equipped with an automatic timer which terminates the exposure at the conclusion of a pre-set time interval. Patient alarm device: An alarm device within the UVA irradiator chamber should be accessible to the patient for emergency activation. Danger label: The unit should have a label prominently displayed which reads as follows:
DANGER -Ultraviolet radiation - Follow your physicians instructions - Failure to use protective eyewear may result in eye injury.

UVA Exposure Dosimetry Measurements

The maximum radiant exposure or irradiance (within ±15 percent) of UVA (320 to 400 nm) delivered to the patient should be determined by using an appropriate radiometer calibrated to be read in Joules/cm2 or mW/cm2. In the absence of a standard measuring technique approved by the National Bureau of Standards, the system should use a detector corrected to a cosine spatial response. The use and recalibration frequency of such a radiometer for a specific UVA irradiator chamber should be specified by the manufacturer because the UVA dose (exposure) is determined by the design of the irradiator, the number of lamps, and the age of the lamp. If irradiance is measured, the radiometer reading in mW/cm2 is used to calculate the exposure time in minutes to deliver the required UVA in Joules/cm2 to a patient in the UVA irradiator cabinet. The equation is:

Exposure Time = Desired UVA Dose (J/cm2)

(minutes) 0.06 x Irradiance (mW/cm2)

Overexposure due to human error should be minimized by using an accurate automatic timing device, which is set by the operator and controlled by energizing and de-energizing the UVA irradiator lamp. The timing device calibration interval should be specified by the manufacturer. Safety systems should be included to minimize the possibility of delivering a UVA exposure which exceeds the prescribed dose, in the event the timer or radiometer should malfunction.

UVA Spectral Output Distribution

The spectral distributions of the lamps should meet the following specifications:
Wavelength band (nanometers) Output1 1As a percentage of total irradiance between 320 and 400 nanometers. <310 <1 310 to 320 1 to 3 320 to 330 4 to 8 330 to 340 11 to 17 340 to 350 18 to 25 350 to 360 19 to 28 360 to 370 15 to 23 370 to 380 8 to 12 380 to 390 3 to 7 390 to 400 1 to 3
PUVA TREATMENT PROTOCOL

Introduction

The Methoxsalen Capsules, USP (Soft Gelatin Capsules) reach their maximum bioavailability in 1 1/2 to 2 hours after ingestion.

On average, the serum level achieved with Methoxsalen Capsules, USP (Soft Gelatin Capsules) is twice that obtained with methoxsalen hard gelatin capsules (formerly methoxsalen capsules) and reach their peak concentration in less than 1/2 the time of the methoxsalen hard gelatin capsules.

As a result the mean MED J/cm2 for the Methoxsalen Capsules, USP (Soft Gelatin Capsules) is substantially less than that required for methoxsalen hard gelatin capsules (Levins et al., 1984 and private communication1).

Photosensitivity studies demonstrate a shorter time of peak photosensitivity of 1.5 to 2.1 hours vs. 3.9 to 4.25 hours for regular methoxsalen capsules.

Initial Exposure

The initial UVA exposures should be conducted according to the guidelines presented previously under UVA RADIATION SOURCE SPECIFICATIONS & INFORMATION : Patient Safety Features 1 and 2, Psoriasis therapy, Drug Dosage-Initial Therapy and Exposure.

Clearing Phase

Specific recommendations for patient treatment are as follows:

Skin Types I, II, & III

Patients with skin types I, II, and III may be treated 2 or 3 times per week. UVA exposure may be held constant or increased by up to 1.0 Joule/cm2 at each treatment, according to the patient’s response. If erythema occurs, however, do not increase exposure time until erythema resolves. The severity and extent of the patient’s erythema may be used to determine whether the next exposure should be shortened, omitted, or maintained at the previous dosage. See Adverse Reactions section for additional information.

Skin Types IV, V, & VI

Patients with skin types IV, V, and VI may be treated 2 or 3 times per week. UVA exposure may be held constant or increased by up to 1.5 Joules/cm2 at each treatment unless erythema occurs. If erythema occurs, follow instructions outlined above in the procedures for patients with skin types I, II, and III.

Erythrodermic Psoriasis

Patients with erythrodermic psoriasis should be treated with special attention because pre-existing erythema may obscure observations of possible treatment-related phototoxic erythema. These patients may be treated 2 or 3 times per week, as a Type I patient.

Miscellaneous Situations

If there is no response after a total of 10 treatments, the exposure of UVA energy may be increased by an additional 0.5 to 1.0 Joules/cm2 above the prior incremental increases for each treatment. (Example: a patient whose exposure dosage is being increased by 1.0 Joule/cm2 may now have all subsequent doses increased by 1.5 to 2.0 Joules/cm2.)

If there is no response, or only minimal response, after 15 treatments, the dosage of methoxsalen may be increased by 10 mg (a one-time increase in dosage). This increased dosage may be continued for the remainder of the course of treatment but should not be exceeded.

If a patient misses a treatment, the UVA exposure time of the next treatment should not be increased. If more than one treatment is missed, reduce the exposure by 0.5 Joules/cm2 for each treatment missed.

If the lower extremities are not responding as well as the rest of the body and do not show erythema, cover all other body areas and give 25 percent of the present exposure dose as an additional exposure to the lower extremities. This additional exposure to the lower extremities should be terminated if erythema develops on these areas.

Non-Responsive Psoriasis

If a patient’s generalized psoriasis is not responding, or if the condition appears to be worsening during treatment, the possibility of a generalized phototoxic reaction should be considered. This may be confirmed by the improvement of the condition following temporary discontinuance of this therapy for two weeks. If no improvement occurs during the interruption of treatment, this patient may be considered a treatment failure.

Alternative Exposure Schedule

As an alternative to increasing the UVA exposure at each treatment, the following schedule may be followed; this schedule may reduce the total number of Joules/cm2 received by the patient over the entire course of therapy.
Incremental increases in UVA exposure for all patients may range from 0.5 to 1.5 Joules/cm2, according to the patient’s response to therapy. Once Grade 2 clearing (see Table 2) has been reached and the patient is progressing adequately, UVA dosage is held constant. This dosage is maintained until Grade 4 clearing is reached. If the rate of clearing significantly decreases, exposure dosage may be increased at each treatment (0.1 to 1.5 Joules/cm2) until Grade 3 clearing and a satisfactory progress rate is attained. The UVA exposure will be held constant again until Grade 4 clearing is attained. These increases may be used also if the rate of clearing significantly decreases between Grade 3 and Grade 4 response. However, the possibility of a phototoxic reaction should be considered; see Non-responsive Psoriasis, above. In summary, this schedule raises slightly the increments (Joules/cm2) of UVA dosage, but limits these increases to those periods when the patient is not responding adequately. Otherwise, the UVA exposure is held at the lowest effective dose.
Maintenance Phase

The goal of maintenance treatment is to keep the patient as symptom-free as possible with the least amount of UVA exposure.

Schedule of Exposures

When patients have achieved 95 percent clearing, or Grade 4 response (Table 2), they may be placed on the following maintenance schedules (M1 to M4), in sequence. It is recommended that each maintenance schedule be adhered to for at least 2 treatments (unless erythema or psoriatic flare occurs, in which case see Length of Exposure, Erythema and Length of Exposure, Psoriasis, below).
Maintenance Schedules M1 - once/week M2 - once/2 weeks M3 - once/3 weeks M4 - p.r.n. (i.e., for flares)
Length of Exposure

The UVA exposure for the first maintenance treatment of any schedule (except M4 as noted below) is the same as that of the patient’s last treatment under the previous schedule. For skin types I–IV, however, it is recommended that the maximum UVA dosage during maintenance treatments not exceed the following:
Skin Types Joules/cm2/treatment I 12 II 14 III 18 IV 22
If the patient develops erythema or new lesions of psoriasis, proceed as follows:

Erythema

During maintenance therapy, the patient’s tan and threshold dose for erythema may gradually decrease. If maintenance treatments produce significant erythema, the exposure to UVA should be decreased by 25 percent until further treatments no longer produce erythema.

Psoriasis

If the patient develops new areas of psoriasis during maintenance therapy (but still is classified as having a Grade 4 response), the exposure to UVA may be increased by 0.5 to 1.5 Joules/cm2 at each treatment; this is appropriate for all types of patients. These increases are continued until the psoriasis is brought under control and the patient is again clear. The exposure being administered when this clearing is reached should be used for further maintenance treatment.

Flares During Maintenance

If the patient flares during maintenance treatment (i.e., develops psoriasis on more than 5 percent of the originally involved areas of the body), his maintenance treatment schedule may be changed to the preceding maintenance or clearing schedule. The patient may be kept on his schedule until again 95 percent clear. If the original maintenance treatment schedule is unable to control the psoriasis, the schedule may be changed to a more frequent regimen. If a flare occurs less than 6 weeks after the last treatment, 25 percent of the maximum exposure received during the clearing phase, with the clearing schedule received during the clearing phase, may be used and then proceed with the clearing schedule previously followed for this patient. (At 95 percent clearing, follow regular maintenance until the optimum maintenance schedule is determined for the patient.) If more than 6 weeks have elapsed since the last treatment was given, treat patients as if they were beginning therapy insofar as exposure dosages are concerned, since their threshold for erythema may have decreased.
Table 1. Grades of Erythema Grade Erythema 0 No erythema 1 Minimally perceptible erythema – faint pink 2 Marked erythema but with no edema 3 Fiery erythema with edema 4 Fiery erythema with edema and blistering Table 2. Response to Therapy Percent Improvement (compared to original Grade Criteria extent of disease) -1 Psoriasis worse 0 0 No change 0 1 Minimal improvement - slightly less scale and/or erythema 5 to 20 2 Definite improvement - partial flattening of all plaques—less scaling and less erythema 20 to 50 3 Considerable improvement – nearly complete flattening of all plaques but borders of plaques still palpable 50 to 95 4 Clearing; complete flattening of plaques including borders; plaques may be outlined by pigmentation 95
Bupropion Hydrochloride...

Bupropion Hydrochloride

2.1 Usual Dosage

Treatment with bupropion hydrochloride extended-release tablets (SR) should be initiated before the patient’s planned quit day, while the patient is still smoking, because it takes approximately 1 week of treatment to achieve steady-state blood levels of bupropion. The patient should set a “target quit date” within the first 2 weeks of treatment with bupropion hydrochloride extended-release tablets (SR).

Dosing: To minimize the risk of seizure:
Begin dosing with one 150 mg tablet per day for 3 days. Increase dose to 300 mg/day given as one 150 mg tablet twice each day with an interval of at least 8 hours between each dose. Do not exceed 300 mg/day.
Bupropion hydrochloride extended-release tablets (SR) should be swallowed whole and not crushed, divided, or chewed, as this may lead to an increased risk of adverse effects including seizures [see Warnings and Precautions (5.3)].

Bupropion hydrochloride extended-release tablets (SR) may be taken with or without food [see Clinical Pharmacology (12.3)].

2.2 Duration of Treatment

Treatment with bupropion hydrochloride extended-release tablets (SR) should be continued for 7 to 12 weeks. If the patient has not quit smoking after 7 to 12 weeks, it is unlikely that he or she will quit during that attempt so treatment with bupropion hydrochloride extended-release tablets (SR) should probably be discontinued and the treatment plan reassessed. The goal of therapy with bupropion hydrochloride extended-release tablets (SR) is complete abstinence.

Discuss discontinuing treatment with bupropion hydrochloride extended-release tablets (SR) after 12 weeks if the patient feels ready but consider whether the patient may benefit from ongoing treatment. Patients who successfully quit after 12 weeks of treatment but do not feel ready to discontinue treatment should be considered for ongoing therapy with bupropion hydrochloride extended-release tablets (SR); longer treatment should be guided by the relative benefits and risks for individual patients.

It is important that patients continue to receive counseling and support throughout treatment with bupropion hydrochloride extended-release tablets (SR) and for a period of time thereafter.

2.3 Individualization of Therapy

Patients are more likely to quit smoking and remain abstinent if they are seen frequently and receive support from their physicians or other healthcare professionals. It is important to ensure that patients read the instructions provided to them and have their questions answered. Physicians should review the patient’s overall smoking cessation program that includes treatment with bupropion hydrochloride extended-release tablets (SR). Patients should be advised of the importance of participating in the behavioral interventions, counseling, and/or support services to be used in conjunction with bupropion hydrochloride extended-release tablets (SR) [see Medication Guide].

Patients who fail to quit smoking during an attempt may benefit from interventions to improve their chances for success on subsequent attempts. Patients who are unsuccessful should be evaluated to determine why they failed. A new quit attempt should be encouraged when factors that contributed to failure can be eliminated or reduced, and conditions are more favorable.

2.4 Maintenance

Tobacco dependence is a chronic condition. Some patients may need on-going treatment. Whether to continue treatment with bupropion hydrochloride extended-release tablets (SR) for periods longer than 12 weeks for smoking cessation must be determined for individual patients.

2.5 Combination Treatment with Bupropion Hydrochloride Extended-Release Tablets (SR) and a Nicotine Transdermal System (NTS)

Combination treatment with bupropion hydrochloride extended-release tablets (SR) and NTS may be prescribed for smoking cessation. The prescriber should review the complete prescribing information for both bupropion hydrochloride extended-release tablets (SR) and NTS before using combination treatment [see Clinical Studies (14)]. Monitoring for treatment-emergent hypertension in patients treated with the combination of bupropion hydrochloride extended-release tablets (SR) and NTS is recommended.

2.6 Dose Adjustment in Patients with Hepatic Impairment

In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose should not exceed 150 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

2.7 Dose Adjustment in Patients with Renal Impairment

Consider reducing the dose and/or frequency of bupropion hydrochloride extended-release tablets (SR) in patients with renal impairment (Glomerular Filtration Rate less than 90 mL/min) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.8 Use of Bupropion Hydrochloride Extended-Release Tablets (SR) with Reversible MAOIs Such as Linezolid or Methylene Blue

Do not start bupropion hydrochloride extended-release tablets (SR) in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase the risk of hypertensive reactions [see Contraindications (4), Drug Interactions (7.6)].

In some cases, a patient already receiving therapy with bupropion hydrochloride extended-release tablets (SR) may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of hypertensive reactions in a particular patient, bupropion hydrochloride extended-release tablets (SR) should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with bupropion hydrochloride extended-release tablets (SR) may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with bupropion hydrochloride extended-release tablets (SR) is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use [see Contraindications (4), Drug Interactions (7.6)].
Lorazepam

Lorazepam

Lorazepam is administered orally. For optimal results, dose, frequency of administration, and duration of therapy should be individualized according to patient response. To facilitate this, 0.5 mg, 1 mg, and 2 mg tablets are available.

The usual range is 2 to 6 mg/day given in divided doses, the largest dose being taken before bedtime, but the daily dosage may vary from 1 to 10 mg/day.

For anxiety, most patients require an initial dose of 2 to 3 mg/day given b.i.d. or t.i.d.

For insomnia due to anxiety or transient situational stress, a single daily dose of 2 to 4 mg may be given, usually at bedtime.

For elderly or debilitated patients, an initial dosage of 1 to 2 mg/day in divided doses is recommended, to be adjusted as needed and tolerated.

The dosage of lorazepam should be increased gradually when needed to help avoid adverse effects. When higher dosage is indicated, the evening dose should be increased before the daytime doses.
Nifedipine

Nifedipine

The dosage of nifedipine needed to suppress angina and that can be tolerated by the patient must be established by titration. Excessive doses can result in hypotension.

Therapy should be initiated with the 10 mg capsule. The starting dose is one 10 mg capsule, swallowed whole, 3 times/day. The usual effective dose range is 10 to 20 mg three times daily. Some patients, especially those with evidence of coronary artery spasm, respond only to higher doses, more frequent administration, or both. In such patients, doses of 20 to 30 mg three or four times daily may be effective. Doses above 120 mg daily are rarely necessary. More than 180 mg per day is not recommended.

In most cases, nifedipine titration should proceed over a 7 to 14 day period so that the physician can assess the response to each dose level and monitor the blood pressure before proceeding to higher doses.

If symptoms so warrant, titration may proceed more rapidly provided that the patient is assessed frequently. Based on the patient’s physical activity level, attack frequency, and sublingual nitroglycerin consumption, the dose of nifedipine may be increased from 10 mg three times a day. to 20 mg three times a day and then to 30 mg three times a day over a three-day period.

In hospitalized patients under close observation, the dose may be increased in 10 mg increments over four- to six-hour periods as required to control pain and arrhythmias due to ischemia. A single dose should rarely exceed 30 mg.

Avoid coadministration of nifedipine with grapefruit juice (see CLINICAL PHARMACOLOGY and PRECAUTIONS: Other Interactions).

No “rebound effect” has been observed upon discontinuation of nifedipine. However, if discontinuation of nifedipine is necessary, sound clinical practice suggests that the dosage should be decreased gradually with close physician supervision.

Coadministration with Other Antianginal Drugs:

Sublingual nitroglycerin may be taken as required for the control of acute manifestations of angina, particularly during nifedipine titration. See PRECAUTIONS, Drug Interactions, for information on coadministration of nifedipine with beta blockers or long-acting nitrates.
Anti-diarrheal

Anti-diarrheal

The dose is one drop of dorzolamide hydrochloride ophthalmic solution in the affected eye(s) three times daily. Dorzolamide hydrochloride ophthalmic solution may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.
Clopidogrel Bisulfate

Clopidogrel Bisulfate

2.1 Dosing Information

The recommended dose of sumatriptan tablets is 25 mg, 50 mg, or 100 mg. Doses of 50 mg and 100 mg may provide a greater effect than the 25-mg dose, but doses of 100 mg may not provide a greater effect than the 50-mg dose. Higher doses may have a greater risk of adverse reactions [see Clinical Studies (14)].If the migraine has not resolved by 2 hours after taking sumatriptan tablets, or returns after a transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose is 200 mg in a 24-hour period. Use after Sumatriptan Injection: If the migraine returns following an initial treatment with sumatriptan succinate injection, additional single sumatriptan tablets (up to 100 mg/day) may be given with an interval of at least 2 hours between tablet doses.The safety of treating an average of more than 4 headaches in a 30-day period has not been established.

2.2 Dosing in Patients With Hepatic Impairment

If treatment is deemed advisable in the presence of mild to moderate hepatic impairment, the maximum single dose should not exceed 50 mg [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Pain Relief Childrens

Pain Relief Childrens

2.1 General Dosing Recommendations
Ropinirole extended-release tablets are taken once daily, with or without food [see Clinical Pharmacology (12.3)]. Tablets must be swallowed whole and must not be chewed, crushed, or divided. If a significant interruption in therapy with ropinirole extended-release tablets has occurred, retitration of therapy may be warranted.
2.2 Dosing for Parkinson’s Disease

The starting dose is 2 mg taken once daily for 1 to 2 weeks, followed by increases of 2 mg/day at 1-week or longer intervals as appropriate, based on therapeutic response and tolerability. The maximum recommended dose of ropinirole extended-release tablets is 24 mg/day.

In clinical trials, dosage was initiated at 2 mg/day and gradually titrated based on individual patient therapeutic response and tolerability. Doses greater than 24 mg/day have not been studied in clinical trials. Patients should be assessed for therapeutic response and tolerability at a minimal interval of 1 week or longer after each dose increment. Monitor patients during dose titration because too rapid a rate of titration may lead to dose selection that may not provide additional benefit, but that may increase the risk of adverse reactions [see Clinical Studies (14.2)]. Due to the flexible dosing design used in clinical trials, specific dose-response information could not be determined.

Ropinirole extended-release tablets should be discontinued gradually over a 7-day period.

Renal Impairment No dose adjustment is necessary in patients with moderate renal impairment (creatinine clearance of 30 to 50 mL/min). The recommended initial dose of ropinirole extended-release tablets for patients with end-stage renal disease on hemodialysis is 2 mg once daily. Further dose escalations should be based on tolerability and need for efficacy. The recommended maximum total daily dose is 18 mg/day in patients receiving regular dialysis. Supplemental doses after dialysis are not required. The use of ropinirole extended-release tablets in patients with severe renal impairment without regular dialysis has not been studied.

2.3 Switching from Immediate-Release Ropinirole Tablets to Ropinirole Extended-Release Tablets

Patients may be switched directly from immediate-release ropinirole tablets to ropinirole extended-release tablets. The initial dose of ropinirole extended-release tablets should most closely match the total daily dose of the immediate-release formulation of ropinirole tablets, as shown in Table 1.
Table 1. Conversion from Immediate-Release Ropinirole Tablets to Ropinirole Extended-Release Tablets Immediate-Release Ropinirole Tablets Ropinirole Extended-Release Tablets Total Daily Dose (mg) Total Daily Dose (mg) 0.75 to 2.25 2 3 to 4.5 4 6 6 7.5 to 9 8 12 12 15 16 18 18 21 20 24 24
Following conversion to ropinirole extended-release tablets, the dose may be adjusted depending on therapeutic response and tolerability [see Dosage and Administration (2.2)].

2.4 Effect of Gastrointestinal Transit Time on Medication Release

Ropinirole extended-release tablets are designed to release medication over a 24-hour period. If rapid gastrointestinal transit occurs, there may be risk of incomplete release of medication and medication residue being passed in the stool.
Day Time

Day Time

In order to ensure that the patient is fully aware of the correct method of therapy and to identify which specific warts should be treated, the technique for initial application of the medication should be demonstrated by the prescriber.

Apply twice daily morning and evening (every 12 hours), for 3 consecutive days, then withhold use for 4 consecutive days. This 1 week cycle of treatment may be repeated up to four times until there is no visible wart tissue. If there is incomplete response after four treatment weeks, alternative treatment should be considered. Safety and effectiveness of more than four treatment weeks have not been established.

Podofilox 0.5% solution is applied to the warts with a cotton-tipped applicator supplied with the drug. The drug-dampened applicator should be touched to the wart to be treated, applying the minimum amount of solution necessary to cover the lesion. Treatment should be limited to less than 10 cm2 of wart tissue and to no more than 0.5 mL of the solution per day. There is no evidence to suggest that more frequent application will increase efficacy, but additional applications would be expected to increase the rate of local adverse reactions and systemic absorption.

Care should be taken to allow the solution to dry before allowing the return of opposing skin surfaces to their normal positions. After each treatment, the used applicator should be carefully disposed of and the patient should wash his or her hands.
Ciprofloxacin

Ciprofloxacin

The recommended regimen of isosorbide mononitrate tablets is 20 mg twice daily, with the doses seven hours apart. A starting dose of 5 mg (½ tablet of the 10 mg dosing strength) might be appropriate for persons of particularly small stature but should be increased to at least 10 mg by the second or third day of therapy. Dosage adjustments are not necessary for elderly patients or patients with altered hepatic or renal function.

As noted above (CLINICAL PHARMACOLOGY), multiple studies of organic nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. The asymmetric (2 doses, 7 hours apart) dosing regimen for isosorbide mononitrate tablets provides a daily nitrate-free interval to minimize the development of tolerance.

As also noted under CLINICAL PHARMACOLOGY, well-controlled studies have shown that tolerance to isosorbide mononitrate tablets occurs to some extent when using the twice-daily regimen in which the two doses are given seven hours apart. This regimen has been shown to have antianginal efficacy beginning one hour after the first dose and lasting at least seven hours after the second dose. The duration (if any) of antianginal activity beyond fourteen hours has not been studied.

In clinical trials, isosorbide mononitrate has been administered in a variety of regimens and doses. Doses above 20 mg twice-a-day (with the doses seven hours apart) have not been adequately studied. Doses of 5 mg twice-a-day are clearly effective (effectiveness based on exercise tolerance) for only the first day of a twice-a-day (with doses 7 hours apart) regimen.
Omeprazole

Omeprazole

Omeprazole delayed-release capsules should be taken before eating. In the clinical trials, antacids were used concomitantly with omeprazole.

Patients should be informed that the omeprazole delayed-release capsule should be swallowed whole.

For patients unable to swallow an intact capsule, alternative administration options are available [see Dosage and Administration (2.8)].

2.1 Short-Term Treatment of Active Duodenal Ulcer

The recommended adult oral dose of omeprazole delayed-release capsules are 20 mg once daily. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy.

2.2 H. pylori Eradication for the Reduction of the Risk of Duodenal Ulcer Recurrence

Triple Therapy (omeprazole/clarithromycin/amoxicillin) — The recommended adult oral regimen is omeprazole delayed-release capsules 20 mg plus clarithromycin 500 mg plus amoxicillin 1000 mg each given twice daily for 10 days. In patients with an ulcer present at the time of initiation of therapy, an additional 18 days of omeprazole delayed-release capsules 20 mg once daily is recommended for ulcer healing and symptom relief.

Dual Therapy (omeprazole/clarithromycin) — The recommended adult oral regimen is omeprazole delayed-release capsules 40 mg once daily plus clarithromycin 500 mg three times daily for 14 days. In patients with an ulcer present at the time of initiation of therapy, an additional 14 days of omeprazole delayed-release capsules 20 mg once daily is recommended for ulcer healing and symptom relief.

2.3 Gastric Ulcer

The recommended adult oral dose is 40 mg once daily for 4 to 8 weeks.

2.4 Gastroesophageal Reflux Disease (GERD)

The recommended adult oral dose for the treatment of patients with symptomatic GERD and no esophageal lesions is 20 mg daily for up to 4 weeks. The recommended adult oral dose for the treatment of patients with erosive esophagitis and accompanying symptoms due to GERD is 20 mg daily for 4 to 8 weeks.

2.5 Maintenance of Healing of Erosive Esophagitis

The recommended adult oral dose is 20 mg daily. Controlled studies do not extend beyond 12 months [see Clinical Studies (14.4)].

2.6 Pathological Hypersecretory Conditions

The dosage of omeprazole delayed-release capsules in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult oral starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 120 mg three times daily have been administered. Daily dosages of greater than 80 mg should be administered in divided doses. Some patients with Zollinger-Ellison syndrome have been treated continuously with omeprazole delayed-release capsules for more than 5 years.

2.7 Pediatric Patients

For the treatment of GERD and maintenance of healing of erosive esophagitis, the recommended daily dose for pediatric patients 2 to 16 years of age is as follows:
Patient Weight Omeprazole Daily Dose 10 < 20 kg 10 mg ≥ 20 kg 20 mg
On a per kg basis, the doses of omeprazole required to heal erosive esophagitis in pediatric patients are greater than those for adults.

Alternative administrative options can be used for pediatric patients unable to swallow an intact capsule [see Dosage and Administration (2.8)].

2.8 Alternative Administration Options

Omeprazole is available as a delayed-release capsule.

For patients who have difficulty swallowing capsules, the contents of an omeprazole delayed-release capsule can be added to applesauce. One tablespoon of applesauce should be added to an empty bowl and the capsule should be opened. All of the pellets inside the capsule should be carefully emptied on the applesauce. The pellets should be mixed with the applesauce and then swallowed immediately with a glass of cool water to ensure complete swallowing of the pellets. The applesauce used should not be hot and should be soft enough to be swallowed without chewing. The pellets should not be chewed or crushed. The pellets/applesauce mixture should not be stored for future use.
Bupropion Hydrochloride...

Bupropion Hydrochloride

2.1 General Instructions for Use

To minimize the risk of seizure, increase the dose gradually [see Warnings and Precautions (5.3)]. Bupropion hydrochloride extended-release tablets (SR) should be swallowed whole and not crushed, divided, or chewed. Bupropion hydrochloride extended-release tablets (SR) may be taken with or without food.

The usual adult target dose for bupropion hydrochloride extended-release tablets (SR) is 300 mg per day, given as 150 mg twice daily. Initiate dosing with 150 mg per day given as a single daily dose in the morning. After 3 days of dosing, the dose may be increased to the 300-mg-per-day target dose, given as 150 mg twice daily. There should be an interval of at least 8 hours between successive doses. A maximum of 400 mg per day, given as 200 mg twice daily, may be considered for patients in whom no clinical improvement is noted after several weeks of treatment at 300 mg per day. To avoid high peak concentrations of bupropion and/or its metabolites, do not exceed 200 mg in any single dose.

It is generally agreed that acute episodes of depression require several months or longer of antidepressant drug treatment beyond the response in the acute episode. It is unknown whether the dose of bupropion hydrochloride extended-release tablets (SR) needed for maintenance treatment is identical to the dose that provided an initial response. Periodically reassess the need for maintenance treatment and the appropriate dose for such treatment.

2.2 Dose Adjustment in Patients With Hepatic Impairment

In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose of bupropion hydrochloride extended-release tablets (SR) is 100 mg per day or 150 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

2.3 Dose Adjustment in Patients With Renal Impairment

Consider reducing the dose and/or frequency of bupropion hydrochloride extended-release tablets (SR) in patients with renal impairment (Glomerular Filtration Rate less than 90 mL/min) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.4 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Antidepressant

At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with bupropion hydrochloride extended-release tablets (SR). Conversely, at least 14 days should be allowed after stopping bupropion hydrochloride extended-release tablets (SR) before starting an MAOI antidepressant [see Contraindications (4), Drug Interactions (7.6)].

2.5 Use of Bupropion Hydrochloride Extended-release Tablets (SR) With Reversible MAOIs Such as Linezolid or Methylene Blue

Do not start bupropion hydrochloride extended-release tablets (SR) in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase the risk of hypertensive reactions. In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered [see Contraindications (4), Drug Interactions (7.6)].

In some cases, a patient already receiving therapy with bupropion hydrochloride extended-release tablets (SR) may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of hypertensive reactions in a particular patient, bupropion hydrochloride extended-release tablets (SR) should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with bupropion hydrochloride extended-release tablets (SR) may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with bupropion hydrochloride extended-release tablets (SR) is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use [see Contraindications (4), Drug Interactions (7.6)].
Duloxetine

Duloxetine

Duloxetine delayed-release should be swallowed whole and should not be chewed or crushed, nor should the capsule be opened and its contents sprinkled on food or mixed with liquids. All of these might affect the enteric coating. Duloxetine delayed-release can be given without regard to meals.

2.1 Initial Treatment

Major Depressive Disorder - Duloxetine delayed-release should be administered at a total dose of 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily). For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. While a 120 mg/day dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer any additional benefits. The safety of doses above 120 mg/day has not been adequately evaluated [see Clinical Studies (14.1)].

Generalized Anxiety Disorder - For most patients, the recommended starting dose for duloxetine delayed-release is 60 mg administered once daily. For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. While a 120 mg once daily dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefit. Nevertheless, if a decision is made to increase the dose beyond 60 mg once daily, dose increases should be in increments of 30 mg once daily. The safety of doses above 120 mg once daily has not been adequately evaluated [see Clinical Studies (14.2)].

Diabetic Peripheral Neuropathic Pain - The recommended dose for duloxetine delayed-release is 60 mg administered once daily. There is no evidence that doses higher than 60 mg confer additional significant benefit and the higher dose is clearly less well tolerated [see Clinical Studies (14.3)]. For patients for whom tolerability is a concern, a lower starting dose may be considered.

Since diabetes is frequently complicated by renal disease, a lower starting dose and gradual increase in dose should be considered for patients with renal impairment [see Dosage and Administration (2.3), Use in Specific Populations (8.10), and Clinical Pharmacology (12.3)].

Fibromyalgia - The recommended dose for duloxetine delayed-release is 60 mg administered once daily. Treatment should begin at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. Some patients may respond to the starting dose. There is no evidence that doses greater than 60 mg/day confer additional benefit, even in patients who do not respond to a 60 mg dose, and higher doses are associated with a higher rate of adverse reactions [see Clinical Studies (14.4)].

Chronic Musculoskeletal Pain — The recommended dose for duloxetine delayed-release is 60 mg once daily. Dosing may be started at 30 mg for one week, to allow patients to adjust to the medication before increasing to 60 mg once daily. There is no evidence that higher doses confer additional benefit, even in patients who do not respond to a 60 mg dose, and higher doses are associated with a higher rate of adverse reactions [see Clinical Studies (14.5)].

2.2 Maintenance/Continuation/Extended Treatment

Major Depressive Disorder - It is generally agreed that acute episodes of major depression require several months or longer of sustained pharmacologic therapy. Maintenance of efficacy in MDD was demonstrated with duloxetine delayed-release as monotherapy. Duloxetine delayed-release should be administered at a total dose of 60 mg once daily. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.1)].

Generalized Anxiety Disorder - It is generally agreed that episodes of generalized anxiety disorder require several months or longer of sustained pharmacological therapy. Maintenance of efficacy in GAD was demonstrated with duloxetine delayed-release as monotherapy. Duloxetine delayed-release should be administered in a dose range of 60 to 120 mg once daily. Patients should be periodically reassessed to determine the continued need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.2)].

Diabetic Peripheral Neuropathic Pain - As the progression of diabetic peripheral neuropathy is highly variable and management of pain is empirical, the effectiveness of duloxetine delayed-release must be assessed individually. Efficacy beyond 12 weeks has not been systematically studied in placebo-controlled trials.

Fibromyalgia - Fibromyalgia is recognized as a chronic condition. The efficacy of duloxetine delayed-release in the management of fibromyalgia has been demonstrated in placebo-controlled studies up to 3 months. The efficacy of duloxetine delayed-release was not demonstrated in longer studies; however, continued treatment should be based on individual patient response.

Chronic Musculoskeletal Pain — The efficacy of duloxetine delayed-release has not been established in placebo-controlled studies beyond 13 weeks.

2.3 Dosing in Special Populations

Hepatic Insufficiency - It is recommended that duloxetine delayed-release should ordinarily not be administered to patients with any hepatic insufficiency [see Warnings and Precautions (5.14) and Use in Specific Populations (8.9)].

Severe Renal Impairment - Duloxetine delayed-release is not recommended for patients with end-stage renal disease or severe renal impairment (estimated creatinine clearance <30 mL/min) [see Warnings and Precautions (5.14) and Use in Specific Populations (8.10)].

Elderly Patients - No dose adjustment is recommended for elderly patients on the basis of age. As with any drug, caution should be exercised in treating the elderly. When individualizing the dosage in elderly patients, extra care should be taken when increasing the dose [see Use in Specific Populations (8.5)].

Pregnant Women - There are no adequate and well-controlled studies in pregnant women; therefore, duloxetine delayed-release should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [see Use in Specific Populations (8.1)].

Nursing Mothers - Because the safety of duloxetine in infants is not known, nursing while on duloxetine delayed-release is not recommended [see Use in Specific Populations (8.3)].

2.4 Discontinuing Duloxetine Delayed-Release

Symptoms associated with discontinuation of duloxetine delayed-release and other SSRIs and SNRIs have been reported. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible [see Warnings and Precautions (5.7)].

2.5 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with duloxetine delayed-release. Conversely, at least 5 days should be allowed after stopping duloxetine delayed-release before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.1)].

2.6 Use of Duloxetine Delayed-Release with Other MAOIs such as Linezolid or Methylene Blue

Do not start duloxetine delayed-release in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4.1)].

In some cases, a patient already receiving duloxetine delayed-release therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, duloxetine delayed-release should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with duloxetine delayed-release may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.4)].

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with duloxetine delayed-release is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.4)].
Telmisartan

Telmisartan

2.1 Hypertension

Dosage must be individualized. The usual starting dose of telmisartan tablets, USP is 40 mg once a day. Blood pressure response is dose-related over the range of 20 to 80 mg [see Clinical Studies (14.1)].

Most of the antihypertensive effect is apparent within 2 weeks and maximal reduction is generally attained after 4 weeks. When additional blood pressure reduction beyond that achieved with 80 mg telmisartan tablets, USP is required, a diuretic may be added.

No initial dosage adjustment is necessary for elderly patients or patients with renal impairment, including those on hemodialysis. Patients on dialysis may develop orthostatic hypotension; their blood pressure should be closely monitored.

Telmisartan tablets, USP may be administered with other antihypertensive agents.

Telmisartan tablets, USP may be administered with or without food.
Clozapine

Clozapine

2.1 Dosing Information

The recommended dose is 8 mg orally once daily with a meal.

Patients who have difficulty swallowing pills and capsules may carefully open the RAPAFLO capsule and sprinkle the powder inside on a tablespoonful of applesauce. The applesauce should be swallowed immediately (within 5 minutes) without chewing and followed with an 8 oz glass of cool water to ensure complete swallowing of the powder. The applesauce used should not be hot, and it should be soft enough to be swallowed without chewing. Any powder/applesauce mixture should be used immediately (within 5 minutes) and not stored for future use. Subdividing the contents of a RAPAFLO capsule is not recommended [see CLINICAL PHARMACOLOGY (12.3)].

2.2 Dosage Adjustment in Special Populations

Renal impairment: RAPAFLO is contraindicated in patients with severe renal impairment (CCr < 30 mL/min). In patients with moderate renal impairment (CCr 30-50 mL/min), the dose should be reduced to 4 mg once daily taken with a meal. No dosage adjustment is needed in patients with mild renal impairment (CCr 50-80 mL/min) [see CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS (5.2), USE IN SPECIFIC POPULATIONS (8.6), and CLINICAL PHARMACOLOGY (12.3)].

Hepatic impairment: RAPAFLO has not been studied in patients with severe hepatic impairment (Child-Pugh score > 10) and is therefore contraindicated in these patients. No dosage adjustment is needed in patients with mild or moderate hepatic impairment [see CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS (5.3), USE IN SPECIFIC POPULATIONS (8.7) and CLINICAL PHARMACOLOGY (12.3)].
Lisinopril

Lisinopril

Apply a thin film of adapalene gel, 0.3% to the entire face and any other affected areas of the skin once daily in the evening, after washing gently with a non-medicated soap. Avoid application to the areas of skin around eyes, lips, and mucous membranes. A mild transitory sensation of warmth or slight stinging may occur shortly after the application of adapalene gel, 0.3%. Patients should be instructed to minimize sun exposure. Patients may be instructed to use moisturizers for relief of dry skin or irritation.

If therapeutic results are not noticed after 12 weeks of treatment, therapy should be re-evaluated.

For topical use only. Not for ophthalmic, oral or intravaginal use.
Bare Perfecting Makeup ...

Bare Perfecting Makeup Merle Norman

Fluocinonide cream 0.05% is generally applied to the affected area as a thin film from two to four times daily depending on the severity of the condition.Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions.If an infection develops, the use of occlusive dressings should be discontinued and appropriate antimicrobial therapy instituted.
Pravastatin Sodium

Pravastatin Sodium

Clarithromycin extended-release tablets should be taken with food. Clarithromycin extended-release tablets should be swallowed whole and not chewed, broken or crushed.

Clarithromycin may be administered without dosage adjustment in the presence of hepatic impairment if there is normal renal function. In patients with severe renal impairment (CLCR < 30 mL/min), the dose of clarithromycin should be reduced by 50%. However, when patients with moderate or severe renal impairment are taking clarithromycin concomitantly with atazanavir or ritonavir, the dose of clarithromycin should be reduced by 50% or 75% for patients with CLCR of 30 to 60 mL/min or < 30 mL/min, respectively.
ADULT DOSAGE GUIDELINES Clarithromycin Extended-release Tablets Infection Dosage(q24h) Duration(days) Acute maxillary sinusitis due to 2 x 500 mg 14 H. influenzae M. catarrhalis S. pneumoniae Acute exacerbation of chronic bronchitis due to: H. influenzae 2 x 500 mg 7 H. parainfluenzae 2 x 500 mg 7 M. catarrhalis 2 x 500 mg 7 S. pneumoniae 2 x 500 mg 7 Community-Acquired Pneumonia due to: H. influenzae 2 x 500 mg 7 H. parainfluenzae 2 x 500 mg 7 M. catarrhalis 2 x 500 mg 7 S. pneumoniae 2 x 500 mg 7 C. pneumoniae 2 x 500 mg 7 M. pneumoniae 2 x 500 mg 7
Ivory Perfecting Makeup...

Ivory Perfecting Makeup Broad Spectrum Spf 25 Merle Norman

To achieve maximum contraceptive effectiveness, Jolivette® must be taken exactly as directed. One tablet is taken every day, at the same time. Administration is continuous, with no interruption between pill packs. See Detailed Patient Labeling for detailed instruction.
Mirtazapine

Mirtazapine

Initial Treatment

The recommended starting dose for mirtazapine orally disintegrating tablets is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day. While the relationship between dose and satisfactory response in the treatment of major depressive disorder for mirtazapine has not been adequately explored, patients not responding to the initial 15-mg dose may benefit from dose increases up to a maximum of 45 mg/day. Mirtazapine has an elimination half-life of approximately 20 to 40 hours; therefore, dose changes should not be made at intervals of less than 1 to 2 weeks in order to allow sufficient time for evaluation of the therapeutic response to a given dose.

Administration of Mirtazapine Orally Disintegrating Tablets

Patients should be instructed to open tablet blister pack with dry hands and place the tablet on the tongue. The tablet should be used immediately after removal from its blister; once removed, it cannot be stored. Mirtazapine orally disintegrating tablets will disintegrate rapidly on the tongue and can be swallowed with saliva. No water is needed for taking the tablet. Patients should not attempt to split the tablet.

Elderly and Patients with Renal or Hepatic Impairment

The clearance of mirtazapine is reduced in elderly patients and in patients with moderate to severe renal or hepatic impairment. Consequently, the prescriber should be aware that plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in younger adults without renal or hepatic impairment (see PRECAUTIONS and CLINICAL PHARMACOLOGY).

Maintenance/Extended Treatment

It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of mirtazapine tablets has demonstrated that its efficacy in major depressive disorder is maintained for periods of up to 40 weeks following 8 to 12 weeks of initial treatment at a dose of 15 to 45 mg/day (see CLINICAL PHARMACOLOGY). Based on these limited data, it is unknown whether or not the dose of mirtazapine needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with mirtazapine orally disintegrating tablets. Conversely, at least 14 days should be allowed after stopping mirtazapine orally disintegrating tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).

Use of Mirtazapine Orally Disintegrating Tablets With Other MAOIs, Such as Linezolid or Methylene Blue

Do not start mirtazapine orally disintegrating tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).

In some cases, a patient already receiving therapy with mirtazapine orally disintegrating tablets may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, mirtazapine orally disintegrating tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with mirtazapine orally disintegrating tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with mirtazapine orally disintegrating tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).

Discontinuation of Mirtazapine Treatment

Symptoms associated with the discontinuation or dose reduction of mirtazapine orally disintegrating tablets have been reported. Patients should be monitored for these and other symptoms when discontinuing treatment or during dosage reduction. A gradual reduction in the dose over several weeks, rather than abrupt cessation, is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient’s clinical response (see PRECAUTIONS and ADVERSE REACTIONS).

Information for Patients

Patients should be advised that taking mirtazapine orally disintegrating tablets can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle-closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.
Trospium Chloride

Trospium Chloride

The recommended dosage of trospium chloride extended-release capsules is one 60 mg capsule daily in the morning. Trospium chloride extended-release capsules should be dosed with water on an empty stomach, at least one hour before a meal.

Trospium chloride extended-release capsules are not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) [see Warnings and Precautions (5.6), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].
Unisom Sleeptabs

Unisom Sleeptabs

2.1 Recommended Dose

In Combination with Cisplatin 100 mg/m2
The recommended dose of vinorelbine is 25 mg/m2 administered as an intravenous injection or infusion over 6 to 10 minutes on days 1, 8, 15 and 21 of a 28 day cycle in combination with cisplatin 100 mg/m2 on day 1 only of each 28 day cycle.
In Combination with Cisplatin 120 mg/m2
The recommended dose of vinorelbine is 30 mg/m2 administered as an intravenous injection or infusion over 6 to 10 minutes once a week in combination with cisplatin 120 mg/m2 on days 1 and 29, then every 6 weeks.
Single-Agent
The recommended dose of vinorelbine is 30 mg/m2 administered intravenously over 6 to 10 minutes once a week.
2.2 Dose Modifications

Hematologic Toxicity

[see Warnings and Precautions (5.1)]

Hold or decrease the dose of vinorelbine in patients with decreased neutrophil counts using the following schema.
Neutrophils on Day of Treatment (Cells/mm3) Percentage of Starting Dose of Vinorelbine ≥ 1,500 100% 1,000 to 1,499 50% < 1,000 Do not administer vinorelbine. Repeat neutrophil count in one week. If three consecutive weekly doses are held because Neutrophil count is < 1,000 cells/mm3, discontinue vinorelbine Note : For patients who experience fever and/or sepsis while neutrophil count is < 1,500 or had 2 consecutive weekly doses held due to neutropenia, subsequent doses of vinorelbine should be: > 1,500 75% 1,000 to 1,499 37.5% < 1,000 Do not administer vinorelbine. Repeat neutrophil count in one week.
Hepatic Impairment/Toxicity

[see Warnings and Precautions (5.2) and Use in Specific Populations (8.6)]

Reduce vinorelbine dose in patients with elevated serum total bilirubin concentration according to the following schema:
Serum total bilirubin concentration (mg/dl) Percentage of Starting Dose of Vinorelbine ≤ 2.0 100% 2.1 to 3.0 50% > 3.0 25%
Concurrent Hematologic Toxicity and Hepatic Impairment

In patients with both hematologic toxicity and hepatic impairment, administer the lower of the doses based on the corresponding starting dose of vinorelbine determined from the above schemas.

Neurologic Toxicity

[see Warnings and Precautions (5.5)]

Discontinue vinorelbine for NCI CTCAE Grade 2 or higher peripheral neuropathy or autonomic neuropathy causing constipation.

2.3 Preparation and Administration

Preparation of Vinorelbine Injection, USP

Dilute Vinorelbine Injection, USP in either a syringe or intravenous bag using one of the recommended solutions.

Syringe

Dilute to a concentration between 1.5 and 3 mg/mL. The following solutions may be used for dilution:
5% Dextrose Injection, USP 0.9% Sodium Chloride Injection, USP
Intravenous Bag

Dilute to a concentration between 0.5 and 2 mg/mL. The following solutions may be used for dilution:
5% Dextrose Injection, USP 0.9% Sodium Chloride Injection, USP 0.45% Sodium Chloride Injection, USP 5% Dextrose and 0.45% Sodium Chloride Injection, USP Ringer's Injection, USP Lactated Ringer's Injection, USP
Stability

Diluted Vinorelbine Injection, USP may be used for up to 24 hours under normal room light when stored in polypropylene syringes or polyvinyl chloride bags at 5° to 30°C (41° to 86°F).

Administration

Administer diluted Vinorelbine Injection, USP over 6 to 10 minutes into the side port of a free-flowing intravenous line followed by flushing with at least 75 to 125 mL of one of the solutions.

Vinorelbine Injection, USP must only be administered intravenously. It is extremely important that the intravenous needle or catheter be properly positioned before any vinorelbine is injected.

Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit. If particulate matter is seen, Vinorelbine Injection, USP should not be administered.

Management of Suspected Extravasation
If vinorelbine leakage into surrounding tissue occurs or is suspected, immediately stop administration of vinorelbine and initiate appropriate management measures in accordance with institutional policies. [see Warnings and Precautions (5.4).]
2.4 Procedures for Proper Handling and Disposal

Handle and dispose Vinorelbine Injection, USP consistent with recommendations for the handling and disposal of hazardous drugs1.

Exercise caution in handling and preparing the solution of Vinorelbine Injection, USP. The use of gloves is recommended. If the solution of Vinorelbine Injection, USP contacts the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water.

Avoid contamination of the eye with Vinorelbine Injection, USP. If exposure occurs, flush the eyes with water immediately and thoroughly.
Alprazolam

Alprazolam

2.1 Dosage in Adults

Use the lowest effective dose for the patient. The recommended initial dose is 6.25 mg for women and either 6.25 or 12.5 mg for men, taken only once per night immediately before bedtime with at least 7 to 8 hours remaining before the planned time of awakening. If the 6.25 mg dose is not effective, the dose can be increased to 12.5 mg. In some patients, the higher morning blood levels following use of the 12.5 mg dose increase the risk of next day impairment of driving and other activities that require full alertness [see Warnings and Precautions (5.1)]. The total dose of zolpidem tartrate extended-release tablets should not exceed 12.5 mg once daily immediately before bedtime.

The recommended initial doses for women and men are different because zolpidem clearance is lower in women.

2.2 Special Populations

Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate. Patients with hepatic insufficiency do not clear the drug as rapidly as normal subjects. The recommended dose of zolpidem tartrate extended-release tablets in both of these patient populations is 6.25 mg once daily immediately before bedtime [see Warnings and Precautions (5.1); Use in Specific Populations (8.5)].

2.3 Use with CNS Depressants

Dosage adjustment may be necessary when zolpidem tartrate extended-release tablets are combined with other CNS depressant drugs because of the potentially additive effects [see Warnings and Precautions (5.1)].

2.4 Administration

Zolpidem tartrate extended-release tablets should be swallowed whole, and not be divided, crushed, or chewed. The effect of zolpidem tartrate extended-release tablets may be slowed by ingestion with or immediately after a meal.
Simbrinza

Simbrinza

Apply lidocaine patch 5% to intact skin to cover the most painful area. Apply the prescribed number of patches (maximum of 3), only once for up to 12 hours within a 24-hour period. Patches may be cut into smaller sizes with scissors prior to removal of the release liner. (See HANDLING AND DISPOSAL) Clothing may be worn over the area of application. Smaller areas of treatment are recommended in a debilitated patient, or a patient with impaired elimination.

If irritation or a burning sensation occurs during application, remove the patch(es) and do not reapply until the irritation subsides.

When lidocaine patch 5% is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered.

Lidocaine patch 5% may not stick if it gets wet. Avoid contact with water, such as bathing, swimming or showering.
Gabapentin

Gabapentin

Gabapentin capsules are given orally with or without food.

Gabapentin capsules should be swallowed whole with plenty of water.

If gabapentin dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).

2.1 Postherpetic Neuralgia

In adults with postherpetic neuralgia, gabapentin therapy may be initiated on Day 1 as a single 300 mg dose, on Day 2 as 600 mg/day (300 mg two times a day), and on Day 3 as 900 mg/day (300 mg three times a day). The dose can subsequently be titrated up as needed for pain relief to a dose of 1800 mg/day (600 mg three times a day). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range; however, in these clinical studies, the additional benefit of using doses greater than 1800 mg/day was not demonstrated.

2.2 Epilepsy with Partial Onset Seizures

Gabapentin is recommended for add-on therapy in patients 3 years of age and older. Effectiveness in pediatric patients below the age of 3 years has not been established.

Patients 12 years of age and above: The starting dose is 300 mg three times a day. The effective dose of gabapentin is 300 mg to 600 mg three times a day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. Gabapentin should be administered three times a day using 300 mg or 400 mg capsules. The maximum time between doses should not exceed 12 hours.

Pediatric Patients Age 3 to 11 years: The starting dose range is 10 mg/kg/day to 15 mg/kg/day, given in three divided doses, and the effective dose reached by upward titration over a period of approximately 3 days. The effective dose of gabapentin in patients 3 to 4 years of age is 40 mg/kg/day, given in three divided doses. The effective dose of gabapentin in patients 5 to 11 years of age is 25 mg/kg/day to 35 mg/kg/day, given in three divided doses. Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.

It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further, because there are no significant pharmacokinetic interactions among gabapentin and other commonly used antiepileptic drugs, the addition of gabapentin does not alter the plasma levels of these drugs appreciably.

If gabapentin is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.

2.3 Patients with Renal Impairment

Dosage adjustment in patients 12 years of age and older with compromised renal function or undergoing hemodialysis is recommended, as follows (see dosing recommendations above for effective doses in each indication):
TABLE 1. Gabapentin Dosage Based on Renal Function
Renal Function

Total Daily

Dose Regimen

Creatinine Clearance (mL/min)

Dose Range(mg/day)

(mg)

≥60

900 to 3600

300 TID

400 TID

600 TID

800 TID

1200 TID

>30 to 59

400 to 1400

200 BID

300 BID

400 BID

500 BID

700 BID

>15 to 29

200 to 700

200 QD

300 QD

400 QD

500 QD

700 QD

15a

100 to 300

100 QD

125 QD

150 QD

200 QD

300 QD

Post-Hemodialysis Supplemental Dose (mg)b

Hemodialysis

125b

150b

200b

250b

350b

TID = Three times a day; BID = Two times a day; QD = Single daily dose

a For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table.

Creatinine clearance (CLCr) is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance can be reasonably well estimated using the equation of Cockcroft and Gault:

The use of gabapentin in patients less than 12 years of age with compromised renal function has not been studied.

2.4 Dosage in Elderly

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.
Dronabinol

Dronabinol

Appetite Stimulation: Initially, 2.5 mg dronabinol capsules should be administered orally twice daily (b.i.d.), before lunch and supper. For patients unable to tolerate this 5 mg/day dosage of dronabinol capsules, the dosage can be reduced to 2.5 mg/day, administered as a single dose in the evening or at bedtime. If clinically indicated and in the absence of significant adverse effects, the dosage may be gradually increased to a maximum of 20 mg/day dronabinol capsules, administered in divided oral doses. Caution should be exercised in escalating the dosage of dronabinol capsules because of the increased frequency of dose-related adverse experiences at higher dosages. (See PRECAUTIONS.)Antiemetic: Dronabinol capsules are best administered at an initial dose of 5 mg/m2, given 1 to 3 hours prior to the administration of chemotherapy, then every 2 to 4 hours after chemotherapy is given, for a total of 4 to 6 doses/day. Should the 5 mg/m2 dose prove to be ineffective, and in the absence of significant side effects, the dose may be escalated by 2.5 mg/m2 increments to a maximum of 15 mg/m2 per dose. Caution should be exercised in dose escalation, however, as the incidence of disturbing psychiatric symptoms increases significantly at maximum dose. (See PRECAUTIONS.)Storage Conditions Dronabinol capsules should be packaged in a well-closed container and stored in a cool environment between 8° C and 15° C (46° F and 59° F) and alternatively could be stored in a refrigerator. Protect from freezing.
Proleukin

Proleukin

2.1 Adult Hypertension

The recommended starting dose of valsartan tablets is 80 mg or 160 mg once daily when used as monotherapy in patients who are not volume-depleted. Patients requiring greater reductions may be started at the higher dose. Valsartan tablets may be used over a dose range of 80 mg to 320 mg daily, administered once a day.

The antihypertensive effect is substantially present within 2 weeks and maximal reduction is generally attained after 4 weeks. If additional antihypertensive effect is required over the starting dose range, the dose may be increased to a maximum of 320 mg or a diuretic may be added. Addition of a diuretic has a greater effect than dose increases beyond 80 mg.

No initial dosage adjustment is required for elderly patients, for patients with mild or moderate renal impairment, or for patients with mild or moderate liver insufficiency. Care should be exercised with dosing of valsartan tablets in patients with hepatic or severe renal impairment.

Valsartan tablets may be administered with other antihypertensive agents.

Valsartan tablets may be administered with or without food.

2.2 Pediatric Hypertension 6 to 16 Years of Age

For children who can swallow tablets, the usual recommended starting dose is 1.3 mg/kg once daily (up to 40 mg total). The dosage should be adjusted according to blood pressure response. Doses higher than 2.7 mg/kg (up to 160 mg) once daily have not been studied in pediatric patients 6 to 16 years old.

For children who cannot swallow tablets, or children for whom the calculated dosage (mg/kg) does not correspond to the available tablet strengths of valsartan, the use of a suspension is recommended. Follow the suspension preparation instructions below (see Preparation of Suspension) to administer valsartan as a suspension. When the suspension is replaced by a tablet, the dose of valsartan may have to be increased. The exposure to valsartan with the suspension is 1.6 times greater than with the tablet.

No data are available in pediatric patients either undergoing dialysis or with a glomerular filtration rate less than 30 mL/min/1.73 m2[see Pediatric Use (8.4)].

Valsartan tablets are not recommended for patients less than 6 years old see Adverse Reactions (6.1), Clinical Studies (14.1)].

Preparation of Suspension (for 160 mL of a 4 mg/mL suspension)

Add 80 mL of Ora-Plus®* oral suspending vehicle to an amber glass bottle containing 8 valsartan 80 mg tablets, and shake for a minimum of 2 minutes. Allow the suspension to stand for a minimum of 1 hour. After the standing time, shake the suspension for a minimum of 1 additional minute. Add 80 mL of Ora-Sweet SF®* oral sweetening vehicle to the bottle and shake the suspension for at least 10 seconds to disperse the ingredients. The suspension is homogenous and can be stored for either up to 30 days at room temperature (below 30ºC/86ºF) or up to 75 days at refrigerated conditions (2° to 8°C/35° to 46°F) in the glass bottle with a child-resistant screw-cap closure. Shake the bottle well (at least 10 seconds) prior to dispensing the suspension.

*Ora-Sweet SF® and Ora-Plus® are registered trademarks of Paddock Laboratories, Inc.

2.3 Heart Failure

The recommended starting dose of valsartan tablets is 40 mg twice daily. Uptitration to 80 mg and 160 mg twice daily should be done to the highest dose, as tolerated by the patient. Consideration should be given to reducing the dose of concomitant diuretics. The maximum daily dose administered in clinical trials is 320 mg in divided doses.
Crinone

Crinone

Assisted Reproductive Technology

Crinone 8% is administered vaginally at a dose of 90 mg once daily in women who require progesterone supplementation. Crinone 8% is administered vaginally at a dose of 90 mg twice daily in women with partial or complete ovarian failure who require progesterone replacement. If pregnancy occurs, treatment may be continued until placental autonomy is achieved, up to 10 to 12 weeks.

Secondary Amenorrhea

Crinone 4% is administered vaginally every other day up to a total of six doses. For women who fail to respond, a trial of Crinone 8% every other day up to a total of six doses may be instituted.

It is important to note that a dosage increase from the 4% gel can only be accomplished by using the 8% gel. Increasing the volume of gel administered does not increase the amount of progesterone absorbed.
Testosterone Cypionate

Testosterone Cypionate

Prior to initiating testosterone cypionate, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.

Testosterone cypionate injection is for intramuscular use only.

It should not be given intravenously. Intramuscular injections should be given deep in the gluteal muscle.

The suggested dosage for testosterone cypionate injection varies depending on the age, sex, and diagnosis of the individual patient. Dosage is adjusted according to the patient‘s response and the appearance of adverse reactions.

Various dosage regimens have been used to induce pubertal changes in hypogonadal males; some experts have advocated lower dosages initially, gradually increasing the dose as puberty progresses, with or without a decrease to maintenance levels. Other experts emphasize that higher dosages are needed to induce pubertal changes and lower dosages can be used for maintenance after puberty. The chronological and skeletal ages must be taken into consideration, both in determining the initial dose and in adjusting the dose.

For replacement in the hypogonadal male, 50 to 400 mg should be administered every two to four weeks.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Warming and shaking the vial should redissolve any crystals that may have formed during storage at temperatures lower than recommended.
Equaline Anti Itch

Equaline Anti Itch

Clobetasol propionate topical solution should be applied to the affected scalp areas twice daily, once in the morning and once at night. Clobetasol propionate topical solution is potent; therefore, treatment must be limited to 2 consecutive weeks and amounts greater than 50 mL/week should not be used. Clobetasol propionate topical solution is not to be used with occlusive dressings.
Solodyn

Solodyn

2.1 Initial Dosing

Fentanyl transdermal system should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Due to the risk of respiratory depression, fentanyl transdermal system is only indicated for use in patients who are already opioid-tolerant. Discontinue or taper all other extended-release opioids when beginning fentanyl transdermal system therapy. As fentanyl transdermal system is only for use in opioid-tolerant patients, do not begin any patient on fentanyl transdermal system as the first opioid.

Patients considered opioid-tolerant are those who are taking at least 60 mg of morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.

Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with fentanyl transdermal system when serum concentrations from the initial patch will peak [see Warnings and Precautions (5.2)].

The recommended starting dose when converting from other opioids to fentanyl transdermal system is intended to minimize the potential for overdosing patients with the first dose.

Discontinue all other around-the-clock opioid drugs when fentanyl transdermal system therapy is initiated.

While there are useful tables of opioid equivalents readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. As such, it is preferable to underestimate a patient’s 24-hour fentanyl requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour fentanyl requirements which could result in adverse reactions. In a fentanyl transdermal system clinical trial, patients were converted from their prior opioid to fentanyl transdermal system using Table 1 as a guide for the initial fentanyl transdermal system dose.

Consider the following when using the information in Table 1:

•       This is not a table of equianalgesic doses.

•       The conversion doses in this table are only for the conversion from one of the listed oral or parenteral opioid analgesics to fentanyl transdermal system.

•       The table cannot be used to convert from fentanyl transdermal system to another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in fatal overdose.

To convert patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 to convert from fentanyl transdermal system to other therapies because this conversion to fentanyl transdermal system is conservative and will overestimate the dose of the new agent.
Table 11: DOSE CONVERSION TO FENTANYL TRANSDERMAL SYSTEM Current Analgesic Daily Dosage (mg/day) Oral morphine 60 to 134 135 to 224 225 to 314 315 to 404 Intramuscular or Intravenous morphine 10 to 22 23 to 37 38 to 52 53 to 67 Oral oxycodone 30 to 67 67.5 to 112 112.5 to 157 157.5 to 202 Oral codeine 150 to 447 Oral hydromorphone 8 to 17 17.1 to 28 28.1 to 39 39.1 to 51 Intravenous Hydromorphone 1.5 to 3.4 3.5 to 5.6 5.7 to 7.9 8 to 10 Intramuscular meperidine 75 to 165 166 to 278 279 to 390 391 to 503 Oral methadone 20 to 44 45 to 74 75 to 104 105 to 134 ↓ ↓ ↓ ↓ Recommended Fentanyl Transdermal 25 mcg/hour 50 mcg/hour 75 mcg/hour 100 mcg/hour System Dose
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.

1 Table 1 should not be used to convert from fentanyl transdermal system to other therapies because this conversion to fentanyl transdermal system is conservative. Use of Table 1 for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible [see Dosage and Administration(2.3)].

Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:

1. Calculate the previous 24-hour analgesic requirement.

2. Convert this amount to the equianalgesic oral morphine dose using a reliable reference.

Refer to Table 2 for the range of 24-hour oral morphine doses that are recommended for conversion to each fentanyl transdermal system dose. Use this table to find the calculated 24-hour morphine dose and the corresponding fentanyl transdermal system dose. Initiate fentanyl transdermal system treatment using the recommended dose and titrate patients upwards (no more frequently than 3 days after the initial dose and every 6 days thereafter) until analgesic efficacy is attained.

3. Do not use Table 2 to convert from fentanyl transdermal system to other therapies because this conversion to fentanyl transdermal system is conservative and will overestimate the dose of the new agent.


Table 21: RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSE Oral 24-hourMorphine(mg/day) Fentanyl Transdermal SystemDose(mcg/hour) 60 to 134 25 135 to 224 50 225 to 314 75 315 to 404 100 405 to 494 125 495 to 584 150 585 to 674 175 675 to 764 200 765 to 854 225 855 to 944 250 945 to 1034 275 1035 to 1124
300

NOTE: In clinical trials, these ranges of daily oral morphine doses were used as a basis for conversion to

fentanyl transdermal system.

1 Table 2 should not be used to convert from fentanyl transdermal system to other therapies because this conversion to fentanyl transdermal system is conservative. Use of Table 2 for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible [see Dosage and Administration(2.5)].

       For delivery rates in excess of 100 mcg/hour, multiple systems may be used.

Hepatic Impairment

Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system.

Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.14), Use in Specific Populations (8.6) and ClinicalPharmacology (12.3)].

Renal Impairment

Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.15), Use in Specific Populations (8.7) and Clinical Pharmacology(12.3)].

2.2 Titration and Maintenance of Therapy

Individually titrate fentanyl transdermal system to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving fentanyl transdermal system to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for opioid analgesics.

The dosing interval for fentanyl transdermal system is 72 hours. Do not increase the fentanyl transdermal system dose for the first time until at least 3 days after the initial application. Titrate the dose based on the daily dose of supplemental opioid analgesics required by the patient on the second or third day of the initial application.

It may take up to 6 days for fentanyl levels to reach equilibrium on a new dose [see Clinical Pharmacology (12.3)]. Therefore, evaluate patients for further titration after no less than two 3-day applications before any further increase in dosage is made.

Base dosage increments on the daily dosage of supplementary opioids, using the ratio of 45 mg/24 hours of oral morphine to a 12 mcg/hour increase in fentanyl transdermal system dose.

If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

A small proportion of adult patients may not achieve adequate analgesia using a 72-hour dosing interval and may require systems to be applied at 48 hours rather than at 72 hours, only if adequate pain control cannot be achieved using a 72-hour regimen. An increase in the fentanyl transdermal system dose should be evaluated before changing dosing intervals in order to maintain patients on a 72-hour regimen.

Dosing intervals less than every 72 hours were not studied in children and adolescents and are not recommended.

2.3 Administration of Fentanyl Transdermal System

Fentanyl transdermal system patches are for transdermal use, only.

Proper handling of fentanyl transdermal system is necessary in order to prevent serious adverse outcomes, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].

Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non-irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system application. If the site of fentanyl transdermal system application must be cleansed prior to application of the patch, do so with clear water. Do not use soaps, oils, lotions, alcohol, or any other agents that might irritate the skin or alter its characteristics. Allow the skin to dry completely prior to patch application. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system patch may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system patch occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system patch from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.
Avoidance of Heat

Instruct patients to avoid exposing the fentanyl transdermal system application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, sunbathing, hot baths, saunas, hot tubs, and heated water beds, while wearing the system [see Warnings and Precautions (5.11)].

2.4 Disposal Instructions

Failure to properly dispose of fentanyl transdermal system has resulted in accidental exposures and deaths [see Warnings and Precautions (5.3)].

Patients should dispose of used patches immediately upon removal by folding the adhesive side of the patch to itself, then flushing down the toilet.

Unused patches should be removed from their pouches, the protective liners removed, the patches folded so that the adhesive side of the patch adheres to itself, and immediately flushed down the toilet.

Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed.

2.5 Discontinuation of Fentanyl Transdermal System

Significant amounts of fentanyl continue to be absorbed from the skin for 24 hours or more after the patch is removed [see Clinical Pharmacology (12.3)].

To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.17)].

Do not use Tables 1 and 2 to convert from fentanyl transdermal system to other therapies to avoid

overestimating the dose of the new agent resulting in overdose of the new analgesic and possibly death.

When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.17)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
Alendronate Sodium

Alendronate Sodium

2.1 Treatment of Osteoporosis in Postmenopausal Women

The recommended dosage is:
one 70 mg tablet once weekly
or
one 10 mg tablet once daily
2.2 Prevention of Osteoporosis in Postmenopausal Women

The recommended dosage is:
one 35 mg tablet once weekly
or
one 5 mg tablet once daily
2.3 Treatment to Increase Bone Mass in Men with Osteoporosis

The recommended dosage is:
one 70 mg tablet once weekly
or
one 10 mg tablet once daily
2.4 Treatment of Glucocorticoid-Induced Osteoporosis

The recommended dosage is one 5 mg tablet once daily, except for postmenopausal women not receiving estrogen, for whom the recommended dosage is one 10 mg tablet once daily.

2.5 Treatment of Paget's Disease of Bone

The recommended treatment regimen is 40 mg once a day for six months.

Re-treatment of Paget’s Disease Re-treatment with alendronate sodium tablets may be considered, following a six-month post-treatment evaluation period in patients who have relapsed, based on increases in serum alkaline phosphatase, which should be measured periodically. Re-treatment may also be considered in those who failed to normalize their serum alkaline phosphatase.

2.6 Important Administration Instructions

Instruct patients to do the following:
Take alendronate sodium tablets at least one-half hour before the first food, beverage, or medication of the day with plain water only [see Patient Counseling Information (17.2)]. Other beverages (including mineral water), food, and some medications are likely to reduce the absorption of alendronate sodium tablets [see Drug Interactions (7.1)]. Waiting less than 30 minutes, or taking alendronate sodium tablets with food, beverages (other than plain water) or other medications will lessen the effect of alendronate sodium tablets by decreasing its absorption into the body. Take alendronate sodium tablets upon arising for the day. To facilitate delivery to the stomach and thus reduce the potential for esophageal irritation, an alendronate sodium tablet should be swallowed with a full glass of water (6 to 8 ounces). Patients should not lie down for at least 30 minutes and until after their first food of the day. Alendronate sodium tablets should not be taken at bedtime or before arising for the day. Failure to follow these instructions may increase the risk of esophageal adverse experiences [see Warnings and Precautions (5.1) and Patient Counseling Information (17.2)].
2.7 Recommendations for Calcium and Vitamin D Supplementation

Instruct patients to take supplemental calcium if dietary intake is inadequate [see Warnings and Precautions (5.2)]. Patients at increased risk for vitamin D insufficiency (e.g., over the age of 70 years, nursing home-bound, or chronically ill) may need vitamin D supplementation. Patients with gastrointestinal malabsorption syndromes may require higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.

Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D.

2.8 Administration Instructions for Missed Doses

If a once-weekly dose of alendronate sodium tablets is missed, instruct patients to take one dose on the morning after they remember. They should not take two doses on the same day but should return to taking one dose once a week, as originally scheduled on their chosen day.
Della Soft Enhanced

Della Soft Enhanced

The usual dietary intake of potassium by the average adult is 50 to 100 mEq per day. Potassium depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of potassium from the total body store.

Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40 to 100 mEq per day or more are used for the treatment of potassium depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose.

Each potassium chloride extended-release tablet, USP 20 mEq provides 20 mEq of potassium chloride.

Each potassium chloride extended-release tablet, USP 10 mEq provides 10 mEq of potassium chloride.

Potassium chloride tablets should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS).

Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration:
Break the tablet in half, and take each half separately with a glass of water. Prepare an aqueous (water) suspension as follows: Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces). Allow approximately 2 minutes for the tablet(s) to disintegrate. Stir for about half a minute after the tablet(s) has disintegrated. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw. Add another 1 fluid ounce of water, swirl, and consume immediately. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.
Aqueous suspension of potassium chloride that is not taken immediately should be discarded. The use of other liquids for suspending potassium chloride tablets is not recommended.
Pre Post 5000

Pre Post 5000

The recommended dosage is three pumps of GELNIQUE 3% (84 mg/day) applied once daily to clean, dry, intact skin on the abdomen, or upper arms/shoulders, or thighs. Apply immediately after actuating the dose. Application sites may be rotated to reduce the potential for local site reactions [see Adverse Reactions (6.1)]. GELNIQUE 3% is for topical application only and should not be ingested.

Wash hands immediately after product application. Patients should cover the application site with clothing after the gel has dried if direct skin-to-skin contact at the application site is anticipated [see Warnings and Precautions (5.3)].
Morphine Sulfate

Morphine Sulfate

2.1 Initial Dosing

Morphine sulfate extended-release capsules should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Morphine sulfate extended-release 90 mg and 120 mg capsules are for use only in patients in whom tolerance to an opioid of comparable potency has been established. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.

Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with morphine sulfate extended-release capsules [see Warnings and Precautions (5.2)].

Morphine sulfate extended-release capsules must be taken whole. Crushing, chewing, or dissolving the pellets in morphine sulfate extended-release capsules will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.2)]. Patients who are unable to swallow morphine sulfate extended-release capsules should be instructed to sprinkle the capsule contents on applesauce and immediately swallow without chewing [see Administration of Morphine Sulfate Extended-Release Capsules (2.4)].

Morphine sulfate extended-release capsules are administered at a frequency of once daily (every 24 hours).

Use of Morphine Sulfate Extended-Release Capsules as the First Opioid AnalgesicInitiate treatment with morphine sulfate extended-release with 30 mg capsule orally every 24 hours. Adjust the dose of morphine sulfate extended-release capsules in increments not greater than 30 mg every 3 to 4 days.

Use of Morphine Sulfate Extended-Release Capsules in Patients who are not Opioid TolerantThe starting dose for patients who are not opioid tolerant is morphine sulfate extended-release capsules 30 mg orally every 24 hours. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from Other Opioids to Morphine Sulfate Extended-Release CapsulesThere are no established conversion ratios from other opioids to morphine sulfate extended-release capsules defined by clinical trials. Discontinue all other around-the-clock opioid drugs when morphine sulfate extended-release capsules therapy is initiated and initiate dosing using morphine sulfate extended-release capsules 30 mg orally every 24 hours.

While there are useful tables of opioid equivalents readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. As such, it is safer to underestimate a patient’s 24-hour oral morphine requirements and provide rescue medication (e.g., immediate-release morphine) than to overestimate the 24-hour oral morphine requirements which could result in adverse reactions.

Conversion from Other Oral Morphine Formulations to Morphine Sulfate Extended-Release CapsulesPatients receiving other oral morphine formulations may be converted to morphine sulfate extended-release capsules by administering the patient's total daily oral morphine dose as morphine sulfate extended-release capsules once-daily. Morphine sulfate extended-release capsules should not be given more frequently than every 24 hours.

Conversion from Parenteral Morphine or Other Non-Morphine Opioids (Parenteral or Oral) to Morphine Sulfate Extended-Release CapsulesWhen converting from parenteral morphine or other non-morphine opioids (parenteral or oral) to morphine sulfate extended-release capsules, consider the following general points:

Parenteral to oral morphine ratio: Between 2 to 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of morphine that is approximately three times the previous daily parenteral morphine requirement is sufficient.

Other parenteral or oral non-morphine opioids to oral morphine sulfate: Specific recommendations are not available because of a lack of systematic evidence for these types of analgesic substitutions. Published relative potency data are available, but such ratios are approximations. In general, begin with half of the estimated daily morphine requirement as the initial dose, managing inadequate analgesia by supplementation with immediate-release morphine.

Conversion from Methadone to Morphine Sulfate Extended-Release CapsulesClose monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

The first dose of morphine sulfate extended-release capsules may be taken with the last dose of any immediate-release opioid medication due to the extended-release characteristics of the morphine sulfate extended-release capsules formulation.

2.2 Titration and Maintenance of Therapy

Individually titrate morphine sulfate extended-release capsules to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving morphine sulfate extended-release capsules to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for opioid analgesics.

If the level of pain increases, attempt to identify the source of increased pain, while adjusting the morphine sulfate extended-release capsules dose to decrease the level of pain. Because steady-state plasma concentrations are approximated within 2 to 3 days, morphine sulfate extended-release capsules dosage adjustments may be done every 3 to 4 days.

Patients who experience breakthrough pain may require a dose increase of morphine sulfate extended-release capsules, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the morphine sulfate extended-release capsules dose.

The daily dose of morphine sulfate extended-release capsules must be limited to a maximum of 1600 mg/day. Morphine sulfate extended-release capsules doses of over 1600 mg/day contain a quantity of fumaric acid that has not been demonstrated to be safe, and which may result in serious renal toxicity.

If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.3 Discontinuation of Morphine Sulfate Extended-Release Capsules

When a patient no longer requires therapy with morphine sulfate extended-release capsules, use a gradual downward titration of the dose every 2 to 4 days, to prevent signs and symptoms of withdrawal in the physically-dependent patient. Do not abruptly discontinue morphine sulfate extended-release capsules.

2.4 Administration of Morphine Sulfate Extended-Release Capsules

Morphine sulfate extended-release capsules must be taken whole. Crushing, chewing, or dissolving the pellets in morphine sulfate extended-release capsules will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.2)].

Alternatively, the contents of the morphine sulfate extended-release capsules (pellets) may be sprinkled over applesauce and then swallowed. This method is appropriate only for patients able to reliably swallow the applesauce without chewing. Other foods have not been tested and should not be substituted for applesauce. Instruct the patient to:
Sprinkle the pellets onto a small amount of applesauce and consume immediately without chewing. Rinse the mouth to ensure all pellets have been swallowed. Discard any unused portion of the morphine sulfate extended-release capsules after the contents have been sprinkled on applesauce.
Do not administer morphine sulfate extended-release capsules pellets through a nasogastric or gastric tubes.
Amlodipine Besylate And...

Amlodipine Besylate And Benazepril Hydrochloride

2.1 General Considerations

The recommended initial dose of amlodipine besylate and benazepril hydrochloride capsules is one capsule of amlodipine 2.5 mg/benazepril 10 mg orally once daily.

It is usually appropriate to begin therapy with amlodipine besylate and benazepril hydrochloride capsules only after a patient has either (a) failed to achieve the desired antihypertensive effect with amlodipine or benazepril monotherapy, or (b) demonstrated inability to achieve adequate antihypertensive effect with amlodipine therapy without developing edema.

The antihypertensive effect of amlodipine besylate and benazepril hydrochloride capsules is largely attained within 2 weeks. If blood pressure remains uncontrolled, the dose may be titrated up to amlodipine 10 mg/benazepril 40 mg once daily. The dosing should be individualized and adjusted according to the patient’s clinical response.

Amlodipine is an effective treatment of hypertension in once-daily doses of 2.5 to 10 mg while benazepril is effective in doses of 10 to 80 mg. In clinical trials of amlodipine/benazepril combination therapy using amlodipine doses of 2.5 to 10 mg and benazepril doses of 10 to 40 mg, the antihypertensive effects increased with increasing dose of amlodipine in all patient groups, and the effects increased with increasing dose of benazepril in nonblack groups.

2.2 Dosage Adjustment in Renal Impairment

Renal Impairment: Amlodipine besylate and benazepril hydrochloride capsules is not recommended in patients with creatinine clearance ≤ 30 mL/min. No dose adjustment of amlodipine besylate and benazepril hydrochloride capsules is required in patients creatinine clearance >30 mL/min (serum creatinine roughly ≤3 mg/dL or 265 μmol/L). [see Warnings and Precautions (5.7), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.3 Replacement Therapy

Amlodipine besylate and benazepril hydrochloride capsules may be substituted for the titrated components.
Trinessa

Trinessa

Oral Contraception

To achieve maximum contraceptive effectiveness, TriNessa® must be taken exactly as directed and at intervals not exceeding 24 hours. The possibility of ovulation and conception prior to initiation of medication should be considered. TriNessa® is available in a blister card with a tablet dispenser which is preset for a Sunday Start. Day 1 Start is also provided.

Sunday Start

When taking TriNessa® the first white tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first tablet should be taken that day. Take one active tablet daily for 21 days followed by one dark green inactive tablet daily for 7 days. After 28 tablets have been taken, a new course is started the next day (Sunday). For the first cycle of a Sunday Start regimen, another method of contraception should be used until after the first 7 consecutive days of administration.

If the patient misses one (1) active tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) active tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) active tablets in the third week or misses three (3) or more active tablets in a row, the patient should continue taking one tablet every day until Sunday. On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills.

Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling ("How to Take the Pill" section).

Day 1 Start

The dosage of TriNessa® for the initial cycle of therapy is one active tablet administered daily from the 1st day through the 21st day of the menstrual cycle, counting the first day of menstrual flow as "Day 1" followed by one dark green inactive tablet daily for 7 days. Tablets are taken without interruption for 28 days. After 28 tablets have been taken, a new course is started the next day.

If the patient misses one (1) active tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) active tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) active tablets in the third week or misses three (3) or more active tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills.

Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling ("How to Take the Pill" section).

The use of TriNessa® for contraception may be initiated 4 weeks postpartum in women who elect not to breastfeed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS: Nursing Mothers.) The possibility of ovulation and conception prior to initiation of medication should be considered.

(See Discussion of Dose-Related Risk of Vascular Disease from Oral Contraceptives.)

ADDITIONAL INSTRUCTIONS

Breakthrough bleeding, spotting, and amenorrhea are frequent reasons for patients discontinuing oral contraceptives. In breakthrough bleeding, as in all cases of irregular bleeding from the vagina, nonfunctional causes should be borne in mind. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, adequate diagnostic measures are indicated to rule out pregnancy or malignancy. If pathology has been excluded, time or a change to another formulation may solve the problem. Changing to an oral contraceptive with a higher estrogen content, while potentially useful in minimizing menstrual irregularity, should be done only if necessary since this may increase the risk of thromboembolic disease.

Use of oral contraceptives in the event of a missed menstrual period:
If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period and oral contraceptive use should be discontinued if pregnancy is confirmed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out.
ACNE

The timing of initiation of dosing with TriNessa® for acne should follow the guidelines for use of TriNessa® as an oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section for oral contraceptives. The dosage regimen for TriNessa® for treatment of facial acne, as available in a blister card with a tablet dispenser, utilizes a 21-day active and a 7-day placebo schedule. Take one active tablet daily for 21 days followed by one dark green inactive tablet for 7 days. After 28 tablets have been taken, a new course is started the next day.
Mononessa

Mononessa

2.1 How to Start MonoNessa or TriNessa

MonoNessa and TriNessa are dispensed in a VERIDATE Tablet Dispenser [see How Supplied/Storage and Handling (16)]. MonoNessa and TriNessa may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.

2.2 How to Take MonoNessa or TriNessa
Table 1: Instructions for Administration of MonoNessa or TriNessa Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling. Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start)Important: Consider the possibility of ovulation and conception prior to initiation of this product.Tablet Color: MonoNessa active tablets are blue (Day 1 to Day 21). TriNessa active tablets are white (Day 1 to Day 7), light blue (Day 8 to Day 15) and blue (Day 16 to Day 21). MonoNessa and TriNessa both have dark green inactive tablets (Day 22 to Day 28). Day 1 Start: Take first active tablet without regard to meals on the first day of menses. Take subsequent active tablets once daily at the same time each day for a total of 21 days. Take one dark green inactive tablet daily for 7 days and at the same time of day that active tablets were taken. Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet) Sunday Start: Take first active tablet without regard to meals on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient's first cycle pack of MonoNessa or TriNessa. Take subsequent active tablets once daily at the same time each day for a total of 21 days. Take one dark green inactive tablet daily for the following 7 days and at the same time of day that active tablets were taken. Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed. Switching to MonoNessa or TriNessa from another oral contraceptive Start on the same day that a new pack of the previous oral contraceptive would have started. Switching from another contraceptive method to MonoNessa or TriNessa Start MonoNessa or TriNessa: Transdermal patch On the day when next application would have been scheduled Vaginal ring On the day when next insertion would have been scheduled Injection On the day when next injection would have been scheduled Intrauterine contraceptive On the day of removal If the IUD is not removed on first day of the patient's menstrual cycle, additional non-hormonal contraceptive (such as condoms and spermicide) is needed for the first seven days of the first cycle pack. Implant On the day of removal
Starting MonoNessa or TriNessa after Abortion or Miscarriage

First-trimester
After a first-trimester abortion or miscarriage, MonoNessa or TriNessa may be started immediately. An additional method of contraception is not needed if MonoNessa or TriNessa is started immediately. If MonoNessa or TriNessa is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of her first cycle pack of MonoNessa or TriNessa.
Second-trimester
Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start MonoNessa or TriNessa, following the instructions in Table 1 for Day 1 or Sunday start, as desired. If using Sunday start, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient's first cycle pack of MonoNessa or TriNessa. [See Contraindications (4), Warnings and Precautions (5.1), and FDA-Approved Patient Labeling.]
Starting MonoNessa or TriNessa after Childbirth
Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with MonoNessa or TriNessa following the instructions in Table 1 for women not currently using hormonal contraception. MonoNessa or TriNessa are not recommended for use in lactating women [see Use in Specific Populations (8.3)]. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of MonoNessa or TriNessa. [See Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 and 8.3), and FDA-Approved Patient Labeling].
VERIDATE® Tablet Dispenser
Place the refill in the VERIDATE Tablet Dispenser so that the V notch in the refill is at the top of the dispenser. Press the refill down so that it fits firmly under all the nibs (see illustration below). If the patient starts pill-taking on Sunday, the first active pill should be taken on the first Sunday after the patient's menstrual period begins. Remove the first active pill at the top of the dispenser (Sunday) by pressing the pill through the hole in the bottom of the dispenser.
MonoNessa:
If the patient will start pill-taking on "Day 1," choose a blue pill that corresponds with the day of the week the patient will take the first pill. Remove that blue pill by pressing the pill through the hole in the bottom of the dispenser.
TriNessa:
If the patient will start pill-taking on a day other than Sunday, a calendar label has been provided and should be placed over the calendar in the center of the VERIDATE. To place the label correctly, identify the correct starting day, locate that day printed in blue on the label, and line that day up with the first white pill directly under the V notch at the top of the dispenser. Remove the label from the backing. Press the center of the label down onto the center of the printed calendar. Remove that white pill by pressing the pill through the hole in the bottom of the dispenser. After all the dark green pills have been taken, insert a new refill into the VERIDATE. The patient should take the first pill on the next day, even if the patient's period is not over yet.
To Insert New Refill (MonoNessa or TriNessa):
Lift the empty refill out of the VERIDATE Tablet Dispenser. Insert the new refill so that the V notch in the refill is at the top of the dispenser. Press the refill down so that it fits firmly under the nibs.
2.3 Missed Tablets
Table 2: Instructions for Missed MonoNessa or TriNessa Tablets If one active tablet is missed in Weeks 1, 2, or 3 Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished. If two active tablets are missed in Week 1 or Week 2 Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets. If two active tablets are missed in the third week or three or more active tablets are missed in a row in Weeks 1, 2, or 3 Day 1 start: Throw out the rest of the pack and start a new pack that same day.Sunday start: Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets.
2.4 Advice in Case of Gastrointestinal Disturbances

In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling].

2.5 TriNessa Use for Acne

The timing of initiation of dosing with TriNessa for acne should follow the guidelines for use of TriNessa as an oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section (2.1) for instructions.
Desmopressin Acetate

Desmopressin Acetate

Central Diabetes Insipidus:

The dosage of desmopressin acetate tablets must be determined for each individual patient and adjusted according to the diurnal pattern of response. Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover. Patients previously on intranasal desmopressin acetate therapy should begin tablet therapy twelve hours after the last intranasal dose. During the initial dose titration period, patients should be observed closely and appropriate safety parameters measured to assure adequate response. Patients should be monitored at regular intervals during the course of desmopressin acetate tablets therapy to assure adequate antidiuretic response. Modifications in dosage regimen should be implemented as necessary to assure adequate water turnover. Fluid restriction should be observed. (See WARNINGS, PRECAUTIONS, Pediatric Use and Geriatric Use.)

Adults and Children: It is recommended that patients be started on doses of 0.05 mg (1/2 of the 0.1 mg tablet) two times a day and individually adjusted to their optimum therapeutic dose. Most patients in clinical trials found that the optimal dosage range is 0.1 mg to 0.8 mg daily, administered in divided doses. Each dose should be separately adjusted for an adequate diurnal rhythm of water turnover. Total daily dosage should be increased or decreased in the range of 0.1 mg to 1.2 mg divided into two or three daily doses as needed to obtain adequate antidiuresis. See Pediatric Use subsection for special considerations when administering desmopressin acetate to pediatric diabetes insipidus patients.

Geriatric Use:

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See CLINICAL PHARMACOLOGY, Human Pharmacokinetics, CONTRAINDICATIONS, and PRECAUTIONS, Geriatric Use.)

Primary Nocturnal Enuresis:

The dosage of desmopressin acetate tablets must be determined for each individual patient and adjusted according to response. Patients previously on intranasal desmopressin acetate therapy can begin tablet therapy the night following (24 hours after) the last intranasal dose. The recommended initial dose for patients age 6 years and older is 0.2 mg at bedtime. The dose may be titrated up to 0.6 mg to achieve the desired response. Fluid restriction should be observed, and fluid intake should be limited to a minimum from 1 hour before desmopressin administration, until the next morning, or at least 8 hours after administration. (See WARNINGS, PRECAUTIONS, Pediatric Use and Geriatric Use.)
Gabapentin

Gabapentin

Gabapentin is given orally with or without food. Patients should be informed that, should they break the scored 600 or 800 mg tablet in order to administer a half-tablet, they should take the unused half-tablet as the next dose. Half-tablets not used within several days of breaking the scored tablet should be discarded.

If gabapentin dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).

Postherpetic Neuralgia

In adults with postherpetic neuralgia, gabapentin therapy may be initiated as a single 300-mg dose on Day 1, 600 mg/day on Day 2 (divided BID), and 900 mg/day on Day 3 (divided TID). The dose can subsequently be titrated up as needed for pain relief to a daily dose of 1800 mg (divided TID). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range. Additional benefit of using doses greater than 1800 mg/day was not demonstrated.

Epilepsy

Gabapentin is recommended for add-on therapy in patients 3 years of age and older. Effectiveness in pediatric patients below the age of 3 years has not been established.

Patients >12 Years of Age: The effective dose of gabapentin is 900 to 1800 mg/day and given in divided doses (three times a day) using 600 or 800 mg tablets. The starting dose is 300 mg three times a day. If necessary, the dose may be increased using 600 or 800 mg tablets three times a day up to 1800 mg/day. Dosages up to 2400 mg/day have been well-tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. The maximum time between doses in the TID schedule should not exceed 12 hours.

Pediatric Patients Age 3 to 12 Years: The starting dose should range from 10 to 15 mg/kg/day in 3 divided doses, and the effective dose reached by upward titration over a period of approximately 3 days. The effective dose of gabapentin in patients 5 years of age and older is 25 to 35 mg/kg/day and given in divided doses (three times a day). The effective dose in pediatric patients ages 3 and 4 years is 40 mg/kg/day and given in divided doses (three times a day) (see CLINICAL PHARMACOLOGY, Pediatric). Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.

It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further, because there are no significant pharmacokinetic interactions among gabapentin and other commonly used antiepileptic drugs, the addition of gabapentin does not alter the plasma levels of these drugs appreciably.

If gabapentin is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.

Dosage in Renal Impairment

Creatinine clearance is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance (CCr) can be reasonably well estimated using the equation of Cockcroft and Gault:

for females CCr = (0.85)(140-age)(weight)/[(72)(SCr)]

for males CCr = (140-age)(weight)/[(72)(SCr)]

in which age is in years, weight is in kilograms, and SCr is serum creatinine in mg/dL.

Dosage adjustment in patients ≥ 12 years of age with compromised renal function or undergoing hemodialysis is recommended as follows (see dosing recommendations above for effective doses in each indication).
Table 6. Gabapentin Dosage Based on Renal Function Renal Function Total Daily Dose Regimen Creatinine Clearance Dose Range (mg) (mL/min) (mg/day) a For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive). b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table. ≥60 900 to 3600 300 TID 400 TID 600 TID 800 TID 1200 TID >30 to 59 400 to 1400 200 BID 300 BID 400 BID 500 BID 700 BID >15 to 29 200 to 700 200 QD 300 QD 400 QD 500 QD 700 QD 15a 100 to 300 100 QD 125 QD 150 QD 200 QD 300 QD Post-Hemodialysis Supplemental Dose (mg)b Hemodialysis 125b 150b 200b 250b 350b
The use of gabapentin in patients <12 years of age with compromised renal function has not been studied.

Dosage in Elderly

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.
1-10 Teat Dip

1-10 Teat Dip

Apply clonidine transdermal system once every 7 days to a hairless area of intact skin on the upper outer arm or chest. Each new application of clonidine transdermal system should be on a different skin site from the previous location. If the system loosens during 7-day wearing, the adhesive cover should be applied directly over the system to ensure good adhesion. There have been rare reports of the need for patch changes prior to 7 days to maintain blood pressure control.

To initiate therapy, clonidine transdermal system dosage should be titrated according to individual therapeutic requirements, starting with clonidine transdermal system, 0.1 mg per day for one week. If after one or two weeks the desired reduction in blood pressure is not achieved, increase the dosage by adding another clonidine transdermal system, 0.1 mg per day for one week or changing to a larger system. An increase in dosage above two clonidine transdermal systems, 0.3 mg per day for one week is usually not associated with additional efficacy.

When substituting clonidine transdermal system for oral clonidine or for other antihypertensive drugs, physicians should be aware that the antihypertensive effect of clonidine transdermal system may not commence until 2 to 3 days after initial application. Therefore, gradual reduction of prior drug dosage is advised. Some or all previous antihypertensive treatment may have to be continued, particularly in patients with more severe forms of hypertension.

Renal Impairment

Patients with renal impairment may benefit from a lower initial dose. Patients should be carefully monitored. Since only a minimal amount of clonidine is removed during routine hemodialysis, there is no need to give supplemental clonidine following dialysis.
Votrient

Votrient

2.1 Schizophrenia

Adults

The recommended dose of Paliperidone Extended-release Tablets for the treatment of schizophrenia in adults is 6 mg administered once daily. Initial dose titration is not required. Although it has not been systematically established that doses above 6 mg have additional benefit, there was a general trend for greater effects with higher doses. This must be weighed against the dose-related increase in adverse reactions. Thus, some patients may benefit from higher doses, up to 12 mg/day, and for some patients, a lower dose of 3 mg/day may be sufficient. Dose increases above 6 mg/day should be made only after clinical reassessment and generally should occur at intervals of more than 5 days. When dose increases are indicated, increments of 3 mg/day are recommended. The maximum recommended dose is 12 mg/day.

In a longer-term study, paliperidone has been shown to be effective in delaying time to relapse in patients with schizophrenia who were stabilized on paliperidone for 6 weeks [see Clinical Studies (14)]. Paliperidone Extended-release Tablets should be prescribed at the lowest effective dose for maintaining clinical stability and the physician should periodically reevaluate the long-term usefulness of the drug in individual patients.

Adolescents (12-17 years of age)

The recommended starting dose of Paliperidone Extended-Release Tablets for the treatment of schizophrenia in adolescents 12 to 17 years of age is 3 mg administered once daily. Initial dose titration is not required. Dose increases, if considered necessary, should be made only after clinical reassessment and should occur at increments of 3 mg/day at intervals of more than 5 days. Prescribers should be mindful that, in the adolescent schizophrenia study, there was no clear enhancement to efficacy at the higher doses, i.e., 6 mg for subjects weighing less than 51 kg and 12 mg for subjects weighing 51 kg or greater, while adverse events were dose-related.

2.2 Schizoaffective Disorder

The recommended dose of Paliperidone Extended-release Tablets for the treatment of schizoaffective disorder in adults is 6 mg administered once daily. Initial dose titration is not required. Some patients may benefit from lower or higher doses within the recommended dose range of 3 to 12 mg once daily. A general trend for greater effects was seen with higher doses. This trend must be weighed against dose-related increase in adverse reactions. Dosage adjustment, if indicated, should occur only after clinical reassessment. Dose increases, if indicated, generally should occur at intervals of more than 4 days. When dose increases are indicated, increments of 3 mg/day are recommended. The maximum recommended dose is 12 mg/day.

2.3 Administration Instructions

Paliperidone Extended-release tablets can be taken with or without food.

Paliperidone Extended-release tablets must be swallowed whole with the aid of liquids. Tablets should not be chewed, divided, or crushed. The medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. The tablet shell, along with insoluble core components, is eliminated from the body; patients should not be concerned if they occasionally notice in their stool something that looks like a tablet.

2.4 Use with Risperidone

Concomitant use of paliperidone with risperidone has not been studied. Since paliperidone is the major active metabolite of risperidone, consideration should be given to the additive paliperidone exposure if risperidone is coadministered with paliperidone.

2.5 Dosage in Special Populations

Renal Impairment

Dosing must be individualized according to the patient’s renal function status. For patients with mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min), the recommended initial dose of paliperidone extended-release tablets is 3 mg once daily. The dose may then be increased to a maximum of 6 mg once daily based on clinical response and tolerability. For patients with moderate to severe renal impairment (creatinine clearance ≥ 10 mL/min to < 50 mL/min), the recommended initial dose of paliperidone extended-release tablets is 1.5 mg once daily, which may be increased to a maximum of 3 mg once daily after clinical reassessment. As paliperidone extended-release tablets have not been studied in patients with creatinine clearance below 10 mL/min, use is not recommended in such patients. [See Clinical Pharmacology (12.3)]

Hepatic Impairment

For patients with mild to moderate hepatic impairment, (Child-Pugh Classification A and B), no dose adjustment is recommended [see Clinical Pharmacology (12.3)]. Paliperidone extended-release tablets have not been studied in patients with severe hepatic impairment.

Elderly

Because elderly patients may have diminished renal function, dose adjustments may be required according to their renal function status. In general, recommended dosing for elderly patients with normal renal function is the same as for younger adult patients with normal renal function. For patients with moderate to severe renal impairment (creatinine clearance 10 mL/min to < 50 mL/min), the maximum recommended dose of paliperidone extended-release tablets are 3 mg once daily [see Renal Impairment above].
Levalbuterol Hydrochlor...

Levalbuterol Hydrochloride Solution

Children 6–11 years old: The recommended dosage of Levalbuterol HCl Inhalation Solution for patients 6–11 years old is 0.31 mg administered three times a day, by nebulization. Routine dosing should not exceed 0.63 mg three times a day.

Adults and Adolescents ≥ 12 years old: The recommended starting dosage of Levalbuterol HCl Inhalation Solution for patients 12 years of age and older is 0.63 mg administered three times a day, every 6 to 8 hours, by nebulization.

Patients 12 years of age and older with more severe asthma or patients who do not respond adequately to a dose of 0.63 mg of Levalbuterol HCl Inhalation Solution may benefit from a dosage of 1.25 mg three times a day.

Patients receiving the highest dose of Levalbuterol HCl Inhalation Solution should be monitored closely for adverse systemic effects, and the risks of such effects should be balanced against the potential for improved efficacy.

The use of Levalbuterol HCl Inhalation Solution can be continued as medically indicated to control recurring bouts of bronchospasm. During this time, most patients gain optimal benefit from regular use of the inhalation solution.

If a previously effective dosage regimen fails to provide the expected relief, medical advice should be sought immediately, since this is often a sign of seriously worsening asthma that would require reassessment of therapy.

The drug compatibility (physical and chemical), efficacy, and safety of Levalbuterol HCl Inhalation Solution when mixed with other drugs in a nebulizer have not been established.

The safety and efficacy of Levalbuterol HCl Inhalation Solution have been established in clinical trials when administered using the PARI LC Jet™ and PARI LC Plus™ nebulizers, and the PARI Master® Dura-Neb® 2000 and Dura-Neb® 3000 compressors. The safety and efficacy of Levalbuterol HCl Inhalation Solution when administered using other nebulizer systems have not been established.
Fibromyalgia Relief

Fibromyalgia Relief

1 or 2 capsules every 4 hours as needed. Total daily dosage should not exceed 6 capsules.

Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Ursodiol

Ursodiol

2.1 General Dosing Information

The recommended adult dosage for ursodiol in the treatment of PBC is 13-15 mg/kg/day administered in two to four divided doses with food. Dosing regimen should be adjusted according to each patient’s need at the discretion of the physician.

2.2 Liver Function Tests

Liver function tests (γ-GT, alkaline phosphatase, AST, ALT) and bilirubin levels should be monitored every month for three months after start of therapy, and every six months thereafter [see Warnings and Precautions (5.1)].

2.3 Scoring the Ursodiol Tablet USP, 500 mg.

The ursodiol 500 mg scored tablet can be broken in halves to provide recommended dosage. To break ursodiol scored tablet easily, place the tablet on a flat surface with the scored section on top. Hold the tablet with your thumbs placed close to the scored part of the tablet (groove). Then apply gentle pressure and snap the tablet segments apart (segments breaking incorrectly should not be used). The segments should be washed down unchewed, with water, keeping the segments in the mouth can reveal a bitter taste. Due to the bitter taste, segments should be stored separately from whole tablets. [see How Supplied/Storage and Handling (16.2)].
Minastrin 24 Fe

Minastrin 24 Fe

Primary Hyperaldosteronism: Spironolactone may be employed as an initial diagnostic measure to provide presumptive evidence of primary hyperaldosteronism while patients are on normal diets.

Long Test: Spironolactone is administered at a daily dosage of 400 mg for three to four weeks. Correction of hypokalemia and of hypertension provides presumptive evidence for the diagnosis of primary hyperaldosteronism.

Short Test: Spironolactone is administered at a daily dosage of 400 mg for four days. If serum potassium increases during spironolactone administration but drops when spironolactone is discontinued, a presumptive diagnosis of primary hyperaldosteronism should be considered.

After the diagnosis of hyperaldosteronism has been established by more definitive testing procedures, spironolactone may be administered in doses of 100 mg to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, spironolactone may be employed for long-term maintenance therapy at the lowest effective dosage determined for the individual patient.

Edema in Adults (Congestive Heart Failure, Hepatic Cirrhosis, or Nephrotic Syndrome): An initial daily dosage of 100 mg of spironolactone administered in either single or divided doses is recommended, but may range from 25 mg to 200 mg daily. When given as the sole agent for diuresis, spironolactone should be continued for at least five days at the initial dosage level, after which it may be adjusted to the optimal therapeutic or maintenance level administered in either single or divided daily doses. If, after five days, an adequate diuretic response to spironolactone has not occurred, a second diuretic that acts more proximally in the renal tubule may be added to the regimen. Because of the additive effect of spironolactone when administered concurrently with such diuretics, an enhanced diuresis usually begins on the first day of combined treatment; combined therapy is indicated when more rapid diuresis is desired. The dosage of spironolactone should remain unchanged when other diuretic therapy is added.

Essential Hypertension: For adults, an initial daily dosage of 50 mg to 100 mg of spironolactone administered in either single or divided doses is recommended. Spironolactone may also be given with diuretics that act more proximally in the renal tubule or with other antihypertensive agents. Treatment with spironolactone should be continued for at least two weeks since the maximum response may not occur before this time. Subsequently, dosage should be adjusted according to the response of the patient.

Hypokalemia: Spironolactone in a dosage ranging from 25 mg to 100 mg daily is useful in treating a diuretic-induced hypokalemia, when oral potassium supplements or other potassium-sparing regimens are considered inappropriate.

Severe Heart Failure In Conjunction With Standard Therapy (NYHA class III to IV):

Treatment should be initiated with spironolactone 25 mg once daily if the patient’s serum potassium is less than or equal to 5.0 mEq/L and the patient’s serum creatinine is less than or equal to 2.5 mg/dL. Patients who tolerate 25 mg once daily may have their dosage increased to 50 mg once daily as clinically indicated. Patients who do not tolerate 25 mg once daily may have their dosage reduced to 25 mg every other day. See WARNINGS: Hyperkalemia in Patients with Severe Heart Failure for advice on monitoring serum potassium and serum creatinine.
Trifluoperazine Hydroch...

Trifluoperazine Hydrochloride

Patients controlled on diltiazem alone or in combination with other medications may be switched to diltiazem hydrochloride extended-release capsules USP (once-a-day dosage) at the nearest equivalent total daily dose. Higher doses of diltiazem hydrochloride extended-release capsules USP (once-a-day dosage) may be needed in some patients. Patients should be closely monitored. Subsequent titration to higher or lower doses may be necessary and should be initiated as clinically warranted. There is limited general clinical experience with doses above 360 mg, but doses to 540 mg have been studied in clinical trials. The incidence of side effects increases as the dose increases with first-degree AV block, dizziness, and sinus bradycardia bearing the strongest relationship to dose.

Hypertension. Dosage needs to be adjusted by titration to individual patient needs. When used as monotherapy, reasonable starting doses are 180 to 240 mg once daily, although some patients may respond to lower doses. Maximum antihypertensive effect is usually observed by 14 days of chronic therapy; therefore, dosage adjustments should be scheduled accordingly. The usual dosage range studied in clinical trials was 240 to 360 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily.

Angina. Dosages for the treatment of angina should be adjusted to each patient’s needs, starting with a dose of 120 or 180 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily. When necessary, titration may be carried out over a 7- to 14-day period.
Diltiazem Hydrochloride Extended-release Capsules USP (Once-a-day dosage) Strength Qty. NDC# Description 120 mg 7's 62037-597-07 White/orange opaque capsule 30's 62037-597-30 imprinted with "Andrx 597" 90's 62037-597-90 on one end and "120 mg" on 500's 60237-597-05 the other. 1000's 62037-597-10 180 mg 7's 62037-598-07 Yellow/orange opaque capsule 30's 62037-598-30 imprinted with "Andrx 598" 90's 62037-598-90 on one end and "180 mg" on 500's 62037-598-05 the other. 1000's 62037-598-10 240 mg 7's 62037-599-07 Light brown/orange opaque 30's 62037-599-30 capsule imprinted with 90's 62037-599-90 "Andrx 599" on one end and 500's 62037-599-05 "240 mg" on the other. 1000's 62037-599-10 300 mg 7's 62037-600-07 Orange/orange opaque capsule 30's 62037-600-30 imprinted with "Andrx 600" 90's 62037-600-90 on one end and "300 mg" on 500's 62037-600-05 the other. 1000's 62037-600-10
Concomitant Use With Other Cardiovascular Agents

1. Sublingual NTG. May be taken as required to abort acute anginal attacks during diltiazem hydrochloride extended-release capsules, (Once A Day Dosage) therapy.

2. Prophylactic Nitrate Therapy. Diltiazem hydrochloride extended-release capsules, (Once A Day Dosage) may be safely coadministered with short- and long-acting nitrates.

3. Beta-blockers (see WARNINGS and PRECAUTIONS).

4. Antihypertensives. Diltiazem hydrochloride extended-release capsules (Once A Day Dosage) have an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of diltiazem hydrochloride extended-release capsules USP (once-a-day dosage) or the concomitant antihypertensives may need to be adjusted when adding one to the other.
Lidocaine And Prilocain...

Lidocaine And Prilocaine

Adult Patients-Intact Skin

A thick layer of lidocaine and prilocaine cream is applied to intact skin and covered with an occlusive dressing (see INSTRUCTIONS FOR APPLICATION).

Minor Dermal Procedures: For minor procedures such as intravenous cannulation and venipuncture, apply 2.5 grams of lidocaine and prilocaine cream (1/2 the 5 g tube) over 20 to 25 cm2 of skin surface for at least 1 hour. In controlled clinical trials using lidocaine and prilocaine cream, two sites were usually prepared in case there was a technical problem with cannulation or venipuncture at the first site.

Major Dermal Procedures: For more painful dermatological procedures involving a larger skin area such as split thickness skin graft harvesting, apply 2 grams of lidocaine and prilocaine cream per 10 cm2 of skin and allow to remain in contact with the skin for at least 2 hours.

Adult Male Genital Skin: As an adjunct prior to local anesthetic infiltration, apply a thick layer of lidocaine and prilocaine cream (1 g/10 cm2 ) to the skin surface for 15 minutes. Local anesthetic infiltration should be performed immediately after removal of lidocaine and prilocaine cream.

Dermal analgesia can be expected to increase for up to 3 hours under occlusive dressing and persist for 1 to 2 hours after removal of the cream. The amount of lidocaine and prilocaine absorbed during the period of application can be estimated from the information in Table 2, ** footnote, in Individualization of Dose.

Adult Female Patients-Genital Mucous Membranes

For minor procedures on the female external genitalia, such as removal of condylomata acuminata, as well as for use as pretreatment for anesthetic infiltration, apply a thick layer (5 to 10 grams) of lidocaine and prilocaine cream for 5 to 10 minutes.

Occlusion is not necessary for absorption, but may be helpful to keep the cream in place. Patients should be lying down during the lidocaine and prilocaine cream application, especially if no occlusion is used. The procedure or the local anesthetic infiltration should be performed immediately after the removal of lidocaine and prilocaine cream.

Pediatric Patients-Intact Skin

The following are the maximum recommended doses, application areas and application times for lidocaine and prilocaine cream based on a child's age and weight:
Age and Body WeightRequirements Maximum TotalDose of Lidocaine andPrilocaine Cream MaximumApplication Area MaximumApplication Time 0 up to 3 months or < 5 kg 1 g 10 cm2 1 hour 3 up to 12 months and > 5 kg 2 g 20 cm2 4 hours 1 to 6 years and > 10 kg 10 g 100 cm2 4 hours 7 to 12 years and > 20 kg 20 g 200 cm2 4 hours
Please note: If a patient greater than 3 months old does not meet the minimum weight requirement, the maximum total dose of lidocaine and prilocaine cream should be restricted to that which corresponds to the patient's weight (see INSTRUCTIONS FOR APPLICATION).

Practitioners should carefully instruct caregivers to avoid application of excessive amounts of lidocaine and prilocaine cream (see PRECAUTIONS).

When applying lidocaine and prilocaine cream to the skin of young children, care must be taken to maintain careful observation of the child to prevent accidental ingestion of lidocaine and prilocaine cream or the occlusive dressing. A secondary protective covering to prevent inadvertent disruption of the application site may be useful.

Lidocaine and prilocaine cream should not be used in neonates with a gestational age less than 37 weeks nor in infants under the age of 12 months who are receiving treatment with methemoglobin-inducing agents (see Methemoglobinemia subsection of WARNINGS).

When lidocaine and prilocaine cream (lidocaine 2.5% and prilocaine 2.5%) is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered (see Individualization of Dose). The amount absorbed in the case of lidocaine and prilocaine cream is determined by the area over which it is applied and the duration of application under occlusion (see Table 2, ** footnote, in Individualization of Dose).

Although the incidence of systemic adverse reactions with lidocaine and prilocaine cream is very low, caution should be exercised, particularly when applying it over large areas and leaving it on for longer than 2 hours. The incidence of systemic adverse reactions can be expected to be directly proportional to the area and time of exposure (see Individualization of Dose).
Risedronate Sodium

Risedronate Sodium

2.1 Treatment of Postmenopausal Osteoporosis

[see Indications and Usage (1.1)]

The recommended regimen is:
one 5 mg tablet orally, taken dailyor one 35 mg tablet orally, taken once-a-weekor one 75 mg tablet orally, taken on two consecutive days for a total of two tablets each monthor one 150 mg tablet orally, taken once-a-month
2.2 Prevention of Postmenopausal Osteoporosis

[see Indications and Usage (1.1)]

The recommended regimen is:
one 5 mg tablet orally, taken dailyor one 35 mg tablet orally, taken once-a-weekor alternatively, one 75 mg tablet orally, taken on two consecutive days for a total of two tablets each month may be consideredor alternatively, one 150 mg tablet orally, taken once-a-month may be considered
2.3 Treatment to Increase Bone Mass in Men with Osteoporosis

[see Indications and Usage (1.2)]

The recommended regimen is:
one 35 mg tablet orally, taken once-a-week
2.4 Treatment and Prevention of Glucocorticoid-Induced Osteoporosis

[see Indications and Usage (1.3)]

The recommended regimen is:
one 5 mg tablet orally, taken daily
2.5 Treatment of Paget’s Disease

[see Indications and Usage (1.4)]

The recommended treatment regimen is 30 mg orally once daily for 2 months. Retreatment may be considered (following post-treatment observation of at least 2 months) if relapse occurs, or if treatment fails to normalize serum alkaline phosphatase. For retreatment, the dose and duration of therapy are the same as for initial treatment. No data are available on more than 1 course of retreatment.

2.6 Important Administration Instructions

Instruct patients to do the following:
Take risedronate sodium tablets at least 30 minutes before the first food or drink of the day other than water, and before taking any oral medication or supplementation, including calcium, antacids, or vitamins to maximize absorption and clinical benefit, [see Drug Interactions (7.1)]. Avoid the use of water with supplements, including mineral water, because they may have a higher concentration of calcium. Swallow risedronate sodium tablets whole with a full glass of plain water (6 to 8 ounces). Avoid lying down for 30 minutes after taking the medication [see Warnings and Precautions (5.1)]. Do not chew or suck the tablet because of a potential for oropharyngeal ulceration. Do not eat or drink anything except plain water, or take other medications for at least 30 minutes after taking risedronate sodium tablets.
2.7 Recommendations for Calcium and Vitamin D Supplementation

Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate; and to take calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations at a different time of the day as they interfere with the absorption of risedronate sodium tablets.

2.8 Administration Instructions for Missed Doses

Instruct patients about missing risedronate sodium tablets doses as follows:
If a dose of risedronate sodium tablets 35 mg once-a-week is missed: Take 1 tablet on the morning after they remember and return to taking 1 tablet once-a-week, as originally scheduled on their chosen day. Do not take 2 tablets on the same day. If one or both tablets of risedronate sodium tablets 75 mg on two consecutive days per month are missed, and the next month’s scheduled doses are more than 7 days away: If both tablets are missed, take one risedronate sodium tablets 75 mg tablet in the morning after the day it is remembered and then the other tablet on the next consecutive morning. If only one risedronate sodium tablets 75 mg tablet is missed, take the missed tablet in the morning after the day it is remembered Return to taking their risedronate sodium tablets 75 mg on two consecutive days per month as originally scheduled. Do not take more than two 75 mg tablets within 7 days. If one or both tablets of risedronate sodium tablets 75 mg on two consecutive days per month are missed, and the next month's scheduled doses are within 7 days: Wait until their next month’s scheduled doses and then continue taking risedronate sodium tablets 75 mg on two consecutive days per month as originally scheduled. If the dose of risedronate sodium tablets 150 mg once-a-month is missed, and the next month’s scheduled dose is more than 7 days away: Take the missed tablet in the morning after the day it is remembered and then return to taking their risedronate sodium tablets 150 mg once-a-month as originally scheduled. Do not take more than one 150 mg tablet within 7 days. If the dose of risedronate sodium tablets 150 mg once-a-month is missed, and the next month's scheduled dose is within 7 days: Wait until their next month’s scheduled dose and then continue taking risedronate sodium tablets 150 mg once-a-month as originally scheduled.
Zestril

Zestril

2.1 Dosing Considerations for all Patients

Individualize the dosage according to the therapeutic needs and response of the patient. Administer dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release at the lowest effective dosage.

Based on bioequivalence data, patients taking divided doses of immediate-release dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate, (for example, twice daily), may be switched to dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release at the same total daily dose taken once daily. Titrate at weekly intervals to appropriate efficacy and tolerability as indicated.

Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules may be taken whole, or the capsule may be opened and the entire contents sprinkled on applesauce. If the patient is using the sprinkle administration method, the sprinkled applesauce should be consumed immediately; it should not be stored. Patients should take the applesauce with sprinkled beads in its entirety without chewing. The dose of a single capsule should not be divided. The contents of the entire capsule should be taken, and patients should not take anything less than one capsule per day.

Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release may be taken with or without food.

Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release should be given upon awakening. Afternoon doses should be avoided because of the potential for insomnia.

Where possible, dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release therapy should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

2.2 Children

In children with ADHD who are 6 to 12 years of age and are either starting treatment for the first time or switching from another medication, start with 10 mg once daily in the morning; daily dosage may be adjusted in increments of 5 mg or 10 mg at weekly intervals. When in the judgment of the clinician a lower initial dose is appropriate, patients may begin treatment with 5 mg once daily in the morning. The maximum recommended dose for children is 30 mg/day; doses greater than 30 mg/day of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release have not been studied in children. Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release has not been studied in children under 6 years of age.

2.3 Adolescents

The recommended starting dose for adolescents with ADHD who are 13 to 17 years of age and are either starting treatment for the first time or switching from another medication is 10 mg/day. The dose may be increased to 20 mg/day after one week if ADHD symptoms are not adequately controlled.

2.4 Adults

In adults with ADHD who are either starting treatment for the first time or switching from another medication, the recommended dose is 20 mg/day.
Kadian

Kadian

2.1 Initial Dosing

KADIAN should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

KADIAN 100 mg, and 200 mg capsules are only for patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg of morphine daily, at least 30 mg of oral oxycodone daily, at least 8 mg of oral hydromorphone daily, or an equianalgesic dose of another opioid.

Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with KADIAN [see Warnings and Precautions (5.2)].

KADIAN capsules must be taken whole. Crushing, chewing, or dissolving the pellets in KADIAN capsules will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.2)]. Patients who are unable to swallow KADIAN should be instructed to sprinkle the capsule contents on applesauce and immediately swallow without chewing [see Administration of KADIAN (2.4)].

KADIAN is administered at a frequency of either once daily (every 24 hours) or twice daily (every 12 hours).

Use of KADIAN as the First Opioid Analgesic

There has been no evaluation of KADIAN as an initial opioid analgesic in the management of pain. Because it may be more difficult to titrate a patient to adequate analgesia using an extended-release morphine, begin treatment using an immediate-release morphine formulation and then convert patients to KADIAN as described below.

Use of KADIAN in Patients who are not Opioid Tolerant

The starting dose for patients who are not opioid tolerant is KADIAN 30 mg orally every 24 hours. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from Other Opioids to KADIAN

There are no established conversion ratios from other opioids to KADIAN defined by clinical trials. Discontinue all other around-the-clock opioid drugs when KADIAN therapy is initiated and initiate dosing using KADIAN 30 mg orally every 24 hours.

While there are useful tables of opioid equivalents readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. As such, it is safer to underestimate a patient's 24-hour oral morphine requirements and provide rescue medication (e.g. immediate-release morphine) than to overestimate the 24-hour oral morphine requirements which could result in an adverse reaction.

Conversion from Other Oral Morphine Formulations to KADIAN

Patients receiving other oral morphine formulations may be converted to KADIAN by administering one-half of the patient's total daily oral morphine dose as KADIAN twice daily or by administering the total daily oral morphine dose as KADIAN once daily. There are no data to support the efficacy or safety of prescribing KADIAN more frequently than every 12 hours.

KADIAN is not bioequivalent to other extended-release morphine preparations. Conversion from the same total daily dose of another extended-release morphine product to KADIAN may lead to either excessive sedation at peak or inadequate analgesia at trough. Therefore, monitor patients closely when initiating KADIAN therapy and adjust the dosage of KADIAN as needed.

Conversion from Parenteral Morphine, or Other Opioids to KADIAN

When converting from parenteral morphine or other non-morphine opioids (parenteral or oral) to KADIAN, consider the following general points:

Parenteral to Oral Morphine Ratio: Between 2 mg and 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of oral morphine that is three times the daily parenteral morphine requirement is sufficient.

Other Oral or Parenteral Opioids to Oral Morphine Sulfate: Specific recommendations are not available because of a lack of systematic evidence for these types of analgesic substitutions. Published relative potency data are available, but such ratios are approximations. In general, begin with half of the estimated daily morphine requirement as the initial dose, managing inadequate analgesia by supplementation with immediate-release morphine.

Conversion from Methadone to KADIAN

Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

2.2 Titration and Maintenance of Therapy

Individually titrate KADIAN to a dose that provides adequate analgesia and minimizes adverse reactions at a frequency of either once or twice daily. Continually reevaluate patients receiving KADIAN to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for the use of opioid analgesics.

If the level of pain increases, attempt to identify the source of increased pain, while adjusting the KADIAN dose to decrease the level of pain. Because steady-state plasma concentrations are approximated within 24 to 36 hours, KADIAN dosage adjustments may be done every 1 to 2 days.

Patients who experience breakthrough pain may require a dose increase of KADIAN, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the KADIAN dose. In patients experiencing inadequate analgesia with once daily dosing of KADIAN, consider a twice daily regimen.

If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.3 Discontinuation of KADIAN

When a patient no longer requires therapy with KADIAN, use a gradual downward titration, of the dose every two to four days, to prevent signs and symptoms of withdrawal in the physically-dependent patient. Do not abruptly discontinue KADIAN.

2.4 Administration of KADIAN

KADIAN capsules must be taken whole. Crushing, chewing, or dissolving the pellets in KADIAN capsules will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.2)].

Alternatively, the contents of the KADIAN capsules (pellets) may be sprinkled over applesauce and then swallowed. This method is appropriate only for patients able to reliably swallow the applesauce without chewing. Other foods have not been tested and should not be substituted for applesauce. Instruct the patient to:
Sprinkle the pellets onto a small amount of applesauce and consume immediately without chewing. Rinse the mouth to ensure all pellets have been swallowed. Discard any unused portion of the KADIAN capsules after the contents have been sprinkled on applesauce.
The contents of the KADIAN capsules (pellets) may be administered through a 16 French gastrostomy tube.
Flush the gastrostomy tube with water to ensure that it is wet. Sprinkle the KADIAN Pellets into 10 mL of water. Use a swirling motion to pour the pellets and water into the gastrostomy tube through a funnel. Rinse the beaker with a further 10 mL of water and pour this into the funnel. Repeat rinsing until no pellets remain in the beaker.
Do not administer KADIAN pellets through a nasogastric tube.
Desipramine Hydrochlori...

Desipramine Hydrochloride

Not recommended for use in children (see WARNINGS).

Lower dosages are recommended for elderly patients and adolescents. Lower dosages are also recommended for outpatients compared to hospitalized patients, who are closely supervised. Dosage should be initiated at a low level and increased according to clinical response and any evidence of intolerance. Following remission, maintenance medication may be required for a period of time and should be at the lowest dose that will maintain remission.

Usual Adult Dose

The usual adult dose is 100 to 200 mg per day. In more severely ill patients, dosage may be further increased gradually to 300 mg/day if necessary. Dosages above 300 mg/day are not recommended.

Dosage should be initiated at a lower level and increased according to tolerance and clinical response.

Treatment of patients requiring as much as 300 mg should generally be initiated in hospitals, where regular visits by the physician, skilled nursing care, and frequent electrocardiograms (ECGs) are available.

The best available evidence of impending toxicity from very high doses of desipramine is prolongation of the QRS or QT intervals on the ECG. Prolongation of the PR interval is also significant, but less closely correlated with plasma levels. Clinical symptoms of intolerance, especially drowsiness, dizziness, and postural hypotension, should also alert the physician to the need for reduction in dosage.

Initial therapy may be administered in divided doses or a single daily dose.

Maintenance therapy may be given on a once-daily schedule for patient convenience and compliance.

Adolescent and Geriatric Dose

The usual adolescent and geriatric dose is 25 to 100 mg daily.

Dosage should be initiated at a lower level and increased according to tolerance and clinical response to a usual maximum of 100 mg daily. In more severely ill patients, dosage may be further increased to 150 mg/day. Doses above 150 mg/day are not recommended in these age groups.

Initial therapy may be administered in divided doses or a single daily dose.

Maintenance therapy may be given on a once-daily schedule for patient convenience and compliance.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders: At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with desipramine hydrochloride. Conversely, at least 14 days should be allowed after stopping desipramine hydrochloride before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).

Use of Desipramine Hydrochloride With Other MAOI’s Such as Linezolid or Methylene Blue: Do not start desipramine hydrochloride in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).

In some cases, a patient already receiving desipramine hydrochloride therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, desipramine hydrochloride should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with desipramine hydrochloride may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with desipramine hydrochloride is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).
Diethylpropion Hcl Imme...

Diethylpropion Hcl Immediate-release

Diethylpropion hydrochloride immediate-release:

One immediate-release 25 mg tablet three times daily, one hour before meals, and in midevening if desired to overcome night hunger.

Diethylpropion hydrochloride controlled-release:

One controlled-release 75 mg tablet daily, swallowed whole, in midmorning.

Geriatric Use:

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See PRECAUTIONS, Geriatric Use.)
Infed

Infed

Oral iron should be discontinued prior to administration of INFeD.

Dosage:

I. Iron Deficiency Anemia: Periodic hematologic determination (hemoglobin and hematocrit) is a simple and accurate technique for monitoring hematological response, and should be used as a guide in therapy. It should be recognized that iron storage may lag behind the appearance of normal blood morphology. Serum iron, total iron binding capacity (TIBC) and percent saturation of transferrin are other important tests for detecting and monitoring the iron deficient state.

After administration of iron dextran complex, evidence of a therapeutic response can be seen in a few days as an increase in the reticulocyte count.

Although serum ferritin is usually a good guide to body iron stores, the correlation of body iron stores and serum ferritin may not be valid in patients on chronic renal dialysis who are also receiving iron dextran complex.

Although there are significant variations in body build and weight distribution among males and females, the accompanying table and formula represent a convenient means for estimating the total iron required. This total iron requirement reflects the amount of iron needed to restore hemoglobin concentration to normal or near normal levels plus an additional allowance to provide adequate replenishment of iron stores in most individuals with moderately or severely reduced levels of hemoglobin. It should be remembered that iron deficiency anemia will not appear until essentially all iron stores have been depleted. Therapy, thus, should aim at not only replenishment of hemoglobin iron but iron stores as well.

Factors contributing to the formula are shown below.
Blood volume . . . . . . . . . . . . . . . .65 mL/kg of body weight Normal hemoglobin (males and females) over 15 kg (33 lbs) . . . . . . . . . . . .14.8 g/dl15 kg (33 lbs) or less . . . . . . . . . .12.0 g/dl Iron content of hemoglobin . . . . .   0.34% Hemoglobin deficit Weight
Based on the above factors, individuals with normal hemoglobin levels will have approximately 33 mg of blood iron per kilogram of body weight (15 mg/lb).

Note: The table and accompanying formula are applicable for dosage determinations only in patients with iron deficiency anemia; they are not to be used for dosage determinations in patients requiring iron replacement for blood loss.
TOTAL INFeD REQUIREMENT FOR HEMOGLOBIN RESTORATION AND IRON STORES REPLACEMENT* PATIENT LEAN BODY WEIGHT Milliliter Requirement of INFeD Based On ObservedHemoglobin of kg lb 3 (g/dl) 4 (g/dl) 5 (g/dl) 6 (g/dl) 7 (g/dl) 8 (g/dl) 9 (g/dl) 10 (g/dl) 5 11 3 3 3 3 2 2 2 2 10 22 7 6 6 5 5 4 4 3 15 33 10 9 9 8 7 7 6 5 20 44 16 15 14 13 12 11 10 9 25 55 20 18 17 16 15 14 13 12 30 66 23 22 21 19 18 17 15 14 35 77 27 26 24 23 21 20 18 17 40 88 31 29 28 26 24 22 21 19 45 99 35 33 31 29 27 25 23 21 50 110 39 37 35 32 30 28 26 24 55 121 43 41 38 36 33 31 28 26 60 132 47 44 42 39 36 34 31 28 65 143 51 48 45 42 39 36 34 31 70 154 55 52 49 45 42 39 36 33 75 165 59 55 52 49 45 42 39 35 80 176 63 59 55 52 48 45 41 38 85 187 66 63 59 55 51 48 44 40 90 198 70 66 62 58 54 50 46 42 95 209 74 70 66 62 57 53 49 45 100 220 78 74 69 65 60 56 52 47 105 231 82 77 73 68 63 59 54 50 110 242 86 81 76 71 67 62 57 52 115 253 90 85 80 75 70 64 59 54 120 264 94 88 83 78 73 67 62 57
*Table values were calculated based on a normal adult hemoglobin of 14.8 g/dl for weights greater than 15 kg (33 lbs) and a hemoglobin of 12.0 g/dl for weights less than or equal to 15 kg (33 lbs).

The total amount of INFeD in mL required to treat the anemia and replenish iron stores may be approximated as follows:

Adults and Children over 15 kg (33 lbs): See Dosage Table. Alternatively the total dose may be calculated:

Dose (mL) = 0.0442 (Desired Hb - Observed Hb) x LBW + (0.26 x LBW)Based on: Desired Hb = the target Hb in g/dl.Observed Hb = the patient’s current hemoglobin in g/dl.LBW = Lean body weight in kg. A patient’s lean body weight (or actual body weight if less than lean body weight) should be utilized when determining dosage.For males: LBW = 50 kg + 2.3 kg for each inch of patient’s height over 5 feetFor females: LBW = 45.5 kg + 2.3 kg for each inch of patient’s height over 5 feetTo calculate a patient's weight in kg when lbs are known:

Children 5 - 15 kg (11 - 33 lbs): See Dosage Table.

INFeD should not normally be given in the first four months of life. (See PRECAUTIONS: Pediatric Use.)Alternatively the total dose may be calculated:Dose (mL) = 0.0442 (Desired Hb - Observed Hb) x W + (0.26 x W)Based on: Desired Hb = the target Hb in g/dl. (Normal Hb for Children 15 kg or less is 12 g/dl)W = Weight in kg.To calculate a patient's weight in kg when lbs are known:

II. Iron Replacement for Blood Loss: Some individuals sustain blood losses on an intermittent or repetitive basis. Such blood losses may occur periodically in patients with hemorrhagic diatheses (familial telangiectasia; hemophilia; gastrointestinal bleeding) and on a repetitive basis from procedures such as renal hemodialysis.

Iron therapy in these patients should be directed toward replacement of the equivalent amount of iron represented in the blood loss. The table and formula described under I. Iron Deficiency Anemia are not applicable for simple iron replacement values.

Quantitative estimates of the individual’s periodic blood loss and hematocrit during the bleeding episode provide a convenient method for the calculation of the required iron dose.

The formula shown below is based on the approximation that 1 mL of normocytic, normochromic red cells contains 1 mg of elemental iron:Replacement iron (in mg) = Blood loss (in mL) x hematocritExample: Blood loss of 500 mL with 20% hematocrit                Replacement Iron = 500 x 0.20 = 100 mg                INFeD dose = 100 mg = 2 mL                                            50

Administration:

The total amount of INFeD required for the treatment of iron deficiency anemia or iron replacement for blood loss is determined from the table or appropriate formula. (See Dosage).

I. Intravenous Injection - PRIOR TO THE FIRST INTRAVENOUS INFeD THERAPEUTIC DOSE, ADMINISTER AN INTRAVENOUS TEST DOSE OF 0.5 ML. ADMINISTER THE TEST DOSE AT A GRADUAL RATE OVER AT LEAST 30 SECONDS. Although anaphylactic reactions known to occur following INFeD administration are usually evident within a few minutes, or sooner, it is recommended that a period of an hour or longer elapse before the remainder of the initial therapeutic dose is given.

Individual doses of 2 mL or less may be given on a daily basis until the calculated total amount required has been reached. INFeD is given undiluted at a slow gradual rate not to exceed 50 mg (1 mL) per minute.

2. Intramuscular Injection - PRIOR TO THE FIRST INTRAMUSCULAR INFeD THERAPEUTIC DOSE, ADMINISTER AN INTRAMUSCULAR TEST DOSE OF 0.5 ML. (See BOXED WARNING  and PRECAUTIONS.) The test dose should be administered in the buttock using the same technique as described in the last paragraph of this section. Although anaphylactic reactions known to occur following INFeD administration are usually evident within a few minutes or sooner, it is recommended that at least an hour or longer elapse before the remainder of the initial therapeutic dose is given.

If no adverse reactions are observed, INFeD can be given according to the following schedule until the calculated total amount required has been reached. Each day’s dose should ordinarily not exceed 0.5 mL (25 mg of iron) for infants under 5 kg (11 lbs); 1.0 mL (50 mg of iron) for children under 10 kg (22 lbs); and 2.0 mL (100 mg of iron) for other patients.

INFeD should be injected only into the muscle mass of the upper outer quadrant of the buttock - never into the arm or other exposed areas - and should be injected deeply, with a 2-inch or 3-inch 19 or 20 gauge needle. If the patient is standing, he/she should be bearing his/her weight on the leg opposite the injection site, or if in bed, he/she should be in the lateral position with injection site uppermost. To avoid injection or leakage into the subcutaneous tissue, a Z-track technique (displacement of the skin laterally prior to injection) is recommended.

NOTE: Do not mix INFeD with other medications or add to parenteral nutrition solutions for intravenous infusion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit.
Bicillin L-a

Bicillin L-a

Adults

The usual initial adult dose is 1 tablet every three or four hours. This may be increased to 2 tablets when needed. Total daily dosage should not exceed 12 tablets.

Discontinuation

Due to the potential for withdrawal symptoms associated with abrupt discontinuation, consideration should be given to tapering patients off pentazocine and naloxone tablets after prolonged periods of treatment with pentazocine and naloxone tablets (See PRECAUTIONS, Drug Abuse and Dependence).
Doxycycline Hyclate

Doxycycline Hyclate

2.1 Usual Dosage and Administration

The usual dosage and frequency of administration of doxycycline differs from that of the other tetracyclines. Exceeding the recommended dosage may result in an increased incidence of side effects.

Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours), followed by a maintenance dose of 100 mg daily. The maintenance dose may be administered as a single dose or as 50 mg every 12 hours. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

For pediatric patients above eight years of age: The recommended dosage schedule for children weighing 45 kg or less is 4.4 mg/kg of body weight divided into two doses on the first day of treatment, followed by 2.2 mg/kg of body weight given as a single daily dose or divided into two doses on subsequent days. For more severe infections up to 4.4 mg/kg of body weight may be used. For children over 45 kg, the usual adult dose should be used.

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline-class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration [see Adverse Reactions (6.1)].

If gastric irritation occurs, doxycycline may be given with food or milk [see Clinical Pharmacology (12)].

When used in streptococcal infections, therapy should be continued for 10 days.

Uncomplicated urethral, endocervical, or rectal infection caused by Chlamydia trachomatis: 100 mg by mouth twice a day for 7 days. As an alternate dosing regimen for uncomplicated urethral or endocervical infection caused by Chlamydia trachomatis, administer 200 mg by mouth once-a-day for 7 days.

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice-a-day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose.

Nongonococcal urethritis (NGU) caused by U. urealyticum: 100 mg by mouth twice-a-day for 7 days.

Syphilis – early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg by mouth twice-a-day for 2 weeks.

Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg by mouth twice-a-day for 4 weeks.

Acute epididymo-orchitis caused by C. trachomatis: 100 mg, by mouth, twice-a-day for at least 10 days.

2.2 For Prophylaxis of Malaria

For adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up to the adult dose. Prophylaxis should begin 1 or 2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area.

2.3 Inhalational Anthrax (post-exposure)

Adults: 100 mg, of doxycycline, by mouth, twice-a-day for 60 days.

Children: weighing less than 45 kg, 2.2 mg/kg of body weight, by mouth, twice-a-day for 60 days. Children weighing 45 kg or more should receive the adult dose.

2.4 Sprinkling the Tablet Over Applesauce

Doxycycline hyclate delayed-release tablets may also be administered by carefully breaking up the tablet and sprinkling the tablet contents (delayed-release pellets) on a spoonful of applesauce. The delayed-release pellets must not be crushed or damaged when breaking up the tablet. Any loss of pellets in the transfer would prevent using the dose. The applesauce/ doxycycline hyclate delayed-release tablets mixture should be swallowed immediately without chewing and may be followed by a glass of water if desired. The applesauce should not be hot, and it should be soft enough to be swallowed without chewing. In the event that a prepared dose of applesauce/ doxycycline hyclate delayed-release tablet cannot be taken immediately, the mixture should be discarded and not stored for later use.
Trelstar

Trelstar

2.1 Dosing Information

TRELSTAR must be administered under the supervision of a physician.

TRELSTAR is administered by a single intramuscular injection in either buttock. Dosing schedule depends on the product strength selected (Table 1). The lyophilized microgranules are to be reconstituted in sterile water. No other diluent should be used.
Table 1. TRELSTAR Recommended Dosing Dosage 3.75 mg 11.25 mg 22.5 mg Recommended dose 1 injection every 4 weeks 1 injection every 12 weeks 1 injection every 24 weeks
Due to different release characteristics, the dosage strengths are not additive and must be selected based upon the desired dosing schedule.

The suspension should be administered immediately after reconstitution.

As with other drugs administered by intramuscular injection, the injection site should be alternated periodically.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

2.2 Reconstitution Instructions for TRELSTAR

Please read the instructions completely before you begin.
Wash your hands with soap and hot water and put on gloves immediately prior to preparing the injection. Place the vial in a standing upright position on a clean, flat surface that is covered with a sterile pad or cloth. Remove the Flip-Off® button from the top of the vial, revealing the rubber stopper. Disinfect the rubber stopper with an alcohol wipe. Discard the alcohol wipe and allow the stopper to dry. Using a syringe fitted with a sterile 21-gauge needle, withdraw 2 mL sterile water for injection, and inject into the vial. Shake well to thoroughly disperse particles to obtain a uniform suspension. The suspension will appear milky. Slowly withdraw the entire contents of the reconstituted suspension into the syringe. The suspension should be administered immediately after reconstitution. Inject the patient in either buttock with the contents of the syringe.
2.3 Reconstitution Instructions for TRELSTAR with MIXJECT SYSTEM

Please read the instructions completely before you begin.

MIXJECT Preparation

Wash your hands with soap and hot water and put on gloves immediately prior to preparing the injection. Place the sealed tray on a clean, flat surface that is covered with a sterile pad or cloth. Peel the cover away from the tray and remove the MIXJECT components and the TRELSTAR vial. Remove the Flip-Off button from the top of the vial, revealing the rubber stopper. Place the vial in a standing upright position on the prepared surface. Disinfect the rubber stopper with the alcohol wipe. Discard the alcohol wipe and allow the stopper to dry. Proceed to MIXJECT Activation.

MIXJECT Activation
Cal Dex Cmpk

Cal Dex Cmpk

2.1 Recommended Dosing

The recommended dosage is one 60 mg raloxifene hydrochloride tablet daily, which may be administered any time of day without regard to meals [see Clinical Pharmacology (12.3)].

For the indications in risk of invasive breast cancer the optimum duration of treatment is not known [see Clinical Studies (14.3, 14.4)].

2.2 Recommendations for Calcium and Vitamin D Supplementation

For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. Postmenopausal women require an average of 1500 mg/day of elemental calcium. Total daily intake of calcium above 1500 mg has not demonstrated additional bone benefits while daily intake above 2000 mg has been associated with increased risk of adverse effects, including hypercalcemia and kidney stones. The recommended intake of vitamin D is 400 to 800 IU daily. Patients at increased risk for vitamin D insufficiency (e.g., over the age of 70 years, nursing home bound, or chronically ill) may need additional vitamin D supplements. Patients with gastrointestinal malabsorption syndromes may require higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.
Guanfacine

Guanfacine

The recommended initial dose of guanfacine hydrochloride when given alone or in combination with another antihypertensive drug is 1 mg daily given at bedtime to minimize somnolence. If after 3 to 4 weeks of therapy 1 mg does not give a satisfactory result, a dose of 2 mg may be given, although most of the effect of guanfacine is seen at 1 mg (see CLINICAL PHARMACOLOGY). Higher daily doses have been used, but adverse reactions increase significantly with doses above 3 mg/day.

The frequency of rebound hypertension is low, but it can occur. When rebound occurs, it does so after 2-4 days, which is delayed compared with clonidine hydrochloride. This is consistent with the longer half-life of guanfacine. In most cases, after abrupt withdrawal of guanfacine, blood pressure returns to pretreatment levels slowly (within 2-4 days) without ill effects.
Halaven

Halaven

Dexmethylphenidate hydrochloride extended-release is for oral administration once daily in the morning.

Dexmethylphenidate hydrochloride extended-release may be swallowed as whole capsules or alternatively may be administered by sprinkling the capsule contents on a small amount of applesauce (see specific instructions below). Dexmethylphenidate hydrochloride extended-release capsules and/or their contents should not be crushed, chewed, or divided.

The capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. The mixture of drug and applesauce should be consumed immediately in its entirety. The drug and applesauce mixture should not be stored for future use.

Dosage should be individualized according to the needs and responses of the patient.

2.1 Patients New to Methylphenidate

The recommended starting dose of dexmethylphenidate hydrochloride extended-release for patients who are not currently taking dexmethylphenidate or racemic methylphenidate, or for patients who are on stimulants other than methylphenidate, is 5 mg/day for pediatric patients and 10 mg/day for adult patients.

Dosage may be adjusted in 5 mg increments for pediatric patients and in 10 mg increments for adult patients. In general, dosage adjustments may proceed at approximately weekly intervals. The patient should be observed for a sufficient duration at a given dose to ensure that a maximal benefit has been achieved before a dose increase is considered. In dose-response (fixed-dose) studies (pediatric from 10 to 30 mg/day and adult from 20 to 40 mg/day), all doses were effective vs. placebo. There was no clear finding, however, of greater average benefits for the higher doses compared to the lower doses. Adverse events and discontinuations, however, were dose-related. Doses above 30 mg/day in pediatrics and 40 mg/day in adults have not been studied and are not recommended.

2.2 Patients Currently Using Methylphenidate

For patients currently using methylphenidate, the recommended starting dose of dexmethylphenidate hydrochloride extended-release is half the total daily dose of racemic methylphenidate. Patients currently using dexmethylphenidate hydrochloride may be switched to the same daily dose of dexmethylphenidate hydrochloride extended-release.

2.3 Maintenance/Extended Treatment

There is no body of evidence available from controlled trials to indicate how long the patient with ADHD should be treated with dexmethylphenidate hydrochloride extended-release. It is generally agreed, however, that pharmacological treatment of ADHD may be needed for extended periods. Nevertheless, the physician who elects to use dexmethylphenidate hydrochloride extended-release for extended periods in patients with ADHD should periodically reevaluate the long-term usefulness of the drug for the individual patient with periods off medication to assess the patient’s functioning without pharmacotherapy. Improvement may be sustained when the drug is either temporarily or permanently discontinued.

2.4 Dose Reduction and Discontinuation

If paradoxical aggravation of symptoms or other adverse events occur, the dosage should be reduced, or, if necessary, the drug should be discontinued.

If improvement is not observed after appropriate dosage adjustment over a 1-month period, the drug should be discontinued.
Dilacor Xr

Dilacor Xr

Hypertensive or anginal patients who are treated with other formulations of diltiazem can safely be switched to Dilacor XR capsules at the nearest equivalent total daily dose. Subsequent titration to higher or lower doses may, however, be necessary and should be initiated as clinically indicated.

Studies have shown a slight increase in the rate of absorption of Dilacor XR when ingested with a high-fat breakfast; therefore, administration in the morning on an empty stomach is recommended.

Patients should be cautioned that the Dilacor XR capsules should not be opened, chewed or crushed, and should be swallowed whole.

Dosage: Hypertension: Dosages must be adjusted to each patient’s needs, starting with 180 mg or 240 mg once daily. Based on the antihypertensive effect, the dose may be adjusted as needed. Individual patients, particularly ≥60 years of age, may respond to a lower dose of 120 mg. The usual dosage range studied in clinical trials was 180 mg to 480 mg once daily.

Current clinical experience with the 540 mg dose is limited; the dose may be increased to 540 mg with little or no increased risk of adverse reactions. Doses should not exceed 540 mg once daily.

While a dose of Dilacor XR given once daily may produce an antihypertensive effect similar to the same total daily dose given in divided doses, individual dose adjustment may be needed.

Dosage: Angina: Dosages for the treatment of angina should be adjusted to each patient’s needs, starting with a dose of 120 mg once daily, which may be titrated to doses of up to 480 mg once daily. When necessary, titration may be carried out over a 7 to 14 day period.

Concomitant Use with Other Cardiovascular Agents.

Sublingual Nitroglycerin may be taken as required to abort acute anginal attacks during diltiazem hydrochloride therapy.

Prophylactic Nitrate Therapy – Diltiazem hydrochloride may be safely co-administered with short- and long-acting nitrates.

Beta-blockers. (See WARNINGS and PRECAUTIONS.)

Antihypertensives – Diltiazem hydrochloride has an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of diltiazem hydrochloride or the concomitant antihypertensives may need to be adjusted when adding one to the other.
Brevicon

Brevicon

To achieve maximum contraceptive effectiveness, oral contraceptives must be taken exactly as directed and at intervals not exceeding 24 hours.

28-Day Schedule: For a DAY 1 START, count the first day of menstrual flow as Day 1 and the first tablet (white or yellow-green or blue) is then taken on Day 1. For a SUNDAY START when menstrual flow begins on or before Sunday, the first tablet (white or yellow-green or blue) is taken on that day. With either a DAY 1 START or SUNDAY START, 1 tablet (white or yellow-green or blue) is taken each day at the same time for 21 days. Then the orange tablets are taken for 7 days, whether bleeding has stopped or not. After all 28 tablets have been taken, whether bleeding has stopped or not, the same dosage schedule is repeated beginning on the following day.
Telmisartan And Hydroch...

Telmisartan And Hydrochlorothiazide

When possible, to reduce the risk of developing cardiotoxicity in patients receiving doxorubicin after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, doxorubicin-based therapy should be delayed until the other agents have cleared from the circulation (See WARNINGS and PRECAUTIONS, General).

Care in the administration of doxorubicin will reduce the chance of perivenous infiltration (see WARNINGS). It may also decrease the chance of local reactions such as urticaria and erythematous streaking. On intravenous administration of doxorubicin, extravasation may occur with or without an accompanying burning or stinging sensation, even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation have occurred, the injection or infusion should be immediately terminated and restarted in another vein. If extravasation is suspected, intermittent application of ice to the site for 15 min. q.i.d. x 3 days may be useful. The benefit of local administration of drugs has not been clearly established. Because of the progressive nature of extravasation reactions, close observation and plastic surgery consultation is recommended. Blistering, ulceration and/or persistent pain are indications for wide excision surgery, followed by split-thickness skin grafting.

The most commonly used dose schedule when used as a single agent is 60 to 75 mg/m2 as a single intravenous injection administered at 21-day intervals. The lower dosage should be given to patients with inadequate marrow reserves due to old age, or prior therapy, or neoplastic marrow infiltration.

Doxorubicin has been used concurrently with other approved chemotherapeutic agents. Evidence is available that in some types of neoplastic disease, combination chemotherapy is superior to single agents. The benefits and risks of such therapy continue to be elucidated. When used in combination with other chemotherapy drugs, the most commonly used dosage of doxorubicin is 40 to 60 mg/m2 given as a single intravenous injection every 21 to 28 days.

In a large randomized study (NSABP B-15) of patients with early breast cancer involving axillary lymph nodes ( CLINICAL PHARMACOLOGY, Clinical Studies and ADVERSE REACTIONS, Adverse Reactions in Patients with Early Breast Cancer Receiving Doxorubicin-Containing Adjuvant Therapy), the combination dosage regimen of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) was administered intravenously on day 1 of each 21-day treatment cycle. Four cycles of treatment were administered.

Dose Modifications

Patients in the NSABP B-15 study could have dose modifications of AC to 75% of the starting doses for neutropenic fever/infection. When necessary, the next cycle of treatment cycle was delayed until the absolute neutrophil count (ANC) was ≥1000 cells/mm3 and the platelet count was ≥100,000 cells/mm3 and

nonhematologic toxicities had resolved.
Doxorubicin dosage must be reduced in case of hyperbilirubinemia as follows: Plasma bilirubin concentration (mg/dL) Dosage reduction (%) 1.2 to 3.0 50 3.1 to 5.0 75
Reconstitution Directions

It is recommended that doxorubicin be slowly administered into the tubing of a freely running intravenous infusion of Sodium Chloride Injection or 5% Dextrose Injection. The tubing should be attached to a Butterfly® needle inserted preferably into a large vein. If possible, avoid veins over joints or in extremities with compromised venous or lymphatic drainage. The rate of administration is dependent on the size of the vein and the dosage. However, the dose should be administered in not less than 3 to 5 minutes. Local erythematous streaking along the vein as well as facial flushing may be indicative of too rapid an administration. A burning or stinging sensation may be indicative of perivenous infiltration and the infusion should be immediately terminated and restarted in another vein. Perivenous infiltration may occur painlessly.

Doxorubicin should not be mixed with heparin or fluorouracil since it has been reported that these drugs are incompatible to the extent that a precipitate may form. Contact with alkaline solutions should be avoided since this can lead to hydrolysis of doxorubicin. Until specific compatibility data are available, it is not recommended that doxorubicin be mixed with other drugs. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Handling and Disposal

Procedures for proper handling and disposal of anti-cancer drugs should be considered. Several guidelines on this subject have been published.1-4 There is no general agreement that all the procedures recommended in the guidelines are necessary or appropriate. However, given the toxic nature of this substance, the following protective recommendations are provided:
Personnel should be trained in good technique for reconstitution and handling. Pregnant staff should be excluded from working with this drug. Personnel handling doxorubicin should wear protective clothing: goggles, gowns, and disposable gloves and masks. A designated area should be defined for reconstitution (preferably under a laminar flow system). The work surface should be protected by disposable, plastic-backed, absorbent paper. All items used for reconstitution, administration or cleaning, including gloves, should be placed in high-risk waste-disposal bags for high-temperature incineration. Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. All cleaning materials should be disposed of as indicated previously. In case of skin contact, thoroughly wash the affected area with soap and water or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. In case of contact with the eye(s), hold back the eyelid(s) and flush the affected eye(s) with copious amounts of water for at least 15 minutes. Then seek medical evaluation by a physician. Always wash hands after removing gloves.
Caregivers of pediatric patients receiving doxorubicin should be counseled to take precautions (such as wearing latex gloves) to prevent contact with the patient’s urine and other body fluids for at least 5 days after each treatment.
Tudorza Pressair

Tudorza Pressair

Carefully consider the potential benefits and risks of naproxen sodium extended-release tablets and other treatment options before deciding to use naproxen sodium extended-release tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with naproxen sodium extended-release tablets, the dose and frequency should be adjusted to suit an individual patient's needs.

For the relief of:Rheumatoid Arthritis, Osteoarthritis, and Ankylosing Spondylitis

The recommended starting dose of naproxen sodium extended-release tablets in adults is two naproxen sodium extended-release 375 mg tablets (750 mg) once daily, or two naproxen sodium extended-release 500 mg tablets (1000 mg) once daily. Patients already taking naproxen 250 mg, 375 mg or 500 mg twice daily (morning and evening) may have their total daily dose replaced with naproxen sodium extended-release tablets as a single daily dose.

During long-term administration, the dose of naproxen sodium extended-release tablets may be adjusted up or down depending on the clinical response of the patient. In patients who tolerate lower doses of naproxen sodium extended-release tablets well, the dose may be increased to three naproxen sodium extended-release 500 mg tablets (1500 mg) once daily for limited periods when a higher level of anti-inflammatory/analgesic activity is required. When treating patients, especially at the higher dose levels, the physician should observe sufficient increased clinical benefit to offset the potential increased risk. (See Clinical Pharmacology). The lowest effective dose should be sought and used in every patient. Symptomatic improvement in arthritis usually begins within one week; however, treatment for two weeks may be required to achieve a therapeutic benefit.

A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see Precautions). Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly it is prudent to use the lowest effective dose.

Management of Pain, Primary Dysmenorrhea, and Acute Tendinitis and Bursitis

The recommended starting dose is two naproxen sodium extended-release 500 mg tablets (1000 mg) once daily. For patients requiring greater analgesic benefit, three naproxen sodium extended-release 500 mg tablets (1500 mg) may be used for a limited period. Thereafter, the total daily dose should not exceed two naproxen sodium extended-release 500 mg tablets (1000 mg).

Acute Gout

The recommended dose on the first day is two to three naproxen sodium extended-release 500 mg tablets (1000 - 1500 mg) once daily, followed by two naproxen sodium extended-release 500 mg tablets (1000 mg) once daily, until the attack has subsided.
Alora

Alora

Alora should be administered twice weekly, as instructed. The adhesive side of the Alora system should be placed on a clean, dry area of skin. The recommended application site is the lower abdomen. In addition, the upper quadrant of the buttocks or outer aspect of the hip may be used. Alora should not be applied to the breasts. The sites of application should be rotated, with an interval of at least 1 week allowed between applications to a particular site. The area selected should not be oily, damaged, or irritated. The waistline should be avoided, since tight clothing may rub the system off. The system should be applied immediately after opening the pouch and removing the protective liner. The system should be pressed firmly in place with the palm of the hand for about 10 seconds, making sure there is good contact, especially around the edges.

In the event that a system should fall off, the same system may be reapplied. If necessary, a new system may be applied to another site. The original treatment schedule should be maintained.

Initiation of Therapy

For treatment of moderate-to-severe vasomotor symptoms, vulvar and vaginal atrophy associated with the menopause, hypogonadism, castration, or primary ovarian failure, treatment is usually initiated with Alora 0.05 mg/day applied to the skin twice weekly. The lowest dose and regimen that will control symptoms should be chosen and medication should be discontinued as promptly as possible. Attempts to discontinue or taper medication should be made at 3-month to 6-month intervals.

For the prevention of postmenopausal osteoporosis, the minimum dose of Alora that has been studied and shown to be effective is 0.025 mg/day applied to the skin twice weekly. Bone mineral density measurements should be repeated to monitor treatment efficacy. The dosage may be increased as necessary, depending on bone mineral density and adverse events.

In women who are not currently taking oral estrogens or in women switching from topical therapy or another transdermal estradiol therapy, treatment with Alora can be initiated at once. In women who are currently taking oral estrogens, treatment with Alora should be initiated 1 week after withdrawal of oral therapy or sooner if menopausal symptoms reappear in less than 1 week.

When estrogen is prescribed for a postmenopausal woman with a uterus, progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. Use of estrogen, alone or in combination with a progestin, should be limited to the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be reevaluated periodically as clinically appropriate (e.g., 3-month to 6-month intervals) to determine if treatment is still necessary [see BOXED WARNINGS and WARNINGS]. For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.

Therapeutic Regimen

Alora may be administered in a continuous regimen in patients who do not possess an intact uterus. In those patients with an intact uterus who are not using concomitant progestin therapy, Alora can be administered on a cyclic schedule (e.g., 3 weeks of therapy followed by 1 week without) for the treatment of postmenopausal symptoms. However, no studies have been conducted using this intermittent regimen for the prevention of postmenopausal osteoporosis.
Mirtazapine

Mirtazapine

Initial Treatment

The recommended starting dose for mirtazapine tablets is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day. While the relationship between dose and satisfactory response in the treatment of major depressive disorder for mirtazapine has not been adequately explored, patients not responding to the initial 15-mg dose may benefit from dose increases up to a maximum of 45 mg/day.

Mirtazapine has an elimination half-life of approximately 20 to 40 hours; therefore, dose changes should not be made at intervals of less than 1 to 2 weeks in order to allow sufficient time for evaluation of the therapeutic response to a given dose.

Elderly and Patients with Renal or Hepatic Impairment

The clearance of mirtazapine is reduced in elderly patients and in patients with moderate to severe renal or hepatic impairment. Consequently, the prescriber should be aware that plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in younger adults without renal or hepatic impairment (see PRECAUTIONS and CLINICAL PHARMACOLOGY).

Maintenance/Extended Treatment

It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of mirtazapine tablets has demonstrated that its efficacy in major depressive disorder is maintained for periods of up to 40 weeks following 8 to 12 weeks of initial treatment at a dose of 15 to 45 mg/day (see CLINICAL PHARMACOLOGY). Based on these limited data, it is unknown whether or not the dose of mirtazapine needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with mirtazapine tablets. Conversely, at least 14 days should be allowed after stopping mirtazapine tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).

Use of Mirtazapine With Other MAOIs, Such as Linezolid or Methylene Blue

Do not start mirtazapine in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).

In some cases, a patient already receiving therapy with mirtazapine may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, mirtazapine tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with mirtazapine may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with mirtazapine is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).

Discontinuation of Mirtazapine Treatment

Symptoms associated with the discontinuation or dose reduction of mirtazapine tablets have been reported. Patients should be monitored for these and other symptoms when discontinuing treatment or during dosage reduction. A gradual reduction in the dose over several weeks, rather than abrupt cessation, is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient’s clinical response (see PRECAUTIONS and ADVERSE REACTIONS).

Information for Patients

Patients should be advised that taking mirtazapine can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Preexisting glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle-closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.
Dicyclomine Hydrochlori...

Dicyclomine Hydrochloride Capsule Dicyclomine Hydrochloride

Dosage must be adjusted to individual patient needs.

2.1 Oral Dosage and Administration in Adults

The recommended initial dose is 20 mg four times a day.

After one week treatment with the initial dose, the dose may be increased to 40 mg four times a day unless side effects limit dosage escalation.

If efficacy is not achieved within 2 weeks or side effects require doses below 80 mg per day, the drug should be discontinued. Documented safety data are not available for doses above 80 mg daily for periods longer than 2 weeks.
Terconazole

Terconazole

Terconazole Vaginal Cream 0.4%

One full applicator (5 g) of Terconazole Vaginal Cream (20 mg terconazole) should be administered intravaginally once daily at bedtime for seven consecutive days.

Terconazole Vaginal Cream 0.8%

One full applicator (5 g) of Terconazole Vaginal Cream (40 mg terconazole) should be administered intravaginally once daily at bedtime for three consecutive days.

Before prescribing another course of therapy, the diagnosis should be reconfirmed by smears and/or cultures and other pathogens commonly associated with vulvovaginitis ruled out. The therapeutic effect of these products is not affected by menstruation.
Methylphenidate Hydroch...

Methylphenidate Hydrochloride

2.1 General Dosing Information

Methylphenidate HCl Extended-Release Tablets should be administered orally once daily in the morning with or without food.

Methylphenidate HCl Extended-Release Tablets must be swallowed whole with the aid of liquids, and must not be chewed, divided, or crushed [see Patient Counseling Information (17)].

2.2 Patients New to Methylphenidate

The recommended starting dose of Methylphenidate HCl Extended-Release Tablets for patients who are not currently taking methylphenidate or stimulants other than methylphenidate is 18 mg once daily for children and adolescents and 18 or 36 mg once daily for adults (see Table 1).
Table 1. Methylphenidate HCl Extended-Release Tablets Recommended Starting Doses and Dose Ranges Patient Age Recommended Starting Dose Dose Range Children 6–12 years of age 18 mg/day 18 mg – 54 mg/day Adolescents 13–17 years of age 18 mg/day 18 mg – 72 mg/daynot to exceed 2 mg/kg/day Adults 18–65 years of age 18 or 36 mg/day 18 mg – 72 mg/day
2.3 Patients Currently Using Methylphenidate

The recommended dose of Methylphenidate HCl Extended-Release Tablets for patients who are currently taking methylphenidate twice daily or three times daily at doses of 10 to 60 mg/day is provided in Table 2. Dosing recommendations are based on current dose regimen and clinical judgment. Conversion dosage should not exceed 72 mg daily.
Table 2. Recommended Dose Conversion from Methylphenidate Regimens to Methylphenidate HCl Extended-Release Tablets Previous Methylphenidate Daily Dose Recommended Methylphenidate HCl Extended-Release Tablets Starting Dose 5 mg Methylphenidate twice daily or three times daily 18 mg every morning 10 mg Methylphenidate twice daily or three times daily 36 mg every morning 15 mg Methylphenidate twice daily or three times daily 54 mg every morning 20 mg Methylphenidate twice daily or three times daily 72 mg every morning
Other methylphenidate regimens: Clinical judgment should be used when selecting the starting dose.

2.4 Dose Titration

Doses may be increased in 18 mg increments at weekly intervals for patients who have not achieved an optimal response at a lower dose. Daily dosages above 54 mg in children and 72 mg in adolescents have not been studied and are not recommended. Daily dosages above 72 mg in adults are not recommended.

A 27 mg dosage strength is available for physicians who wish to prescribe between the 18 mg and 36 mg dosages.

2.5 Maintenance/Extended Treatment

There is no body of evidence available from controlled trials to indicate how long the patient with ADHD should be treated with Methylphenidate HCl Extended-Release Tablets. It is generally agreed, however, that pharmacological treatment of ADHD may be needed for extended periods.

The effectiveness of Methylphenidate HCl Extended-Release Tablets for long-term use, i.e., for more than 7 weeks, has not been systematically evaluated in controlled trials. The physician who elects to use Methylphenidate HCl Extended-Release Tablets for extended periods in patients with ADHD should periodically re-evaluate the long-term usefulness of the drug for the individual patient with trials off medication to assess the patient's functioning without pharmacotherapy. Improvement may be sustained when the drug is either temporarily or permanently discontinued.

2.6 Dose Reduction and Discontinuation

If paradoxical aggravation of symptoms or other adverse events occur, the dosage should be reduced, or, if necessary, the drug should be discontinued.

If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.
Docetaxel

Docetaxel

For all indications, toxicities may warrant dosage adjustments [see Dosage and Administration (2.7)].

Administer in a facility equipped to manage possible complications (e.g. anaphylaxis).

2.1 Breast Cancer
For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose of docetaxel injection concentrate is 60 mg/m2 to 100 mg/m2 administered intravenously over 1 hour every 3 weeks. For the adjuvant treatment of operable node-positive breast cancer, the recommended docetaxel injection concentrate dose is 75 mg/m2 administered 1 hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 courses. Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities [see Dosage and Administration (2.7)].
2.2 Non-Small Cell Lung Cancer
For treatment after failure of prior platinum-based chemotherapy, docetaxel injection concentrate was evaluated as monotherapy, and the recommended dose is 75 mg/m2 administered intravenously over 1 hour every 3 weeks. A dose of 100 mg/m2 in patients previously treated with chemotherapy was associated with increased hematologic toxicity, infection, and treatment-related mortality in randomized, controlled trials [see Boxed Warning, Dosage and Administration (2.7), Warnings and Precautions (5), Clinical Studies (14)]. For chemotherapy-naïve patients, docetaxel injection concentrate was evaluated in combination with cisplatin. The recommended dose of docetaxel injection concentrate is 75 mg/m2 administered intravenously over 1 hour immediately followed by cisplatin 75 mg/m2 over 30 to 60 minutes every 3 weeks [see Dosage and Administration (2.7)].
2.3 Prostate Cancer
For hormone-refractory metastatic prostate cancer, the recommended dose of docetaxel injection concentrate is 75 mg/m2 every 3 weeks as a 1 hour intravenous infusion. Prednisone 5 mg orally twice daily is administered continuously [see Dosage and Administration (2.7)].
2.4 Gastric Adenocarcinoma
For gastric adenocarcinoma, the recommended dose of docetaxel injection concentrate is 75 mg/m2 as a 1 hour intravenous infusion, followed by cisplatin 75 mg/m2, as a 1 to 3 hour intravenous infusion (both on day 1 only), followed by fluorouracil 750 mg/m2 per day given as a 24-hour continuous intravenous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration [see Dosage and Administration (2.7)].
2.5 Head and Neck Cancer

Patients must receive premedication with antiemetics, and appropriate hydration (prior to and after cisplatin administration). Prophylaxis for neutropenic infections should be administered. All patients treated on the docetaxel injection concentrate containing arms of the TAX323 and TAX324 studies received prophylactic antibiotics.
Induction chemotherapy followed by radiotherapy (TAX323)
For the induction treatment of locally advanced inoperable SCCHN, the recommended dose of docetaxel injection concentrate is 75 mg/m2 as a 1 hour intravenous infusion followed by cisplatin 75 mg/m2 intravenously over 1 hour, on day one, followed by fluorouracil as a continuous intravenous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. [see Dosage and Administration (2.7)].
Induction chemotherapy followed by chemoradiotherapy (TAX324)
For the induction treatment of patients with locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN, the recommended dose of docetaxel injection concentrate is 75 mg/m2 as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 3 hour infusion, followed by fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy [see Dosage and Administration (2.7)].

2.6 Premedication Regimen

All patients should be premedicated with oral corticosteroids (see below for prostate cancer) such as dexamethasone 16 mg per day (e.g., 8 mg twice daily) for 3 days starting 1 day prior to docetaxel injection concentrate administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions [see Boxed Warning, Warnings and Precautions (5.4)].

For hormone-refractory metastatic prostate cancer, given the concurrent use of prednisone, the recommended premedication regimen is oral dexamethasone 8 mg, at 12 hours, 3 hours and 1 hour before the docetaxel injection concentrate infusion [see Warnings and Precautions (5.4)].

2.7 Dosage Adjustments During Treatment

Breast Cancer

Patients who are dosed initially at 100 mg/m2 and who experience either febrile neutropenia, neutrophils <500 cells/mm3 for more than 1 week, or severe or cumulative cutaneous reactions during docetaxel injection concentrate therapy should have the dosage adjusted from 100 mg/m2 to 75 mg/m2. If the patient continues to experience these reactions, the dosage should either be decreased from 75 mg/m2 to 55 mg/m2 or the treatment should be discontinued. Conversely, patients who are dosed initially at 60 mg/m2 and who do not experience febrile neutropenia, neutrophils <500 cells/mm3 for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during docetaxel injection concentrate therapy may tolerate higher doses. Patients who develop ≥grade 3 peripheral neuropathy should have docetaxel injection concentrate treatment discontinued entirely.

Combination Therapy with Docetaxel Injection Concentrate in the Adjuvant Treatment of Breast Cancer

Docetaxel injection concentrate in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is ≥1,500 cells/mm3. Patients who experience febrile neutropenia should receive G-CSF in all subsequent cycles. Patients who continue to experience this reaction should remain on G-CSF and have their docetaxel injection concentrate dose reduced to 60 mg/m². Patients who experience grade 3 or 4 stomatitis should have their docetaxel injection concentrate dose decreased to 60 mg/m². Patients who experience severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during docetaxel injection concentrate therapy should have their dosage of docetaxel injection concentrate reduced from 75 mg/m² to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², treatment should be discontinued.

Non-Small Cell Lung Cancer

Monotherapy with docetaxel injection concentrate for NSCLC treatment after failure of prior platinum-based chemotherapy

Patients who are dosed initially at 75 mg/m2 and who experience either febrile neutropenia, neutrophils <500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions, or other grade 3/4 non-hematological toxicities during docetaxel injection concentrate treatment should have treatment withheld until resolution of the toxicity and then resumed at 55 mg/m2. Patients who develop ≥grade 3 peripheral neuropathy should have docetaxel injection concentrate treatment discontinued entirely.

Combination therapy with docetaxel injection concentrate for chemotherapy-naïve NSCLC

For patients who are dosed initially at docetaxel injection concentrate 75 mg/m2 in combination with cisplatin, and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm3, in patients who experience febrile neutropenia, and in patients with serious non-hematologic toxicities, the docetaxel injection concentrate dosage in subsequent cycles should be reduced to 65 mg/m2. In patients who require a further dose reduction, a dose of 50 mg/m2 is recommended. For cisplatin dosage adjustments, see manufacturers’ prescribing information.

Prostate Cancer

Combination therapy with docetaxel injection concentrate for hormone-refractory metastatic prostate cancer

Docetaxel injection concentrate should be administered when the neutrophil count is ≥1,500 cells/mm3. Patients who experience either febrile neutropenia, neutrophils <500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during docetaxel injection concentrate therapy should have the dosage of docetaxel injection concentrate reduced from 75 mg/m² to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be discontinued.

Gastric or Head and Neck Cancer

Docetaxel injection concentrate in combination with cisplatin and fluorouracil in gastric cancer or head and neck cancer

Patients treated with docetaxel injection concentrate in combination with cisplatin and fluorouracil must receive antiemetics and appropriate hydration according to current institutional guidelines. In both studies, G-CSF was recommended during the second and/or subsequent cycles in case of febrile neutropenia, or documented infection with neutropenia, or neutropenia lasting more than 7 days. If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the docetaxel injection concentrate dose should be reduced from 75 mg/m2 to 60 mg/m2. If subsequent episodes of complicated neutropenia occur the docetaxel injection concentrate dose should be reduced from 60 mg/m2 to 45 mg/m2. In case of grade 4 thrombocytopenia the docetaxel injection concentrate dose should be reduced from 75 mg/m2 to 60 mg/m2. Patients should not be retreated with subsequent cycles of docetaxel injection concentrate until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. Discontinue treatment if these toxicities persist. [see Warnings and Precautions (5.3)].

Recommended dose modifications for toxicities in patients treated with docetaxel injection concentrate in combination with cisplatin and fluorouracil are shown in Table 1.
Table 1 - Recommended Dose Modifications for Toxicities in Patients Treated with Docetaxel Injection Concentrate in Combination with Cisplatin and Fluorouracil Toxicity Dosage adjustment Diarrhea grade 3 First episode: reduce fluorouracil dose by 20%. Second episode: then reduce docetaxel injection concentrate dose by 20%. Diarrhea grade 4 First episode: reduce docetaxel injection concentrate and fluorouracil doses by 20%. Second episode: discontinue treatment. Stomatitis/mucositis grade 3 First episode: reduce fluorouracil dose by 20%. Second episode: stop fluorouracil only, at all subsequent cycles. Third episode: reduce docetaxel injection concentrate dose by 20%. Stomatitis/mucositis grade 4 First episode: stop fluorouracil only, at all subsequent cycles. Second episode: reduce docetaxel injection concentrate dose by 20%.
Liver dysfunction:

In case of AST/ALT >2.5 to ≤5 x ULN and AP ≤2.5 x ULN, or AST/ALT >1.5 to ≤5 x ULN and AP >2.5 to ≤5 x ULN, docetaxel injection concentrate should be reduced by 20%.

In case of AST/ALT >5 x ULN and/or AP >5 x ULN docetaxel injection concentrate should be stopped.

The dose modifications for cisplatin and fluorouracil in the gastric cancer study are provided below:

Cisplatin dose modifications and delays

Peripheral neuropathy: A neurological examination should be performed before entry into the study, and then at least every 2 cycles and at the end of treatment. In the case of neurological signs or symptoms, more frequent examinations should be performed and the following dose modifications can be made according to NCIC-CTC grade:
Grade 2: Reduce cisplatin dose by 20%. Grade 3: Discontinue treatment.
Ototoxicity: In the case of grade 3 toxicity, discontinue treatment.

Nephrotoxicity: In the event of a rise in serum creatinine ≥grade 2 (>1.5 x normal value) despite adequate rehydration, CrCl should be determined before each subsequent cycle and the following dose reductions should be considered (see Table 2).

For other cisplatin dosage adjustments, also refer to the manufacturers’ prescribing information.
Table 2 – Dose Reductions for Evaluation of Creatinine Clearance Creatinine clearance result before next cycle Cisplatin dose next cycle CrCl = Creatinine clearance CrCl ≥60 mL/min Full dose of cisplatin was given. CrCl was to be repeated before each treatment cycle. Dose of cisplatin was reduced by 50% at subsequent cycle. If CrCl was CrCl between 40 and 59 mL/min >60 mL/min at end of cycle, full cisplatin dose was reinstituted at the next cycle. If no recovery was observed, then cisplatin was omitted from the next treatment cycle. Dose of cisplatin was omitted in that treatment cycle only. If CrCl was still <40 mL/min at the end of cycle, cisplatin was discontinued. CrCl <40 mL/min If CrCl was >40 and <60 mL/min at end of cycle, a 50% cisplatin dose was given at the next cycle. If CrCl was >60 mL/min at end of cycle, full cisplatin dose was given at next cycle.
Fluorouracil dose modifications and treatment delays

For diarrhea and stomatitis, see Table 1.

In the event of grade 2 or greater plantar-palmar toxicity, fluorouracil should be stopped until recovery. The fluorouracil dosage should be reduced by 20%.

For other greater than grade 3 toxicities, except alopecia and anemia, chemotherapy should be delayed (for a maximum of 2 weeks from the planned date of infusion) until resolution to grade ≤1 and then recommenced, if medically appropriate.

For other fluorouracil dosage adjustments, also refer to the manufacturers’ prescribing information.

Combination Therapy with Strong CYP3A4 inhibitors:

Avoid using concomitant strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole). There are no clinical data with a dose adjustment in patients receiving strong CYP3A4 inhibitors. Based on extrapolation from a pharmacokinetic study with ketoconazole in 7 patients, consider a 50% docetaxel dose reduction if patients require co-administration of a strong CYP3A4 inhibitor [see Drug Interactions (7), Clinical Pharmacology (12.3)].

2.8 Administration Precautions

Docetaxel injection concentrate is a cytotoxic anticancer drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing docetaxel injection concentrate solutions. The use of gloves is recommended. Please refer to [see How Supplied/ Storage and Handling (16.3)].

If docetaxel injection concentrate, or diluted infusion solution should come into contact with the skin or mucosa, wash immediately and thoroughly with soap and water.

Do not use plasticized PVC equipment or devices that comes in direct contact with docetaxel injection solution during preparation and administration of solutions for infusion. In order to minimize patient exposure to the plasticizer DEHP (di-2-ethylhexyl phthalate), which may leach from PVC infusion bags or sets, the diluted docetaxel infusion solution should be stored in bottles made of glass, polypropylene or plastic bags made with polypropylene, polyolefin and administered through polyethylene-lined administration sets.

One-vial Docetaxel Injection Concentrate

Docetaxel injection concentrate requires NO prior dilution with a diluent and is ready to add to the infusion solution.

Please follow the preparation instructions provided below.

2.9 Preparation and Administration

DO NOT use the two-vial formulation (Injection Concentrate and diluent) with the one-vial formulation.

One-vial Docetaxel Injection Concentrate

Docetaxel injection concentrate (20 mg/mL) requires NO prior dilution with a diluent and is ready to add to the infusion solution. Use only a 21 gauge needle to withdraw docetaxel injection concentrate from the vial because larger bore needles (e.g., 18 and 19 gauge) may result in stopper coring and rubber particulates.
Docetaxel injection concentrate vials should be stored at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) protected from light. Using only a 21 gauge needle, aseptically withdraw the required amount of docetaxel injection concentrate (20 mg docetaxel/mL) with a calibrated syringe and inject via a single injection into a 250 mL infusion bag or bottle of either 0.9% Sodium Chloride solution or 5% Dextrose solution to produce a final concentration of 0.3 mg/mL to 0.74 mg/mL. If a dose greater than 200 mg of docetaxel injection concentrate is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL docetaxel injection concentrate is not exceeded. Thoroughly mix the infusion solution by gentle manual rotation. As with all parenteral products, docetaxel injection concentrate should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the docetaxel injection concentrate dilution for intravenous infusion is not clear or appears to have precipitation, it should be discarded.
The docetaxel injection concentrate dilution for infusion should be administered intravenously as a 1-hour infusion under ambient room temperature (below 25°C) and lighting conditions.

2.10 Stability

Docetaxel injection concentrate dilution for infusion is stable for 4 hours, if stored between 2°C and 25°C (36°F and 77°F). Docetaxel injection concentrate dilution for infusion (in either 0.9% Sodium Chloride solution or 5% Dextrose solution) should be used within 4 hours (including the 1 hour intravenous administration).
Morphine Sulfate

Morphine Sulfate

Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions.

If an infection develops, the use of Cordran Tape and other occlusive dressings should be discontinued and appropriate antimicrobial therapy instituted.

Replacement of the tape every 12 hours produces the lowest incidence of adverse reactions, but it may be left in place for 24 hours if it is well tolerated and adheres satisfactorily. When necessary, the tape may be used at night only and removed during the day.

If ends of the tape loosen prematurely, they may be trimmed off and replaced with fresh tape.

The directions given below are included for the patient to follow unless otherwise instructed by the physician.

________________________________________________________________________

APPLICATION OF CORDRAN TAPE
IMPORTANT: Skin should be clean and dry before tape is applied. Tape should always be cut, never torn.
DIRECTIONS FOR USE:
Prepare skin as directed by your physician or as follows: Gently clean the area to be covered to remove scales, crusts, dried exudates, and any previously used ointments or creams. A germicidal soap or cleanser should be used to prevent the development of odor under the tape. Shave or clip the hair in the treatment area to allow both good contact with the skin and comfortable removal. If shower or tub bath is to be taken, it should be completed before the tape is applied. The skin should be dry before application of the tape. Remove tape from package and cut a piece slightly larger than area to be covered. Round off corners. Pull white paper from transparent tape. Be careful that tape does not stick to itself. Apply tape, keeping skin smooth; press tape into place.
REPLACEMENT OF TAPE:

Unless instructed otherwise by your physician, replace tape after 12 hours. Cleanse skin and allow it to dry for 1 hour before applying new tape.

IF IRRITATION OR INFECTION DEVELOPS, REMOVE TAPE AND CONSULT PHYSICIAN.

________________________________________________________________________
Rituxan

Rituxan

Propafenone hydrochloride extended-release capsules can be taken with or without food. Do not crush or further divide the contents of the capsule.

The dose of propafenone hydrochloride extended-release capsules must be individually titrated on the basis of response and tolerance. Initiate therapy with propafenone hydrochloride extended-release capsules 225 mg given every 12 hours. Dosage may be increased at a minimum of 5 day interval to 325 mg given every 12 hours. If additional therapeutic effect is needed, the dose of propafenone hydrochloride extended-release capsules may be increased to 425 mg given every 12 hours.

In patients with hepatic impairment or those with significant widening of the QRS complex or second or third degree AV block, consider reducing the dose.

The combination of CYP3A4 inhibition and either CYP2D6 deficiency or CYP2D6 inhibition with the simultaneous administration of propafenone may significantly increase the concentration of propafenone and thereby increase the risk of proarrhythmia and other adverse events. Therefore, avoid simultaneous use of propafenone hydrochloride extended-release capsules with both a CYP2D6 inhibitor and a CYP3A4 inhibitor [see Warnings and Precautions (5.4) and Drug Interactions (7.1)].
Oxycodone Hydrochloride...

Oxycodone Hydrochloride

2.1 Initial Dosing

OXYCODONE HCl EXTENDED-RELEASE TABLETS should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

OXYCODONE HCl EXTENDED-RELEASE TABLETS 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid.

Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with OXYCODONE HCl EXTENDED-RELEASE TABLETS [see Warnings and Precautions (5.2)].

OXYCODONE HCl EXTENDED-RELEASE TABLETS must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving OXYCODONE HCl EXTENDED-RELEASE TABLETS will result in uncontrolled delivery of oxycodone and can lead to overdose or death [see Warnings and Precautions (5.1)].

Use of OXYCODONE HCl EXTENDED-RELEASE TABLETS as the First Opioid Analgesic

Initiate treatment with OXYCODONE HCl EXTENDED-RELEASE TABLETS with one 10 mg tablet orally every 12 hours.

Use of OXYCODONE HCl EXTENDED-RELEASE TABLETS in Patients who are not Opioid Tolerant

The starting dose for patients who are not opioid tolerant is OXYCODONE HCl EXTENDED-RELEASE TABLETS 10 mg orally every 12 hours. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from other Oral Oxycodone Formulations to OXYCODONE HCl EXTENDED-RELEASE TABLETS

Patients receiving other oral oxycodone formulations may be converted to OXYCODONE HCl EXTENDED-RELEASE TABLETS by administering one-half of the patient's total daily oral oxycodone dose as OXYCODONE HCl EXTENDED-RELEASE TABLETS every 12 hours.

Conversion from other Opioids to OXYCODONE HCl EXTENDED-RELEASE TABLETS

Discontinue all other around-the-clock opioid drugs when OXYCODONE HCl EXTENDED-RELEASE TABLETS therapy is initiated.

There are no established conversion ratios for conversion from other opioids to OXYCODONE HCl EXTENDED-RELEASE TABLETS defined by clinical trials. Discontinue all other around-the-clock opioid drugs when OXYCODONE HCl EXTENDED-RELEASE TABLETS therapy is initiated and initiate dosing using OXYCODONE HCl EXTENDED-RELEASE TABLETS 10 mg orally every 12 hours.

It is safer to underestimate a patient’s 24-hour oral oxycodone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxycodone requirements which could result in adverse reactions. While useful tables of opioid equivalents are readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products.

Conversion from Methadone to OXYCODONE HCl EXTENDED-RELEASE TABLETS

Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

Conversion from Transdermal Fentanyl to OXYCODONE HCl EXTENDED-RELEASE TABLETS

Eighteen hours following the removal of the transdermal fentanyl patch, OXYCODONE HCl EXTENDED-RELEASE TABLETS treatment can be initiated. Although there has been no systematic assessment of such conversion, a conservative oxycodone dose, approximately 10 mg every 12 hours of OXYCODONE HCl EXTENDED-RELEASE TABLETS, should be initially substituted for each 25 mcg/hr fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to OXYCODONE HCl EXTENDED-RELEASE TABLETS, as there is limited documented experience with this conversion.

2.2 Titration and Maintenance of Therapy

Individually titrate OXYCODONE HCl EXTENDED-RELEASE TABLETS to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving OXYCODONE HCl EXTENDED-RELEASE TABLETS to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse and misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for the use of opioid analgesics.

Patients who experience breakthrough pain may require a dose increase of OXYCODONE HCl EXTENDED-RELEASE TABLETS or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the OXYCODONE HCl EXTENDED-RELEASE TABLETS dose. Because steady-state plasma concentrations are approximated in 1 day, OXYCODONE HCl EXTENDED-RELEASE TABLETS dosage may be adjusted every 1 to 2 days. If unacceptable opioid-related adverse reactions are observed, the subsequent dose may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours. As a guideline, the total daily oxycodone dose usually can be increased by 25% to 50% of the current dose, each time an increase is clinically indicated.

2.3 Patients with Hepatic Impairment

For patients with hepatic impairment, start dosing patients at 1/3 to 1/2 the usual starting dose followed by careful dose titration [see Clinical Pharmacology (12.3)].

2.4 Discontinuation of OXYCODONE HCl EXTENDED-RELEASE TABLETS

When the patient no longer requires therapy with OXYCODONE HCl EXTENDED-RELEASE TABLETS, use a gradual downward titration of the dose to prevent signs and symptoms of withdrawal in the physically dependent patient. Do not abruptly discontinue OXYCODONE HCl EXTENDED-RELEASE TABLETS.

2.5 Administration of OXYCODONE HCl EXTENDED-RELEASE TABLETS

Instruct patients to swallow OXYCODONE HCl EXTENDED-RELEASE TABLETS intact. The tablets are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of oxycodone [see Warnings and Precautions (5.1)].

Instruct patients to take OXYCODONE HCl EXTENDED-RELEASE TABLETS one tablet at a time and with enough water to ensure complete swallowing immediately after placing in the mouth [see Warnings and Precautions (5.9) and Patient Counseling Information (17)].
Dextroamphetamine Sacch...

Dextroamphetamine Saccharate

Dosage should be adjusted according to the severity of the pain and the response of the patient. However, it should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related.NORCO® 7.5/325 and NORCO® 10/325 - The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dose should not exceed 6 tablets.
Doxycycline Monohydrate...

Doxycycline Monohydrate

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours or 50 mg every 6 hours) followed by a maintenance dose of 100 mg/day. The maintenance dose may be administered as a single dose or as 50 mg every 12 hours. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

For pediatric patients above eight years of age: The recommended dosage schedule for pediatric patients weighing 100 pounds or less is 2 mg/lb of body weight divided into two doses on the first day of treatment, followed by 1 mg/lb of body weight given as a single daily dose or divided into two doses, on subsequent days. For more severe infections up to 2 mg/lb of body weight may be used. For pediatric patients over 100 pounds the usual adult dose should be used.

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose.

Acute epididymo-orchitis caused by N. gonorrhoeae: 100 mg, by mouth, twice a day for at least 10 days.

Primary and secondary syphilis: 300 mg a day in divided doses for at least 10 days.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis: 100 mg, by mouth, twice a day for at least 7 days.

Nongonococcal urethritis caused by C. trachomatis and U. urealyticum: 100 mg, by mouth, twice a day for at least 7 days.

Acute epididymo-orchitis caused by C. trachomatis: 100 mg, by mouth, twice a day for at least 10 days.

Inhalational anthrax (post-exposure): ADULTS: 100 mg of doxycycline, by mouth, twice a day for 60 days. CHILDREN: weighing less than 100 pounds (45 kg); 1 mg/lb (2.2 mg/kg) of body weight, by mouth, twice a day for 60 days. Children weighing 100 pounds or more should receive the adult dose.

When used in streptococcal infections, therapy should be continued for 10 days.

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS.) If gastric irritation occurs, doxycycline may be given with food. Ingestion of a high fat meal has been shown to delay the time to peak plasma concentrations by an average of one hour and 20 minutes. However, in the same study, food enhanced the average peak concentration by 7.5% and the area under the curve by 5.7%.
Butalbital

Butalbital

One or 2 capsules every 4 hours. Total daily dosage should not exceed 6 capsules.

Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Butalbital

Butalbital

One or 2 capsules every 4 hours. Total daily dose should not exceed 6 capsules. Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Finasteride

Finasteride

Finasteride tablets may be administered with or without meals.

2.1 Monotherapy

The recommended dose of finasteride is one tablet (5 mg) taken once a day [see Clinical Studies (14.1)].

2.2 Combination with Alpha-Blocker

The recommended dose of finasteride is one tablet (5 mg) taken once a day in combination with the alpha-blocker doxazosin [see ClinicalStudies (14.2)].
Valacyclovir Hydrochlor...

Valacyclovir Hydrochloride

Valacyclovir tablets may be given without regard to meals. Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) may be prepared extemporaneously from 500 mg valacyclovir tablets for use in pediatric patients for whom a solid dosage form is not appropriate [see Dosage and Administration (2.3)].
2.1 Adult Dosing Recommendations

Cold Sores (Herpes Labialis): The recommended dosage of valacyclovir hydrochloride for treatment of cold sores is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning).

Genital Herpes: Initial Episode: The recommended dosage of valacyclovir hydrochloride for treatment of initial genital herpes is 1 gram twice daily for 10 days. Therapy was most effective when administered within 48 hours of the onset of signs and symptoms.

Recurrent Episodes: The recommended dosage of valacyclovir hydrochloride for treatment of recurrent genital herpes is 500 mg twice daily for 3 days. Initiate treatment at the first sign or symptom of an episode.

Suppressive Therapy: The recommended dosage of valacyclovir hydrochloride for chronic suppressive therapy of recurrent genital herpes is 1 gram once daily in patients with normal immune function. In patients with a history of 9 or fewer recurrences per year, an alternative dose is 500 mg once daily.

In HIV-infected patients with a CD4+ cell count greater than or equal to 100 cells/mm3, the recommended dosage of valacyclovir hydrochloride for chronic suppressive therapy of recurrent genital herpes is 500 mg twice daily.

Reduction of Transmission: The recommended dosage of valacyclovir hydrochloride for reduction of transmission of genital herpes in patients with a history of 9 or fewer recurrences per year is 500 mg once daily for the source partner.

Herpes Zoster: The recommended dosage of valacyclovir hydrochloride for treatment of herpes zoster is 1 gram 3 times daily for 7 days. Therapy should be initiated at the earliest sign or symptom of herpes zoster and is most effective when started within 48 hours of the onset of rash.

2.2 Pediatric Dosing Recommendations

Cold Sores (Herpes Labialis): The recommended dosage of valacyclovir hydrochloride for the treatment of cold sores in pediatric patients greater than or equal to 12 years of age is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning).

Chickenpox: The recommended dosage of valacyclovir hydrochloride for treatment of chickenpox in immunocompetent pediatric patients 2 to less than18 years of age is 20 mg/kg administered 3 times daily for 5 days. The total dose should not exceed 1 gram 3 times daily. Therapy should be initiated at the earliest sign or symptom [see Use in Specific Populations (8.4), Clinical Pharmacology (12.3), Clinical Studies (14.4)].

2.3 Extemporaneous Preparation of Oral Suspension

Ingredients and Preparation per USP-NF: Valacyclovir tablets 500 mg, cherry flavor, and Suspension Structured Vehicle USP-NF (SSV). Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) should be prepared in lots of 100 mL.

Prepare Suspension at Time of Dispensing as Follows:
Prepare SSV according to the USP-NF. Using a pestle and mortar, grind the required number of valacyclovir 500 mg tablets, until a fine powder is produced (5 valacyclovir tablets for 25 mg/mL suspension; 10 valacyclovir tablets for 50 mg/mL suspension). Gradually add approximately 5 mL aliquots of SSV to the mortar and triturate the powder until a paste has been produced. Ensure that the powder has been adequately wetted. Continue to add approximately 5 mL aliquots of SSV to the mortar, mixing thoroughly between additions, until a concentrated suspension is produced, to a minimum total quantity of 20 mL SSV and a maximum total quantity of 40 mL SSV for both the 25 mg/mL and 50 mg/mL suspensions. Transfer the mixture to a suitable 100 mL measuring flask. Transfer the cherry flavor* to the mortar and dissolve in approximately 5 mL of SSV. Once dissolved, add to the measuring flask. Rinse the mortar at least 3 times with approximately 5 mL aliquots of SSV, transferring the rinsing to the measuring flask between additions. Make the suspension to volume (100 mL) with SSV and shake thoroughly to mix. Transfer the suspension to an amber glass medicine bottle with a child-resistant closure. The prepared suspension should be labeled with the following information “Shake well before using. Store suspension between 2° to 8°C (36° to 46°F) in a refrigerator. Discard after 28 days.”
*The amount of cherry flavor added is as instructed by the suppliers of the cherry flavor.

2.4 Patients with Renal Impairment

Dosage recommendations for adult patients with reduced renal function are provided in Table 1 [see Use in Specific Populations (8.5, 8.6), Clinical Pharmacology (12.3)]. Data are not available for the use of valacyclovir hydrochloride in pediatric patients with a creatinine clearance less than 50 mL/min/1.73 m2.
Table 1. Valacyclovir Hydrochloride Dosage Recommendations for Adults With Renal Impairment Normal Dosage Creatinine Clearance (mL/min) Regimen (Creatinine Clearance Indications ≥50 mL/min) 30-49 10-29 <10 Cold sores (Herpes labialis) Two 2 gram Two 1 gram Two 500 mg 500 mg single doses taken doses taken doses taken dose Do not exceed 1 day of treatment. 12 hours apart 12 hours apart 12 hours apart Genital herpes: 1 gram every no reduction 1 gram every 500 mg every Initial episode 12 hours 24 hours 24 hours Genital herpes: 500 mg every no reduction 500 mg every 500 mg every Recurrent episode 12 hours 24 hours 24 hours Genital herpes: Suppressive therapy Immunocompetent patients 1 gram every no reduction 500 mg every 500 mg every 24 hours 24 hours 24 hours Alternate dose for 500 mg every no reduction 500 mg every 500 mg every immunocompetent 24 hours 48 hours 48 hours patients with ≤9 recurrences/year HIV-infected patients 500 mg every no reduction 500 mg every 500 mg every 12 hours 24 hours 24 hours Herpes zoster 1 gram every 1 gram every 1 gram every 500 mg every 8 hours 12 hours 24 hours 24 hours
Hemodialysis: Patients requiring hemodialysis should receive the recommended dose of valacyclovir hydrochloride after hemodialysis. During hemodialysis, the half-life of acyclovir after administration of valacyclovir hydrochloride is approximately 4 hours. About one third of acyclovir in the body is removed by dialysis during a 4-hour hemodialysis session.

Peritoneal Dialysis: There is no information specific to administration of valacyclovir hydrochloride in patients receiving peritoneal dialysis. The effect of chronic ambulatory peritoneal dialysis (CAPD) and continuous arteriovenous hemofiltration/dialysis (CAVHD) on acyclovir pharmacokinetics has been studied. The removal of acyclovir after CAPD and CAVHD is less pronounced than with hemodialysis, and the pharmacokinetic parameters closely resemble those observed in patients with end-stage renal disease (ESRD) not receiving hemodialysis. Therefore, supplemental doses of valacyclovir hydrochloride should not be required following CAPD or CAVHD.
Ciprofloxacin

Ciprofloxacin

Adults

Ciprofloxacin tablets should be administered orally to adults as described in the Dosage Guidelines table.

The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative organism, the integrity of the patient’s host-defense mechanisms, and the status of renal function and hepatic function.

The duration of treatment depends upon the severity of infection. The usual duration is 7 to 14 days; however, for severe and complicated infections more prolonged therapy may be required. Ciprofloxacin should be administered at least 2 hours before or 6 hours after magnesium/aluminum antacids, polymeric phosphate binders (for example, sevelamer, lanthanum carbonate) or sucralfate, Videx® (didanosine) chewable/buffered tablets or pediatric powder for oral solution, other highly buffered drugs, or other products containing calcium, iron or zinc.
ADULT DOSAGE GUIDELINES Infection Severity Dose Frequency Usual Durations† Urinary Tract Acute Uncomplicated 250 mg q 12 h 3 days Mild/Moderate 250 mg q 12 h 7 to 14 days Severe/Complicated 500 mg q 12 h 7 to 14 days Chronic Bacterial Prostatitis Mild/Moderate 500 mg q 12 h 28 days Lower Respiratory Tract Mild/Moderate 500 mg q 12 h 7 to 14 days Severe/Complicated 750 mg q 12 h 7 to 14 days Acute Sinusitis Mild/Moderate 500 mg q 12 h 10 days Skin andSkin Structure Mild/Moderate 500 mg q 12 h 7 to 14 days Severe/Complicated 750 mg q 12 h 7 to 14 days Bone and Joint Mild/Moderate 500 mg q 12 h ≥ 4 to 6 weeks Severe/Complicated 750 mg q 12 h ≥ 4 to 6 weeks Intra-Abdominal* Complicated 500 mg q 12 h 7 to 14 days Infectious Diarrhea Mild/Moderate/Severe 500 mg q 12 h 5 to 7 days Typhoid Fever Mild/Moderate 500 mg q 12 h 10 days Urethral and Cervical Gonococcal Infections Uncomplicated 250 mg single dose single dose Inhalational anthrax (post-exposure)** 500 mg q h 12 60 days * Used in conjunction with metronidazole † Generally ciprofloxacin tablets should be continued for at least 2 days after the signs and symptoms of infection have disappeared, except for inhalational anthrax (post-exposure). ** Drug administration should begin as soon as possible after suspected or confirmed exposure.
This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit.6 For a discussion of ciprofloxacin serum concentrations in various human populations, see Inhalational Anthrax, Additional Information.

Conversion of IV to Oral Dosing in Adults: Patients whose therapy is started with ciprofloxacin hydrochloride I.V. may be switched to ciprofloxacin tablets when clinically indicated at the discretion of the physician (See CLINICAL PHARMACOLOGY and table below for the equivalent dosing regimens).
Equivalent AUC Dosing Regimens Ciprofloxacin Oral Dosage Equivalent Ciprofloxacin IV Dosage 250 mg Tablet q 12 h 200 mg IV q 12 h 500 mg Tablet q 12 h 400 mg IV q 12 h 750 mg Tablet q 12 h 400 mg IV q 8 h
Adults with Impaired Renal Function: Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction. The following table provides dosage guidelines for use in patients with renal impairment:
RECOMMENDED STARTING AND MAINTENANCE DOSES FOR PATIENTS WITH IMPAIRED RENAL FUNCTION Creatinine Clearance (mL/min) Dose > 50 See Usual Dosage. 30 to 50 250 to 500 mg q 12 h 5 to 29 250 to 500 mg q 18 h Patients on hemodialysis or Peritoneal dialysis 250 to 500 mg q 24 h (after dialysis)
When only the serum creatinine concentration is known, the following formula may be used to estimate creatinine clearance.
Men: Creatinine clearance (mL/min) = Weight (kg) x (140 - age) 72 x serum creatinine (mg/dL) Women: 0.85 x the value calculated for men.
The serum creatinine should represent a steady state of renal function.

In patients with severe infections and severe renal impairment, a unit dose of 750 mg may be administered at the intervals noted above. Patients should be carefully monitored.

Pediatrics

Ciprofloxacin tablets should be administered orally as described in the Dosage Guidelines table. An increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues, has been observed. (See ADVERSE REACTIONS and CLINICAL STUDIES.)

Dosing and initial route of therapy (that is, IV or oral) for complicated urinary tract infection or pyelonephritis should be determined by the severity of the infection. In the clinical trial, pediatric patients with moderate to severe infection were initiated on 6 to 10 mg/kg IV every 8 hours and allowed to switch to oral therapy (10 to 20 mg/kg every 12 hours), at the discretion of the physician.
PEDIATRIC DOSAGE GUIDELINES Infection Route of Administration Dose (mg/kg) Frequency Total Duration ComplicatedUrinary TractorPyelonephritis(patients from1 to 17 years ofage) Oral 10 mg/kg to 20 mg/kg(maximum 750 mg per dose; not to be exceeded even in patients weighing > 51 kg) Every 12 hours 10 to 21 days* Inhalational Anthrax (Post-Exposure)** Oral 15 mg/kg(maximum 500 mg per dose) Every 12 hours 60 days * The total duration of therapy for complicated urinary tract infection and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days). ** Drug administration should begin as soon as possible after suspected or confirmed exposure to Bacillus anthracis spores. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit.6 For a discussion of ciprofloxacin serum concentrations in various human populations, see Inhalational Anthrax In Adults and Pediatrics, Additional Information.
Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of complicated urinary tract infection and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (that is, creatinine clearance of < 50 mL/min/1.73m2).
Amoxapine

Amoxapine

Effective dosage of amoxapine may vary from one patient to another. Usual effective dosage is 200 to 300 mg daily. Three weeks constitutes an adequate period of trial providing dosage has reached 300 mg daily (or lower level of tolerance) for at least two weeks. If no response is seen at 300 mg, dosage may be increased, depending upon tolerance, up to 400 mg daily. Hospitalized patients who have been refractory to antidepressant therapy and who have no history of convulsive seizures may have dosage raised cautiously up to 600 mg daily in divided doses.

Amoxapine may be given in a single daily dose, not to exceed 300 mg, preferably at bedtime. If the total daily dosage exceeds 300 mg, it should be given in divided doses.

Initial Dosage for Adults

Usual starting dosage is 50 mg two or three times daily. Depending upon tolerance, dosage may be increased to 100 mg two or three times daily by the end of the first week. (Initial dosage of 300 mg daily may be given, but notable sedation may occur in some patients during the first few days of therapy at this level.) Increases above 300 mg daily should be made only if 300 mg daily has been ineffective during a trial period of at least two weeks. When effective dosage is established, the drug may be given in a single dose (not to exceed 300 mg) at bedtime.

Elderly Patients

In general, lower dosages are recommended for these patients. Recommended starting dosage of amoxapine is 25 mg two or three times daily. If no intolerance is observed, dosage may be increased by the end of the first week to 50 mg two or three times daily. Although 100 to 150 mg daily may be adequate for many elderly patients, some may require higher dosage. Careful increases up to 300 mg daily are indicated in such cases.

Once an effective dosage is established, amoxapine may conveniently be given in a single bedtime dose, not to exceed 300 mg.

Maintenance

Recommended maintenance dosage of amoxapine is the lowest dose that will maintain remission. If symptoms reappear, dosage should be increased to the earlier level until they are controlled.

For maintenance therapy at dosages of 300 mg or less, a single dose at bedtime is recommended.
Tamsulosin Hydrochlorid...

Tamsulosin Hydrochloride

2.1 Initial Dosing

Morphine sulfate extended-release should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with morphine sulfate extended-release [see Warnings and Precautions (5.2)].

Morphine sulfate extended-release tablets must be taken whole. Crushing, chewing, or dissolving morphine sulfate extended-release tablets will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.1)].

Use of Morphine Sulfate Extended-Release as the First Opioid Analgesic

Initiate treatment with morphine sulfate extended-release with 15 mg tablets orally every 8 or 12 hours.

Use of Morphine Sulfate Extended-Release in Patients who are not Opioid Tolerant

The starting dose for patients who are not opioid tolerant is morphine sulfate extended-release 15 mg orally every 12 hours. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mg mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from Other Oral Morphine to Morphine Sulfate Extended-Release

Patients receiving other oral morphine formulations may be converted to morphine sulfate extended-release by administering one-half of the patient's 24-hour requirement as morphine sulfate extended-release on an every-12-hour schedule or by administering one-third of the patient's daily requirement as morphine sulfate extended-release on an every-8-hour schedule.

Conversion from Other Opioids to Morphine Sulfate Extended-Release

There are no established conversion ratios for conversion from other opioids to morphine sulfate extended-release defined by clinical trials. Discontinue all other around-the-clock opioid drugs when morphine sulfate extended-release therapy is initiated and initiate dosing using morphine sulfate extended-release 15 mg orally every 8 to 12 hours.

It is safer to underestimate a patient’s 24-hour oral morphine requirements and provide rescue medication (e.g., immediate-release morphine) than to overestimate the 24-hour oral morphine requirements and manage an adverse reaction. While useful tables of opioid equivalents are readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products.

Conversion from Parenteral Morphine or Other Opioids (Parenteral or Oral) to Morphine Sulfate Extended-Release

When converting from parenteral morphine or other non-morphine opioids (parenteral or oral) to morphine sulfate extended-release, consider the following general points:

Parenteral to oral morphine ratio: Between 2 to 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of morphine that is approximately three times the previous daily parenteral morphine requirement is sufficient.

Other parenteral or oral non-morphine opioids to oral morphine sulfate: Specific recommendations are not available because of a lack of systematic evidence for these types of analgesic substitutions. Published relative potency data are available, but such ratios are approximations. In general, begin with half of the estimated daily morphine requirement as the initial dose, managing inadequate analgesia by supplementation with immediate-release morphine.

Conversion from Methadone to Morphine Sulfate Extended-Release

Close monitoring is of particular importance when converting methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

2.2 Titration and Maintenance of Therapy

Individually titrate morphine sulfate extended-release to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving morphine sulfate extended-release to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy periodically reassess the continued need for the use of opioid analgesics.

Patients who experience breakthrough pain may require a dose increase of morphine sulfate extended-release, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the morphine sulfate extended-release dose. Because steady-state plasma concentrations are approximated in 1 day, morphine sulfate extended-release dosage adjustments may be done every 1 to 2 days.

If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.3 Discontinuation of Morphine Sulfate Extended-Release

When the patient no longer requires therapy with morphine sulfate extended-release, use a gradual downward titration of the dose to prevent signs and symptoms of withdrawal in the physically-dependent patient. Do not abruptly discontinue morphine sulfate extended-release.

2.4 Administration of Morphine Sulfate Extended-Release Tablets

Morphine sulfate extended-release tablets must be taken whole. Crushing, chewing, or dissolving morphine sulfate extended-release tablets will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.1)].
Modafinil

Modafinil

The recommended dose of modafinil is 200 mg given once a day.

For patients with narcolepsy and OSA, modafinil should be taken as a single dose in the morning.

For patients with SWD, modafinil should be taken approximately 1 hour prior to the start of their work shift.

Doses up to 400 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit beyond that of the 200 mg dose (See CLINICAL PHARMACOLOGY and CLINICAL TRIALS).

General Considerations

Dosage adjustment should be considered for concomitant medications that are substrates for CYP3A4, such as triazolam and cyclosporine (See PRECAUTIONS, Drug Interactions).

Drugs that are largely eliminated via CYP2C19 metabolism, such as diazepam, propranolol, phenytoin (also via CYP2C9) or S-mephenytoin may have prolonged elimination upon coadministration with modafinil and may require dosage reduction and monitoring for toxicity.

In patients with severe hepatic impairment, the dose of modafinil should be reduced to one-half of that recommended for patients with normal hepatic function (See CLINICAL PHARMACOLOGY and PRECAUTIONS).

There is inadequate information to determine safety and efficacy of dosing in patients with severe renal impairment (See CLINICAL PHARMACOLOGY and PRECAUTIONS).

In elderly patients, elimination of modafinil and its metabolites may be reduced as a consequence of aging. Therefore, consideration should be given to the use of lower doses in this population (See CLINICAL PHARMACOLOGY and PRECAUTIONS).
Ifosfamide

Ifosfamide

The dose is one drop of dorzolamide hydrochloride-timolol maleate ophthalmic solution in the affected eye(s) two times daily.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart (see also PRECAUTIONS, Drug Interactions).
Pioglitazone Hydrochlor...

Pioglitazone Hydrochloride

2.1       Recommendations for all patients

Pioglitazone tablets USP should be taken once daily and can be taken without regard to meals.

The recommended starting dose for patients without congestive heart failure is 15 mg or 30 mg once daily.

The recommended starting dose for patients with congestive heart failure (NYHA Class I or II) is 15 mg once daily.

The dose can be titrated in increments of 15 mg up to a maximum of 45 mg once daily based on glycemic response as determined by HbA1c.

After initiation of pioglitazone tablets USP or with dose increase, monitor patients carefully for adverse reactions related to fluid retention such as weight gain, edema, and signs and symptoms of congestive heart failure [see Boxed Warning and Warnings and Precautions (5.5)].

Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating pioglitazone tablets USP. Routine periodic monitoring of liver tests during treatment with pioglitazone tablets USP is not recommended in patients without liver disease. Patients who have liver test abnormalities prior to initiation of pioglitazone tablets USP or who are found to have abnormal liver tests while taking pioglitazone tablets USP should be managed as described under Warnings and Precautions [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

Pioglitazone tablets USP should be taken once daily and can be taken without regard to meals.

The recommended starting dose for patients without congestive heart failure is 15 mg or 30 mg once daily.

The recommended starting dose for patients with congestive heart failure (NYHA Class I or II) is 15 mg once daily.

2.2       Concomitant use with an insulin secretagogue or insulin

If hypoglycemia occurs in a patient coadministered pioglitazone tablets USP and an insulin secretagogue (e.g., sulfonylurea), the dose of the insulin secretagogue should be reduced.

If hypoglycemia occurs in a patient coadministered  pioglitazone tablets USP and insulin, the dose of insulin should be decreased by 10% to 25%. Further adjustments to the insulin dose should be individualized based on glycemic response.

2.3       Coadministration with Strong CYP2C8 inhibitors

Coadministration of pioglitazone tablets USP and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure approximately 3-fold. Therefore, the maximum recommended dose of pioglitazone tablets USP is 15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Leena

Leena

To achieve maximum contraceptive effectiveness, oral contraceptives must be taken exactly as directed and at intervals not exceeding 24 hours.

For a DAY 1 START, count the first day of menstrual flow as Day 1 and the first light blue tablet is then taken on Day 1. For a SUNDAY START when menstrual flow begins on or before Sunday, the first light blue tablet is taken on that day. With either a DAY 1 START or SUNDAY START, 1 light blue tablet is taken for 7 days, then 1 light yellow-green tablet for 9 days, then 1 light blue tablet for 5 days, then 1 orange tablet (inert) for 7 days, whether bleeding has stopped or not. With either a DAY 1 START or SUNDAY START 1 tablet is taken each day at the same time for 28 days. After all 28 tablets are taken, whether bleeding has stopped or not, the same dosage schedule is repeated beginning on the following day.
Minocycline Hydrochlori...

Minocycline Hydrochloride

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF MINOCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Minocycline hydrochloride capsules may be taken with or without food. (See CLINICAL PHARMACOLOGY.)

Ingestion of adequate amounts of fluids along with capsule and tablet forms of drugs in the tetracycline-class is recommended to reduce the risk of esophageal irritation and ulceration. The capsules should be swallowed whole.

For Pediatric Patients Above 8 Years of Age

Usual pediatric dose: 4 mg/kg initially followed by 2 mg/kg every 12 hours, not to exceed the usual adult dose.

Adults

The usual dosage of minocycline hydrochloride is 200 mg initially followed by 100 mg every 12 hours. Alternatively, if more frequent doses are preferred, two or four 50 mg capsules may be given initially followed by one 50 mg capsule 4 times daily.

Uncomplicated gonococcal infections other than urethritis and anorectal infections in men: 200 mg initially, followed by 100 mg every 12 hours for a minimum of 4 days, with post-therapy cultures within 2 to 3 days.

In the treatment of uncomplicated gonococcal urethritis in men, 100 mg every 12 hours for 5 days is recommended.

For the treatment of syphilis, the usual dosage of minocycline hydrochloride should be administered over a period of 10 to 15 days. Close follow-up, including laboratory tests, is recommended.

In the treatment of meningococcal carrier state, the recommended dosage is 100 mg every 12 hours for 5 days.

Mycobacterium marinum infections: Although optimal doses have not been established, 100 mg every 12 hours for 6 to 8 weeks have been used successfully in a limited number of cases.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis or Ureaplasma urealyticum: 100 mg orally, every 12 hours for at least 7 days.

Ingestion of adequate amounts of fluids along with capsule and tablet forms of drugs in the tetracycline-class is recommended to reduce the risk of esophageal irritation and ulceration.

The pharmacokinetics of minocycline in patients with renal impairment (CLCR <80 mL/min) have not been fully characterized. Current data are insufficient to determine if a dosage adjustment is warranted. The total daily dosage should not exceed 200 mg in 24 hours. However, due to the anti-anabolic effect of tetracyclines, BUN and creatinine should be monitored. (See WARNINGS.)
Valproic

Valproic

2.1 Epilepsy

Valproic Acid is intended for oral administration. Valproic Acid capsules should be swallowed whole without chewing to avoid local irritation of the mouth and throat.

Patients should be informed to take Valproic Acid every day as prescribed. If a dose is missed it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose.

Valproic Acid is indicated as monotherapy and adjunctive therapy in complex partial seizures in adults and pediatric patients down to the age of 10 years, and in simple and complex absence seizures. As the Valproic Acid dosage is titrated upward, concentrations of clonazepam, diazepam, ethosuximide, lamotrigine, tolbutamide, phenobarbital, carbamazepine, and/or phenytoin may be affected [see Drug Interactions (7.2)].

Complex Partial Seizures

For adults and children 10 years of age or older.

Monotherapy (Initial Therapy)

Valproic Acid has not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.

The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.

Conversion to Monotherapy

Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50-100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. Concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of Valproic Acid therapy, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable, and patients should be monitored closely during this period for increased seizure frequency.

Adjunctive Therapy

Valproic Acid may be added to the patient's regimen at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. If the total daily dose exceeds 250 mg, it should be given in divided doses.

In a study of adjunctive therapy for complex partial seizures in which patients were receiving either carbamazepine or phenytoin in addition to divalproex sodium tablets, no adjustment of carbamazepine or phenytoin dosage was needed [see Clinical Studies (14)]. However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs, periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy [see Drug Interactions (7)].

Simple and Complex Absence Seizures

The recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day. If the total daily dose exceeds 250 mg, it should be given in divided doses.

A good correlation has not been established between daily dose, serum concentrations, and therapeutic effect. However, therapeutic valproate serum concentration for most patients with absence seizures is considered to range from 50 to 100 mcg/mL. Some patients may be controlled with lower or higher serum concentrations [see Clinical Pharmacology (12.3)].

As the Valproic Acid dosage is titrated upward, blood concentrations of phenobarbital and/or phenytoin may be affected [see Drug Interactions (7.2)].

Antiepilepsy drugs should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.

The following Table is a guide for the initial daily dose of Valproic Acid (15 mg/kg/day):
Table 1. Initial Daily Dose
Weight

Total Daily Dose (mg)

Number of Capsules or Teaspoonfuls of Syrup

(Kg)

(Lb)

Dose 1

Dose 2

Dose 3

10 - 24.9

22 - 54.9

250

0

0

1

25 - 39.9

55 - 87.9

500

1

0

1

40 - 59.9

88 - 131.9

750

1

1

1

60 - 74.9

132 - 164.9

1,000

1

1

2

75 - 89.9

165 - 197.9

1,250

2

1

2

2.2 General Dosing Advice

Dosing in Elderly Patients

Due to a decrease in unbound clearance of valproate and possibly a greater sensitivity to somnolence in the elderly, the starting dose should be reduced in these patients. Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. The ultimate therapeutic dose should be achieved on the basis of both tolerability and clinical response [see Warnings and Precautions (5.14), Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)].

Dose-Related Adverse Reactions

The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. The probability of thrombocytopenia appears to increase significantly at total valproate concentrations of ≥ 110 mcg/mL (females) or ≥ 135 mcg/mL (males) [see Warnings and Precautions (5.8)]. The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.

G.I. Irritation

Patients who experience G.I. irritation may benefit from administration of the drug with food or by slowly building up the dose from an initial low level.
Hydrocodone Bitartate A...

Hydrocodone Bitartate And Acetaminophen

Dosage should be adjusted according to the severity of the pain and the response of the patient. However, it should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related.

The usual adult dosage is one or two tablets every four to six hours as needed for pain. The total daily dosage should not exceed 8 tablets.
Microgestin

Microgestin

The tablet dispenser has been designed to make oral contraceptive dosing as easy and as convenient as possible. The tablets are arranged in three or four rows of seven tablets each, with the days of the week appearing on the tablet dispenser above the first row of tablets.

Important: The patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle when utilizing the Sunday-Start Regimen.

The possibility of ovulation and conception prior to initiation of use should be considered.

Dosage and Administration for 21-Day Dosage Regimen

To achieve maximum contraceptive effectiveness, MICROGESTIN 1/20 and MICROGESTIN 1.5/30 should be taken exactly as directed and at intervals not exceeding 24 hours.

MICROGESTIN 1/20 and MICROGESTIN 1.5/30 provide a convenient tablet schedule of “3 weeks on-1 week off.” Two dosage regimens are described, one of which may be more convenient or suitable than the other for an individual patient. For the initial cycle of therapy, the patient begins her tablets according to the Day-1 or Sunday-Start regimen. With either regimen, the patient takes one tablet daily for 21 consecutive days followed by one week of no tablets.

A. Sunday-Start Regimen:

The patient begins taking the first white or green tablet from the top row of the dispenser (labeled Sunday) on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first white or green tablet is taken on the same day. The patient takes one white or green tablet daily for 21 days. The last white or green tablet will be taken on a Saturday, followed by no tablets for a week (7 days). For all subsequent cycles, the patient begins a new 21-tablet regimen on the eighth day, Sunday, after taking her last tablet. Following this regimen of 21 days on-7 days off, the patient will start all subsequent cycles on a Sunday.

B. Day-1 Start Regimen:

The first day of menstrual flow is Day 1. The patient starts taking one white or green tablet daily, beginning with the first white or green tablet in the top row. After the last white or green tablet (Saturday) has been taken, if any white or green tablets remain in the top row, the patient takes the remaining white or green tablets starting with the Sunday white or green tablets in the top row until all of the tablets have been taken. She will then take no tablets for a week (7 days). For all subsequent cycles, the patient begins a new 21- tablet regimen on the eighth day after taking her last white or green tablet, again starting with the first tablet in the top row. Following this regimen of 21 days on–7 days off, the patient will start all subsequent cycles on the same day of the week as the first course. Likewise, the interval of no tablets will always start on the same day of the week.

Tablets should be taken regularly with a meal or at bedtime. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule.

Dosage and Administration for 28-Day Dosage Regimen

To achieve maximum contraceptive effectiveness, MICROGESTIN Fe 1/20 and MICROGESTIN Fe 1.5/30 should be taken exactly as directed and at intervals not exceeding 24 hours.

MICROGESTIN Fe 1/20 and MICROGESTIN Fe 1.5/30 provide a continuous administration regimen consisting of 21 white or green tablets of Microgestin and 7 brown non-hormone containing tablets of ferrous fumarate. The ferrous fumarate tablets are present to facilitate ease of drug administration via a 28-day regimen and do not serve any therapeutic purpose. There is no need for the patient to count days between cycles because there are no “off-tablet days.”

A. Sunday-Start Regimen:

The patient begins taking the first white or green tablet from the top row of the dispenser (labeled Sunday) on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first white or green tablet is taken on the same day. The patient takes one white or green tablet daily for 21 days. The last white or green tablet will be taken on a Saturday. Upon completion of all 21 white or green tablets, and without interruption, the patient takes one brown tablet daily for 7 days. Upon completion of this first course of tablets, the patient begins a second course of 28-day tablets, without interruption, the next day, Sunday, starting with the Sunday white or green tablet in the top row. Adhering to this regimen of one white or green tablet daily for 21 days, followed without interruption by one brown tablet daily for 7 days, the patient will start all subsequent cycles on a Sunday.

B. Day-1 Start Regimen:

The first day of menstrual flow is Day 1. The patient starts taking one white or green tablet daily, beginning with the first white or green tablet in the top row. After the last white or green tablet (Saturday) has been taken, if any white or green tablets remain in the top row, the patient takes the remaining white or green tablets starting with the Sunday white or green tablets in the top row, followed by the brown tablets for a week (7 days). For all subsequent cycles, the patient begins a new 28 tablet regimen on the eighth day after taking her last white or green tablet, again starting with the first tablet in the top row. Following this regimen of 21 white or green tablets and 7 brown tablets, the patient will start all subsequent cycles on the same day of the week as the first course.

Tablets should be taken regularly with a meal or at bedtime. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule.

Special Notes on Administration

Menstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after the patient has taken the last white or green tablet. In any event, the next course of tablets should be started without interruption. If spotting occurs while the patient is taking white or green tablets, continue medication without interruption.

If the patient forgets to take one or more white or green tablets, the following is suggested:

One tablet is missed

take tablet as soon as remembered

take next tablet at the regular time

Two consecutive tablets are missed (week 1 or week 2)

take two tablets as soon as remembered

take two tablets the next day

use another birth control method for seven days following the missed tablets

Two consecutive tablets are missed (week 3)Sunday-Start Regimen:

take one tablet daily until Sunday

discard remaining tablets

start new pack of tablets immediately (Sunday)

use another birth control method for seven days following the missed tablets

Day-1 Start Regimen:

discard remaining tablets

start new pack of tablets that same day

use another birth control method for seven days following the missed tablets

Three (or more) consecutive tablets are missed

Sunday-Start Regimen:

take one tablet daily until Sunday

discard remaining tablets

start new pack of tablets immediately (Sunday)

use another birth control method for seven days following the missed tablets

Day-1 Start Regimen:

discard remaining tablets

start new pack of tablets that same day

use another birth control method for seven days following the missed tablets

The possibility of ovulation occurring increases with each successive day that scheduled white or green tablets are missed. While there is little likelihood of ovulation occurring if only one white or green tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive white or green tablets are missed.

If the patient is taking MICROGESTIN Fe (28-Day Dosage Regimen) and forgets to take any of the seven brown tablets in week four, those brown tablets that were missed are discarded and one brown tablet is taken each day until the pack is empty. A back up birth control method is not required during this time. A new pack of tablets should be started no later than the eighth day after the last white or green tablet was taken.

In the rare case of bleeding which resembles menstruation, the patient should be advised to discontinue medication and then begin taking tablets from a new tablet dispenser on the next Sunday or the first day (Day-1), depending on her regimen. Persistent bleeding which is not controlled by this method indicates the need for re-examination of the patient, at which time nonfunctional causes should be considered.

Use of Oral Contraceptives in the Event of a Missed Menstrual Period

If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and oral contraceptives should be withheld until pregnancy has been ruled out.

If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

After several months on treatment, bleeding may be reduced to a point of virtual absence. This reduced flow may occur as a result of medication, in which event it is not indicative of pregnancy.
Microgestin

Microgestin

The tablet dispenser has been designed to make oral contraceptive dosing as easy and as convenient as possible. The tablets are arranged in either three or four rows of seven tablets each, with the days of the week appearing on the tablet dispenser above the first row of tablets.

Note: Each tablet dispenser has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen. Six different day label strips have been provided with the Detailed Patient & Brief Summary Patient Package Insert in order to accommodate a Day-1 Start regimen. If the patient is using the Day-1 Start regimen, she should place the self-adhesive day label strip that corresponds to her starting day over the preprinted days.

Important: The patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle when utilizing the Sunday-Start regimen.

The possibility of ovulation and conception prior to initiation of use should be considered.

Dosage and Administration for 21-Day Dosage RegimenTo achieve maximum contraceptive effectiveness, MICROGESTIN must be taken exactly as directed and at intervals not exceeding 24 hours. MICROGESTIN provides the patient with a convenient tablet schedule of “3 weeks on—1 week off”. Two dosage regimens are described, one of which may be more convenient or suitable than the other for an individual patient. For the initial cycle of therapy, the patient begins her tablets according to the Day-1 Start or Sunday-Start regimen. With either regimen, the patient takes one tablet daily for 21 consecutive days followed by one week of no tablets.

A. Sunday-Start Regimen: The patient begins taking tablets from the top row on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first tablet is taken on the same day. The last tablet in the dispenser will then be taken on a Saturday, followed by no tablets for a week (7 days). For all subsequent cycles, the patient then begins a new 21-tablet regimen on the eighth day, Sunday, after taking her last tablet. Following this regimen, of 21 days on—7 days off, the patient will start all subsequent cycles on a Sunday.

B. Day-1 Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive day label strip that corresponds to her starting day over the preprinted days on the tablet dispenser. She starts taking one tablet daily, beginning with the first tablet in the top row. The patient completes her 21-tablet regimen when she has taken the last tablet in the tablet dispenser. She will then take no tablets for a week (7 days). For all subsequent cycles, the patient begins a new 21-tablet regimen on the eighth day after taking her last tablet, again starting with the first tablet in the top row after placing the appropriate day label strip over the preprinted days on the tablet dispenser. Following this regimen of 21 days on—7 days off, the patient will start all subsequent cycles on the same day of the week as the first course. Likewise, the interval of no tablets will always start on the same day of the week.

Tablets should be taken regularly with a meal or at bedtime. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule.

Special Notes on AdministrationMenstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after discontinuing medication. If spotting occurs while on the usual regimen of one tablet daily, the patient should continue medication without interruption.

If the patient forgets to take one or more tablets, the following is suggested:

One tablet is missed

take tablet as soon as remembered

take next tablet at the regular time

Two consecutive tablets are missed (week 1 or week 2)

take two tablets as soon as remembered

take two tablets the next day

use another birth control method for seven days following the missed tablets

Two consecutive tablets are missed (week 3) Sunday-Start Regimen:

take one tablet daily until Sunday

discard remaining tablets

start new pack of tablets immediately (Sunday)

use another birth control method for seven days following the missed tablets

Day-1 Start Regimen:

discard remaining tablets

start new pack of tablets that same day

use another birth control method for seven days following the missed tablets

Three (or more) consecutive tablets are missed

Sunday-Start Regimen:

take one tablet daily until Sunday

discard remaining tablets

start new pack of tablets immediately (Sunday)

use another birth control method for seven days following the missed tablets

Day-1 Start Regimen:

discard remaining tablets

start new pack of tablets that same day

use another birth control method for seven days following the missed tablets

The possibility of ovulation occurring increases with each successive day that scheduled tablets are missed. While there is little likelihood of ovulation occurring if only one tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive tablets are missed.

In the rare case of bleeding which resembles menstruation, the patient should be advised to discontinue medication and then begin taking tablets from a new tablet dispenser on the next Sunday or the first day (Day 1), depending on her regimen. Persistent bleeding which is not controlled by this method indicates the need for reexamination of the patient, at which time nonfunctional causes should be considered.

Dosage and Administration for 28-Day Dosage RegimenTo achieve maximum contraceptive effectiveness, MICROGESTIN Fe should be taken exactly as directed and at intervals not exceeding 24 hours.

MICROGESTIN Fe provides a continuous administration regimen consisting of 21 light-colored (white or green) tablets of MICROGESTIN and 7 brown non-hormone containing tablets of ferrous fumarate. The ferrous fumarate tablets are present to facilitate ease of drug administration via a 28-day regimen and do not serve any therapeutic purpose. There is no need for the patient to count days between cycles because there are no “off-tablet days.’’

A. Sunday-Start Regimen: The patient begins taking the first light-colored tablet from the top row of the dispenser (labeled Sunday) on the first Sunday after menstrual flow begins. When the menstrual flow begins on Sunday, the first light-colored tablet is taken on the same day. The patient takes one light-colored tablet daily for 21 days. The last light-colored tablet in the dispenser will be taken on a Saturday. Upon completion of all 21 light-colored tablets, and without interruption, the patient takes one brown tablet daily for 7 days. Upon completion of this first course of tablets, the patient begins a second course of 28-day tablets, without interruption, the next day (Sunday), starting with the Sunday light-colored tablet in the top row. Adhering to this regimen of one light-colored tablet daily for 21 days, followed without interruption by one brown tablet daily for seven days, the patient will start all subsequent cycles on a Sunday.

B. Day-1 Start Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive day label strip that corresponds to her starting day over the preprinted days on the tablet dispenser. She starts taking one light-colored tablet daily, beginning with the first light-colored tablet in the top row. After the last light-colored tablet (at the end of the third row) has been taken, the patient will then take the brown tablets for a week (7 days). For all subsequent cycles, the patient begins a new 28 tablet regimen on the eighth day after taking her last light-colored tablet, again starting with the first tablet in the top row after placing the appropriate day label strip over the preprinted days on the tablet dispenser. Following this regimen of 21 light-colored tablets and 7 brown tablets, the patient will start all subsequent cycles on the same day of the week as the first course.

Tablets should be taken regularly with a meal or at bedtime. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule.

Special Notes on AdministrationMenstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after the brown tablets have been started. In any event, the next course of tablets should be started without interruption. If spotting occurs while the patient is taking light-colored tablets, continue medication without interruption.

If the patient forgets to take one or more light-colored tablets, the following is suggested:

One tablet is missed

take tablet as soon as remembered

take next tablet at the regular time

Two consecutive tablets are missed (week 1 or week 2)

take two tablets as soon as remembered

take two tablets the next day

use another birth control method for seven days following the missed tablets

Two consecutive tablets are missed (week 3) Sunday-Start Regimen:

take one tablet daily until Sunday

discard remaining tablets

start new pack of tablets immediately (Sunday)

use another birth control method for seven days following the missed tablets

Day-1 Start Regimen:

discard remaining tablets

start new pack of tablets that same day

use another birth control method for seven days following the missed tablets

Three (or more) consecutive tablets are missed

Sunday-Start Regimen:

take one tablet daily until Sunday

discard remaining tablets

start new pack of tablets immediately (Sunday)

use another birth control method for seven days following the missed tablets

Day-1 Start Regimen:

discard remaining tablets

start new pack of tablets that same day

use another birth control method for seven days following the missed tablets

The possibility of ovulation occurring increases with each successive day that scheduled light-colored tablets are missed. While there is little likelihood of ovulation occurring if only one light-colored tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive light-colored tablets are missed.

If the patient forgets to take any of the seven brown tablets in week four, those brown tablets that were missed are discarded and one brown tablet is taken each day until the pack is empty. A back-up birth control method is not required during this time. A new pack of tablets should be started no later than the eighth day after the last light-colored tablet was taken.

In the rare case of bleeding which resembles menstruation, the patient should be advised to discontinue medication and then begin taking tablets from a new tablet dispenser on the next Sunday or the first day (Day-1), depending on her regimen. Persistent bleeding which is not controlled by this method indicates the need for reexamination of the patient, at which time nonfunctional causes should be considered.

Use of Oral Contraceptives in the Event of a Missed Menstrual Period

If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and oral contraceptives should be withheld until pregnancy has been ruled out.

If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

After several months on treatment, bleeding may be reduced to a point of virtual absence. This reduced flow may occur as a result of medication, in which event it is not indicative of pregnancy.
Diazepam

Diazepam

Dosage should be individualized for maximum beneficial effect. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In such cases dosage should be increased cautiously to avoid adverse effects.
ADULTS: USUAL DAILY DOSE: Management of Anxiety Disorders and relief of Symptoms of Anxiety. Depending upon severity of symptoms — 2 mg to 10 mg, 2 to 4 times daily Symptomatic Relief in Acute Alcohol Withdrawal. 10 mg, 3 or 4 times during the first 24 hours, reducing to 5 mg, 3 or 4 times daily as needed Adjunctively for Relief of Skeletal Muscle Spasm. 2 mg to 10 mg, 3 or 4 times daily Adjunctively in Convulsive Disorders. 2 mg to 10 mg, 2 to 4 times daily Geriatric Patients, or in the presence of debilitating disease. 2 mg to 2.5 mg, 1 or 2 times daily initially; increase gradually as needed and tolerated PEDIATRIC PATIENTS: Because of varied responses to CNS-acting drugs, initiate therapy with lowest dose and increase as required. Not for use in children under 6 months. 1 mg to 2.5 mg, 3 or 4 times daily initially; increase gradually as needed and tolerated
Hydrocodone Bitartrate ...

Hydrocodone Bitartrate And Acetaminophen

Dosage should be adjusted according to the severity of the pain and the response of the patient. However, it should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related.
2.5 mg/500 mg 5 mg/500 mg The usual adult dosage is one or two tablets every four to six hours as needed for pain. The total daily dosage should not exceed 8 tablets. 7.5 mg/325 mg 7.5 mg/500 mg 7.5 mg/650 mg The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets. 7.5 mg/750 mg The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 5 tablets. 10 mg/325 mg 10 mg/500 mg 10 mg/650 mg 10 mg/660 mg The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets. 10 mg/750 mg The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 5 tablets.
Norco

Norco

Dosage should be adjusted according to the severity of the pain and the response of the patient. However, it should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related.

The usual adult dosage is one or two tablets every four to six hours as needed for pain. The total daily dosage should not exceed 8 tablets.
Hydrocodone Bitartrate ...

Hydrocodone Bitartrate And Ibuprofen

Carefully consider the potential benefits and risks of hydrocodone bitartrate and ibuprofen tablets and other treatment options before deciding to use hydrocodone bitartrate and ibuprofen tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with hydrocodone bitartrate and ibuprofen tablets, the dose and frequency should be adjusted to suit an individual patient's needs.

For the short-term (generally less than 10 days) management of acute pain, the recommended dose of hydrocodone bitartrate and ibuprofen tablets is one tablet every 4 to 6 hours, as necessary. Dosage should not exceed 5 tablets in a 24-hour period. It should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related.

The lowest effective dose or the longest dosing interval should be sought for each patient (see WARNINGS), especially in the elderly. After observing the initial response to therapy with hydrocodone bitartrate and ibuprofen tablets, the dose and frequency of dosing should be adjusted to suit the individual patient need, without exceeding the total daily dose recommended.
Hydrocodone Bitatrate A...

Hydrocodone Bitatrate And Acetaminophen

Dosage should be adjusted according to the severity of the pain and the response of the patient. However, it should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related.

2.5 mg/325 mg
The usual adult dosage is one or two tablets every four to six hours as needed for pain. The total daily dosage should not exceed 8 tablets.

Actavis Pharma, Inc.

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