Barr Laboratories Inc.

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Barr Laboratories Inc. Drugs

Acetazolamide

Acetazolamide

The following is a summary of the instructions given to the patient in the “HOW TO TAKE THE PILL” section of the DETAILED PATIENT LABELING.

The patient is given instructions in five (5) categories:

1. IMPORTANT POINTS TO REMEMBER: The patient is told (a) that she should take one pill every day at the same time, (b) many women have spotting or light bleeding or gastric distress during the first one to three cycles, (c) missing pills can also cause spotting or light bleeding, (d) she should use a back-up method for contraception if she has vomiting or diarrhea or takes some concomitant medications, and/or if she has trouble remembering the pill, (e) if she has any other questions, she should consult her physician.

2. BEFORE SHE STARTS TAKING HER PILLS: She should decide what time of day she wishes to take the pill, check whether her pill pack has 28 pills, and note the order in which she should take the pills (diagrammatic drawings of the pill pack are included in the patient insert).

3. WHEN SHE SHOULD START THE FIRST PACK: The Day-One start is listed as the first choice and the Sunday start (the Sunday after her period starts) is given as the second choice. If she uses the Sunday start she should use a back-up method in the first cycle if she has intercourse before she has taken seven pills.

4. WHAT TO DO DURING THE CYCLE: The patient is advised to take one pill at the same time every day until the pack is empty. If she is on the 28 day regimen, she should start the next pack the day after the last inactive tablet and not wait any days between packs.

5. WHAT TO DO IF SHE MISSES A PILL OR PILLS: The patient is given instructions about what she should do if she misses one, two or more than two pills at varying times in her cycle for both the Day-One and the Sunday start. The patient is warned that she may become pregnant if she has unprotected intercourse in the seven days after missing pills. To avoid this, she must use another birth control method such as condom, foam, or sponge in these seven days.
Tretinoin

Tretinoin

The recommended dose is 45 mg/m2/day administered as two evenly divided doses until complete remission is documented. Therapy should be discontinued 30 days after achievement of complete remission or after 90 days of treatment, whichever occurs first.

If after initiation of treatment of tretinoin the presence of the t(15;17) translocation is not confirmed by cytogenetics and/or by polymerase chain reaction studies and the patient has not responded to tretinoin, alternative therapy appropriate for acute myelogenous leukemia should be considered.

Tretinoin is for the induction of remission only. Optimal consolidation or maintenance regimens have not been determined. All patients should, therefore, receive a standard consolidation and/or maintenance chemotherapy regimen for APL after induction therapy with tretinoin, unless otherwise contraindicated.
Myorisan

Myorisan

2.1 Dosing Information

Hydroxyurea is used alone or in conjunction with other antitumor agents or radiation therapy to treat neoplastic diseases. Individualize treatment based on tumor type, disease state, response to treatment, patient risk factors, and current clinical practice standards.

Base all dosage on the patient’s actual or ideal weight, whichever is less.

Hydroxyurea is a cytotoxic drug. Follow applicable special handling and disposal procedures [see References (15)].

Prophylactic administration of folic acid is recommended [see Warnings and Precautions (5.7)].

2.2 Dose Modifications for Toxicity

Monitor for the following and reduce the dose or discontinue hydroxyurea accordingly:
• Myelosuppression [see Warnings and Precautions (5.1)] • Cutaneous vasculitis [see Warnings and Precautions (5.4)]
Monitor blood counts at least once a week during hydroxyurea therapy. Severe anemia must be corrected before initiating therapy with hydroxyurea. Consider dose modifications for other toxicities.

2.3 Dose Modifications for Renal Impairment

Reduce the dose of hydroxyurea by 50% in patients with measured creatinine clearance of less than 60 mL/min or with end-stage renal disease (ESRD) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Creatinine Clearance

(mL/min)

Recommended Hydroxyurea Initial Dose

(mg/kg daily)

≥60

15

<60 or ESRD*

7.5

* On dialysis days, administer hydroxyurea to patients following hemodialysis.

Close monitoring of hematologic parameters is advised in these patients.
Chlordiazepoxide Hydroc...

Chlordiazepoxide Hydrochloride

Because of the wide range of clinical indications for chlordiazepoxide HCl, the optimum dosage varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects.
ADULTS USUAL DAILY DOSE
Relief of Mild and Moderate Anxiety Disorders and Symptoms of Anxiety
5 mg or 10 mg, 3 or 4 times daily
Relief of Severe Anxiety Disorders and Symptoms of Anxiety
20 mg or 25 mg, 3 or 4 times daily
Geriatric Patients, or in the presence of
debilitating disease. 5 mg, 2 to 4 times daily
Preoperative Apprehension and Anxiety

On days preceding surgery, 5 to 10 mg orally, 3 or 4 times daily. If used as preoperative medication, 50 to 100 mg IM* 1 hour prior to surgery.
PEDIATRIC PATIENTS USUAL DAILY DOSE
Because of the varied response of pediatric patients to CNS-acting drugs, therapy should be initiated with the lowest dose and increased as required. Since clinical experience in pediatric patients under 6 years of age is limited, the use of the drug in this age group is not recommended.
5 mg, 2 to 4 times daily (may be increased in some pediatric patients to 10 mg, 2 to 3 times daily)
For the relief of withdrawal symptoms of acute alcoholism, the parenteral form* is usually used initially. If the drug is administered orally, the suggested initial dose is 50 to 100 mg, to be followed by repeated doses as needed until agitation is controlled — up to 300 mg per day. Dosage should then be reduced to maintenance levels.

*See package insert for Injectable Chlordiazepoxide HCl.
Acetazolamide

Acetazolamide

Glaucoma

The recommended dosage is 1 capsule (500 mg) two times a day. Usually 1 capsule is administered in the morning and 1 capsule in the evening. It may be necessary to adjust the dose, but it has usually been found that dosage in excess of 2 capsules (1 g) does not produce an increased effect. The dosage should be adjusted with careful individual attention both to symptomatology and intraocular tension. In all cases, continuous supervision by a physician is advisable.

In those unusual instances where adequate control is not obtained by the twice-a-day administration of acetazolamide extended-release, the desired control may be established by means of acetazolamide (tablets or parenteral). Use tablets or parenteral in accordance with the more frequent dosage schedules recommended for these dosage forms, such as 250 mg every four hours, or an initial dose of 500 mg followed by 250 mg or 125 mg every four hours, depending on the case in question.

Acute Mountain Sickness

Dosage is 500 mg to 1000 mg daily, in divided doses using tablets or extended-release capsules as appropriate. In circumstances of rapid ascent, such as in rescue or military operations, the higher dose level of 1000 mg is recommended. It is preferable to initiate dosing 24 to 48 hours before ascent and to continue for 48 hours while at high altitude, or longer as necessary to control symptoms.
Norethindrone Acetate

Norethindrone Acetate

Therapy with Norethindrone Acetate Tablets USP must be adapted to the specific indications and therapeutic response of the individual patient.

Secondary amenorrhea, abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology

2.5 to 10 mg Norethindrone Acetate Tablets USP may be given daily for 5 to 10 days to produce secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen.

Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing Norethindrone Acetate Tablets USP therapy. Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with Norethindrone Acetate Tablets USP.

Endometriosis

Initial daily dosage of 5 mg Norethindrone Acetate Tablets USP for two weeks. Dosage should be increased by 2.5 mg per day every two weeks until 15 mg per day of Norethindrone Acetate Tablets USP is reached. Therapy may be held at this level for six to nine months or until annoying breakthrough bleeding demands temporary termination.
Tri-legest Fe 28 Day

Tri-legest Fe 28 Day

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 days of the week stickers 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 days of the week sticker 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 Regimen

To achieve maximum contraceptive effectiveness, Tri-Legest® 21 (norethindrone acetate and ethinyl estradiol tablets, USP) must be taken exactly as directed and at intervals not exceeding 24 hours. Tri-Legest® 21 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 Start Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive days of the week sticker 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 days of the week sticker 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 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 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 light pink, light yellow, or light blue 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 Regimen

To achieve maximum contraceptive effectiveness, Tri-Legest® Fe 28 (norethindrone acetate and ethinyl estradiol tablets, USP and ferrous fumarate tablets [not USP]) should be taken exactly as directed and at intervals not exceeding 24 hours.

Tri-Legest® Fe 28 (norethindrone acetate and ethinyl estradiol tablets, USP and ferrous fumarate tablets [not USP]) provides a continuous administration regimen consisting of 21 light pink, light yellow, and light blue tablets of norethindrone acetate and ethinyl estradiol 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 light pink tablet from the top row of the tablet dispenser (labeled Sunday) on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first light pink tablet is taken on the same day. The patient takes one tablet daily for 21 days. The last light blue tablet in the dispenser will be taken on a Saturday. Upon completion of all 21 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 pink tablet in the top row. Adhering to this regimen of one 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 days of the week sticker that corresponds to her starting day over the preprinted days on the tablet dispenser. She starts taking one light pink tablet daily, beginning with the first light pink tablet in the top row. After the last light blue 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 blue tablet, again starting with the first tablet in the top row after placing the appropriate days of the week sticker over the preprinted days on the tablet dispenser. Following this regimen of 21 light pink, light yellow, and light blue 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 light pink, light yellow, or light blue tablets, continue medication without interruption.

If the patient forgets to take one or more light pink, light yellow or light blue 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 pink, light yellow and light blue 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 light pink, light yellow, and light blue 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 blue 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 Tri-Legest®for acne should follow the guidelines for use of Tri-Legest®as an oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section for oral contraceptives.
Warfarin Sodium

Warfarin Sodium

2.1 Individualized Dosing

The dosage and administration of warfarin sodium must be individualized for each patient according to the patient’s INR response to the drug. Adjust the dose based on the patient’s INR and the condition being treated. Consult the latest evidence-based clinical practice guidelines from the American College of Chest Physicians (ACCP) to assist in the determination of the duration and intensity of anticoagulation with warfarin sodium [see References (15)].

2.2 Recommended Target INR Ranges and Durations for Individual Indications

An INR of greater than 4 appears to provide no additional therapeutic benefit in most patients and is associated with a higher risk of bleeding.

Venous Thromboembolism (including deep venous thrombosis [DVT] and PE)

Adjust the warfarin dose to maintain a target INR of 2.5 (INR range, 2 to 3) for all treatment durations. The duration of treatment is based on the indication as follows:
For patients with a DVT or PE secondary to a transient (reversible) risk factor, treatment with warfarin for 3 months is recommended. For patients with an unprovoked DVT or PE, treatment with warfarin is recommended for at least 3 months. After 3 months of therapy, evaluate the risk-benefit ratio of long-term treatment for the individual patient. For patients with two episodes of unprovoked DVT or PE, long-term treatment with warfarin is recommended. For a patient receiving long-term anticoagulant treatment, periodically reassess the risk-benefit ratio of continuing such treatment in the individual patient.
Atrial Fibrillation

In patients with non-valvular AF, anticoagulate with warfarin to target INR of 2.5 (range, 2 to 3).
In patients with non-valvular AF that is persistent or paroxysmal and at high risk of stroke (i.e., having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, or 2 of the following risk factors: age greater than 75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitus), long-term anticoagulation with warfarin is recommended. In patients with non-valvular AF that is persistent or paroxysmal and at an intermediate risk of ischemic stroke (i.e., having 1 of the following risk factors: age greater than 75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitus), long-term anticoagulation with warfarin is recommended. For patients with AF and mitral stenosis, long-term anticoagulation with warfarin is recommended. For patients with AF and prosthetic heart valves, long-term anticoagulation with warfarin is recommended; the target INR may be increased and aspirin added depending on valve type and position, and on patient factors.
Mechanical and Bioprosthetic Heart Valves
For patients with a bileaflet mechanical valve or a Medtronic Hall (Minneapolis, MN) tilting disk valve in the aortic position who are in sinus rhythm and without left atrial enlargement, therapy with warfarin to a target INR of 2.5 (range, 2 to 3) is recommended. For patients with tilting disk valves and bileaflet mechanical valves in the mitral position, therapy with warfarin to a target INR of 3 (range, 2.5 to 3.5) is recommended. For patients with caged ball or caged disk valves, therapy with warfarin to a target INR of 3 (range, 2.5 to 3.5) is recommended. For patients with a bioprosthetic valve in the mitral position, therapy with warfarin to a target INR of 2.5 (range, 2 to 3) for the first 3 months after valve insertion is recommended. If additional risk factors for thromboembolism are present (AF, previous thromboembolism, left ventricular dysfunction), a target INR of 2.5 (range 2 to 3) is recommended.
Post-Myocardial Infarction
For high-risk patients with MI (e.g., those with a large anterior MI, those with significant heart failure, those with intracardiac thrombus visible on transthoracic echocardiography, those with AF, and those with a history of a thromboembolic event), therapy with combined moderate-intensity (INR, 2 to 3) warfarin plus low-dose aspirin (≤ 100 mg/day) for at least 3 months after the MI is recommended.
Recurrent Systemic Embolism and Other Indications

Oral anticoagulation therapy with warfarin has not been fully evaluated by clinical trials in patients with valvular disease associated with AF, patients with mitral stenosis, and patients with recurrent systemic embolism of unknown etiology. However, a moderate dose regimen (INR 2 to 3) may be used for these patients.

2.3 Initial and Maintenance Dosing

The appropriate initial dosing of warfarin sodium varies widely for different patients. Not all factors responsible for warfarin dose variability are known, and the initial dose is influenced by:
Clinical factors including age, race, body weight, sex, concomitant medications, and comorbidities Genetic factors (CYP2C9 and VKORC1 genotypes) [see Clinical Pharmacology (12.5)].
Select the initial dose based on the expected maintenance dose, taking into account the above factors. Modify this dose based on consideration of patient-specific clinical factors. Consider lower initial and maintenance doses for elderly and/or debilitated patients and in Asian patients [see Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)]. Routine use of loading doses is not recommended as this practice may increase hemorrhagic and other complications and does not offer more rapid protection against clot formation.

Individualize the duration of therapy for each patient. In general, anticoagulant therapy should be continued until the danger of thrombosis and embolism has passed [see Dosage and Administration (2.2)].

Dosage Recommendations without Consideration of Genotype

If the patient’s CYP2C9 and VKORC1 genotypes are not known, the initial dose of warfarin sodium is usually 2 to 5 mg once daily. Determine each patient’s dosing needs by close monitoring of the INR response and consideration of the indication being treated. Typical maintenance doses are 2 to 10 mg once daily.

Dosing Recommendations with Consideration of Genotype

Table 1 displays three ranges of expected maintenance warfarin sodium doses observed in subgroups of patients having different combinations of CYP2C9 and VKORC1 gene variants [see Clinical Pharmacology (12.5)]. If the patient’s CYP2C9 and/or VKORC1 genotype are known, consider these ranges in choosing the initial dose. Patients with CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3 may require more prolonged time (> 2 to 4 weeks) to achieve maximum INR effect for a given dosage regimen than patients without these CYP variants.

Table 1: Three Ranges of Expected Maintenance Warfarin Sodium Daily Doses Based on

CYP2C9 and VKORC1 Genotypes†
VKORC1 CYP2C9 *1/*1 *1/*2 *1/*3 *2/*2 *2/*3 *3/*3 GG 5 to 7 mg 5 to 7 mg 3 to 4 mg 3 to 4 mg 3 to 4 mg 0.5 to 2 mg AG 5 to 7 mg 3 to 4 mg 3 to 4 mg 3 to 4 mg 0.5 to 2 mg 0.5 to 2 mg AA 3 to 4 mg 3 to 4 mg 0.5 to 2 mg 0.5 to 2 mg 0.5 to 2 mg 0.5 to 2 mg
† Ranges are derived from multiple published clinical studies. VKORC1 -1639G > A (rs9923231) variant is used in this table. Other co-inherited VKORC1 variants may also be important determinants of warfarin dose.

2.4Monitoring to Achieve Optimal Anticoagulation

Warfarin sodium is a narrow therapeutic range (index) drug, and its action may be affected by factors such as other drugs and dietary vitamin K. Therefore, anticoagulation must be carefully monitored during warfarin sodium therapy. Determine the INR daily after the administration of the initial dose until INR results stabilize in the therapeutic range. After stabilization, maintain dosing within the therapeutic range by performing periodic INRs. The frequency of performing INR should be based on the clinical situation but generally acceptable intervals for INR determinations are 1 to 4 weeks. Perform additional INR tests when other warfarin products are interchanged with warfarin sodium, as well as whenever other medications are initiated, discontinued, or taken irregularly. Heparin, a common concomitant drug, increases the INR [see Dosage and Administration (2.8) and Drug Interactions (7)].

Determinations of whole blood clotting and bleeding times are not effective measures for monitoring of warfarin sodium therapy.

2.5 Missed Dose

The anticoagulant effect of warfarin sodium persists beyond 24 hours. If a patient misses a dose of warfarin sodium at the intended time of day, the patient should take the dose as soon as possible on the same day. The patient should not double the dose the next day to make up for a missed dose.

2.7 Treatment During Dentistry and Surgery

Some dental or surgical procedures may necessitate the interruption or change in the dose of warfarin sodium therapy. Consider the benefits and risks when discontinuing warfarin sodium even for a short period of time. Determine the INR immediately prior to any dental or surgical procedure. In patients undergoing minimally invasive procedures who must be anticoagulated prior to, during, or immediately following these procedures, adjusting the dosage of warfarin sodium to maintain the INR at the low end of the therapeutic range may safely allow for continued anticoagulation.

2.8 Conversion From Other Anticoagulants

Heparin

Since the full anticoagulant effect of warfarin sodium is not achieved for several days, heparin is preferred for initial rapid anticoagulation. During initial therapy with warfarin sodium, the interference with heparin anticoagulation is of minimal clinical significance. Conversion to warfarin sodium may begin concomitantly with heparin therapy or may be delayed 3 to 6 days. To ensure therapeutic anticoagulation, continue full dose heparin therapy and overlap warfarin sodium therapy with heparin for 4 to 5 days and until warfarin sodium has produced the desired therapeutic response as determined by INR, at which point heparin may be discontinued.

As heparin may affect the INR, patients receiving both heparin and warfarin sodium should have INR monitoring at least:
5 hours after the last intravenous bolus dose of heparin, or 4 hours after cessation of a continuous intravenous infusion of heparin, or 24 hours after the last subcutaneous heparin injection.
Warfarin sodium may increase the activated partial thromboplastin time (aPTT) test, even in the absence of heparin. A severe elevation (> 50 seconds) in aPTT with an INR in the desired range has been identified as an indication of increased risk of postoperative hemorrhage.

Other Anticoagulants

Consult the labeling of other anticoagulants for instructions on conversion to warfarin sodium.
Oxycodone Hydrochloride...

Oxycodone Hydrochloride And Ibuprofen

Carefully consider the potential benefits and risks of oxycodone HCl and ibuprofen tablets and other treatment options before deciding to use oxycodone HCl 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 oxycodone HCl and ibuprofen tablets, the dose and frequency should be adjusted to suit an individual patient's needs.

For the management of acute moderate to severe pain, the recommended dose of oxycodone HCl and ibuprofen tablets is one tablet given orally.

Dosage should not exceed 4 tablets in a 24-hour period and should not exceed 7 days.
Jolessa

Jolessa

Although the occurrence of pregnancy is unlikely if Jolessa is taken according to directions, if withdrawal bleeding does not occur while taking white (inactive) tablets, the possibility of pregnancy must be considered. Appropriate diagnostic measures to rule out pregnancy should be taken at the time of any missed menstrual period. Jolessa should be discontinued if pregnancy is confirmed.

The dosage of Jolessa is one pink (active) tablet daily for 84 consecutive days, followed by 7 days of white (inert) tablets. To achieve maximum contraceptive effectiveness, Jolessa must be taken exactly as directed and at intervals not exceeding 24 hours. Ideally, the tablets should be taken at the same time of the day on each day of active treatment. The tablets should not be removed from the protective blister packaging to avoid damage to the product. The dispenser card should be kept in the foil pouch until dispensed to the patient.

During the first cycle of medication, the patient is instructed to begin taking Jolessa on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (pink) is taken that day. One pink tablet should be taken daily for 84 consecutive days, followed by 7 days on which a white (inert) tablet is taken. Withdrawal bleeding should occur during the 7 days following discontinuation of pink active tablets. During the first cycle, contraceptive reliance should not be placed on Jolessa until a pink (active) tablet has been taken daily for 7 consecutive days and a non-hormonal back-up method of birth control (such as condoms or spermicide) should be used during those 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient begins her next and all subsequent 91-day courses of tablets without interruption on the same day of the week (Sunday) on which she began her first course, following the same schedule: 84 days on which pink tablets are taken followed by 7 days on which white tablets are taken. If in any cycle the patient starts tablets later than the proper day, she should protect herself against pregnancy by using a non-hormonal back-up method of birth control until she has taken a pink tablet daily for 7 consecutive days.

If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding may be transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her healthcare provider.

For patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the DETAILED PATIENT LABELING. Any time the patient misses two or more pink tablets, she should also use another method of nonhormonal back-up contraception until she has taken a pink tablet daily for seven consecutive days. If the patient misses one or more white tablets, she is still protected against pregnancy provided she begins taking pink tablets again on the proper day. The possibility of ovulation increases with each successive day that scheduled pink tablets are missed. The risk of pregnancy increases with each active (pink) tablet missed.

In the nonlactating mother, Jolessa may be initiated no earlier than day 28 postpartum, for contraception due to the increased risk for thromboembolism. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (See CONTRAINDICATIONS, WARNINGS and PRECAUTIONS concerning thromboembolic disease). The patient should be advised to use a nonhormonal back-up method for the first 7 days of tablet-taking. However, if intercourse has already occurred, the possibility of ovulation and conception prior to initiation of medication should be considered. Jolessa may be initiated immediately after a first-trimester abortion; if the patient starts Jolessa immediately, additional contraceptive measures are not needed.
Demeclocycline Hydrochl...

Demeclocycline Hydrochloride

Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided.

Concomitant Therapy

Absorption of tetracycline is impaired by antacids containing aluminum, calcium, or magnesium, and by iron-containing preparations. Foods and some dairy products also interfere with absorption. Oral forms of tetracycline should be given at least 1 hour before or 2 hours after meals.

In Patients With Renal Impairment

(See WARNINGS). Tetracyclines should be used cautiously in patients with impaired renal function. Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.

In Patients With Liver Impairment

Tetracyclines should be used cautiously in patients with impaired liver function. Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses. Administration of adequate amounts of fluid with the oral formulations of tetracyclines is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration (see ADVERSE REACTIONS).

Adults

Usual Daily Dose

Four divided doses of 150 mg each or two divided doses of 300 mg each.

For Pediatric Patients Above Eight Years of Age

Usual daily dose, 7 to 13 mg per kg body weight per day, depending upon the severity of the disease, divided into two to four doses not to exceed adult dosage of 600 mg per day.

Gonorrhea patients sensitive to penicillin may be treated with demeclocycline administered as an initial oral dose of 600 mg followed by 300 mg every 12 hours for four days to a total of 3 grams.
Allergena Zone 2

Allergena Zone 2

2.1 How to Start Sprintec

Sprintec is dispensed in a blister pack tablet dispenser [see HowSupplied/Storage and Handling (16)]. Sprintec 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 Sprintec

Table 1: Instructions for Administration of Sprintec

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:
• Sprintec active tablets are blue (Day 1 to Day 21). • Sprintec has white 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 white 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 Sprintec. • Take subsequent active tablets once daily at the same time each day for a total of 21 days. • Take one white 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 Sprintec 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 Sprintec

Start Sprintec:
• 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
Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.

Starting Sprintec after Abortion or Miscarriage

First-trimester
• After a first-trimester abortion or miscarriage, Sprintec may be started immediately. An additional method of contraception is not needed if Sprintec is started immediately. • If Sprintec 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 Sprintec.
Second-trimester
• Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Sprintec, 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 Sprintec. [See Contraindications (4), Warnings and Precautions (5.1), and FDA-Approved Patient Labeling.]
Starting Sprintec after Childbirth
• Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Sprintec following the instructions in Table 1 for women not currently using hormonal contraception. • Sprintec is 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 Sprintec. [See Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 and 8.3), and FDA-Approved Patient Labeling].
There are two ways to start taking birth-control pills, Sunday Start or Day 1 Start. Your healthcare professional will tell you which to use.

How to Use Blister Cards for the 28 Tablets
1. Pick the Days of the Week Sticker that starts the first day of your period. (This is the day you begin bleeding or spotting, even if it is midnight when bleeding begins.) When you have picked the right sticker, throw away the others and place the sticker on the blister card over the pre-printed days of the week and make sure it lines up with the pills. 2. Your blister package consists of three parts, the foil pouch, wallet, and a blister pack containing 28 individually sealed pills. Note that the pills are arranged in four numbered rows of 7 pills, with the pre-printed days of the week printed above them. All 21 blue pills are “active” birth-control pills, and 7 white “reminder” pills. Refer to the sample of the blister card below: 3. After taking the last white pill, start a new blister card the very next day no matter when your period started. You will be taking a pill every day without interruption. Any time you start the pills later than directed, protect yourself by using another method of birth control until you have taken a pill a day for seven consecutive days. After taking the last white pill, start taking the first blue pill from the blister card the very next day. 4. Take the pills in each new package as before. Start with the blue pill on row #1 and take one pill each day, left to right, until the last white pill has been taken.
Three Ways to Remember in What Order to Take the Pills
1. Follow the sticker with the days of the week (placed above the pills). 2. Always go from left to right. 3. Always finish all your blue pills.
2.3 Missed Tablets

Table 2: Instructions for Missed Sprintec 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 [seeFDA-Approved Patient Labeling].
Quinapril Hydrochloride...

Quinapril Hydrochloride And Hydrochlorothiazide

Amphetamines should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of the resulting insomnia.

Narcolepsy

Usual dose is 5 to 60 mg per day in divided doses, depending on the individual patient response.

Narcolepsy seldom occurs in children under 12 years of age; however, when it does, dextroamphetamine sulfate extended-release capsules may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until an optimal response is obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until an optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Extended-release capsules may be used for once-a-day dosage wherever appropriate.

Attention Deficit Disorder with Hyperactivity

The dextroamphetamine sulfate extended-release capsule formulation is not recommended for pediatric patients younger than 6 years of age.

In pediatric patients 6 years of age and older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg per day.

Extended-release capsules may be used for once-a-day dosage wherever appropriate.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.
Ocella

Ocella

2.1 How to Take OCELLA

Take one tablet by mouth at the same time every day. The failure rate may increase when pills are missed or taken incorrectly.

To achieve maximum contraceptive effectiveness, OCELLA must be taken as directed, in the order directed on the blister pack. Single missed pills should be taken as soon as remembered.

2.2 How to Start OCELLA

Instruct the patient to begin taking OCELLA either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start).

Day 1 Start

During the first cycle of OCELLA use, instruct the patient to take one yellow OCELLA daily, beginning on Day 1 of her menstrual cycle. (The first day of menstruation is Day 1.) She should take one yellow OCELLA daily for 21 consecutive days, followed by one white tablet daily on Days 22 through 28. OCELLA should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. OCELLA can be taken without regard to meals. If OCELLA is first taken later than the first day of the menstrual cycle, OCELLA should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

Sunday Start

During the first cycle of OCELLA use, instruct the patient to take one yellow OCELLA daily, beginning on the first Sunday after the onset of her menstrual period. She should take one yellow OCELLA daily for 21 consecutive days, followed by one white tablet daily on Days 22 through 28. OCELLA should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. OCELLA can be taken without regard to meals. OCELLA should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient should begin her next and all subsequent 28-day regimens of OCELLA on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her yellow tablets on the next day after ingestion of the last white tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of OCELLA is started later than the day following administration of the last white tablet, the patient should use another method of contraception until she has taken a yellow OCELLA daily for seven consecutive days.

When switching from a different birth control pill

When switching from another birth control pill, OCELLA should be started on the same day that a new pack of the previous oral contraceptive would have been started.

When switching from a method other than a birth control pill

When switching from a transdermal patch or vaginal ring, OCELLA should be started when the next application would have been due. When switching from an injection, OCELLA should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, OCELLA should be started on the day of removal.

Withdrawal bleeding usually occurs within 3 days following the last yellow tablet. If spotting or breakthrough bleeding occurs while taking OCELLA, instruct the patient to continue taking OCELLA by the regimen described above. Counsel her that this type of bleeding is usually transient and without significance; however, advise her that if the bleeding is persistent or prolonged, she should consult her healthcare provider.

Although the occurrence of pregnancy is low if OCELLA is taken according to directions, if withdrawal bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy. Discontinue OCELLA if pregnancy is confirmed.

The risk of pregnancy increases with each active yellow tablet missed. For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the FDA-Approved Patient Labeling. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more white tablets, she should still be protected against pregnancy provided she begins taking a new cycle of yellow tablets on the proper day.

For postpartum women who do not breastfeed or after a second trimester abortion, start OCELLA no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts OCELLA postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken OCELLA for 7 consecutive days.

2.3 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 occurs within 3-4 hours after tablet-taking, this can be regarded as a missed tablet.
Clonidine Patch

Clonidine Patch

Apply clonidine transdermal system USP 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 USP 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 USP dosage should be titrated according to individual therapeutic requirements, starting with clonidine transdermal system USP 0.1 mg. If after one or two weeks the desired reduction in blood pressure is not achieved, increase the dosage by adding another clonidine transdermal system USP 0.1 mg or changing to a larger system. An increase in dosage above two clonidine transdermal system USP 0.3 mg is usually not associated with additional efficacy.

When substituting clonidine transdermal system USP for oral clonidine or for other antihypertensive drugs, physicians should be aware that the antihypertensive effect of clonidine transdermal system USP 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.
Mefloquine Hydrochlorid...

Mefloquine Hydrochloride

Malaria Treatment in Adults

Treatment of mild to moderate malaria in adults caused by mefloquine-susceptible strains of P. falciparum or by P. vivax: Dosage: Five tablets (1250 mg) mefloquine hydrochloride to be given as a single oral dose. The drug should not be taken on an empty stomach and should be administered with at least 8 oz (240 mL) of water.

If a full-treatment course with mefloquine does not lead to improvement within 48 to 72 hours, mefloquine should not be used for retreatment. An alternative therapy should be used. Similarly, if previous prophylaxis with mefloquine failed, mefloquine should not be used for curative treatment (see INDICATIONS AND USAGE).

Note: Patients with acute P. vivax malaria, treated with mefloquine, are at high risk of relapse because mefloquine does not eliminate exoerythrocytic (hepatic phase) parasites. To avoid relapse after initial treatment of the acute infection with mefloquine, patients should subsequently be treated with an 8-aminoquinoline derivative (e.g., primaquine).

Malaria Prophylaxis in Adults

Dosage: One 250 mg mefloquine hydrochloride tablet once weekly.

Prophylactic drug administration should begin 1 week before arrival in an endemic area. Subsequent weekly doses should be taken regularly, always on the same day of each week, preferably after the main meal. To reduce the risk of malaria after leaving an endemic area, prophylaxis must be continued for 4 additional weeks to ensure suppressive blood levels of the drug when merozoites emerge from the liver. Tablets should not be taken on an empty stomach and should be administered with at least 8 oz (240 mL) of water.

In certain cases, e.g., when a traveler is taking other medication, it may be desirable to start prophylaxis 2 to 3 weeks prior to departure, in order to ensure that the combination of drugs is well tolerated (see PRECAUTIONS, Drug Interactions).

When prophylaxis with mefloquine fails, physicians should carefully evaluate which antimalarial to use for therapy.

Malaria Treatment in Pediatric Patients

Treatment of mild to moderate malaria in pediatric patients caused by mefloquine-susceptible strains of P. falciparum: Dosage: 20 to 25 mg/kg body weight. Splitting the total therapeutic dose into 2 doses taken 6 to 8 hours apart may reduce the occurrence or severity of adverse effects. The pediatric dose should not exceed the adult dose.

Experience with mefloquine in pediatric patients weighing less than 20 kg is limited.

The drug should not be taken on an empty stomach and should be administered with ample water. The tablets may be crushed and suspended in a small amount of water, milk or other beverage for administration to small children and other persons unable to swallow them whole.

If a full-treatment course with mefloquine does not lead to improvement within 48 to 72 hours, mefloquine should not be used for retreatment. An alternative therapy should be used. Similarly, if previous prophylaxis with mefloquine has failed, mefloquine should not be used for curative treatment.

In pediatric patients, the administration of mefloquine for the treatment of malaria has been associated with early vomiting. In some cases, early vomiting has been cited as a possible cause of treatment failure (see PRECAUTIONS). If a significant loss of drug product is observed or suspected because of vomiting, a second full dose of mefloquine should be administered to patients who vomit less than 30 minutes after receiving the drug. If vomiting occurs 30 to 60 minutes after a dose, an additional half-dose should be given. If vomiting recurs, the patient should be monitored closely and alternative malaria treatment considered if improvement is not observed within a reasonable period of time.

The safety and effectiveness of mefloquine to treat malaria in pediatric patients below the age of 6 months have not been established.

Malaria Prophylaxis in Pediatric Patients

The recommended prophylactic dose of mefloquine is approximately 5 mg/kg body weight once weekly. One 250 mg mefloquine hydrochloride tablet should be taken once weekly in pediatric patients weighing over 45 kg. In pediatric patients weighing less than 45 kg, the weekly dose decreases in proportion to body weight:

30 to 45 kg: 3/4 tablet

20 to 30 kg: 1/2 tablet

Experience with mefloquine in pediatric patients weighing less than 20 kg is limited.
Desoximetasone

Desoximetasone

2.1 How to Start Tri-Sprintec

Tri-Sprintec is dispensed in a blister pack tablet dispenser [see How Supplied/Storage and Handling (16)]. Tri-Sprintec 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 Tri-Sprintec

Table 1: Instructions for Administration of Tri-Sprintec

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:
• Tri-Sprintec active tablets are gray (Day 1 to Day 7), light blue (Day 8 to Day 15) and blue (Day 16 to Day 21). • Tri-Sprintec has white 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 white 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 Tri-Sprintec. • Take subsequent active tablets once daily at the same time each day for a total of 21 days. • Take one white 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 Tri-Sprintec 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 Tri-Sprintec

Start Tri-Sprintec:
• 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
Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.

Starting Tri-Sprintecafter Abortion or Miscarriage

First-trimester
• After a first-trimester abortion or miscarriage, Tri-Sprintec may be started immediately. An additional method of contraception is not needed if Tri-Sprintec is started immediately. • If Tri-Sprintec 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 Tri-Sprintec.
Second-trimester
• Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Tri-Sprintec, 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 Tri-Sprintec. [See Contraindications (4), Warnings and Precautions (5.1), and FDA-Approved Patient Labeling.]
Starting Tri-Sprintec after Childbirth
• Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Tri-Sprintec following the instructions in Table 1 for women not currently using hormonal contraception. • Tri-Sprintec is 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 Tri-Sprintec. [See Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 and 8.3), and FDA-Approved Patient Labeling].
How to Use the Blister Cards

There are two ways to start taking birth control pills, Sunday Start or Day 1 Start. Your healthcare professional will tell you which to use.
1. Pick the Days of the Week Sticker that starts the first day of your period. (This is the day you begin bleeding or spotting, even if it is midnight when bleeding begins.) When you have picked the right sticker, throw away the others and place the sticker on the blister card over the pre-printed days of the week and make sure it lines up with the pills. 2. Your blister package consists of three parts, the foil pouch, wallet, and a blister pack containing 28 individually sealed pills. Note that the pills are arranged in four numbered rows of 7 pills, with the pre-printed days of the week printed above them. There are 7 gray “active” pills, 7 light blue “active” pills, 7 blue “active” pills, and 7 white “reminder” pills. Refer to the sample of the blister card below: 3. After taking the last white pill, start a new blister card the very next day no matter when your period started. You will be taking a pill every day without interruption. Anytime you start the pills later than directed, protect yourself by using another method of birth control until you have taken a pill a day for seven consecutive days. After taking the last white pill, start taking the first gray pill from the blister card the very next day. 4. Take the pills in each new package as before. Start with the gray pill on row #1 and take one pill each day, left to right, until the last white pill has been taken.
Three Ways to Remember in What Order to take the Pills
1. Follow the sticker with the days of the week (placed above the pills). 2. Always go from left to right. 3. Always finish all your pills.
2.3 Missed Tablets

Table 2: Instructions for Missed Tri-Sprintec 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 [seeFDA-Approved Patient Labeling].

2.5 Tri-Sprintec Use for Acne

The timing of initiation of dosing with Tri-Sprintecfor acne should follow the guidelines for use of Tri-Sprintec as an oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section (2.1) for instructions.
Clonazepam

Clonazepam

Clonazepam orally disintegrating tablets should be administered as follows: Peel back the foil on the blister. Do not push tablet through foil. Immediately upon opening the blister, using dry hands, remove the tablet and place it in the mouth. Tablet disintegration occurs rapidly in saliva so it can be easily swallowed with or without water.

Seizure Disorders

Adults

The initial dose for adults with seizure disorders should not exceed 1.5 mg/day divided into three doses. Dosage may be increased in increments of 0.5 to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase. Maintenance dosage must be individualized for each patient depending upon response. Maximum recommended daily dose is 20 mg.

The use of multiple anticonvulsants may result in an increase of depressant adverse effects. This should be considered before adding clonazepam orally disintegrating tablets to an existing anticonvulsant regimen.

Pediatric Patients

Clonazepam orally disintegrating tablets are administered orally. In order to minimize drowsiness, the initial dose for infants and children (up to 10 years of age or 30 kg of body weight) should be between 0.01 and 0.03 mg/kg/day but not to exceed 0.05 mg/kg/day given in two or three divided doses. Dosage should be increased by no more than 0.25 to 0.5 mg every third day until a daily maintenance dose of 0.1 to 0.2 mg/kg of body weight has been reached, unless seizures are controlled or side effects preclude further increase. Whenever possible, the daily dose should be divided into three equal doses. If doses are not equally divided, the largest dose should be given before retiring.

Geriatric Patients

There is no clinical trial experience with clonazepam orally disintegrating tablets in seizure disorder patients 65 years of age and older. In general, elderly patients should be started on low doses of clonazepam orally disintegrating tablets and observed closely (see PRECAUTIONS, Geriatric Use).

Panic Disorder

Adults

The initial dose for adults with panic disorder is 0.25 mg bid. An increase to the target dose for most patients of 1 mg/day may be made after 3 days. The recommended dose of 1 mg/day is based on the results from a fixed dose study in which the optimal effect was seen at 1 mg/day. Higher doses of 2, 3 and 4 mg/day in that study were less effective than the 1 mg/day dose and were associated with more adverse effects. Nevertheless, it is possible that some individual patients may benefit from doses of up to a maximum dose of 4 mg/day, and in those instances, the dose may be increased in increments of 0.125 to 0.25 mg bid every 3 days until panic disorder is controlled or until side effects make further increases undesired. To reduce the inconvenience of somnolence, administration of one dose at bedtime may be desirable.

Treatment should be discontinued gradually, with a decrease of 0.125 mg bid every 3 days, until the drug is completely withdrawn.

There is no body of evidence available to answer the question of how long the patient treated with clonazepam should remain on it. Therefore, the physician who elects to use clonazepam orally disintegrating tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

Pediatric Patients

There is no clinical trial experience with clonazepam orally disintegrating tablets in panic disorder patients under 18 years of age.

Geriatric Patients

There is no clinical trial experience with clonazepam orally disintegrating tablets in panic disorder patients 65 years of age and older. In general, elderly patients should be started on low doses of clonazepam orally disintegrating tablets and observed closely (see PRECAUTIONS, Geriatric Use).
Aranelle

Aranelle

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 light yellow tablet is then taken on Day 1. For a SUNDAY START when menstrual flow begins on or before Sunday, the first light yellow tablet is taken on that day. With either a DAY 1 START or SUNDAY START, 1 light yellow tablet is taken for 7 days, then 1 white tablet for 9 days, then 1 light yellow tablet for 5 days, then 1 peach 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.

INSTRUCTIONS TO PATIENTS
• To achieve maximum contraceptive effectiveness, the oral contraceptive pill must be taken exactly as directed and at intervals not exceeding 24 hours. • Important: Women should be instructed to use an additional method of protection until after the first 7 days of administration in the initial cycle. • Due to the normally increased risk of thromboembolism occurring postpartum, women should be instructed not to initiate treatment with oral contraceptives earlier than 4 weeks after a full-term delivery. If pregnancy is terminated in the first 12 weeks, the patient should be instructed to start oral contraceptives immediately or within 7 days. If pregnancy is terminated after 12 weeks, the patient should be instructed to start oral contraceptives after 2 weeks. 33,77 • If spotting or breakthrough bleeding should occur, the patient should continue the medication according to the schedule. Should spotting or breakthrough bleeding persist, the patient should notify her physician. • If the patient misses 1 pill, she should be instructed to take it as soon as she remembers and then take the next pill at the regular time. The patient should be advised that missing a pill can cause spotting or light bleeding and that she may be a little sick to her stomach on the days she takes the missed pill with her regularly scheduled pill. If the patient has missed more than one pill, see DETAILED PATIENT LABELING, HOW TO TAKE THE PILL,WHAT TO DO IF YOU MISS PILLS. • 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 2 consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.
Ethambutol Hydrochlorid...

Ethambutol Hydrochloride

Ethambutol hydrochloride should not be used alone, in initial treatment or in retreatment. Ethambutol hydrochloride should be administered on a once every 24-hour basis only. Absorption is not significantly altered by administration with food. Therapy, in general, should be continued until bacteriological conversion has become permanent and maximal clinical improvement has occurred.

Ethambutol hydrochloride is not recommended for use in pediatric patients under thirteen years of age since safe conditions for use have not been established.

Initial Treatment

In patients who have not received previous antituberculous therapy, administer ethambutol hydrochloride 15 mg/kg (7 mg/lb) of body weight, as a single oral dose once every 24 hours. In the more recent studies, isoniazid has been administered concurrently in a single, daily, oral dose.

Retreatment

In patients who have received previous antituberculous therapy, administer ethambutol hydrochloride 25 mg/kg (11 mg/lb) of body weight, as a single oral dose once every 24 hours. Concurrently administer at least one other antituberculous drug to which the organisms have been demonstrated to be susceptible by appropriate in vitro tests. Suitable drugs usually consist of those not previously used in the treatment of the patient. After 60 days of ethambutol hydrochloride administration, decrease the dose to 15 mg/kg (7 mg/lb) of body weight, and administer as a single oral dose once every 24 hours.

During the period when a patient is on a daily dose of 25 mg/kg, monthly eye examinations are advised.

See Table for easy selection of proper weight-dose tablet(s).
Weight-Dose Table 15 mg/kg (7 mg/lb) Schedule Weight Range Daily Dose Pounds Kilograms In mg Under 85 lbs Under 37 kg 500 85 to 94.5 37 to 43 600 95 to 109.5 43 to 50 700 110 to 124.5 50 to 57 800 125 to 139.5 57 to 64 900 140 to 154.5 64 to 71 1000 155 to 169.5 71 to 79 1100 170 to 184.5 79 to 84 1200 185 to 199.5 84 to 90 1300 200 to 214.5 90 to 97 1400 215 and Over Over 97 1500 25 mg/kg (11 mg/lb) Schedule Under 85 lbs Under 38 kg 900 85 to 92.5 38 to 42 1000 93 to 101.5 42 to 45.5 1100 102 to 109.5 45.5 to 50 1200 110 to 118.5 50 to 54 1300 119 to128.5 54 to 58 1400 129 to 136.5 58 to 62 1500 137 to 146.5 62 to 67 1600 147 to 155.5 67 to 71 1700 156 to 164.5 71 to 75 1800 165 to 173.5 75 to 79 1900 174 to 182.5 79 to 83 2000 183 to 191.5 83 to 87 2100 192 to 199.5 87 to 91 2200 200 to 209.5 91 to 95 2300 210 to 218.5 95 to 99 2400 219 and Over Over 99 2500
Leucovorin Calcium

Leucovorin Calcium

Leucovorin calcium tablets are intended for oral administration. Because absorption is saturable, oral administration of doses greater than 25 mg is not recommended.

Impaired Methotrexate Elimination or Inadvertent Overdosage

Leucovorin rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion (see WARNINGS). Leucovorin 15 mg (10 mg/m2) should be administered IM, IV, or PO every 6 hours until serum methotrexate level is less than 10 -8 M. In the presence of gastrointestinal toxicity, nausea, or vomiting, leucovorin should be administered parenterally.

Serum creatinine and methotrexate levels should be determined at 24 hour intervals. If the 24 hour serum creatinine has increased 50% over baseline or if the 24 hour methotrexate level is greater than 5 x 10 -6 M or the 48 hour level is greater than 9 x 10 -7 M, the dose of leucovorin should be increased to 150 mg (100 mg/m2) IV every 3 hours until the methotrexate level is less than 10 -8 M. Doses greater then 25 mg should be given parenterally (see CLINICAL PHARMACOLOGY).

Hydration (3 L/d) and urinary alkalinization with sodium bicarbonate should be employed concomitantly. The bicarbonate dose should be adjusted to maintain the urine pH at 7 or greater.

The recommended dose of leucovorin to counteract hematologic toxicity from folic acid antagonists with less affinity for mammalian dihydrofolate reductase than methotrexate (i.e., trimethoprim, pyrimethamine) is substantially less, and 5 to 15 mg of leucovorin per day has been recommended by some investigators.

Patients who experience delayed early methotrexate elimination are likely to develop reversible non-oliguric renal failure. In addition to appropriate leucovorin therapy, these patients require continuing hydration and urinary alkalinization, and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved.

Some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration, which are significant but less severe. These abnormalities may or may not be associated with significant clinical toxicity. If significant clinical toxicity is observed, leucovorin rescue should be extended for an additional 24 hours (total 14 doses over 84 hours) in subsequent courses of therapy. The possibility that the patient is taking other medications which interact with methotrexate (e.g., medications which may interfere with methotrexate elimination or binding to serum albumin) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed.
Fluoxetine

Fluoxetine

2.1 Major Depressive Disorder

Initial Treatment

Adult — In controlled trials used to support the efficacy of fluoxetine, patients were administered morning doses ranging from 20 to 80 mg/day. Studies comparing fluoxetine 20, 40, and 60 mg/day to placebo indicate that 20 mg/day is sufficient to obtain a satisfactory response in Major Depressive Disorder in most cases. Consequently, a dose of 20 mg/day, administered in the morning, is recommended as the initial dose.

A dose increase may be considered after several weeks if insufficient clinical improvement is observed. Doses above 20 mg/day may be administered on a once-a-day (morning) or BID schedule (i.e., morning and noon) and should not exceed a maximum dose of 80 mg/day.

Pediatric (children and adolescents) — In the short-term (8 to 9 week) controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Major Depressive Disorder, patients were administered fluoxetine doses of 10 to 20 mg/day [see Clinical Studies (14.1)]. Treatment should be initiated with a dose of 10 or 20 mg/day. After 1 week at 10 mg/day, the dose should be increased to 20 mg/day.

However, due to higher plasma levels in lower weight children, the starting and target dose in this group may be 10 mg/day. A dose increase to 20 mg/day may be considered after several weeks if insufficient clinical improvement is observed.

All patients — As with other drugs effective in the treatment of Major Depressive Disorder, the full effect may be delayed until 4 weeks of treatment or longer.

Maintenance/Continuation/Extended Treatment — It is generally agreed that acute episodes of Major Depressive Disorder require several months or longer of sustained pharmacologic therapy. Whether the dose needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.

Daily Dosing — Systematic evaluation of fluoxetine in adult patients has shown that its efficacy in Major Depressive Disorder is maintained for periods of up to 38 weeks following 12 weeks of open-label acute treatment (50 weeks total) at a dose of 20 mg/day [see Clinical Studies (14.1)].

Switching Patients to a Tricyclic Antidepressant (TCA) — Dosage of a TCA may need to be reduced, and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Drug Interactions (7.9)].

Switching Patients to or From a Monoamine Oxidase Inhibitor (MAOI) — At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with fluoxetine. In addition, at least 5 weeks, perhaps longer, should be allowed after stopping fluoxetine before starting an MAOI [see Contraindications (4) and Drug Interactions (7.1)].

2.2 Obsessive-Compulsive Disorder

Initial Treatment

Adult — In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fixed daily doses of 20, 40, or 60 mg of fluoxetine or placebo [see Clinical Studies (14.2)]. In one of these studies, no dose-response relationship for effectiveness was demonstrated. Consequently, a dose of 20 mg/day, administered in the morning, is recommended as the initial dose. Since there was a suggestion of a possible dose-response relationship for effectiveness in the second study, a dose increase may be considered after several weeks if insufficient clinical improvement is observed. The full therapeutic effect may be delayed until 5 weeks of treatment or longer.

Doses above 20 mg/day may be administered on a once daily (i.e., morning) or BID schedule (i.e., morning and noon). A dose range of 20 to 60 mg/day is recommended; however, doses of up to 80 mg/day have been well tolerated in open studies of OCD. The maximum fluoxetine dose should not exceed 80 mg/day.

Pediatric (children and adolescents) — In the controlled clinical trial of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fluoxetine doses in the range of 10 to 60 mg/day [see Clinical Studies (14.2)].

In adolescents and higher weight children, treatment should be initiated with a dose of 10 mg/day. After 2 weeks, the dose should be increased to 20 mg/day. Additional dose increases may be considered after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 60 mg/day is recommended.

In lower weight children, treatment should be initiated with a dose of 10 mg/day. Additional dose increases may be considered after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 30 mg/day is recommended. Experience with daily doses greater than 20 mg is very minimal, and there is no experience with doses greater than 60 mg.

Maintenance/Continuation Treatment — While there are no systematic studies that answer the question of how long to continue fluoxetine, OCD is a chronic condition and it is reasonable to consider continuation for a responding patient. Although the efficacy of fluoxetine after 13 weeks has not been documented in controlled trials, adult patients have been continued in therapy under double-blind conditions for up to an additional 6 months without loss of benefit. However, 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 treatment.

2.3 Bulimia Nervosa

Initial Treatment — In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Bulimia Nervosa, patients were administered fixed daily fluoxetine doses of 20 or 60 mg, or placebo [see Clinical Studies (14.3)]. Only the 60 mg dose was statistically significantly superior to placebo in reducing the frequency of binge-eating and vomiting. Consequently, the recommended dose is 60 mg/day, administered in the morning. For some patients it may be advisable to titrate up to this target dose over several days. Fluoxetine doses above 60 mg/day have not been systematically studied in patients with bulimia.

Maintenance/Continuation Treatment — Systematic evaluation of continuing fluoxetine 60 mg/day for periods of up to 52 weeks in patients with bulimia who have responded while taking fluoxetine 60 mg/day during an 8 week acute treatment phase has demonstrated a benefit of such maintenance treatment [see Clinical Studies (14.3)]. Nevertheless, patients should be periodically reassessed to determine the need for maintenance treatment.

2.4 Panic Disorder

Initial Treatment — In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Panic Disorder, patients were administered fluoxetine doses in the range of 10 to 60 mg/day [see Clinical Studies (14.4)]. Treatment should be initiated with a dose of 10 mg/day. After one week, the dose should be increased to 20 mg/day. The most frequently administered dose in the 2 flexible-dose clinical trials was 20 mg/day.

A dose increase may be considered after several weeks if no clinical improvement is observed. Fluoxetine doses above 60 mg/day have not been systematically evaluated in patients with Panic Disorder.

Maintenance/Continuation Treatment — While there are no systematic studies that answer the question of how long to continue fluoxetine, panic disorder is a chronic condition and it is reasonable to consider continuation for a responding patient. Nevertheless, patients should be periodically reassessed to determine the need for continued treatment.

2.5 Fluoxetine and Olanzapine in Combination: Depressive Episodes Associated with Bipolar I Disorder

When using fluoxetine and olanzapine in combination, also refer to the Clinical Studies section of the package insert for olanzapine and fluoxetine hydrochloride capsules.

Fluoxetine should be administered in combination with oral olanzapine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20 mg of fluoxetine. Dosage adjustments, if indicated, can be made according to efficacy and tolerability within dose ranges of fluoxetine 20 to 50 mg and oral olanzapine 5 to 12.5 mg. Antidepressant efficacy was demonstrated with olanzapine and fluoxetine in combination with a dose range of olanzapine 6 to 12 mg and fluoxetine 25 to 50 mg.

Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of olanzapine and fluoxetine hydrochloride capsules (fixed-dose combination of olanzapine and fluoxetine). Olanzapine and fluoxetine hydrochloride capsules are dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. The following table demonstrates the appropriate individual component doses of fluoxetine and olanzapine versus olanzapine and fluoxetine hydrochloride capsules. Dosage adjustments, if indicated, should be made with the individual components according to efficacy and tolerability.
Table 1: Approximate Dose Correspondance Between Olanzapine and Fluoxetine Hydrochloride Capsules1 and the Combination of Fluoxetine and Olanzapine For Olanzapine and Fluoxetine Hydrochloride Capsules Use in Combination Olanzapine (mg/day) Fluoxetine (mg/day) 3 mg olanzapine/25 mg fluoxetine 2.5 20 6 mg olanzapine/25 mg fluoxetine 5 20 12 mg olanzapine/25 mg fluoxetine 10 + 2.5 20 6 mg olanzapine/50 mg fluoxetine 5 40 + 10 12 mg olanzapine/50 mg fluoxetine 10 + 2.5 40 + 10
1 Olanzapine and fluoxetine hydrochloride capsules are a fixed-dose combination of fluoxetine and olanzapine.

While there is no body of evidence to answer the question of how long a patient treated with fluoxetine and olanzapine in combination should remain on it, it is generally accepted that Bipolar I Disorder, including the depressive episodes associated with Bipolar I Disorder, is a chronic illness requiring chronic treatment. The physician should periodically re-examine the need for continued pharmacotherapy.

Safety of coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies.

Fluoxetine monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder.

2.7 Dosing in Specific Populations

Treatment of pregnant Women During the Third Trimester — When treating pregnant women with fluoxetine during the third trimester, the physician should carefully consider the potential risks and potential benefits of treatment. Neonates exposed to SNRIs or SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. The physician may consider tapering fluoxetine in the third trimester [see Use in Specific Populations (8.1)].

Geriatrics — A lower or less frequent dosage should be considered for the elderly [see Use in Specific Populations (8.5)]

Hepatic Impairment — As with many other medications, a lower or less frequent dosage should be used in patients with hepatic impairment [see Clinical Pharmacology (12.4) and Use in Specific Populations (8.6)].

Concomitant Illness — Patients with concurrent disease or on multiple concomitant medications may require dosage adjustments [see Clinical Pharmacology (12.4) and Warnings and Precautions (5.10)].

Fluoxetine and Olanzapine in Combination – The starting dose of oral olanzapine 2.5 to 5 mg with fluoxetine 20 mg should be used for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of olanzapine or fluoxetine in combination (female gender, geriatric age, nonsmoking status), or those patients who may be pharmacodynamically sensitive to olanzapine. Dosing modifications may be necessary in patients who exhibit a combination of factors that may slow metabolism. When indicated, dose escalation should be performed with caution in these patients. Fluoxetine and olanzapine in combination have not been systematically studied in patients over 65 years of age or in patients less than 18 years of age [see Warnings and Precautions (5.14) and Drug Interactions (7.9)].

2.8 Discontinuation of Treatment

Symptoms associated with discontinuation of fluoxetine, SNRIs, and SSRIs, have been reported [see Warnings and Precautions (5.13)].
Trazodone Hydrochloride...

Trazodone Hydrochloride

The dosage should be initiated at a low-dose and increased gradually, noting the clinical response and any evidence of intolerance. Occurrence of drowsiness may require the administration of a major portion of the daily dose at bedtime or a reduction of dosage. Trazodone hydrochloride tablets should be taken shortly after a meal or light snack.

Dose Selection

An initial dose of 150 mg/day in divided doses is suggested. The dose may be increased by 50 mg/day every 3 to 4 days. The maximum dose for outpatients usually should not exceed 400 mg/day in divided doses. Inpatients (i.e., more severely depressed patients) may be given up to but not in excess of 600 mg/day in divided doses.
• Once an adequate response has been achieved, dosage may be gradually reduced, with subsequent adjustment depending on therapeutic response. • Patients should be monitored for withdrawal symptoms when discontinuing treatment with trazodone hydrochloride tablets. The dose should be gradually reduced whenever possible [see Warnings and Precautions (5.13)].
Maintenance Treatment

The efficacy of trazodone hydrochloride tablets for the maintenance treatment of MDD has not been evaluated. While there is no body of evidence available to answer the question of how long a patient treated with trazodone hydrochloride tablets should continue the drug, it is generally recommended that treatment be continued for several months after an initial response. Patients should be maintained on the lowest effective dose and be periodically reassessed to determine the continued need for maintenance treatment.

Important Administration Instructions

Trazodone hydrochloride tablets are scored to provide flexibility in dosing.

Trazodone hydrochloride tablets can be swallowed whole or administered as a half tablet by breaking the tablet along the score line.
Danazol

Danazol

Endometriosis

In moderate to severe disease, or in patients infertile due to endometriosis, a starting dose of 800 mg given in two divided doses is recommended. Amenorrhea and rapid response to painful symptoms is best achieved at this dosage level. Gradual downward titration to a dose sufficient to maintain amenorrhea may be considered depending upon patient response. For mild cases, an initial daily dose of 200 mg to 400 mg given in two divided doses is recommended and may be adjusted depending on patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol capsules (see CONTRAINDICATIONS and WARNINGS). It is essential that therapy continue uninterrupted for 3 to 6 months but may be extended to 9 months if necessary. After termination of therapy, if symptoms recur, treatment can be reinstituted.

Fibrocystic Breast Disease

The total daily dosage of danazol capsules for fibrocystic breast disease ranges from 100 mg to 400 mg given in two divided doses depending upon patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol capsules. A non-hormonal method of contraception is recommended when danazol capsules are administered at this dose, since ovulation may not be suppressed.

In most instances, breast pain and tenderness are significantly relieved by the first month and eliminated in 2 to 3 months. Usually elimination of nodularity requires 4 to 6 months of uninterrupted therapy. Regular menstrual patterns, irregular menstrual patterns, and amenorrhea each occur in approximately one-third of patients treated with 100 mg of danazol capsules. Irregular menstrual patterns and amenorrhea are observed more frequently with higher doses. Clinical studies have demonstrated that 50% of patients may show evidence of recurrence of symptoms within one year. In this event, treatment may be reinstated.

Hereditary Angioedema

The dosage requirements for continuous treatment of hereditary angioedema with danazol capsules should be individualized on the basis of the clinical response of the patient. It is recommended that the patient be started on 200 mg, two or three times a day. After a favorable initial response is obtained in terms of prevention of episodes of edematous attacks, the proper continuing dosage should be determined by decreasing the dosage by 50% or less at intervals of one to three months or longer if frequency of attacks prior to treatment dictates. If an attack occurs, the daily dosage may be increased by up to 200 mg. During the dose adjusting phase, close monitoring of the patient's response is indicated, particularly if the patient has a history of airway involvement.
Megestrol Acetate

Megestrol Acetate

Breast Cancer: 160 mg/day (40 mg qid).

Endometrial Carcinoma: 40 to 320 mg/day in divided doses.

At least 2 months of continuous treatment is considered an adequate period for determining the efficacy of Megestrol Acetate Tablets USP.
Fludrocortisone Acetate...

Fludrocortisone Acetate

Dosage depends on the severity of the disease and the response of the patient. Patients should be continually monitored for signs that indicate dosage adjustment is necessary, such as remissions or exacerbations of the disease and stress (surgery, infection, trauma) (see WARNINGS and PRECAUTIONS, General).

Addison's Disease

In Addison's disease, the combination of fludrocortisone acetate tablets USP with a glucocorticoid such as hydrocortisone or cortisone provides substitution therapy approximating normal adrenal activity with minimal risks of unwanted effects.

The usual dose is 0.1 mg of fludrocortisone acetate daily, although dosage ranging from 0.1 mg three times a week to 0.2 mg daily has been employed. In the event transient hypertension develops as a consequence of therapy, the dose should be reduced to 0.05 mg daily. Fludrocortisone acetate is preferably administered in conjunction with cortisone (10 mg to 37.5 mg daily in divided doses) or hydrocortisone (10 mg to 30 mg daily in divided doses).

Salt-Losing Adrenogenital Syndrome

The recommended dosage for treating the salt-losing adrenogenital syndrome is 0.1 mg to 0.2 mg of fludrocortisone acetate daily.
Dipyridamole

Dipyridamole

Adjunctive Use In Prophylaxis Of Thromboembolism After Cardiac Valve Replacement

The recommended dose is 75 to 100 mg four times daily as an adjunct to the usual warfarin therapy. Please note that aspirin is not to be administered concomitantly with coumarin anticoagulants.
Estradiol

Estradiol

Dosage and Administration

When estrogen is prescribed for a postmenopausal woman with a uterus, a 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 with the lowest effective dose and for 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.

Patients should be started at the lowest dose for the indication.

1. For treatment of moderate to severe vasomotor symptoms, vulval and vaginal atrophy associated with the menopause, 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. The usual initial dosage range is 1 to 2 mg daily of estradiol adjusted as necessary to control presenting symptoms. The minimal effective dose for maintenance therapy should be determined by titration. Administration should be cyclic (e.g., 3 weeks on and 1 week off).

2. For treatment of female hypoestrogenism due to hypogonadism, castration, or primary ovarian failure.

Treatment is usually initiated with a dose of 1 to 2 mg daily of estradiol, adjusted as necessary to control presenting symptoms; the minimal effective dose for maintenance therapy should be determined by titration.

3. For treatment of breast cancer, for palliation only, in appropriately selected women and men with metastatic disease.

Suggested dosage is 10 mg three times daily for a period of at least three months.

4. For treatment of advanced androgen-dependent carcinoma of the prostate, for palliation only.

Suggested dosage is 1 to 2 mg three times daily. The effectiveness of therapy can be judged by phosphatase determinations as well as by symptomatic improvement of the patient.

5. For prevention of osteoporosis.

When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should be considered only for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate.

The lowest effective dose of estradiol has not been determined.
Isoniazid

Isoniazid

-

NOTE -- For preventive therapy of tuberculous infection and treatment of tuberculosis, it is recommended that physicians be familiar with the following publications: (1) the recommen- dations of the Advisory Council for the Elimination of Tuberculosis, published in the MMWR: vol 42; RR-4, 1993 and (2) Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children, American Journal of Respiratory and Critical Care Medicine: vol 149; 1359-1374, 1994.

For Treatment of Tuberculosis

Isoniazid is used in conjunction with other effective anti-tuberculosis agents. Drug susceptibility testing should be performed on the organisms initially isolated from all patients with newly diagnosed tuberculosis. If the bacilli becomes resistant, therapy must be changed to agents to which the bacilli are susceptible.

Usual Oral Dosage (depending on the regimen used):

Adults: 5 mg/kg up to 300 mg daily in a single dose; or 15 mg/kg up to 900 mg/day, two or

three times/week

Children: 10 - 15 mg/kg up to 300 mg daily in a single dose; or 20-40 mg/kg up to 900

mg/day, two or three times/week

Patients with Pulmonary Tuberculosis Without HIV Infection

There are 3 regimen options for the initial treatment of tuberculosis in children and adults:

Option 1: Daily isoniazid, rifampin, and pyrazinamide for 8 weeks followed by 16 weeks of

isoniazid and rifampin daily or 2 to 3 times weekly. Ethambutol or streptomycin

should be added to the initial regimen until sensitivity to isoniazid and rifampin is

demonstrated. The addition of a fourth drug is optional if the relative prevalence of

isoniazid-resistant Mycobacteriumtuberculosis isolates in the community is less

than or equal to four percent.

Option 2: Daily isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol for 2

weeks followed by twice weekly administration of the same drugs for 6 weeks,

subsequently twice weekly isoniazid and rifampin for 16 weeks.

Option 3: Three times weekly with isoniazid, rifampin, pyrazinamide, and ethambutol or

streptomycin for 6 months.

* All regimen given twice weekly or 3 times weekly should be administered by directly observed therapy (see also Directly Observed Therapy).

The above treatment guidelines apply only when the disease is caused by organisms that are sus- ceptible to the standard antituberculous agents. Because of the impact of resistance to isoniazid and rifampin on the response to therapy, it is essential that physicians initiating therapy for tu- berculosis be familiar with the prevalence of drug resistance in their communities. It is suggested that ethambutol not be used in children whose visual acuity cannot be monitored.

Patients with Pulmonary Tuberculosis and HIV Infection

The response of the immunologically impaired host to treatment may not be as satisfactory as that of a person with normal host responsiveness. For this reason, therapeutic decisions for the impaired host must be individualized. Since patients co-infected with HIV may have problems with malabsorption, screening of antimycobacterial drug levels, especially in patients with ad- vanced HIV disease, may be necessary to prevent the emergence of MDRTB.

Patients with Extra Pulmonary Tuberculosis

The basic principles that underlie the treatment of pulmonary tuberculosis also apply to Extra pulmonary forms of the disease. Although there have not been the same kinds of carefully conducted controlled trials of treatment of Extra pulmonary tuberculosis as for pulmonary disease, increasing clinical experience indicates that a 6 to 9 month short-course regimen is effective. Because of the insufficient data, military tuberculosis, bone/joint tuberculosis, and tuberculous meningitis in infants and children should receive 12 month therapy.

Bacteriologic evaluation of Extra pulmonary tuberculosis may be limited by the relative in accessibility of the sites of disease. Thus, response to treatment often must be judged on the basis of clinical and radiographic findings.

The use of adjunctive therapies such as surgery and corticosteroids is more commonly required in Extra pulmonary tuberculosis than in pulmonary disease. Surgery may be necessary to obtain specimens for diagnosis and to treat such processes as constrictive pericarditis and spinal cord compression from Pott’s Disease. Corticosteroids have been shown to be of benefit in preventing cardiac constriction from tuberculous pericarditis and in decreasing the neurologic sequelae of all stages of tuberculosis meningitis, especially when administered early in the course of the disease.

Pregnant Women with Tuberculosis

The options listed above must be adjusted for the pregnant patient. Streptomycin interferes with in utero development of the ear and may cause congenital deafness. Routine use of pyrazinamide is also not recommended in pregnancy because of inadequate teratogenicity data. The initial treatment regimen should consist of isoniazid and rifampin. Ethambutol should be included unless primary isoniazid resistance is unlikely (isoniazid resistance rate documented to be less than 4%).

Treatment of Patients with Multi-Drug Resistant Tuberculosis (MDRTB)

Multiple-drug resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended.

Directly Observed Therapy (DOT)

A major cause of drug-resistant tuberculosis is patient noncompliance with treatment. The use of DOT can help assure patient compliance with drug therapy. DOT is the observation of the pa- tient by a health care provider or other responsible person as the patient ingests anti-tuberculosis medications. DOT can be achieved with daily, twice weekly or thrice weekly regimens, and is recommended for all patients.

For Preventative Therapy of Tuberculosis

Before isoniazid preventive therapy is initiated, bacteriologically positive or radiographically progressive tuberculosis must be excluded. Appropriate evaluations should be performed if Extra pulmonary tuberculosis is suspected.

Adults over 30 Kg: 300 mg per day in a single dose.

Infants and Children: 10 mg/kg (up to 300 mg daily) in a single dose. In situations where adherence with daily preventative therapy cannot be assured, 20-30 mg/kg (not to exceed 900 mg) twice weekly under the direct observation of a health care worker at the time of admin- istration8.

Continuous administration of isoniazid for a sufficient period is an essential part of the regimen because relapse rates are higher if chemotherapy is stopped prematurely. In the treatment of tu- berculosis, resistant organisms may multiply and the emergence of resistant organisms during the treatment may necessitate a change in the regimen.

For following patient compliance: the Potts-Cozart test9, a simple colorimetric6 method of checking for isoniazid in the urine, is a useful tool for assuring patient compliance, which is essential for effective tuberculosis control. Additionally, isoniazid test strips are also available

to check patient compliance.

Concomitant administration of pyridoxine (B6) is recommended in malnourished and in those predisposed to neuropathy (e.g., alcoholics and diabetics).
Ipratropium Bromide And...

Ipratropium Bromide And Albuterol Sulfate Solution

Claravis should be administered with a meal (see PRECAUTIONS, Information for Patients).

The recommended dosage range for Claravis is 0.5 to 1 mg/kg/day given in two divided doses with food for 15 to 20 weeks. In studies comparing 0.1, 0.5, and 1 mg/kg/day,8 it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages. During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects – some of which may be dose related. Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dose adjustments up to 2 mg/kg/day, as tolerated. Failure to take Claravis with food will significantly decrease absorption. Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions.

The safety of once daily dosing with Claravis has not been established. Once daily dosing is not recommended.

If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of Claravis, even in low doses, has not been studied, and is not recommended. It is important that Claravis be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of Claravis on bone loss is unknown (see WARNINGS, Skeletal, Bone Mineral Density, Hyperostosis and Premature Epiphyseal Closure).

Contraceptive measures must be followed for any subsequent course of therapy (see PRECAUTIONS).
Table 4. Claravis Dosing by Body Weight (Based on Administration With Food) * See DOSAGE AND ADMINISTRATION: the recommended dosage range is 0.5 to 1 mg/kg/day.
Body Weight

Total mg/day

kilograms

pounds

0.5 mg/kg

1 mg/kg

2 mg/kg*

40

88

20

40

80

50

110

25

50

100

60

132

30

60

120

70

154

35

70

140

80

176

40

80

160

90

198

45

90

180

100

220

50

100

200

INFORMATION FOR PHARMACISTS

Access the iPLEDGE system via the internet (www.ipledgeprogram.com) or telephone (1-866-495-0654) to obtain an authorization and the “do not dispense to patient after” date. Claravis must only be dispensed in no more than a 30 day supply.

REFILLS REQUIRE A NEW PRESCRIPTION AND A NEW AUTHORIZATION FROM THE iPLEDGE SYSTEM.

A Claravis Medication Guide must be given to the patient each time Claravis is dispensed, as required by law. This Claravis Medication Guide is an important part of the risk management program for the patient.
Naltrexone Hydrochlorid...

Naltrexone Hydrochloride

To achieve maximum contraceptive effectiveness, norethindrone tablets 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.
Methotrexate

Methotrexate

Neoplastic Diseases

Oral administration in tablet form is often preferred when low doses are being administered since absorption is rapid and effective serum levels are obtained.

Choriocarcinoma and similar trophoblastic diseases: Methotrexate is administered orally or intramuscularly in doses of 15 to 30 mg daily for a five-day course. Such courses are usually repeated for 3 to 5 times as required, with rest periods of one or more weeks interposed between courses, until any manifesting toxic symptoms subside. The effectiveness of therapy is ordinarily evaluated by 24 hour quantitative analysis of urinary chorionic gonadotropin (hCG), which should return to normal or less than 50 IU/24 hr usually after the third or fourth course and usually be followed by a complete resolution of measurable lesions in 4 to 6 weeks. One to two courses of methotrexate after normalization of hCG is usually recommended. Before each course of the drug careful clinical assessment is essential. Cyclic combination therapy of methotrexate with other antitumor drugs has been reported as being useful.

Since hydatidiform mole may precede choriocarcinoma, prophylactic chemotherapy with methotrexate has been recommended.

Chorioadenoma destruens is considered to be an invasive form of hydatidiform mole. Methotrexate is administered in these disease states in doses similar to those recommended for choriocarcinoma.

Leukemia: Acute lymphoblastic leukemia in pediatric patients and young adolescents is the most responsive to present day chemotherapy. In young adults and older patients, clinical remission is more difficult to obtain and early relapse is more common.

Methotrexate alone or in combination with steroids was used initially for induction of remission in acute lymphoblastic leukemias. More recently corticosteroid therapy, in combination with other antileukemic drugs or in cyclic combinations with methotrexate included, has appeared to produce rapid and effective remissions. When used for induction, methotrexate in doses of 3.3 mg/m2 in combination with 60 mg/m2 of prednisone, given daily, produced remissions in 50% of patients treated, usually within a period of 4 to 6 weeks. Methotrexate in combination with other agents appears to be the drug of choice for securing maintenance of drug-induced remissions. When remission is achieved and supportive care has produced general clinical improvement, maintenance therapy is initiated, as follows: Methotrexate is administered 2 times weekly either by mouth or intramuscularly in total weekly doses of 30 mg/m2. It has also been given in doses of 2.5 mg/kg intravenously every 14 days. If and when relapse does occur, reinduction of remission can again usually be obtained by repeating the initial induction regimen.

A variety of combination chemotherapy regimens have been used for both induction and maintenance therapy in acute lymphoblastic leukemia. The physician should be familiar with the new advances in antileukemic therapy.

Lymphomas: In Burkitt’s tumor, Stages I-II, methotrexate has produced prolonged remissions in some cases. Recommended dosage is 10 to 25 mg/day orally for 4 to 8 days. In Stage III, methotrexate is commonly given concomitantly with other anti-tumor agents. Treatment in all stages usually consists of several courses of the drug interposed with 7 to 10 day rest periods. Lymphosarcomas in Stage III may respond to combined drug therapy with methotrexate given in doses of 0.625 to 2.5 mg/kg daily.

Mycosis Fungoides (cutaneous T cell lymphoma): Therapy with methotrexate as a single agent appears to produce clinical responses in up to 50% of patients treated. Dosage in early stages is usually 5 to 50 mg once weekly. Dose reduction or cessation is guided by patient response and hematologic monitoring. Methotrexate has also been administered twice weekly in doses ranging from 15 to 37.5 mg in patients who have responded poorly to weekly therapy.

Psoriasis, Rheumatoid Arthritis, and Juvenile Rheumatoid Arthritis

Adult Rheumatoid Arthritis: Recommended Starting Dosage Schedules

1. Single oral doses of 7.5 mg once weekly.

2. Divided oral dosages of 2.5 mg at 12 hour intervals for 3 doses given as a course once weekly.

Polyarticular-Course Juvenile Rheumatoid Arthritis: The recommended starting dose is 10 mg/m2 given once weekly.

For either adult RA or polyarticular-course JRA dosages may be adjusted gradually to achieve an optimal response. Limited experience shows a significant increase in the incidence and severity of serious toxic reactions, especially bone marrow suppression, at doses greater than 20 mg/wk in adults. Although there is experience with doses up to 30 mg/m2/wk in children, there are too few published data to assess how doses over 20 mg/m2/wk might affect the risk of serious toxicity in children. Experience does suggest, however, that children receiving 20 to 30 mg/m2/wk (0.65 to 1 mg/kg/wk) may have better absorption and fewer gastrointestinal side effects if methotrexate is administered either intramuscularly or subcutaneously.

Therapeutic response usually begins within 3 to 6 weeks and the patient may continue to improve for another 12 weeks or more.

The optimal duration of therapy is unknown. Limited data available from long-term studies in adults indicate that the initial clinical improvement is maintained for at least two years with continued therapy. When methotrexate is discontinued, the arthritis usually worsens within 3 to 6 weeks.

The patient should be fully informed of the risks involved and should be under constant supervision of thephysician. (See Information for Patients under PRECAUTIONS.) Assessment of hematologic, hepatic, renal, and pulmonary function should be made by history, physical examination, and laboratory tests before beginning, periodically during, and before reinstituting methotrexate therapy. (See PRECAUTIONS.) Appropriate steps should be taken to avoid conception during methotrexate therapy. (See PRECAUTIONS and CONTRAINDICATIONS.)

All schedules should be continually tailored to the individual patient. An initial test dose may be given prior to the regular dosing schedule to detect any extreme sensitivity to adverse effects. (See ADVERSE REACTIONS.) Maximal myelosuppression usually occurs in seven to ten days.

Psoriasis: Recommended Starting Dose Schedules

1. Weekly single oral, IM or IV dose schedule: 10 to 25 mg per week until adequate response is achieved.

2. Divided oral dose schedule: 2.5 mg at 12-hour intervals for three doses.

Dosages in each schedule may be gradually adjusted to achieve optimal clinical response; 30 mg/week should not ordinarily be exceeded.

Once optimal clinical response has been achieved, each dosage schedule should be reduced to the lowest possible amount of drug and to the longest possible rest period. The use of methotrexate may permit the return to conventional topical therapy, which should be encouraged.
Amiloride Hydrochloride...

Amiloride Hydrochloride And Hydrochlorothiazide

Amiloride hydrochloride and hydrochlorothiazide tablets should be administered with food.

The usual starting dosage is 1 tablet a day. The dosage may be increased to 2 tablets a day, if necessary. More than 2 tablets of amiloride hydrochloride and hydrochlorothiazide daily usually are not needed and there is no controlled experience with such doses.

Hydrochlorothiazide can be given at doses of 12.5 to 50 mg per day when used alone. Patients usually do not require doses of hydrochlorothiazide in excess of 50 mg daily when combined with other antihypertensive agents. The daily dose is usually given as a single dose but may be given in divided doses. Once an initial diuresis has been achieved, dosage adjustment may be necessary. Maintenance therapy may be on an intermittent basis.
Dextroamphetamine Sacch...

Dextroamphetamine Saccharate

2.1 Dosing Considerations for all Patients

Individualize the dosage according to the therapeutic needs and response of the patient. Administer MAS-ER Capsules at the lowest effective dosage.

Based on bioequivalence data, patients taking divided doses of immediate-release ADDERALL, (for example, twice daily), may be switched to MAS-ER Capsules at the same total daily dose taken once daily. Titrate at weekly intervals to appropriate efficacy and tolerability as indicated.

MAS-ER 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.

MAS-ER Capsules may be taken with or without food.

MAS-ER Capsules should be given upon awakening. Afternoon doses should be avoided because of the potential for insomnia.

Where possible, MAS-ER Capsules 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 6-12 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 MAS-ER Capsules have not been studied in children. MAS-ER Capsules has not been studied in children under 6 years of age.

2.3 Adolescents

The recommended starting dose for adolescents with ADHD who are 13-17 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.
Adderall

Adderall

Regardless of indication, amphetamines should be administered at the lowest effective dosage, and dosage should be individually adjusted according to the therapeutic needs and response of the patient. Late evening doses should be avoided because of the resulting insomnia.

Attention Deficit Hyperactivity Disorder

Not recommended for children under 3 years of age. In children from 3 to 5 years of age, start with 2.5 mg daily; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In children 6 years of age and older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg per day. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

Narcolepsy

Usual dose 5 mg to 60 mg per day in divided doses, depending on the individual patient response.

Narcolepsy seldom occurs in children under 12 years of age; however, when it does, dextroamphetamine sulfate may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.
Naltrexone Hydrochlorid...

Naltrexone Hydrochloride

To reduce the risk of precipitated withdrawal in patients dependent on opioids, or exacerbation of a preexisting subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting naltrexone hydrochloride tablets treatment. An opioid-free interval of a minimum of 7 to 10 days is recommended for patients previously dependent on short-acting opioids.

Switching from Buprenorphine, Buprenorphine/Naloxone, or Methadone

There are no systematically collected data that specifically address the switch from buprenorphine or methadone to naltrexone hydrochloride tablets; however, review of postmarketing case reports have indicated that some patients may experience severe manifestations of precipitated withdrawal when being switched from opioid agonist therapy to opioid antagonist therapy (see WARNINGS). Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks. Healthcare providers should be prepared to manage withdrawal symptomatically with non-opioid medications.

Treatment of Alcoholism

A dose of 50 mg once daily is recommended for most patients. The placebo-controlled studies that demonstrated the efficacy of naltrexone hydrochloride tablets as an adjunctive treatment of alcoholism used a dose regimen of naltrexone hydrochloride tablets 50 mg once daily for up to 12 weeks. Other dose regimens or durations of therapy were not evaluated in these trials.

Naltrexone hydrochloride tablets should be considered as only one of many factors determining the success of treatment of alcoholism. Factors associated with a good outcome in the clinical trials with naltrexone hydrochloride tablets were the type, intensity, and duration of treatment; appropriate management of comorbid conditions; use of community-based support groups; and good medication compliance. To achieve the best possible treatment outcome, appropriate compliance-enhancing techniques should be implemented for all components of the treatment program, especially medication compliance.

Treatment of Opioid Dependence

Treatment should be initiated with an initial dose of 25 mg of naltrexone hydrochloride tablets. If no withdrawal signs occur, the patient may be started on 50 mg a day thereafter.

A dose of 50 mg once a day will produce adequate clinical blockade of the actions of parenterally administered opioids. As with many non-agonist treatments for addiction, naltrexone hydrochloride tablets are of proven value only when given as part of a comprehensive plan of management that includes some measure to ensure the patient takes the medication.

Naloxone Challenge Test

Clinicians are reminded that there is no completely reliable method for determining whether a patient has had an adequate opioid-free period. A naloxone challenge test may be helpful if there is any question of occult opioid dependence. If signs of opioid withdrawal are still observed following naloxone challenge, treatment with naltrexone hydrochloride tablets should not be attempted. The naloxone challenge can be repeated in 24 hours.

The naloxone challenge test should not be performed in a patient showing clinical signs or symptoms of opioid withdrawal, or in a patient whose urine contains opioids. The naloxone challenge test may be administered by either the intravenous or subcutaneous routes.

Intravenous

Inject 0.2 mg naloxone.

Observe for 30 seconds for signs or symptoms of withdrawal.

If no evidence of withdrawal, inject 0.6 mg of naloxone.

Observe for an additional 20 minutes.

Subcutaneous

Administer 0.8 mg naloxone.

Observe for 20 minutes for signs or symptoms of withdrawal.

Note: Individual patients, especially those with opioid dependence, may respond to lower doses of naloxone. In some cases, 0.1 mg IV naloxone has produced a diagnostic response.

Interpretation of the Challenge

Monitor vital signs and observe the patient for signs and symptoms of opioid withdrawal. These may include, but are not limited to: nausea, vomiting, dysphoria, yawning, sweating, tearing, rhinorrhea, stuffy nose, craving for opioids, poor appetite, abdominal cramps, sense of fear, skin erythema, disrupted sleep patterns, fidgeting, uneasiness, poor ability to focus, mental lapses, muscle aches or cramps, pupillary dilation, piloerection, fever, changes in blood pressure, pulse or temperature, anxiety, depression, irritability, backache, bone or joint pains, tremors, sensations of skin crawling or fasciculations. If signs or symptoms of withdrawal appear, the test is positive and no additional naloxone should be administered.

Warning: If the test is positive, do NOT initiate naltrexone hydrochloride tablets therapy. Repeat the challenge in 24 hours. If the test is negative, naltrexone hydrochloride tablets therapy may be started if no other contraindications are present. If there is any doubt about the result of the test, hold naltrexone hydrochloride tablets and repeat the challenge in 24 hours.

Alternative Dosing Schedules

A flexible approach to a dosing regimen may need to be employed in cases of supervised administration. Thus, patients may receive 50 mg of naltrexone hydrochloride tablets every weekday with a 100 mg dose on Saturday, 100 mg every other day, or 150 mg every third day. The degree of blockade produced by naltrexone hydrochloride tablets may be reduced by these extended dosing intervals.

There may be a higher risk of hepatocellular injury with single doses above 50 mg, and use of higher doses and extended dosing intervals should balance the possible risks against the probable benefits (see WARNINGS).

Patient Compliance

Naltrexone hydrochloride tablets should be considered as only one of many factors determining the success of treatment. To achieve the best possible treatment outcome, appropriate compliance-enhancing techniques should be implemented for all components of the treatment program, including medication compliance.
Apri

Apri

To achieve maximum contraceptive effectiveness, Apri must be taken exactly as directed and at intervals not exceeding 24 hours. Apri is available in the tablet dispenser which is preset for a Sunday Start. Day 1 Start is also provided.

Day 1 Start

The dosage of Apri for the initial cycle of therapy is one rose-colored “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”. Tablets are taken without interruption as follows: One rose-colored “active” tablet daily for 21 days, then one white “reminder” tablet daily for 7 days. After 28 tablets have been taken, a new course is started and a rose-colored “active” tablet is taken the next day.

The use of Apri 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 for “Nursing Mothers.”). If the patient starts on Apri postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a rose-colored “active” tablet has been taken daily for 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. If the patient misses one (1) rose-colored “active” tablet in Weeks 1, 2, or 3, the rose-colored “active” tablet should be taken as soon as she remembers. If the patient misses two (2) rose-colored “active” tablets in Week 1 or Week 2, the patient should take two (2) rose-colored “active” tablets the day she remembers and two (2) rose-colored “active” tablets the next day; and then continue taking one (1) rose-colored “active” 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) rose-colored “active” tablets in the third week or misses three (3) or more rose-colored “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.

Sunday Start

When taking Apri, the first rose-colored “active” tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first rose-colored “active” tablet is taken on that day. If switching directly from another oral contraceptive, the first rose-colored “active” tablet should be taken on the first Sunday after the last ACTIVE tablet of the previous product. Tablets are taken without interruption as follows: One rose-colored “active” tablet daily for 21 days, then one white “reminder” tablet daily for 7 days. After 28 tablets have been taken, a new course is started and a rose-colored “active” tablet is taken the next day (Sunday). When initiating a Sunday start regimen, another method of contraception should be used until after the first 7 consecutive days of administration.

The use of Apri for contraception may be initiated 4 weeks postpartum. 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 for “Nursing Mothers”). If the patient starts on Apri postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a rose-colored “active” tablet has been taken daily for 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. If the patient misses one (1) rose-colored “active” tablet in Weeks 1, 2, or 3, the rose-colored “active” tablet should be taken as soon as she remembers. If the patient misses two (2) rose-colored “active” tablets in Week 1 or Week 2, the patient should take two (2) rose-colored “active” tablets the day she remembers and two (2) rose-colored “active” tablets the next day; and then continue taking one (1) rose-colored “active” 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) rose-colored “active” tablets in the third week or misses three (3) or more rose-colored “active” tablets in a row, the patient should continue taking one rose-colored “active” 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.
Portia

Portia

To achieve maximum contraceptive effectiveness, Portia® (levonorgestrel and ethinyl estradiol tablets) must be taken exactly as directed and at intervals not exceeding 24 hours.

The dosage of Portia® is one pink tablet daily for 21 consecutive days, followed by one white inert tablet daily for 7 consecutive days, according to prescribed schedule.

It is recommended that tablets be taken at the same time each day, preferably after the evening meal or at bedtime.

During the first cycle of medication, the patient is instructed to begin taking Portia ® on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (pink) is taken that day. One pink tablet should be taken daily for 21 consecutive days, followed by one white inert tablet daily for 7 consecutive days. Withdrawal bleeding should usually occur within three days following discontinuation of pink tablets and may not have finished before the next pack is started. During the first cycle, contraceptive reliance should not be placed on Portia® until a pink tablet has been taken daily for 7 consecutive days and a nonhormonal back-up method of birth control should be used during those 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient begins her next and all subsequent 28 day courses of tablets on the same day of the week (Sunday) on which she began her first course, following the same schedule: 21 days on pink tablets ─ 7 days on white inert tablets. If in any cycle the patient starts tablets later than the proper day, she should protect herself by using another method of birth control until she has taken a pink tablet daily for 7 consecutive days.

When the patient is switching from a 21 day regimen of tablets, she should wait 7 days after her last tablet before she starts Portia®. She will probably experience withdrawal bleeding during that week. She should be sure that no more than 7 days pass after her previous 21 day regimen. When the patient is switching from a 28 day regimen of tablets, she should start her first pack of Portia® on the day after her last tablet. She should not wait any days between packs. The patient may switch any day from a progestin-only pill and should begin Portia® the next day. If switching from an implant or injection, the patient should start Portia® on the day of implant removal or, if using an injection, the day the next injection would be due. In switching from a progestin-only pill, injection or implant, the patient should be advised to use a nonhormonal back-up method of birth control for the first 7 days of tablet-taking.

If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician. Although the occurrence of pregnancy is highly unlikely if Portia® tablets are taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken before the medication is resumed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the DETAILED PATIENT LABELING below.

Anytime the patient misses two or more pink tablets, she should also use another method of contraception until she has taken a pink tablet daily for seven consecutive days. If the patient misses one or more white tablets, she is still protected against pregnancy provided she begins taking pink tablets again on the proper day.

If breakthrough bleeding occurs following missed pink tablets, it will usually be transient and of no consequence. While there is little likelihood of ovulation occurring if only one or two pink tablets are missed, the possibility of ovulation increases with each successive day that scheduled pink tablets are missed.

Portia® may be initiated no earlier than day 28 postpartum in the non-lactating mother or after a second trimester abortion due to the increased risk for thromboembolism (see CONTRAINDICATONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease). The patient should be advised to use a nonhormonal back-up method for the first 7 days of tablet taking. However, if intercourse has already occurred, pregnancy should be excluded before the start of combined oral contraceptive use or the patient must wait for her first menstrual period.

In the case of first trimester abortion, if the patient starts Portia® immediately, additional contraceptive measures are not needed. It is to be noted that early resumption of ovulation may occur if Parlodel® (bromocriptine mesylate) has been used for the prevention of lactation.
Didanosine

Didanosine

Didanosine delayed-release capsules should be administered on an empty stomach. Didanosine delayed-release capsules should be swallowed intact.

2.1 Recommended Dosage (Adult and Pediatric Patients)

The recommended total daily dose is based on body weight and is administered as one capsule given on a once-daily schedule as outlined in Table 1.

The recommended total daily dose to be administered once daily to pediatric patients weighing at least 20 kg who can swallow capsules is based on body weight (kg), consistent with the recommended adult dosing guidelines (see Table 1). Please consult the complete prescribing information for Didanosine Pediatric Powder for Oral Solution for dosage and administration of didanosine to pediatric patients weighing less than 20 kg or who can not swallow capsules.
Table 1: Recommended Dosage (Adult and Pediatric Patients)
Body Weight

Dose

20 kg to less than 25 kg

200 mg once daily

25 kg to less than 60 kg

250 mg once daily

at least 60 kg

400 mg once daily

2.2 Renal Impairment

Dosing recommendations for didanosine delayed-release capsules are different for patients with renal impairment.

Adult Patients

In adult patients with impaired renal function, the dose of didanosine delayed-release capsules should be adjusted to compensate for the slower rate of elimination. The recommended doses and dosing intervals of didanosine delayed-release capsules in adult patients with renal insufficiency are presented in Table 2.
Table 2: Recommended Dosage in Patients with Renal Impairment by Body Weighta
Creatinine Clearance

(mL/min)

Dosage (mg)

at least 60 kg

less than 60 kg
at least 60
400 once daily

250 once daily

30 to 59

200 once daily

125 once daily

10 to 29

125 once daily

125 once daily

less than 10

125 once daily

b

a Based on studies using a buffered formulation of didanosine.

b Not suitable for use in patients less than 60 kg with CLcr less than 10 mL/min. An alternate formulation of didanosine should be used.

Pediatric Patients

Urinary excretion is also a major route of elimination of didanosine in pediatric patients, therefore the clearance of didanosine may be altered in pediatric patients with renal impairment. Although there are insufficient data to recommend a specific dose adjustment of didanosine delayed-release capsules in this patient population, a reduction in the dose should be considered (see Table 2).

Patients Requiring Continuous Ambulatory Peritoneal Dialysis (CAPD) or Hemodialysis

For patients requiring CAPD or hemodialysis, follow dosing recommendations for patients with creatinine clearance of less than 10 mL/min, shown in Table 2. It is not necessary to administer a supplemental dose of didanosine following hemodialysis.

2.3 Dose Adjustment

Concomitant Therapy with Tenofovir Disoproxil Fumarate

In patients who are also taking tenofovir disoproxil fumarate, a dose reduction of didanosine delayed-release capsules to 250 mg (adults weighing at least 60 kg with creatinine clearance of at least 60 mL/min) or 200 mg (adults weighing less than 60 kg with creatinine clearance of at least 60 mL/min) once daily taken together with tenofovir disoproxil fumarate and a light meal (400 kcalories or less, 20% fat or less) or in the fasted state is recommended. The appropriate dose of didanosine delayed-release capsules coadministered with tenofovir disoproxil fumarate in patients with creatinine clearance of less than 60 mL/min has not been established [see Drug Interactions (7) and Clinical Pharmacology (12.3)].

Hepatic Impairment

No dose adjustment is required in patients with hepatic impairment [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].
Aviane

Aviane

To achieve maximum contraceptive effectiveness, Aviane® (levonorgestrel and ethinyl estradiol tablets) must be taken exactly as directed and at intervals not exceeding 24 hours. The dosage of Aviane - 28 is one orange tablet daily for 21 consecutive days, followed by one light-green inert tablet daily for 7 consecutive days, according to the prescribed schedule. It is recommended that Aviane - 28 tablets be taken at the same time each day.

The dispenser should be kept in the wallet supplied to avoid possible fading of the pills. If the pills fade, patients should continue to take them as directed.

During The First Cycle Of Use

The possibility of ovulation and conception prior to initiation of medication should be considered. The patient should be instructed to begin taking Aviane on either the first Sunday after the onset of menstruation (Sunday Start) or on Day 1 of menstruation (Day 1 Start).

Sunday Start

The patient is instructed to begin taking Aviane - 28 on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (orange) is taken that day. One orange tablet should be taken daily for 21 consecutive days, followed by one light-green inert tablet daily for 7 consecutive days. Withdrawal bleeding should usually occur within 3 days following discontinuation of orange tablets and may not have finished before the next pack is started. During the first cycle, contraceptive reliance should not be placed on Aviane - 28 until an orange tablet has been taken daily for 7 consecutive days, and a nonhormonal backup method of birth control should be used during those 7 days.

Day 1 Start

During the first cycle of medication, the patient is instructed to begin taking Aviane - 28 during the first 24 hours of her period (day one of her menstrual cycle). One orange tablet should be taken daily for 21 consecutive days, followed by one light-green inert tablet daily for 7 consecutive days. Withdrawal bleeding should usually occur within 3 days following discontinuation of orange tablets and may not have finished before the next pack is started. If medication is begun on day one of the menstrual cycle, no backup contraception is necessary. If Aviane - 28 tablets are started later than day one of the first menstrual cycle or postpartum, contraceptive reliance should not be placed on Aviane - 28 tablets until after the first 7 consecutive days of administration, and a nonhormonal backup method of birth control should be used during those 7 days.

After the First Cycle of Use

The patient begins her next and all subsequent courses of tablets on the day after taking her last light-green tablet. She should follow the same dosing schedule: 21 days on orange tablets followed by 7 days on light-green tablets. If in any cycle the patient starts tablets later than the proper day, she should protect herself against pregnancy by using a nonhormonal backup method of birth control until she has taken an orange tablet daily for 7 consecutive days.

Switching from Another Hormonal Method of Contraception

When the patient is switching from a 21 day regimen of tablets, she should wait 7 days after her last tablet before she starts Aviane. She will probably experience withdrawal bleeding during that week. She should be sure that no more than 7 days pass after her previous 21 day regimen. When the patient is switching from a 28 day regimen of tablets, she should start her first pack of Aviane on the day after her last tablet. She should not wait any days between packs. The patient may switch any day from a progestin-only pill and should begin Aviane the next day. If switching from an implant or injection, the patient should start Aviane on the day of implant removal or, if using an injection, the day the next injection would be due. In switching from a progestin-only pill, injection, or implant, the patient should be advised to use a nonhormonal backup method of birth control for the first 7 days of tablet taking.

If Spotting or Breakthrough Bleeding Occurs

If spotting or breakthrough bleeding occur, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician.

Risk of Pregnancy if Tablets are Missed

While there is little likelihood of ovulation occurring if only one or two orange tablets are missed, the possibility of ovulation increases with each successive day that scheduled orange tablets are missed. Although the occurrence of pregnancy is unlikely if Aviane is taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out.

The risk of pregnancy increases with each active (orange) tablet missed. For additional patient instructions regarding missed tablets, see the WHAT TO DO IF YOU MISS PILLS section in the DETAILED PATIENT LABELING below.

Use After Pregnancy, Abortion or Miscarriage

Aviane may be initiated no earlier than day 28 postpartum in the nonlactating mother or after a second trimester abortion due to the increased risk for thromboembolism (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease). The patient should be advised to use a nonhormonal backup method for the first 7 days of tablet taking.

Aviane may be initiated immediately after a first trimester abortion or miscarriage. If the patient starts Aviane immediately, backup contraception is not needed.
Dextroamphetamine Sacch...

Dextroamphetamine Saccharate

Regardless of indication, amphetamines should be administered at the lowest effective dosage, and dosage should be individually adjusted according to the therapeutic needs and response of the patient. Late evening doses should be avoided because of the resulting insomnia.

Attention Deficit Hyperactivity Disorder

Not recommended for children under 3 years of age. In children from 3 to 5 years of age, start with 2.5 mg daily; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In children 6 years of age and older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg per day. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

Narcolepsy

Usual dose 5 mg to 60 mg per day in divided doses, depending on the individual patient response.

Narcolepsy seldom occurs in children under 12 years of age; however, when it does, dextroamphetamine sulfate may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.
Nortrel 777

Nortrel 777

To achieve maximum contraceptive effectiveness, Nortrel 7/7/7 tablets must be taken exactly as directed and at intervals not exceeding 24 hours. Nortrel 7/7/7 tablets are available with the Blister Pack Tablet Dispenser which is preset for a Sunday Start. Day 1 Start is also available.

Sunday Start

When taking Nortrel 7/7/7, the first “active” tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first “active” tablet should be taken that day. Take one active tablet daily for 21 days followed by one white “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 Nortrel 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 white “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 Nortrel 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 CONTRAINDICATIONSand WARNINGSconcerning 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.)

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.
Nortrel

Nortrel

To achieve maximum contraceptive effectiveness, Nortrel® (norethindrone and ethinyl estradiol tablets USP) must be taken exactly as directed and at intervals not exceeding 24 hours. Nortrel® (norethindrone and ethinyl estradiol tablets USP) is available in the Blister Pack Tablet Dispenser which is preset for a Sunday Start. Day 1 Start is also available.

21-Day Regimen (Sunday Start):

When taking Nortrel® 1/35 (norethindrone and ethinyl estradiol tablets, USP) (21) Day Regimen,the first "active" tablet should be taken on the first Sunday after menstruation begins. If period begins on Sunday, the first "active" tablet should be taken that day. Take one active tablet daily for 21 days. For subsequent cycles, no tablets are taken for 7 days, then a tablet is taken 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).

21-Day Regimen (Day 1 Start):

The dosage of Nortrel® 1/35 (norethindrone and ethinyl estradiol tablets, USP) (21) Day Regimen,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.” For subsequent cycles, no tablets are taken for 7 days, then a new course is started of one tablet a day for 21 days. The dosage regimen then continues with 7 days of no medication, followed by 21 days of medication, instituting a three-weeks-on, one-week-off dosage regimen.

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).

28-Day Regimen (Sunday Start):

When taking Nortrel® 1/35 and 0.5/35 (norethindrone and ethinyl estradiol tablets, USP) (28) Day Regimen, the first “active” tablet should be taken on the first Sunday after menstruation begins. If period begins on Sunday, the first “active” tablet should be taken that day. Take one active tablet daily for 21 days followed by one white “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).

28-Day Regimen (Day 1 Start):

The dosage of Nortrel® 1/35 and 0.5/35 (norethindrone and ethinyl estradiol tablets, USP) (28) Day Regimen,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 white “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 Nortrel® 1/35 and 0.5/35 (norethindrone and ethinyl estradiol tablets USP)for contraception may be initiated 4 weeks postpartum in women who elect not to breast feed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONSand 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.)
Dextroamphetamine Sulfa...

Dextroamphetamine Sulfate

Amphetamines should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of the resulting insomnia.

Narcolepsy

Usual dose is 5 to 60 mg per day in divided doses, depending on the individual patient response.

Narcolepsy seldom occurs in children under 12 years of age; however, when it does, dextroamphetamine sulfate may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until an optimal response is obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

Attention Deficit Disorder with Hyperactivity

Not recommended for pediatric patients under 3 years of age.

In pediatric patients from 3 to 5 years of age, start with 2.5 mg daily; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In pediatric patients 6 years of age and older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg per day.

Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.
Cryselle

Cryselle

To achieve maximum contraceptive effectiveness, Cryselle® must be taken exactly as directed and at intervals not exceeding 24 hours. The dosage of Cryselle® is one white tablet daily for 21 consecutive days, followed by one light-green inert tablet daily for 7 consecutive days, according to prescribed schedule. It is recommended that tablets be taken at the same time each day, preferably after the evening meal or at bedtime.

During the first cycle of medication, the patient is instructed to begin taking Cryselle® on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (white) is taken that day. One white tablet should be taken daily for 21 consecutive days followed by one light-green inert tablet daily for 7 consecutive days.

Withdrawal bleeding should usually occur within three days following discontinuation of white tablets. During the first cycle, contraceptive reliance should not be placed on Cryselle® until a white tablet has been taken daily for 7 consecutive days. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient begins her next and all subsequent 28 day courses of tablets on the same day of the week (Sunday) on which she began her first course, following the same schedule: 21 days on white tablets – 7 days on light-green inert tablets. If in any cycle the patient starts tablets later than the proper day, she should protect herself by using another method of birth control until she has taken a white tablet daily for 7 consecutive days.

If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician.

Although the occurrence of pregnancy is highly unlikely if Cryselle® is taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken before the medication is resumed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

For additional patient instructions regarding missed pills, see the "WHAT TO DO IF YOU MISS PILLS" section in the DETAILED PATIENT LABELING below.

Any time the patient misses two or more white tablets, she should also use another method of contraception until she has taken a white tablet daily for seven consecutive days. If the patient misses one or more light-green tablets, she is still protected against pregnancy provided she begins taking white tablets again on the proper day. If breakthrough bleeding occurs following missed white tablets, it will usually be transient and of no consequence. While there is little likelihood of ovulation occurring if only one or two tablets are missed, the possibility of ovulation increases with each successive day that scheduled white tablets are missed.

In the nonlactating mother, Cryselle® may be initiated postpartum, for contraception. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease). It is to be noted that early resumption of ovulation may occur if Parlodel® (bromocriptine mesylate) has been used for the prevention of lactation.
Protriptyline Hydrochlo...

Protriptyline Hydrochloride

Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance. Usual Adult Dosage Fifteen to 40 mg a day divided into 3 or 4 doses. If necessary, dosage may be increased to 60 mg a day. Dosages above this amount are not recommended. Increases should be made in the morning dose. Adolescent and Elderly Patients In general, lower dosages are recommended for these patients. Five mg 3 times a day may be given initially, and increased gradually if necessary. In elderly patients, the cardiovascular system must be monitored closely if the daily dose exceeds 20 mg. When satisfactory improvement has been reached, dosage should be reduced to the smallest amount that will maintain relief of symptoms. Minor adverse reactions require reduction in dosage. Major adverse reactions or evidence of hypersensitivity require prompt discontinuation of the drug.
The safety and effectiveness of protriptyline in pediatric patients have not been established.
Kariva

Kariva

To achieve maximum contraceptive effectiveness, Kariva® (desogestrel/ethinyl estradiol and ethinyl estradiol) Tablets must be taken exactly as directed and at intervals not exceeding 24 hours. Kariva® may be initiated using either a Sunday start or a Day 1 start.

NOTE: Each cycle pack dispenser is preprinted with the days of the week, starting with Sunday, to facilitate a Sunday start regimen. Six different “day label strips” are provided with each cycle pack dispenser in order to accommodate a Day 1 start regimen. In this case, the patient should place the self-adhesive “day label strip” that corresponds to her starting day over the preprinted days.

IMPORTANT: The possibility of ovulation and conception prior to initiation of use of Kariva® should be considered.

The use of Kariva® 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 for Nursing mothers).

If the patient starts on Kariva® postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a white tablet has been taken daily for 7 days.

SUNDAY START

When initiating a Sunday start regimen, another method of contraception should be used until after the first 7 consecutive days of administration.

Using a Sunday start, tablets are taken daily without interruption as follows: The first white tablet should be taken on the first Sunday after menstruation begins (if menstruation begins on Sunday, the first white tablet is taken on that day). One white tablet is taken daily for 21 days, followed by 1 light-green (inert) tablet daily for 2 days and 1 light-blue (active) tablet daily for 5 days. For all subsequent cycles, the patient then begins a new 28 tablet regimen on the next day (Sunday) after taking the last light-blue tablet. [If switching from a Sunday start oral contraceptive, the first Kariva® (desogestrel/ethinyl estradiol and ethinyl estradiol) Tablet should be taken on the second Sunday after the last tablet of a 21 day regimen or should be taken on the first Sunday after the last inactive tablet of a 28 day regimen.]

If a patient misses 1 white tablet, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive white tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills. If the patient misses 2 consecutive white tablets in the third week or misses 3 or more white tablets in a row at any time during the cycle, the patient should keep taking 1 white tablet daily until the next Sunday. On Sunday the patient should throw out the rest of that cycle pack and start a new cycle pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills.

DAY 1 START

Counting the first day of menstruation as “Day 1”, tablets are taken without interruption as follows: One white tablet daily for 21 days, one light-green (inert) tablet daily for 2 days followed by 1 light-blue (ethinyl estradiol) tablet daily for 5 days. For all subsequent cycles, the patient then begins a new 28 tablet regimen on the next day after taking the last light-blue tablet. [If switching directly from another oral contraceptive, the first white tablet should be taken on the first day of menstruation which begins after the last ACTIVE tablet of the previous product.]

If a patient misses 1 white tablet, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive white tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills. If the patient misses 2 consecutive white tablets in the third week or if the patient misses 3 or more white tablets in a row at any time during the cycle, the patient should throw out the rest of that cycle pack and start a new cycle pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills.
Meperidine Hydrochlorid...

Meperidine Hydrochloride

For Relief of Pain

Dosage should be adjusted according to the severity of the pain and the response of the patient. Meperidine is less effective orally than on parenteral administration. The dose of meperidine hydrochloride should be proportionately reduced (usually by 25 to 50 percent) when administered concomitantly with phenothiazines and many other tranquilizers since they potentiate the action of meperidine HCl.

Adults: The usual dosage is 50 mg to 150 mg orally, every 3 or 4 hours as necessary.

Pediatric Patients: The usual dosage is 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as necessary (see PRECAUTIONS, Pediatric use).
Meperidine Hydrochlorid...

Meperidine Hydrochloride

For Relief of Pain

Dosage should be adjusted according to the severity of the pain and the response of the patient. Meperidine is less effective orally than on parenteral administration. The dose of meperidine hydrochloride should be proportionately reduced (usually by 25 to 50 percent) when administered concomitantly with phenothiazines and many other tranquilizers since they potentiate the action of meperidine HCl.

Adults: The usual dosage is 50 mg to 150 mg orally, every 3 or 4 hours as necessary.

Pediatric Patients: The usual dosage is 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as necessary (see PRECAUTIONS, Pediatric Use).
Velivet Triphasic Regim...

Velivet Triphasic Regimen

To achieve maximum contraceptive effectiveness, Velivet tablets must be taken exactly as directed, at the same time every day, and at intervals not exceeding 24 hours. Velivet tablets may be initiated using either a Sunday start or a Day 1 start.

NOTE: Each cycle pack dispenser is preprinted with the days of the week, starting with Sunday, to facilitate a Sunday start regimen. Six different "day label strips" are provided with each cycle pack dispenser in order to accommodate a Day 1 start regimen. In this case, the patient should place the self-adhesive "day label strip" that corresponds to her starting day over the preprinted days.

During the First Cycle of Use

IMPORTANT: The possibility of ovulation and conception prior to initiation of use of Velivet tablets should be considered. A woman can begin to take Velivet tablets either on the first Sunday after the onset of her menstrual period (Sunday Start) or on the first day of her menstrual period (Day 1 Start). When switching from another oral contraceptive, Velivet tablets should be started on the same day that a new pack of the previous oral contraceptive would have been started.

Sunday Start

When initiating a Sunday start regimen, another method of contraception, such as condoms or spermicide, should be used for the first 7 consecutive days of taking Velivet tablets.

Using a Sunday start, tablets are taken daily without interruption as follows: The first beige tablet should be taken on the first Sunday after menstruation begins (if menstruation begins on Sunday, the first beige tablet is taken on that day). Tablets are then taken sequentially following the arrows marked on the dispenser. One beige tablet is taken daily for 7 days, followed by 1 orange tablet daily for 7 days, 1 pink tablet daily for 7 days, and then 1 white (inactive) tablet daily for 7 days. For all subsequent cycles, the patient then begins a new 28 tablet regimen on the next day (Sunday) after taking the last white (inactive) tablet. [If switching from a Sunday Start oral contraceptive, the first Velivet tablet should be taken on the second Sunday after the last tablet of a 21 day oral contraceptive regimen or should be taken on the first Sunday after the last inactive tablet of a 28 day regimen.]

If a patient misses 1 active tablet in Weeks 1, 2, or 3, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive active tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack. The patient should be instructed to use a back-up method of birth control (such as condoms or spermicide) if she has intercourse in the 7 days after she restarts her pills. If the patient misses 2 consecutive pink (active) tablets in the third week or misses 3 or more active tablets in a row at any time during the cycle, the patient should keep taking 1 active tablet daily until the next Sunday. On Sunday the patient should throw out the rest of that cycle pack and start a new cycle pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after restarting her pills.

Complete instructions to facilitate patient counseling on proper pill usage can be found in Detailed or Brief Patient Labeling ("HOW TO TAKE THE PILL" section).

Day 1 Start

Counting the first day of menstruation as "Day 1", the first beige tablet should be taken on the first day of menstrual bleeding. Tablets are then taken sequentially without interruption as follows: One beige tablet daily for 7 days, then 1 orange tablet daily for 7 days, followed by 1 pink tablet daily for 7 days and then 1 white (inactive) tablet daily for 7 days. For all subsequent cycles, the patient then begins a new 28-tablet regimen on the next day after taking the last white (inactive) tablet. [If switching directly from another oral contraceptive, the first beige tablet should be taken on the same day that a new pack of the previous oral contraceptive would have been started.]

If a patient misses 1 active tablet in Weeks 1, 2, or 3, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive active tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack. The patient should be instructed to use a back-up method of birth control (such as condoms or spermicide) if she has intercourse in the 7 days after she restarts her pills. If the patient misses 2 consecutive pink tablets in the third week or misses 3 or more active tablets in a row at any time during the cycle, the patient should throw out the rest of that cycle pack and start a new cycle pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after she restarts her pills.

Complete instructions to facilitate patient counseling on proper pill usage can be found in Detailed or Brief Patient Labeling ("HOW TO TAKE THE PILL" section).

ADDITIONAL INSTRUCTIONS FOR BOTH SUNDAY AND DAY 1 STARTS

If Spotting or Breakthrough Bleeding Occurs

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, non-functional causes should be considered. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, adequate diagnostic measures are indicated to rule out pregnancy or malignancy. If both pregnancy and pathology have been excluded, time or a change to another preparation 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:

1. 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.

2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out. Oral contraceptive use should be discontinued if pregnancy is confirmed.
Use of Oral Contraceptives Postpartum:
The use of Velivet for contraception may be initiated 4 to 6 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).

If the patient starts on Velivet postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a beige tablet has been taken daily for 7 consecutive days.
Oxycodone And Acetamino...

Oxycodone And Acetaminophen

Dosage should be adjusted according to the severity of the pain and the response of the patient. It may occasionally be necessary to exceed the usual dosage recommended below in cases of more severe pain or in those patients who have become tolerant to the analgesic effect of opioids. If pain is constant, the opioid analgesic should be given at regular intervals on an around-the-clock schedule. Oxycodone and acetaminophen capsules are given orally.

The usual adult dosage is one capsule every 6 hours as needed for pain. The total daily dose of acetaminophen should not exceed 4 grams.

Cessation of Therapy

In patients treated with oxycodone and acetaminophen capsules for more than a few weeks who no longer require therapy, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.
Benzonatate

Benzonatate

Adults and Children over 10 years of age: Usual dose is one 100 mg or 200 mg capsule three times a day as needed for cough. If necessary to control cough, up to 600 mg daily in three divided doses may be given. BENZONATATE should be swallowed whole. BENZONATATE Capsules are not to be broken, chewed, dissolved, cut or crushed.
Donepezil Hydrochloride...

Donepezil Hydrochloride

For patients with sustained VT, no matter what their cardiac status, flecainide, like other antiarrhythmics, should be initiated in-hospital with rhythm monitoring.

Flecainide has a long half-life (12 to 27 hours in patients). Steady-state plasma levels, in patients with normal renal and hepatic function, may not be achieved until the patient has received 3 to 5 days of therapy at a given dose. Therefore, increases in dosage should be made no more frequently than once every four days, since during the first 2 to 3 days of therapy the optimal effect of a given dose may not be achieved.

For patients with PSVT and patients with PAF the recommended starting dose is 50 mg every 12 hours. Flecainide acetate doses may be increased in increments of 50 mg bid every four days until efficacy is achieved. For PAF patients, a substantial increase in efficacy without a substantial increase in discontinuations for adverse experiences may be achieved by increasing the flecainide acetate dose from 50 to 100 mg bid. The maximum recommended dose for patients with paroxysmal supraventricular arrhythmias is 300 mg/day.

For sustained VT the recommended starting dose is 100 mg every 12 hours. This dose may be increased in increments of 50 mg bid every four days until efficacy is achieved. Most patients with sustained VT do not require more than 150 mg every 12 hours (300 mg/day) and the maximum dose recommended is 400 mg/day.

In patients with sustained VT, use of higher initial doses and more rapid dosage adjustments have resulted in an increased incidence of proarrhythmic events and CHF, particularly during the first few days of dosing (see WARNINGS). Therefore, a loading dose is not recommended.

Intravenous lidocaine has been used occasionally with flecainide while awaiting the therapeutic effect of flecainide. No adverse drug interactions were apparent. However, no formal studies have been performed to demonstrate the usefulness of this regimen.

An occasional patient not adequately controlled by (or intolerant to) a dose given at 12 hour intervals may be dosed at eight-hour intervals.

Once adequate control of the arrhythmia has been achieved, it may be possible in some patients to reduce the dose as necessary to minimize side effects or effects on conduction. In such patients, efficacy at the lower dose should be evaluated.

Flecainide should be used cautiously in patients with a history of CHF or myocardial dysfunction (see WARNINGS).

Any use of flecainide in children should be directly supervised by a cardiologist skilled in the treatment of arrhythmias in children. Because of the evolving nature of information in this area, specialized literature should be consulted. Under six months of age, the initial starting dose of flecainide in children is approximately 50 mg/M2 body surface area daily, divided into two or three equally spaced doses. Over six months of age, the initial starting dose may be increased to 100 mg/M2 per day. The maximum recommended dose is 200 mg/M2 per day. This dose should not be exceeded. In some children on higher doses, despite previously low plasma levels, the level has increased rapidly to far above therapeutic values while taking the same dose. Small changes in dose may also lead to disproportionate increases in plasma levels. Plasma trough (less than one hour pre-dose) flecainide levels and electrocardiograms should be obtained at presumed steady state (after at least five doses) either after initiation or change in flecainide dose, whether the dose was increased for lack of effectiveness, or increased growth of the patient. For the first year on therapy, whenever the patient is seen for reasons of clinical follow-up, it is suggested that a 12 lead electrocardiogram and plasma trough flecainide level are obtained. The usual therapeutic level of flecainide in children is 200 to 500 ng/mL. In some cases, levels as high as 800 ng/mL may be required for control.

In patients with severe renal impairment (creatinine clearance of 35 mL/min/1.73 square meters or less), the initial dosage should be 100 mg once daily (or 50 mg bid); when used in such patients, frequent plasma level monitoring is required to guide dosage adjustments (see Plasma Level Monitoring). In patients with less severe renal disease, the initial dosage should be 100 mg every 12 hours; plasma level monitoring may also be useful in these patients during dosage adjustment. In both groups of patients, dosage increases should be made very cautiously when plasma levels have plateaued (after more than four days), observing the patient closely for signs of adverse cardiac effects or other toxicity. It should be borne in mind that in these patients it may take longer than four days before a new steady-state plasma level is reached following a dosage change.

Based on theoretical considerations, rather than experimental data, the following suggestion is made: when transferring patients from another antiarrhythmic drug to flecainide allow at least two to four plasma half-lives to elapse for the drug being discontinued before starting flecainide at the usual dosage. In patients where withdrawal of a previous antiarrhythmic agent is likely to produce life-threatening arrhythmias, the physician should consider hospitalizing the patient.

When flecainide is given in the presence of amiodarone, reduce the usual flecainide dose by 50% and monitor the patient closely for adverse effects. Plasma level monitoring is strongly recommended to guide dosage with such combination therapy (see below).

Plasma Level Monitoring

The large majority of patients successfully treated with flecainide were found to have trough plasma levels between 0.2 and 1 mcg/mL. The probability of adverse experiences, especially cardiac, may increase with higher trough plasma levels, especially when these exceed 1 mcg/mL. Periodic monitoring of trough plasma levels may be useful in patient management. Plasma level monitoring is required in patients with severe renal failure or severe hepatic disease, since elimination of flecainide from plasma may be markedly slower. Monitoring of plasma levels is strongly recommended in patients on concurrent amiodarone therapy and may also be helpful in patients with CHF and in patients with moderate renal disease.
Kelnor 135

Kelnor 135

To achieve maximum contraceptive effectiveness, oral contraceptives must be taken exactly as directed and at intervals of 24 hours.

IMPORTANT: If the Sunday start schedule is selected, the patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle. The possibility of ovulation and conception prior to initiation of use should be considered.

Kelnor 1/35 (28 Day Regimen) (ethynodiol diacetate and ethinyl estradiol tablets)

Dosage Schedule

The Kelnor 1/35 (28 Day Regimen) tablet dispenser contains 21 light yellow active tablets arranged in three numbered rows of 7 tablets each, followed by a fourth row of 7 white placebo tablets.

Days of the week are printed above the tablets, starting with Sunday on the left.

28 Day Schedule

For a DAY 1 START, count the first day of menstrual flow as Day 1 and the first tablet (light yellow) is then taken on Day 1. For a SUNDAY START when menstrual flow begins on or before Sunday, the first tablet (light yellow) is taken on that day. With either a DAY 1 START or SUNDAY START, 1 tablet (light yellow) is taken each day at the same time for 21 days. Then the white 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.

Special Notes

Spotting, Breakthrough Bleeding, or Nausea

If spotting (bleeding insufficient to require a pad), breakthrough bleeding (heavier bleeding similar to a menstrual flow), or nausea occurs the patient should continue taking her tablets as directed. The incidence of spotting, breakthrough bleeding or nausea is minimal, most frequently occurring in the first cycle. Ordinarily spotting or breakthrough bleeding will stop within a week. Usually the patient will begin to cycle regularly within two to three courses of tablet-taking. In the event of spotting or breakthrough bleeding organic causes should be borne in mind. (See WARNINGS, No. 11.)

Missed Menstrual Periods

Withdrawal flow will normally occur 2 or 3 days after the last active tablet is taken. Failure of withdrawal bleeding ordinarily does not mean that the patient is pregnant, providing the dosage schedule has been correctly followed. (See WARNINGS, No. 6.)

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.

The first intermenstrual interval after discontinuing the tablets is usually prolonged; consequently, a patient for whom a 28 day cycle is usual might not begin to menstruate for 35 days or longer. Ovulation in such prolonged cycles will occur correspondingly later in the cycle. Posttreatment cycles after the first one, however, are usually typical for the individual woman prior to taking tablets. (See WARNINGS, No. 11.)

Missed Tablets

If a woman misses taking one active tablet, the missed tablet should be taken as soon as it is remembered. In addition, the next tablet should be taken at the usual time. If two consecutive active tablets are missed in week 1 or week 2 of the dispenser, the dosage should be doubled for the next 2 days. The regular schedule should then be resumed, but an additional method of protection must be used as backup for the next 7 days if she has sex during that time or she may become pregnant.

If two consecutive active tablets are missed in week 3 of the dispenser or three consecutive active tablets are missed during any of the first 3 weeks of the dispenser, direct the patient to do one of the following: Day 1 Starters should discard the rest of the dispenser and begin a new dispenser that same day; Sunday Starters should continue to take 1 tablet daily until Sunday, discard the rest of the dispenser and begin a new dispenser that same day. The patient may not have a period this month; however, if she has missed two consecutive periods, pregnancy should be ruled out. An additional method of protection must be used as a backup for the next 7 days after the tablets are missed if she has sex during that time or she may become pregnant.

While there is little likelihood of ovulation if only one active tablet is missed, the possibility of spotting or breakthrough bleeding is increased and should be expected if two or more successive active tablets are missed. However, the possibility of ovulation increases with each successive day that scheduled active tablets are missed.

If one or more placebo tablets of Kelnor are missed, the Kelnor schedule should be resumed on the eighth day after the last light yellow tablet was taken. Omission of placebo tablets in the 28 tablet courses does not increase the possibility of conception provided that this schedule is followed.
Junel 120

Junel 120

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 days of the week stickers 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 days of the week sticker 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 Regimen

To achieve maximum contraceptive effectiveness, Junel ®21 must be taken exactly as directed and at intervals not exceeding 24 hours.

Junel ®21 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.
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. Day 1 Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive days of the week sticker that corresponds to her starting day over the preprinted days on the blister card. 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 days of the week sticker 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 Administration

Menstruation 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 a 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 Regimen

To achieve maximum contraceptive effectiveness, Junel ® Fe 28 must be taken exactly as directed and at intervals not exceeding 24 hours.

Junel ® Fe 28 provides a continuous administration regimen consisting of 21 light yellow or pink tablets of Junel ® and 7 brown nonhormone 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.”
Sunday Start Regimen: The patient begins taking the first light yellow or pink 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 light yellow or pink tablet is taken on the same day. The patient takes one light yellow or pink tablet daily for 21 days. The last light yellow or pink tablet in the dispenser will be taken on a Saturday. Upon completion of all 21 light yellow or pink 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-tablets, without interruption, the next day (Sunday), starting with the Sunday light yellow or pink tablet in the top row. Adhering to this regimen of one light yellow or pink 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. Day 1 Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive days of the week sticker that corresponds to her starting day over the preprinted days on the blister card. She starts taking one light yellow or pink tablet daily, beginning with the first light yellow or pink tablet in the top row. After the last light yellow or pink 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 yellow or pink tablet, again starting with the first tablet in the top row after placing the appropriate days of the week sticker over the preprinted days on the tablet dispenser. Following this regimen of 21 light yellow or pink 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 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 yellow or pink tablets, continue medication without interruption.

If a patient forgets to take one or more light yellow or pink 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 yellow or pink tablets are missed. While there is little likelihood of ovulation occurring if only one light yellow or pink tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive light yellow or pink 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 yellow or pink 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.
Camila

Camila

To achieve maximum contraceptive effectiveness, Camila® 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 PATIENT LABELING for detailed instructions.
Hydroxyzine Pamoate

Hydroxyzine Pamoate

For symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested: in adults, 50 to 100 mg q.i.d.; children under 6 years, 50 mg daily in divided doses; and over 6 years, 50 to 100 mg daily in divided doses.

For use in the management of pruritus due to allergic conditions such as chronic urticaria and atopic and contact dermatoses, and in histamine-mediated pruritus: in adults, 25 mg t.i.d. or q.i.d.; children under 6 years, 50 mg daily in divided doses; and over 6 years, 50 to 100 mg daily in divided doses.

As a sedative when used as a premedication and following general anesthesia: 50 to 100 mg in adults, and 0.6 mg/kg in children.

When treatment is initiated by the intramuscular route of administration, subsequent doses may be administered orally.

As with all medications, the dosage should be adjusted according to the patient’s response to therapy.
Lessina

Lessina

To achieve maximum contraceptive effectiveness, Lessina® (levonorgestrel and ethinyl estradiol tablets USP) must be taken exactly as directed at intervals not exceeding 24-hours.

Lessina Tablets are a monophasic preparation plus 7 inert tablets. The dosage of Lessina Tablets is one tablet daily for 21 consecutive days per menstrual cycle plus 7 white inert tablets according to the prescribed schedule. It is recommended that LessinaTablets be taken at the same time each day, preferably after the evening meal or at bedtime. During the first cycle of medication, the patient should be instructed to take one pink Lessina Tablet daily and then 7 white inert tablets for twenty-eight (28) consecutive days, beginning on day one (1) of her menstrual cycle. (The first day of menstruation is day one.) Withdrawal bleeding usually occurs within 3 days following the last pink tablet. (If LessinaTablets are first taken later than the first day of the first menstrual cycle of medication or postpartum, contraceptive reliance should not be placed on Lessina Tablets until after the first 7 consecutive days of administration. The possibility of ovulation and conception prior to initiation of medication should be considered.)

When switching from another oral contraceptive, Lessina Tablets should be started on the first day of bleeding following the last active tablet taken of the previous oral contraceptive.

The patient begins her next and all subsequent 28-day courses of Lessina Tablets on the same day of the week that she began her first course, following the same schedule. She begins taking her pink tablets on the next day after ingestion of the last white tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Lessina Tablets is started later than the next day, the patient should be protected by another means of contraception until she has taken a tablet daily for seven consecutive days.

If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance, however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician. Although the occurrence of pregnancy is highly unlikely if Lessina Tablets are taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more active tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken before the medication is resumed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

The risk of pregnancy increases with each active (pink) tablet missed. For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the DETAILED PATIENT LABELING below. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more white tablets, she is still protected against pregnancy provided she begins taking pink tablets again on the proper day.

In the nonlactating mother, Lessina Tablets may be initiated postpartum, for contraception. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease.) It is to be noted that early resumption of ovulation may occur if bromocriptine mesylate has been used for the prevention of lactation.
Medroxyprogesterone Ace...

Medroxyprogesterone Acetate

Secondary Amenorrhea

Medroxyprogesterone acetate tablets may be given in dosages of 5 or 10 mg daily for 5 to 10 days. A dose for inducing an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen is 10 mg of medroxyprogesterone acetate daily for 10 days. In cases of secondary amenorrhea, therapy may be started at any time. Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing medroxyprogesterone acetate therapy.

Abnormal Uterine Bleeding Due to Hormonal Imbalance in the Absence of Organic Pathology

Beginning on the calculated 16th or 21st day of the menstrual cycle, 5 or 10 mg of medroxyprogesterone acetate may be given daily for 5 to 10 days. To produce an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen, 10 mg of medroxyprogesterone acetate daily for 10 days beginning on the 16th day of the cycle is suggested. Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing therapy with medroxyprogesterone acetate. Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with medroxyprogesterone acetate.

Reduction of Endometrial Hyperplasia in Postmenopausal Women Receiving Daily 0.625 mg Conjugated Estrogens

When estrogen is prescribed for a postmenopausal woman with a uterus, a 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 with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be re-evaluated periodically as clinically appropriate (for example, 3 to 6 month intervals) to determine if treatment is still necessary (see 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.

Medroxyprogesterone acetate tablets may be given in dosages of 5 or 10 mg daily for 12 to 14 consecutive days per month, in postmenopausal women receiving daily 0.625 mg conjugated estrogens, either beginning on the 1st day of the cycle or the 16th day of the cycle.

Patients should be started at the lowest dose.

The lowest effective dose of medroxyprogesterone acetate has not been determined.
Enpresse

Enpresse

To achieve maximum contraceptive effectiveness, Enpresse Tablets (levonorgestrel and ethinyl estradiol tablets USP—triphasic regimen) must be taken exactly as directed and at intervals not exceeding 24 hours.

Enpresse Tablets are a three-phase preparation plus 7 inert tablets. The dosage of Enpresse Tablets is one tablet daily for 28 consecutive days per menstrual cycle in the following order: 6 pink tablets (phase 1), followed by 5 white tablets (phase 2), followed by 10 orange tablets (phase 3), plus 7 light-green inert tablets, according to the prescribed schedule.

It is recommended that Enpresse Tablets be taken at the same time each day, preferably after the evening meal or at bedtime. During the first cycle of medication, the patient should be instructed to take one Enpresse Tablet daily in the order of 6 pink, 5 white, 10 orange tablets, and then 7 light-green inert tablets for twenty-eight (28) consecutive days, beginning on day one (1) of her menstrual cycle. (The first day of menstruation is day one.) Withdrawal bleeding usually occurs within 3 days following the last orange tablet and may not have finished before the next pack is started. (If Enpresse Tablets are first taken later than the first day of the first menstrual cycle of medication or postpartum, contraceptive reliance should not be placed on Enpresse Tablets until after the first 7 consecutive days of administration and a nonhormonal back-up method of birth control should be used during those 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.)

When switching from another oral contraceptive, Enpresse Tablets should be started on the first day of bleeding following the last active tablet taken of the previous oral contraceptive.

The patient may switch any day from a progestin-only pill and should begin Enpresse the next day. If switching from an implant or injection, the patient should start Enpresse on the day of implant removal or, if using an injection, the day the next injection would be due. In switching from a progestin-only pill, injection, or implant, the patient should be advised to use a non-hormonal back-up method of birth control for the first 7 days of tablet-taking.

The patient begins her next and all subsequent 28-day courses of Enpresse Tablets on the same day of the week that she began her first course, following the same schedule. She begins taking her pink tablets on the next day after ingestion of the last light-green tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Any time a subsequent cycle of Enpresse Tablets is started later than the next day, the patient should be protected by another means of contraception until she has taken a tablet daily for seven consecutive days.

If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician. Although the occurrence of pregnancy is highly unlikely if Enpresse Tablets are taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken before the medication is resumed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

The risk of pregnancy increases with each active (pink, white, or orange) tablet missed. For additional patient instructions regarding missed pills, see the "WHAT TO DO IF YOU MISS PILLS" section in the DETAILED PATIENT LABELING below. If breakthrough bleeding occurs following missed active tablets, it will usually be transient and of no consequence. If the patient misses one or more light-green tablets, she is still protected against pregnancy provided she begins taking pink tablets again on the proper day.

Enpresse Tablets may be initiated no earlier than day 28 postpartum in the non-lactating mother or after a second trimester abortion due to the increased risk for thromboembolism (see “CONTRAINDICATIONS”,“WARNINGS” and “PRECAUTIONS” concerning thromboembolic disease). The patient should be advised to use a nonhormonal back-up method for the first 7 days of tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the start of combined oral contraceptive use or the patient must wait for her first menstrual period. In the case of first-trimester abortion, if the patient starts Enpresse immediately, additional contraceptive measures are not needed. It is to be noted that early resumption of ovulation may occur if Parlodel® (bromocriptine mesylate) has been used for the prevention of lactation.
Metronidazole

Metronidazole

2.1 Galantamine Hydrobromide Extended-Release Capsules

Galantamine hydrobromide extended-release capsules should be administered once daily in the morning, preferably with food.

The recommended starting dosage of galantamine hydrobromide extended-release capsules is 8 mg/day. The dosage should be increased to the initial maintenance dose of 16 mg/day after a minimum of 4 weeks. A further increase to 24 mg/day should be attempted after a minimum of 4 weeks at 16 mg/day. Dosage increases should be based upon assessment of clinical benefit and tolerability of the previous dose.

The dosage of galantamine hydrobromide extended-release capsules shown to be effective in a controlled clinical trial is 16 to 24 mg/day.

Patients currently being treated with galantamine tablets can convert to galantamine hydrobromide extended-release capsules by taking their last dose of galantamine tablets in the evening and starting galantamine hydrobromide extended-release capsules once daily treatment the next morning. Converting from galantamine tablets to galantamine hydrobromide extended-release capsules should occur at the same total daily dosage.

2.2 Galantamine Immediate-Release Tablets

The dosage of galantamine tablets shown to be effective in controlled clinical trials is 16 to 32 mg/day given as twice daily dosing. As the dosage of 32 mg/day is less well tolerated than lower dosages and does not provide increased effectiveness, the recommended dosage range is 16 to 24 mg/day given twice daily. The dosage of 24 mg/day did not provide a statistically significant greater clinical benefit than 16 mg/day. It is possible, however, that a daily dosage of 24 mg of galantamine tablets might provide additional benefit for some patients.

The recommended starting dosage of galantamine tablets is 4 mg twice a day (8 mg/day). The dosage should be increased to the initial maintenance dosage of 8 mg twice a day (16 mg/day) after a minimum of 4 weeks. A further increase to 12 mg twice a day (24 mg/day) should be attempted after a minimum of 4 weeks at 8 mg twice a day (16 mg/day).

Dosage increases should be based upon assessment of clinical benefit and tolerability of the previous dose.

Galantamine tablets should be administered twice a day, preferably with morning and evening meals.

Patients and caregivers should be advised to ensure adequate fluid intake during treatment. If therapy has been interrupted for more than three days, the patient should be restarted at the lowest dosage and the dosage escalated to the current dose.

The abrupt withdrawal of galantamine hydrobromide extended-release capsules and galantamine tablets in those patients who had been receiving dosages in the effective range was not associated with an increased frequency of adverse events in comparison with those continuing to receive the same dosages of that drug. The beneficial effects of galantamine hydrobromide extended-release capsules and galantamine tablets are lost, however, when the drug is discontinued.

2.3 Dosage in Patients With Hepatic Impairment

In patients with moderate hepatic impairment (Child-Pugh score of 7 to 9), the dosage should generally not exceed 16 mg/day. The use of galantamine hydrobromide extended-release capsules and galantamine tablets in patients with severe hepatic impairment (Child-Pugh score of 10 to 15) is not recommended [see Clinical Pharmacology (12.3)].

2.4 Dosage in Patients With Renal Impairment

In patients with creatinine clearance of 9 to 59 mL/min, the dosage should generally not exceed 16 mg/day. In patients with creatinine clearance less than 9 mL/min, the use of galantamine hydrobromide extended-release capsules and galantamine tablets is not recommended [see Clinical Pharmacology (12.3)].

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