Ranbaxy Pharmaceuticals Inc.

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Ranbaxy Pharmaceuticals Inc. Drugs

Amlodipine Besylate

Amlodipine Besylate

2.1 Adults

The usual initial antihypertensive oral dose of amlodipine besylate tablets is 5 mg once daily, and the maximum dose is 10 mg once daily.

Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding amlodipine besylate tablets to other antihypertensive therapy.

Adjust dosage according to blood pressure goals. In general, wait 7 to 14 days between titration steps. Titrate more rapidly, however, if clinically warranted, provided the patient is assessed frequently.

Angina: The recommended dose for chronic stable or vasospastic angina is 5 to 10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg for adequate effect.

Coronary artery disease: The recommended dose range for patients with coronary artery disease is 5 to 10 mg once daily. In clinical studies, the majority of patients required 10 mg [see Clinical Studies (14.4)].

2.2 Children

The effective antihypertensive oral dose in pediatric patients ages 6 to 17 years is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been studied in pediatric patients [see Clinical Pharmacology (12.4), Clinical Studies (14.1)].
Oxycodone Hcl

Oxycodone Hcl

2.1 Initial Dosing

OXYCODONE HCL EXTENDED-RELEASE TABLETS should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

OXYCODONE HCL EXTENDED-RELEASE TABLETS 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid.

Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with OXYCODONE HCL EXTENDED-RELEASE TABLETS [see Warnings and Precautions (5.2)].

OXYCODONE HCL EXTENDED-RELEASE TABLETS must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving OXYCODONE HCL EXTENDED-RELEASE TABLETS tablets will result in uncontrolled delivery of oxycodone and can lead to overdose or death [see Warnings and Precautions (5.1)].

Use of OXYCODONE HCL EXTENDED-RELEASE TABLETS as the First Opioid Analgesic Initiate treatment with OXYCODONE HCL EXTENDED-RELEASE TABLETS with one 10 mg tablet orally every 12 hours. Use of OXYCODONE HCL EXTENDED-RELEASE TABLETS in Patients who are not Opioid Tolerant The starting dose for patients who are not opioid tolerant is OXYCODONE HCL EXTENDED-RELEASE TABLETS 10 mg orally every 12 hours. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid. Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from other Oral Oxycodone Formulations to OXYCODONE HCL EXTENDED-RELEASE TABLETS

Patients receiving other oral oxycodone formulations may be converted to OXYCODONE HCL EXTENDED-RELEASE TABLETS by administering one-half of the patient's total daily oral oxycodone dose as OXYCODONE HCL EXTENDED-RELEASE TABLETS every 12 hours.

Conversion from other Opioids to OXYCODONE HCL EXTENDED-RELEASE TABLETS Discontinue all other around-the-clock opioid drugs when OXYCODONE HCL EXTENDED-RELEASE TABLETS therapy is initiated. There are no established conversion ratios for conversion from other opioids to OXYCODONE HCL EXTENDED-RELEASE TABLETS defined by clinical trials. Discontinue all other around-the-clock opioid drugs when OXYCODONE HCL EXTENDED-RELEASE TABLETS therapy is initiated and initiate dosing using OXYCODONE HCL EXTENDED-RELEASE TABLETS 10 mg orally every 12 hours. It is safer to underestimate a patient’s 24-hour oral oxycodone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxycodone requirements which could result in adverse reactions. While useful tables of opioid equivalents are readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. Conversion from Methadone to OXYCODONE HCL EXTENDED-RELEASE TABLETS Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

Conversion from Transdermal Fentanyl to OXYCODONE HCL EXTENDED-RELEASE TABLETS

Eighteen hours following the removal of the transdermal fentanyl patch, OXYCODONE HCL EXTENDED-RELEASE TABLETS treatment can be initiated. Although there has been no systematic assessment of such conversion, a conservative oxycodone dose, approximately 10 mg every 12 hours of OXYCODONE HCL EXTENDED-RELEASE TABLETS, should be initially substituted for each 25 mcg/hr fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to OXYCODONE HCL EXTENDED-RELEASE TABLETS, as there is limited documented experience with this conversion.

2.2 Titration and Maintenance of Therapy

Individually titrate OXYCODONE HCL EXTENDED-RELEASE TABLETS to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving OXYCODONE HCL EXTENDED-RELEASE TABLETS to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse and misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for the use of opioid analgesics. Patients who experience breakthrough pain may require a dose increase of OXYCODONE HCL EXTENDED-RELEASE TABLETS or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the OXYCODONE HCL EXTENDED-RELEASE TABLETS dose. Because steady-state plasma concentrations are approximated in 1 day, OXYCODONE HCL EXTENDED-RELEASE TABLETS dosage may be adjusted every 1 to 2 days. If unacceptable opioid-related adverse reactions are observed, the subsequent dose may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours. As a guideline, the total daily oxycodone dose usually can be increased by 25% to 50% of the current dose, each time an increase is clinically indicated.

2.3 Patients with Hepatic Impairment

For patients with hepatic impairment, start dosing patients at 1/3 to 1/2 the usual starting dose followed by careful dose titration [see Clinical Pharmacology (12.3)].

2.4 Discontinuation of OXYCODONE HCL EXTENDED-RELEASE TABLETS

When the patient no longer requires therapy with OXYCODONE HCL EXTENDED-RELEASE TABLETS tablets, use a gradual downward titration of the dose to prevent signs and symptoms of withdrawal in the physically dependent patient. Do not abruptly discontinue OXYCODONE HCL EXTENDED-RELEASE TABLETS.

2.5 Administration of OXYCODONE HCL EXTENDED-RELEASE TABLETS

Instruct patients to swallow OXYCODONE HCL EXTENDED-RELEASE TABLETS tablets intact. The tablets are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of oxycodone [see Warnings and Precautions (5.1)].

Instruct patients to take OXYCODONE HCL EXTENDED-RELEASE TABLETS one tablet at a time and with enough water to ensure complete swallowing immediately after placing in the mouth [see Warnings and Precautions (5.9) and Patient Counseling Information (17)].
Meloxicam

Meloxicam

Osteoarthritis

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

For the relief of the signs and symptoms of osteoarthritis the recommended starting and maintenance oral dose of meloxicam is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily.

The maximum recommended daily oral dose of Meloxicam is 15 mg.

Meloxicam may be taken without regard to timing of meals.
Seconal Sodium

Seconal Sodium

Dosages of barbiturates must be individualized with full knowledge of their particular characteristics. Factors of consideration are the patient’s age, weight, and condition.

Adults—As a hypnotic, 100 mg at bedtime. Preoperatively, 200 to 300 mg 1 to 2 hours before surgery.

Pediatric Patients—Preoperatively, 2 to 6 mg/kg, with a maximum dosage of 100 mg.

Special patient population—Dosage should be reduced in the elderly or debilitated because these patients may be more sensitive to barbiturates. Dosage should be reduced for patients with impaired renal function or hepatic disease.
Carvedilol

Carvedilol

Carvedilol should be taken with food to slow the rate of absorption and reduce the incidence of orthostatic effects.

2.1 Left Ventricular Dysfunction Following Myocardial Infarction

DOSAGE MUST BE INDIVIDUALIZED AND MONITORED DURING UP- TITRATION. Treatment with carvedilol may be started as an inpatient or outpatient and should be started after the patient is hemodynamically stable and fluid retention has been minimized. It is recommended that carvedilol be started at 6.25 mg twice daily and increased after 3 to 10 days, based on tolerability, to 12.5 mg twice daily, then again to the target dose of 25 mg twice daily. A lower starting dose may be used (3.125 mg twice daily) and/or the rate of up-titration may be slowed if clinically indicated (e.g., due to low blood pressure or heart rate, or fluid retention). Patients should be maintained on lower doses if higher doses are not tolerated. The recommended dosing regimen need not be altered in patients who received treatment with an IV or oral β-blocker during the acute phase of the myocardial infarction.

2.2 Hypertension

DOSAGE MUST BE INDIVIDUALIZED. The recommended starting dose of carvedilol is 6.25 mg twice daily. If this dose is tolerated, using standing systolic pressure measured about 1 hour after dosing as a guide, the dose should be maintained for 7 to 14 days, and then increased to 12.5 mg twice daily if needed, based on trough blood pressure, again using standing systolic pressure one hour after dosing as a guide for tolerance. This dose should also be maintained for 7 to 14 days and can then be adjusted upward to 25 mg twice daily if tolerated and needed. The full antihypertensive effect of carvedilol is seen within 7 to 14 days. Total daily dose should not exceed 50 mg.

Concomitant administration with a diuretic can be expected to produce additive effects and exaggerate the orthostatic component of carvedilol action.

2.3 Hepatic Impairment

Carvedilol should not be given to patients with severe hepatic impairment [see Contraindications (4)].
Amoxicillin And Clavula...

Amoxicillin And Clavulanate Potassium

Dosage:

Pediatric Patients:Based on the amoxicillin component, amoxicillin and clavulanate potassium for oral suspension, and amoxicillin and clavulanate potassium tablets (chewable) should be dosed as follows:

Neonates and infants aged < 12 weeks (3 months):Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended dose of amoxicillin and clavulanate potassium is 30 mg/kg/day divided q12h, based on the amoxicillin component. Clavulanate elimination is unaltered in this age group. Experience with the 200 mg/5 mL formulation in this age group is limited and, thus, use of the 125 mg/5 mL oral suspension is recommended.
Patients aged 12 weeks (3 months) and older INFECTIONS DOSING REGIMEN q12h* q8h 200 mg/5 mL or 400 mg/5 mL oral suspension† 125 mg/5 mL or 250 mg/5 mL oral suspension Otitis media‡, sinusitis, lower respiratory tract infections, and more severe infections 45 mg/kg/day q12h 40 mg/kg/day q8h Less severe infections 25 mg/kg/day q12h 20 mg/kg/day q8h
*The q12h regimen is recommended as it is associated with significantly less diarrhea. (See CLINICAL STUDIES.) However, the q12h formulations (200 mg and 400 mg) contain aspartame and should not be used by phenylketonurics.

†Each strength of suspension of amoxicillin and clavulanate potassium is available as a chewable tablet for use by older children.

‡Duration of therapy studied and recommended for acute otitis media is 10 days.

Pediatric Patients Weighing 40 kg and More:Should be dosed according to the following adult recommendations: The usual adult dose is one amoxicillin 500 mg and clavulanate potassium tablet every 12 hours or one amoxicillin 250 mg and clavulanate potassium tablet every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one amoxicillin 875 mg and clavulanate potassium tablet every 12 hours or one amoxicillin 500 mg and clavulanate potassium tablet every 8 hours. Among adults treated with 875 mg every 12 hours, significantly fewer experienced severe diarrhea or withdrawals with diarrhea versus adults treated with 500 mg every 8 hours. For detailed adult dosage recommendations, please see complete prescribing information for amoxicillin and clavulanate potassium tablets.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals. (See WARNINGS.)

Adults:Adults who have difficulty swallowing may be given the 125 mg/5 mL or 250 mg/5 mL suspension in place of the 500 mg tablet. The 200 mg/5 mL suspension or the 400 mg/5 mL suspension may be used in place of the 875 mg tablet. See dosage recommendations above for children weighing 40 kg or more.

The amoxicillin/clavulanate potassium 250 mg tablet and the 250 mg chewable tablet do not contain the same amount of clavulanic acid (as the potassium salt). Amoxicillin/clavulanate potassium 250 mg tablet contains 125 mg of clavulanic acid, whereas the 250 mg chewable tablet contains 62.5 mg of clavulanic acid. Therefore, amoxicillin/clavulanate potassium 250 mg tablet and the 250 mg chewable tablet should not be substituted for each other, as they are not interchangeable.

Due to the different amoxicillin to clavulanic acid ratios in amoxicillin/clavulanate potassium 250 mg tablet (250/125) versus amoxicillin/clavulanate potassium 250 mg chewable tablet (250/62.5), amoxicillin/clavulanate potassium 250 mg tablet should not be used until the child weighs at least 40 kg and more.

Directions for Mixing Oral Suspension: Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Add approximately 2/3 of the total amount of water for reconstitution (see table below) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.
Amoxicillin/Clavulanate Potassium for Oral Suspension, 200 mg/5 mL Bottle Size Amount of Water Required for Reconstitution 50 mL 47 mL 75 mL 70 mL 100 mL 94 mL
Each teaspoonful (5 mL) will contain 200 mg amoxicillin and 28.5 mg clavulanic acid as the potassium salt.
Amoxicillin/Clavulanate Potassium for Oral Suspension, 400 mg/5 mL Bottle Size Amount of Water Required for Reconstitution 50 mL 46 mL 75 mL 68 mL 100 mL 90 mL
Each teaspoonful (5 mL) will contain 400 mg amoxicillin and 57 mg clavulanic acid as the potassium salt.

Note:SHAKE ORAL SUSPENSION WELL BEFORE USING.

Reconstituted suspension must be stored under refrigeration and discarded after 10 days.

Administration:Amoxicillin and clavulanate potassium may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when amoxicillin and clavulanate potassium is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium should be taken at the start of a meal.
Clarithromycin Extended...

Clarithromycin Extended Release

Clarithromycin extended-release tablets should be taken with food.

Clarithromycin extended-release tablets should be swallowed whole and not chewed, broken or crushed.
ADULT DOSAGE GUIDELINES Clarithromycin Extended-Release Tablets Infection Dosage (q24h) Duration (days) Acute maxillary sinusitis due to 1 gram 14 H. influenzae M. catarrhalis S. pneumoniae Acute exacerbation of chronic bronchitis due to H. influenzae 1 gram 7 H. parainfluenzae 1 gram 7 M. catarrhalis 1 gram 7 S. pneumoniae 1 gram 7 Community-Acquired Pneumonia due to H. influenzae 1 gram 7 H. parainfluenzae 1 gram 7 M. catarrhalis 1 gram 7 S. pneumoniae 1 gram 7 C. pneumoniae 1 gram 7 M. pneumoniae 1 gram 7
Cephalexin

Cephalexin

Cephalexin is administered orally.

Adults— The adult dosage ranges from 1 to 4 g daily in divided doses. The usual adult dose is 250 mg every 6 hours. For the following infections, a dosage of 500 mg may be administered every 12 hours: streptococcal pharyngitis, skin and skin structure infections, and uncomplicated cystitis in patients over 15 years of age. Cystitis therapy should be continued for 7 to 14 days. For more severe infections or those caused by less susceptible organisms, larger doses may be needed. If daily doses of cephalexin greater than 4 g are required, parenteral cephalosporins, in appropriate doses, should be considered.

Pediatric Patients — The usual recommended daily dosage for pediatric patients is 25 to 50 mg/kg in divided doses. For streptococcal pharyngitis in patients over 1 year of age and for skin and skin structure infections, the total daily dose may be divided and administered every 12 hours.
Cephalexin Suspension Weight 125 mg/5 mL 10 kg (22 lb) 1/2 to 1 tsp q.i.d. 20 kg (44 lb) 1 to 2 tsp q.i.d. 40 kg (88 lb) 2 to 4 tsp q.i.d. Weight 250 mg/5 mL 10 kg (22 lb) 1/4 to 1/2 tsp q.i.d. 20 kg (44 lb) 1/2 to 1 tsp q.i.d. 40 kg (88 lb) 1 to 2 tsp q.i.d. or Weight 125 mg/5 mL 10 kg (22 lb) 1 to 2 tsp q.i.d. 20 kg (44 lb) 2 to 4 tsp q.i.d. 40 kg (88 lb) 4 to 8 tsp q.i.d. Weight 250 mg/5 mL 10 kg (22 lb) 1/2 to 1 tsp b.i.d. 20 kg (44 lb) 1 to 2 tsp b.i.d. 40 kg (88 lb) 2 to 4 tsp b.i.d.
In severe infections, the dosage may be doubled.

In the therapy of otitis media, clinical studies have shown that a dosage of 75 to 100 mg/kg/day in 4 divided doses is required.

In the treatment of β-hemolytic streptococcal infections, a therapeutic dosage of cephalexin should be administered for at least 10 days.
Cefuroxime Axetil

Cefuroxime Axetil

NOTE: CEFUROXIME AXETIL TABLETS AND CEFUROXIME AXETIL FOR ORAL SUSPENSION ARE NOT BIOEQUIVALENT AND ARE NOT SUBSTITUTABLE ON A MILLIGRAM-PER-MILLIGRAM BASIS (SEE CLINICAL PHARMACOLOGY).
Table 4: Cefuroxime Axetil Tablets(May be administered without regard to meals.) Population/Infection Dosage Duration (days) Adolescents and Adults (13 years and older) Pharyngitis/tonsillitis 250 mg b.i.d. 10 Acute bacterial maxillary sinusitis 250 mg b.i.d. 10 Acute bacterial exacerbations of chronic bronchitis 250 or 500 mg b.i.d. 10* Secondary bacterial infections of acute bronchitis 250 or 500 mg b.i.d. 5 to 10 Uncomplicated skin and skin-structure infections 250 or 500 mg b.i.d. 10 Uncomplicated urinary tract infections 250 mg b.i.d. 7 to 10 Uncomplicated gonorrhea 1,000 mg once single dose Early Lyme disease 500 mg b.i.d. 20 Pediatric Patients (who can swallow tablets whole) Acute otitis media 250 mg b.i.d. 10 Acute bacterial maxillary sinusitis 250 mg b.i.d. 10
*The safety and effectiveness of cefuroxime axetil administered for less than 10 days in patients with acute exacerbations of chronic bronchitis have not been established.

Patients With Renal Failure: The safety and efficacy of cefuroxime axetil in patients with renal failure have not been established. Since cefuroxime is renally eliminated, its half-life will be prolonged in patients with renal failure.
Nefazodone Hydrochlorid...

Nefazodone Hydrochloride

When deciding among alternative treatments available for depression, the prescriber should consider the risk of hepatic failure associated with nefazodone hydrochloride tablets, USP treatment (see WARNINGS).

Initial Treatment

The recommended starting dose for nefazodone hydrochloride tablet, USP is 200 mg/day, administered in two divided doses (BID). In the controlled clinical trials establishing the antidepressant efficacy of nefazodone, the effective dose range was generally 300 to 600 mg/day. Consequently, most patients, depending on tolerability and the need for further clinical effect, should have their dose increased. Dose increases should occur in increments of 100 mg/day to 200 mg/day, again on a BID schedule, at intervals of no less than 1 week. As with all antidepressants, several weeks on treatment may be required to obtain a full antidepressant response.

Dosage for Elderly or Debilitated Patients

The recommended initial dose for elderly or debilitated patients is 100 mg/day, administered in two divided doses (BID). These patients often have reduced nefazodone clearance and/or increased sensitivity to the side effects of CNS-active drugs. It may also be appropriate to modify the rate of subsequent dose titration. As steady-state plasma levels do not change with age, the final target dose based on a careful assessment of the patient’s clinical response may be similar in healthy younger and older patients.

Maintenance/Continuation/Extended Treatment

There is no body of evidence available from controlled trials to indicate how long the depressed patient should be treated with nefazodone. It is generally agreed, however, that pharmacological treatment for acute episodes of depression should continue for up to 6 months or longer. Whether the dose of antidepressant needed to induce remission is identical to the dose needed to maintain euthymia is unknown. Systematic evaluation of the efficacy of nefazodone has shown that efficacy is maintained for periods of up to 36 weeks following 16 weeks of open-label acute treatment (treated for 52 weeks total) at dosages that averaged 438 mg/day. For most patients, their maintenance dose was that associated with response during acute treatment. (See CLINICAL PHARMACOLOGY.) The safety of nefazodone in long-term use is supported by data from both double-blind and open-label trials involving more than 250 patients treated for at least one year.

Switching Patients to or from a Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with nefazodone. In addition, at least 7 days should be allowed after stopping nefazodone before starting an MAOI.
Felodipineextended-rele...

Felodipineextended-release

The recommended starting dose is 5 mg once a day. Depending on the patient's response, the dosage can be decreased to 2.5 mg or increased to 10 mg once a day. These adjustments should occur generally at intervals of not less than 2 weeks. The recommended dosage range is 2.5 - 10 mg once daily. In clinical trials, doses above 10 mg daily showed an increased blood pressure response but a large increase in the rate of peripheral edema and other vasodilatory adverse events (see ADVERSE REACTIONS). Modification of the recommended dosage is usually not required in patients with renal impairment.

Felodipine extended-release tablets should regularly be taken either without food or with a light meal (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism). Felodipine extended-release tablets should be swallowed whole and not crushed or chewed.

Geriatric Use

Patients over 65 years of age are likely to develop higher plasma concentrations of felodipine (see CLINICAL PHARMACOLOGY). In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range (2.5 mg daily). Elderly patients should have their blood pressure closely monitored during any dosage adjustment.

Patients with Impaired Liver Function

Patients with impaired liver function may have elevated plasma concentrations of felodipine and may respond to lower doses of felodipine extended-release tablets; therefore, patients should have their blood pressure monitored closely during dosage adjustment of felodipine extended-release tablets (see CLINICAL PHARMACOLOGY).
Oxycodone Hcl Controlle...

Oxycodone Hcl Controlled-release

General Principles

OXYCODONE HCl CONTROLLED-RELEASE TABLETS ARE AN OPIOID AGONIST AND A SCHEDULE II CONTROLLED SUBSTANCE WITH AN ABUSE LIABILITY SIMILAR TO MORPHINE. OXYCODONE, LIKE MORPHINE AND OTHER OPIOIDS USED IN ANALGESIA, CAN BE ABUSED AND IS SUBJECT TO CRIMINAL DIVERSION.

OXYCODONE HCl CONTROLLED-RELEASE TABLETS ARE TO BE SWALLOWED WHOLE AND ARE NOT TO BE BROKEN, CHEWED, OR CRUSHED. TAKING BROKEN, CHEWED, OR CRUSHED OXYCODONE HCl CONTROLLED-RELEASE TABLETS LEADS TO RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF OXYCODONE.

One Oxycodone HCl controlled-release 160 mg tablet is comparable to two 80 mg tablets when taken on an empty stomach. With a high-fat meal, however, there is a 25% greater peak plasma concentration following one 160 mg tablet. Dietary caution should be taken when patients are initially titrated to 160 mg tablets (see DOSAGE AND ADMINISTRATION).

Patients should be started on the lowest appropriate dose (see DOSAGE AND ADMINISTRATION; Initiation of Therapy).

In treating pain it is vital to assess the patient regularly and systematically. Therapy should also be regularly reviewed and adjusted based upon the patient's own reports of pain and side effects and the health professional's clinical judgment.

Oxycodone HCl Controlled-Release Tablets are a controlled-release oral formulation of oxycodone hydrochloride indicated for the management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time. The controlled-release nature of the formulation allows Oxycodone HCl Controlled-Release Tablets to be effectively administered every 12 hours (see CLINICAL PHARMACOLOGY; PHARMACOKINETICS AND METABOLISM). While symmetric (same dose AM and PM), around-the-clock, q12h dosing is appropriate for the majority of patients, some patients may benefit from asymmetric (different dose given in AM than in PM) dosing, tailored to their pain pattern. It is usually appropriate to treat a patient with only one opioid for around-the-clock therapy.

Physicians should individualize treatment using a progressive plan of pain management such as outlined by the World Health Organization, the American Pain Society and the Federation of State Medical Boards Model Guidelines. Healthcare professionals should follow appropriate pain management principles of careful assessment and ongoing monitoring (see BOXED WARNING).

Initiation of Therapy

It is critical to initiate the dosing regimen for each patient individually, taking into account the patient's prior opioid and non-opioid analgesic treatment. Attention should be given to:
the general condition and medical status of the patient; the daily dose, potency, and kind of the analgesic(s) the patient has been taking; the reliability of the conversion estimate used to calculate the dose of oxycodone; the patient's opioid exposure and opioid tolerance (if any); the Special Instructions for Oxycodone HCl Controlled-Release 80 mg, and 160 mg Tablets, or a Single Dose Greater Than 40 mg; and the balance between pain control and adverse experiences.
Care should be taken to use low initial doses of Oxycodone HCl Controlled-Release Tablets in patients who are not already opioid-tolerant, especially those who are receiving concurrent treatment with muscle relaxants, sedatives, or other CNS active medications (see PRECAUTIONS: Drug-Drug Interactions).

For initiation of Oxycodone HCl Controlled-Release Tablets therapy for patients previously taking opioids, the conversion ratios from Foley, KM. [NEJM, 1985; 313:84-95], found below, are a reasonable starting point, although not verified in well-controlled, multiple-dose trials.

Experience indicates a reasonable starting dose of Oxycodone HCl Controlled-Release Tablets for patients who are taking non-opioid analgesics and require continuous around-the-clock therapy for an extended period of time is 10 mg q12h. If a non-opioid analgesic is being provided, it may be continued. Oxycodone HCl Controlled-Release Tablets should be individually titrated to a dose that provides adequate analgesia and minimizes side effects.
Using standard conversion ratio estimates (see Table 4 below), multiply the mg/day of the previous opioids by the appropriate multiplication factors to obtain the equivalent total daily dose of oral oxycodone. When converting from oxycodone, divide the 24-hour oxycodone dose in half to obtain the twice a day (q12h) dose of Oxycodone HCl Controlled-Release Tablets. Round down to a dose which is appropriate for the tablet strengths available (10 mg,20 mg, 40 mg, and 80 mg tablets). Discontinue all other around-the-clock opioid drugs when Oxycodone HCl Controlled-Release Tablet therapy is initiated. No fixed conversion ratio is likely to be satisfactory in all patients, especially patients receiving large opioid doses. The recommended doses shown in Table 4 are only a starting point, and close observation and frequent titration are indicated until patients are stable on the new therapy. TABLE 4.
* To be used only for conversion to oral oxycodone. For patients receiveing high-dose parenteral opiods, a more conservative conversion is warranted. For example, for high-dose parenteral morphone, use 1.5 instead of 3 as a multiplication factor.
Multiplication Factors for Converting the Daily Dose of Prior Opiods to the Daily Dose of Oral Oxycodone* (Mg/Day Prior Opiod x Factor = Mg/Day Oral Oxycodone) Oral Prior Opiod Parenteral Prior Opiod Oxycodone 1 -- Codeine 0.15 -- Hydrocodone 0.9 -- Hydromorphone 4 20 Levorphanol 7.5 15 Meperidine 0.1 0.4 Methadone 1.5 3 Morphine 0.5 3
In all cases, supplemental analgesia should be made available in the form of a suitable short-acting analgesic.

Oxycodone HCl Controlled-Release Tablets can be safely used concomitantly with usual doses of non-opioid analgesics and analgesic adjuvants, provided care is taken to select a proper initial dose (see PRECAUTIONS).

Conversion from Transdermal Fentanyl to Oxycodone HCl Controlled-Release Tablets

Eighteen hours following the removal of the transdermal fentanyl patch, Oxycodone HCl Controlled-Release Tablet treatment can be initiated. Although there has been no systematic assessment of such conversion, a conservative oxycodone dose, approximately 10 mg q12h of Oxycodone HCl Controlled-Release Tablets, should be initially substituted for each 25-µg/hr fentanyl transdermal patch. The patient should be followed closely for early titration, as there is very limited clinical experience with this conversion.

Managing Expected Opioid Adverse Experiences

Most patients receiving opioids, especially those who are opioid-naive, will experience side effects. Frequently the side effects from Oxycodone HCl Controlled-Release Tablets are transient, but may require evaluation and management. Adverse events such as constipation should be anticipated and treated aggressively and prophylactically with a stimulant laxative and/or stool softener. Patients do not usually become tolerant to the constipating effects of opioids.

Other opioid-related side effects such as sedation and nausea are usually self-limited and often do not persist beyond the first few days. If nausea persists and is unacceptable to the patient, treatment with antiemetics or other modalities may relieve these symptoms and should be considered.

Patients receiving Oxycodone HCl Controlled-Release Tablets may pass an intact matrix “ghost” in the stool or via colostomy. These ghosts contain little or no residual oxycodone and are of no clinical consequence.

Individualization of Dosage

Once therapy is initiated, pain relief and other opioid effects should be frequently assessed. Patients should be titrated to adequate effect (generally mild or no pain with the regular use of no more than two doses of supplemental analgesia per 24 hours). Patients who experience breakthrough pain may require dosage adjustment or rescue medication. Because steady-state plasma concentrations are approximated within 24 to 36 hours, dosage adjustment may be carried out every 1 to 2 days. It is most appropriate to increase the q12h dose, not the dosing frequency. There is no clinical information on dosing intervals shorter than q12h. As a guideline, the total daily oxycodone dose usually can be increased by 25% to 50% of the current dose at each increase.

If signs of excessive opioid-related adverse experiences are observed, the next dose may be reduced. If this adjustment leads to inadequate analgesia, a supplemental dose of immediate-release oxycodone may be given. Alternatively, non-opioid analgesic adjuvants may be employed. Dose adjustments should be made to obtain an appropriate balance between pain relief and opioid-related adverse experiences.

If significant adverse events occur before the therapeutic goal of mild or no pain is achieved, the events should be treated aggressively. Once adverse events are under control, upward titration should continue to an acceptable level of pain control.

During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient and the caregiver/family.

Special Instructions for Oxycodone HCl Controlled-Release 80 mg Tablets, or a single dose greater than 40 mg (for use in opioid-tolerant patients only.)

Oxycodone HCl Controlled-Release 80 mg Tablets, or a single dose greater than 40 mg, are for use in opioid-tolerant patients only. A single daily dose greater than 40 mg, or total daily doses greater than 80 mg, may cause fatal respiratory depression when administered to patients who are not tolerant to the respiratory depressant effects of opioids. Patients should be instructed against use by individuals other than the patient for whom it was prescribed, as such inappropriate use may have severe medical consequences, including death.

One Oxycodone HCl Controlled-Release 160 mg tablet is comparable to two 80 mg tablets when taken on an empty stomach. With a high-fat meal, however, there is a 25% greater peak plasma concentration following one 160 mg tablet. Dietary caution should be taken when patients are initially titrated to 160 mg tablets.

Supplemental Analgesia

Most patients given around-the-clock therapy with controlled-release opioids may need to have immediate-release medication available for exacerbations of pain or to prevent pain that occurs predictably during certain patient activities (incident pain).

Maintenance of Therapy

The intent of the titration period is to establish a patient-specific q12h dose that will maintain adequate analgesia with acceptable side effects for as long as pain relief is necessary. Should pain recur then the dose can be incrementally increased to re-establish pain control. The method of therapy adjustment outlined above should be employed to re-establish pain control.

During chronic therapy, especially for non-cancer pain syndromes, the continued need for around-the-clock opioid therapy should be reassessed periodically (e.g., every 6 to 12 months) as appropriate.

Cessation of Therapy

When the patient no longer requires therapy with Oxycodone HCl Controlled-Release Tablets, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.

Conversion from Oxycodone HCl Controlled-Release Tablets to Parenteral Opioids

To avoid overdose, conservative dose conversion ratios should be followed.
Benazepril Hydrochlorid...

Benazepril Hydrochloride

Hypertension

Adults

The recommended initial dose for patients not receiving a diuretic is 10 mg once a day. The usual maintenance dosage range is 20-40 mg per day administered as a single dose or in two equally divided doses. A dose of 80 mg gives an increased response, but experience with this dose is limited. The divided regimen was more effective in controlling trough (pre-dosing) blood pressure than the same dose given as a once-daily regimen. Dosage adjustment should be based on measurement of peak (2-6 hours after dosing) and trough responses. If a once-daily regimen does not give adequate trough response, an increase in dosage or divided administration should be considered. If blood pressure is not controlled with benazepril hydrochloride tablets alone, a diuretic can be added.

Total daily doses above 80 mg have not been evaluated.

Concomitant administration of benazepril hydrochloride tablets with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics can lead to increases of serum potassium (see PRECAUTIONS).

In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of benazepril hydrochloride tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued two to three days prior to beginning therapy with benazepril hydrochloride tablets (see WARNINGS). Then, if blood pressure is not controlled with benazepril hydrochloride tablets alone, diuretic therapy should be resumed.

If the diuretic cannot be discontinued, an initial dose of 5 mg benazepril hydrochloride tablets should be used to avoid excessive hypotension.

Pediatrics

In children, doses of benazepril hydrochloride between 0.1 and 0.6 mg/kg once daily have been studied, and doses greater than 0.1 mg/kg were shown to reduce blood pressure (see Pharmacodynamics). Based on this, the recommended starting dose of benazepril hydrochloride is 0.2 mg/kg once per day as monotherapy. Doses above 0.6 mg/kg (or in excess of 40 mg daily) have not been studied in pediatric patients.

For pediatric patients who cannot swallow tablets, or for whom the calculated dosage (mg/kg) does not correspond to the available tablet strengths for benazepril hydrochloride tablets, follow the suspension preparation instructions below to administer benazepril hydrochloride tablets as a suspension.

Treatment with benazepril hydrochloride tablets is not advised for children below the age of 6 years (see PRECAUTIONS, Pediatric Use) and in pediatric patients with glomerular filtration rate <30 mL, as there are insufficient data available to support a dosing recommendation in these groups.

For Hypertensive Patients with Renal Impairment

For patients with a creatinine clearance <30 mL/min/1.73 m2 (serum creatinine >3 mg/dL), the recommended initial dose is 5 mg benazepril hydrochloride tablet once daily. Dosage may be titrated upward until blood pressure is controlled or to a maximum total daily dose of 40 mg (see WARNINGS).

Preparation of Suspension (for 150 mL of a 2 mg/mL suspension)

Add 75 mL of Ora-Plus®* oral suspending vehicle to an amber polyethylene terephthalate (PET) bottle containing fifteen benazepril hydrochloride 20 mg tablets, and shake for at least 2 minutes. Allow the suspension to stand for a minimum of 1 hour. After the standing time, shake the suspension for a minimum of 1 additional minute. Add 75 mL of Ora-Sweet®* oral syrup vehicle to the bottle and shake the suspension to disperse the ingredients. The suspension should be refrigerated at 2°-8°C (36°-46°F) and can be stored for up to 30 days in the PET bottle with a child-resistant screw-cap closure. Shake the suspension before each use.

*Ora-Plus® and Ora-Sweet® are registered trademarks of Paddock Laboratories, Inc. Ora-Plus® contains carrageenan, citric acid, methylparaben, microcrystalline cellulose, carboxymethylcellulose sodium, potassium sorbate, simethicone, sodium phosphate monobasic, xanthan gum, and water. Ora-Sweet® contains berry citrus flavorant, glycerin, methylparaben, potassium sorbate, sodium phosphate monobasic, sorbitol, sucrose, and water.
Ibuprofen

Ibuprofen

2.1 General Considerations

Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibrate capsules, and should continue this diet during treatment with fenofibrate capsules. Fenofibrate capsules can be given without regard to meals.

Patients should be advised to swallow fenofibrate capsules whole. Do not open, crush, dissolve or chew capsules.

The initial treatment for dyslipidemia is dietary therapy specific for the type of lipoprotein abnormality. Excess body weight and excess alcoholic intake may be important factors in hypertriglyceridemia and should be addressed prior to any drug therapy. Physical exercise can be an important ancillary measure. Diseases contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. Estrogen therapy, thiazide diuretics and beta-blockers are sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia. In such cases, discontinuation of the specific etiologic agent may obviate the need for specific drug therapy of hypertriglyceridemia.

Lipid levels should be monitored periodically and consideration should be given to reducing the dosage of fenofibrate capsules if lipid levels fall significantly below the targeted range.

Therapy should be withdrawn in patients who do not have an adequate response after two months of treatment with the maximum recommended dose of 130 mg once daily.

2.2 Primary Hypercholesterolemia and Mixed Dyslipidemia

The initial dose of fenofibrate capsules is 130 mg per day.

2.3 Severe Hypertriglyceridemia

The initial dose is 43 to 130 mg per day. Dosage should be individualized according to patient response, and should be adjusted if necessary following repeat lipid determinations at 4 to 8 week intervals. The maximum dose is 130 mg per day.

2.4 Impaired Renal Function

Treatment with fenofibrate capsules should be initiated at a dose of 43 mg per day in patients having mild to moderately impaired renal function, and increased only after evaluation of the effects on renal function and lipid levels at this dose. The use of fenofibrate capsules should be avoided in patients with severe renal impairment [ see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.5 Geriatric Patients

Dose selection for the elderly should be made on the basis of renal function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Ondansetron

Ondansetron

Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy

The recommended adult oral dosage of ondansetron tablets, USP is 24 mg given as three 8-mg tablets administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥ 50 mg/m

. Multiday, single-dose administration of a 24 mg dosage has not been studied.

There is no experience with the use of a 24 mg dosage in pediatric patients.

The dosage recommendation is the same as for the general population.

Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Cancer Chemotherapy

The recommended adult oral dosage is one 8-mg ondansetron tablet, USP given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8-mg ondansetron tablet, USP should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.

For pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4-mg ondansetron tablet, USP or one 4-mg given 3 times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4-mg ondansetron tablet, USP should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy.

The dosage is the same as for the general population.

Prevention of Nausea and Vomiting Associated With Radiotherapy, Either Total Body Irradiation, or Single High-Dose Fraction or Daily Fractions to the Abdomen

The recommended oral dosage is one 8-mg ondansetron tablet, USP given 3 times a day.

For total body irradiation, one 8-mg ondansetron tablet, USP should be administered 1 to 2 hours before each fraction of radiotherapy administered each day.

For single high-dose fraction radiotherapy to the abdomen, one 8-mg ondansetron tablet, USP should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.

, one 8-mg ondansetron tablet, USP should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.

There is no experience with the use of ondansetron tablet, USP in the prevention of radiation-induced nausea and vomiting in pediatric patients.

The dosage recommendation is the same as for the general population.

Postoperative Nausea and Vomiting

The recommended dosage is 16 mg given as two 8-mg ondansetron tablets, USP 1 hour before induction of anesthesia.

There is no experience with the use of ondansetron tablets, USP in the prevention of postoperative nausea and vomiting in pediatric patients.

The dosage is the same as for the general population.

Dosage Adjustment for Patients With Impaired Renal Function

The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.

Dosage Adjustment for Patients With Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh

score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life. In such patients, a total daily dose of 8 mg should not be exceeded.
Calcitriol

Calcitriol

The optimal daily dose of calcitriol must be carefully determined for each patient. Calcitriol can be administered orally either as a capsule (0.25 mcg or 0.50 mcg) or as an oral solution (1 mcg/mL). Calcitriol therapy should always be started at the lowest possible dose and should not be increased without careful monitoring of serum calcium.

The effectiveness of calcitriol therapy is predicated on the assumption that each patient is receiving an adequate but not excessive daily intake of calcium. Patients are advised to have a dietary intake of calcium at a minimum of 600 mg daily. The U.S. RDA for calcium in adults is 800 mg to 1200 mg. To ensure that each patient receives an adequate daily intake of calcium, the physician should either prescribe a calcium supplement or instruct the patient in proper dietary measures.

Because of improved calcium absorption from the gastrointestinal tract, some patients on calcitriol may be maintained on a lower calcium intake. Patients who tend to develop hypercalcemia may require only low doses of calcium or no supplementation at all.

During the titration period of treatment with calcitriol, serum calcium levels should be checked at least twice weekly. When the optimal dosage of calcitriol has been determined, serum calcium levels should be checked every month (or as given below for individual indications). Samples for serum calcium estimation should be taken without a tourniquet.

Dialysis Patients

The recommended initial dose of calcitriol is 0.25 mcg/day. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease state is not observed, dosage may be increased by 0.25 mcg/day at 4- to 8-week intervals. During this titration period, serum calcium levels should be obtained at least twice weekly, and if hypercalcemia is noted, the drug should be immediately discontinued until normocalcemia ensues (see PRECAUTIONS: General). Phosphorus, magnesium, and alkaline phosphatase should be determined periodically.

Patients with normal or only slightly reduced serum calcium levels may respond to calcitriol doses of 0.25 mcg every other day. Most patients undergoing hemodialysis respond to doses between 0.5 and 1 mcg/day.

Oral calcitriol may normalize plasma-ionized calcium in some uremic patients, yet fail to suppress parathyroid hyperfunction. In these individuals with autonomous parathyroid hyperfunction, oral calcitriol may be useful to maintain normocalcemia, but has not been shown to be adequate treatment for hyperparathyroidism.

Hypoparathyroidism

The recommended initial dosage of calcitriol is 0.25 mcg/day given in the morning. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease is not observed, the dose may be increased at 2- to 4-week intervals. During the dosage titration period, serum calcium levels should be obtained at least twice weekly and, if hypercalcemia is noted, calcitriol should be immediately discontinued until normocalcemia ensues (see PRECAUTIONS: General). Careful consideration should also be given to lowering the dietary calcium intake. Serum calcium, phosphorus, and 24-hour urinary calcium should be determined periodically.

Most adult patients and pediatric patients age 6 years and older have responded to dosages in the range of 0.5 mcg to 2 mcg daily. Pediatric patients in the 1- to 5-year age group with hypoparathyroidism have usually been given 0.25 mcg to 0.75 mcg daily. The number of treated patients with pseudohypoparathyroidism less than 6 years of age is too small to make dosage recommendations.

Malabsorption is occasionally noted in patients with hypoparathyroidism; hence, larger doses of calcitriol may be needed.

Predialysis Patients

The recommended initial dosage of calcitriol is 0.25 mcg/day in adults and pediatric patients 3 years of age and older. This dosage may be increased if necessary to 0.5 mcg/day.

For pediatric patients less than 3 years of age, the recommended initial dosage of calcitriol is 10 to 15 ng/kg/day.
Minocycline Hydrochlori...

Minocycline Hydrochloride

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF MINOCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Minocycline hydrochloride tablets may be taken with or without food (see CLINICALPHARMACOLOGY).

Ingestion of adequate amounts of fluids along with capsule and tablet forms of drugs in the tetracycline-class is recommended to reduce the risk of esophageal irritation and ulceration.

For Pediatric Patients Above 8 Years Of Age

Usual pediatric dose: 4 mg/kg initially followed by 2 mg/kg every 12 hours, not to exceed the usual adult dose.

Adults

The usual dosage of minocycline hydrochloride tablets is 200 mg initially followed by 100 mg every 12 hours. Alternatively, if more frequent doses are preferred, two or four 50 mg tablets may be given initially followed by one 50 mg tablet 4 times daily.

Uncomplicated gonococcal infections other than urethritis and anorectal infections in men: 200 mg initially, followed by 100 mg every 12 hours for a minimum of 4 days, with post-therapy cultures within 2 to 3 days.

In the treatment of uncomplicated gonococcal urethritis in men, 100 mg every 12 hours for 5 days is recommended.

For the treatment of syphilis, the usual dosage of minocycline hydrochloride should be administered over a period of 10 to 15 days. Close follow-up, including laboratory tests, is recommended.

In the treatment of meningococcal carrier state, the recommended dosage is 100 mg every 12 hours for 5 days.

Mycobacterium marinum infections: Although optimal doses have not been established, 100 mg every 12 hours for 6 to 8 weeks have been used successfully in a limited number of cases.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis or Ureaplasma urealyticum: 100 mg orally, every 12 hours for at least 7 days.

Ingestion of adequate amounts of fluids along with capsule and tablet forms of drugs in the tetracycline-class is recommended to reduce the risk of esophageal irritation and ulceration.

The pharmacokinetics of minocycline in patients with renal impairment (CL CR < 80 mL/min) have not been fully characterized. Current data are insufficient to determine if a dosage adjustment is warranted. The total daily dosage should not exceed 200 mg in 24 hours. However, due to the anti-anabolic effect of tetracyclines, BUN and creatinine should be monitored (see WARNINGS).
Doxycycline

Doxycycline

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE TABLETS DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Adults: The usual dose of oral doxycycline tablets is 200 mg on the first day of treatment (administered 100 mg every 12 hours or 50 mg every 6 hours) followed by a maintenance dose of 100 mg/day. The maintenance dose may be administered as a single dose or as 50 mg every 12 hours. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

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

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose.

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

Primary and secondary syphilis: 300 mg a day in divided doses for at least 10 days.

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

Nongonococcal urethritis caused by C. trachomatis and U. urealyticum: 100 mg, by mouth, twice a day for at least 7 days.

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

Inhalational anthrax (post-exposure):

ADULTS: 100 mg of doxycycline tablets, by mouth, twice a day for 60 days. CHILDREN: weighing less than 100 pounds (45 kg); 1 mg/lb (2.2 mg/kg) of body weight, by mouth, twice a day for 60 days. Children weighing 100 pounds or more should receive the adult dose.

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

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS.) If gastric irritation occurs, doxycycline tablets may be given with food. Ingestion of a high fat meal has been shown to delay the time to peak plasma concentrations by an average of one hour and 20 minutes. However, in the same study, food enhanced the average peak concentration by 7.5% and the area under the curve by 5.7%.
Flecainide Acetate

Flecainide Acetate

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 dose from 50 mg 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 maybe 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.
Metoclopramide

Metoclopramide

Therapy with metoclopramide tablets should not exceed 12 weeks in duration.

For the Relief of Symptomatic Gastroesophageal Reflux

Administer from 10 mg to 15 mg metoclopramide tablets, USP orally up to q.i.d. 30 minutes before each meal and at bedtime, depending upon symptoms being treated and clinical response (see CLINICAL PHARMACOLOGY and INDICATIONS AND USAGE). If symptoms occur only intermittently or at specific times of the day, use of metoclopramide in single doses up to 20 mg prior to the provoking situation may be preferred rather than continuous treatment. Occasionally, patients (such as elderly patients) who are more sensitive to the therapeutic or adverse effects of metoclopramide will require only 5 mg per dose.

Experience with esophageal erosions and ulcerations is limited, but healing has thus far been documented in one controlled trial using q.i.d. therapy at 15 mg/dose, and this regimen should be used when lesions are present, so long as it is tolerated (see ADVERSE REACTIONS). Because of the poor correlation between symptoms and endoscopic appearance of the esophagus, therapy directed at esophageal lesions is best guided by endoscopic evaluation.

Therapy longer than 12 weeks has not been evaluated and cannot be recommended.

For the Relief of Symptoms Associated with Diabetic Gastroparesis (Diabetic Gastric Stasis)

Administer 10 mg of metoclopramide 30 minutes before each meal and at bedtime for two to eight weeks, depending upon response and the likelihood of continued well-being upon drug discontinuation.

The initial route of administration should be determined by the severity of the presenting symptoms. If only the earliest manifestations of diabetic gastric stasis are present, oral administration of metoclopramide tablets may be initiated. However, if severe symptoms are present, therapy should begin with metoclopramide injection (consult labeling of the injection prior to initiating parenteral administration).

Administration of metoclopramide injection up to 10 days may be required before symptoms subside, at which time oral administration may be instituted. Since diabetic gastric stasis is frequently recurrent, metoclopramide tablets therapy should be reinstituted at the earliest manifestation.

Use in Patients with Renal or Hepatic Impairment

Since metoclopramide is excreted principally through the kidneys, in those patients whose creatinine clearance is below 40 mL/min, therapy should be initiated at approximately one-half the recommended dosage. Depending upon clinical efficacy and safety considerations, the dosage may be increased or decreased as appropriate.

See OVERDOSAGEsection for information regarding dialysis.

Metoclopramide undergoes minimal hepatic metabolism, except for simple conjugation. Its safe use has been described in patients with advanced liver disease whose renal function was normal.
Clorazepate Dipotassium...

Clorazepate Dipotassium

For the symptomatic relief of anxiety: Clorazepate dipotassium tablets are administered orally in divided doses. The usual daily dose is 30 mg. The dose should be adjusted gradually within the range of 15 to 60 mg daily in accordance with the response of the patient. In elderly or debilitated patients it is advisable to initiate treatment at a daily dose of 7.5 to 15 mg.

Clorazepate dipotassium tablets may also be administered in a single dose daily at bedtime; the recommended initial dose is 15 mg. After the initial dose, the response of the patient may require adjustment of subsequent dosage. Lower doses may be indicated in the elderly patient. Drowsiness may occur at the initiation of treatment and with dosage increment.

For the symptomatic relief of acute alcohol withdrawal:

The following dosage schedule is recommended:
1st 24 hours (Day 1) 30 mg initially; followed by 30 to 60 mg in divided doses 2nd 24 hours (Day 2) 45 to 90 mg in divided doses 3rd 24 hours (Day 3) 22.5 to 45 mg in divided doses Day 4 15 to 30 mg in divided doses
Thereafter, gradually reduce the daily dose to 7.5 to 15 mg. Discontinue drug therapy as soon as patient's condition is stable.

The maximum recommended total daily dose is 90 mg. Avoid excessive reductions in the total amount of drug administered on successive days.

As an Adjunct to Antiepileptic Drugs: In order to minimize drowsiness, the recommended initial dosages and dosage increments should not be exceeded.

Adults: The maximum recommended initial dose in patients over 12 years old is 7.5 mg three times a day. Dosage should be increased by no more than 7.5 mg every week and should not exceed 90 mg/day.

Children (9 to 12 years): The maximum recommended initial dose is 7.5 mg two times a day. Dosage should be increased by no more than 7.5 mg every week and should not exceed 60 mg/day.
Cevimeline

Cevimeline

The recommended dose of cevimeline hydrochloride capsules is 30 mg taken three times a day. There is insufficient safety information to support doses greater than 30 mg tid. There is also insufficient evidence for additional efficacy of cevimeline hydrochloride at doses greater than 30 mg tid.
Nars Pro-prime Light Op...

Nars Pro-prime Light Optimizing Primer

Hypertension

Adults

The recommended initial dose for patients not receiving a diuretic is 10 mg once a day. The usual maintenance dosage range is 20 to 40 mg per day administered as a single dose or in two equally divided doses. A dose of 80 mg gives an increased response, but experience with this dose is limited. The divided regimen was more effective in controlling trough (pre-dosing) blood pressure than the same dose given as a once-daily regimen. Dosage adjustment should be based on measurement of peak (2 to 6 hours after dosing) and trough responses. If a once-daily regimen does not give adequate trough response, an increase in dosage or divided administration should be considered. If blood pressure is not controlled with benazepril hydrochloride tablet alone, a diuretic can be added.

Total daily doses above 80 mg have not been evaluated.

Concomitant administration of benazepril hydrochloride tablet with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics can lead to increases of serum potassium (see PRECAUTIONS).

In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of benazepril hydrochloride tablet. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued two to three days prior to beginning therapy with benazepril hydrochloride tablet (see WARNINGS). Then, if blood pressure is not controlled with benazepril hydrochloride tablets alone, diuretic therapy should be resumed.

If the diuretic cannot be discontinued, an initial dose of 5 mg benazepril hydrochloride tablet should be used to avoid excessive hypotension.

Pediatrics

In children, doses of benazepril hydrochloride tablet between 0.1 and 0.6 mg/kg once daily have been studied, and doses greater than 0.1 mg/kg were shown to reduce blood pressure (see Pharmacodynamics). Based on this, the recommended starting dose of benazepril hydrochloride tablet is 0.2 mg/kg once per day as monotherapy. Doses above 0.6 mg/kg (or in excess of 40 mg daily) have not been studied in pediatric patients.

Treatment with benazepril hydrochloride tablet is not advised for children below the age of 6 years (see PRECAUTIONS, Pediatric Use) and in pediatric patients with glomerular filtration rate < 30 mL, as there are insufficient data available to support a dosing recommendation in these groups.

For Hypertensive Patients with Renal Impairment

For patients with a creatinine clearance < 30 mL/min/1.73 m2 (serum creatinine > 3 mg/dL), the recommended initial dose is 5 mg benazepril hydrochloride tablet once daily. Dosage may be titrated upward until blood pressure is controlled or to a maximum total daily dose of 40 mg (see WARNINGS).
Atorvastatin Calcium

Atorvastatin Calcium

2.1 Hyperlipidemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb)

The recommended starting dose of atorvastatin calcium tablets is 10 or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range of atorvastatin calcium tablets is 10 to 80 mg once daily. Atorvastatin calcium tablets can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance doses of atorvastatin calcium tablets should be individualized according to patient characteristics such as goal of therapy and response (see current NCEP Guidelines). After initiation and/or upon titration of atorvastatin calcium tablets, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly.

2.2 Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10 to 17 years of age)

The recommended starting dose of atorvastatin calcium tablets is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy [see current NCEP Pediatric Panel Guidelines, Clinical Pharmacology(12), and Indications and Usage (1.2)]. Adjustments should be made at intervals of 4 weeks or more.

2.3 Homozygous Familial Hypercholesterolemia

The dosage of atorvastatin calcium tablets in patients with homozygous FH is 10 to 80 mg daily. Atorvastatin calcium tablets should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

2.4 Concomitant Lipid-Lowering Therapy

Atorvastatin calcium tablets may be used with bile acid resins. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should generally be used with caution [see Warnings and Precautions, Skeletal Muscle (5.1), Drug Interactions (7)].

2.5 Dosage in Patients With Renal Impairment

Renal disease does not affect the plasma concentrations nor LDL-C reduction of atorvastatin calcium tablets; thus, dosage adjustment in patients with renal dysfunction is not necessary [see Warnings and Precautions, Skeletal Muscle (5.1), Clinical Pharmacology, Pharmacokinetics (12.3)].

2.6 Dosage in Patients Taking Cyclosporine, Clarithromycin, Itraconazole, or Certain Protease Inhibitors

In patients taking cyclosporine or the HIV protease inhibitors (tipranavir plus ritonavir) or the hepatitis C protease inhibitor (telaprevir), therapy with atorvastatin calcium tablets should be avoided. In patients with HIV taking lopinavir plus ritonavir, caution should be used when prescribing atorvastatin calcium tablets and the lowest dose necessary employed. In patients taking clarithromycin, itraconazole, or in patients with HIV taking a combination of saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, therapy with atorvastatin calcium tablets should be limited to 20 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin calcium tablets is employed. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, therapy with atorvastatin calcium tablets should be limited to 40 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin calcium tablets is employed [see Warnings and Precautions, Skeletal Muscle (5.1), Drug Interactions (7)].
Pioglitazone

Pioglitazone

2.1 Recommendations for All Patients

Pioglitazone tablets should be taken once daily and can be taken without regard to meals.

The recommended starting dose for patients without congestive heart failure is 15 mg or 30 mg once daily.

The recommended starting dose for patients with congestive heart failure (NYHA Class I or II) is 15 mg once daily.

The dose can be titrated in increments of 15 mg up to a maximum of 45 mg once daily based on glycemic response as determined by HbA1c.

After initiation of pioglitazone tablets or with dose increase, monitor patients carefully for adverse reactions related to fluid retention such as weight gain, edema, and signs and symptoms of congestive heart failure [see Boxed Warning and Warnings and Precautions (5.2)].

Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating pioglitazone tablets. Routine periodic monitoring of liver tests during treatment with pioglitazone tablets is not recommended in patients without liver disease. Patients who have liver test abnormalities prior to initiation of pioglitazone tablets or who are found to have abnormal liver tests while taking pioglitazone tablets should be managed as described under Warnings and Precautions [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

2.2 Concomitant Use with an Insulin Secretagogue or Insulin

If hypoglycemia occurs in a patient coadministered pioglitazone tablets and an insulin secretagogue (e.g., sulfonylurea), the dose of the insulin secretagogue should be reduced.

If hypoglycemia occurs in a patient coadministered pioglitazone tablets and insulin, the dose of insulin should be decreased by 10% to 25%. Further adjustments to the insulin dose should be individualized based on glycemic response.

2.3 Coadministration with Strong CYP2C8 Inhibitors

Coadministration of pioglitazone tablets and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure approximately 3-fold. Therefore, the maximum recommended dose of pioglitazone tablets is 15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Kirkland Signature Mino...

Kirkland Signature Minoxidil

Dose once daily. The dosage may then be increased after 2 to 3 weeks as needed to help achieve blood pressure goals. The maximum recommended dose is 20 mg/25 mg.

Switch Therapy: A patient whose blood pressure is not adequately controlled with benazepril alone or with hydrochlorothiazide alone may be switched to combination therapy with benazepril hydrochloride and hydrochlorothiazide tablets. The usual recommended starting dose is 10/12.5 mg once daily to control blood pressure.

Replacement Therapy: The combination may be substituted for the titrated individual components.
Glycopyrrolate

Glycopyrrolate

The dosage of glycopyrrolate tablets, USP should be adjusted to the needs of the individual patient to assure symptomatic control with a minimum of adverse reactions. The presently recommended maximum daily dosage of glycopyrrolate is 8 mg.

Glycopyrrolate 1 mg tablets. The recommended initial dosage of glycopyrrolate tablets, USP for adults is one tablet three times daily (in the morning, early afternoon, and at bedtime). Some patients may require two tablets at bedtime to assure overnight control of symptoms. For maintenance, a dosage of one tablet twice a day is frequently adequate.

Glycopyrrolate 2 mg tablets. The recommended dosage of glycopyrrolate tablets, USP for adults is one tablet two or three times daily at equally spaced intervals.

Glycopyrrolate tablets, USP are not recommended for use in pediatric patients under the age of 12 years.
Sertraline Hydrochlorid...

Sertraline Hydrochloride

Initial Treatment

Dosage for Adults

Major Depressive Disorder and Obsessive-Compulsive Disorder–Sertraline hydrochloride treatment should be administered at a dose of 50 mg once daily.

Panic Disorder, Posttraumatic Stress Disorder and Social Anxiety Disorder–Sertraline hydrochloride treatment should be initiated with a dose of 25 mg once daily. After one week, the dose should be increased to 50 mg once daily.

While a relationship between dose and effect has not been established for major depressive disorder, OCD, panic disorder, PTSD or social anxiety disorder, patients were dosed in a range of 50 to 200 mg/day in the clinical trials demonstrating the effectiveness of sertraline for the treatment of these indications. Consequently, a dose of 50 mg, administered once daily, is recommended as the initial therapeutic dose. Patients not responding to a 50 mg dose may benefit from dose increases up to a maximum of 200 mg/day. Given the 24 hour elimination half-life of sertraline, dose changes should not occur at intervals of less than 1 week.

Premenstrual Dysphoric Disorder–Sertraline hydrochloride treatment should be initiated with a dose of 50 mg/day, either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle, depending on physician assessment.

While a relationship between dose and effect has not been established for PMDD, patients were dosed in the range of 50 to 150 mg/day with dose increases at the onset of each new menstrual cycle (see Clinical Trials under CLINICAL PHARMACOLOGY). Patients not responding to a 50 mg/day dose may benefit from dose increases (at 50 mg increments/menstrual cycle) up to 150 mg/day when dosing daily throughout the menstrual cycle, or 100 mg/day when dosing during the luteal phase of the menstrual cycle. If a 100 mg/day dose has been established with luteal phase dosing, a 50 mg/day titration step for three days should be utilized at the beginning of each luteal phase dosing period.

Sertraline hydrochloride tablets should be administered once daily, either in the morning or evening.

Dosage for Pediatric Population (Children and Adolescents)

Obsessive-Compulsive Disorder–Sertraline hydrochloride treatment should be initiated with a dose of 25 mg once daily in children (ages 6 to 12) and at a dose of 50 mg once daily in adolescents (ages 13 to 17).

While a relationship between dose and effect has not been established for OCD, patients were dosed in a range of 25 to 200 mg/day in the clinical trials demonstrating the effectiveness of sertraline hydrochloride for pediatric patients (6 to 17 years) with OCD. Patients not responding to an initial dose of 25 or 50 mg/day may benefit from dose increases up to a maximum of 200 mg/day. For children with OCD, their generally lower body weights compared to adults should be taken into consideration in advancing the dose, in order to avoid excess dosing. Given the 24 hour elimination half-life of sertraline hydrochloride, dose changes should not occur at intervals of less than 1 week.

Sertraline hydrochloride should be administered once daily, either in the morning or evening.

Maintenance/Continuation/Extended Treatment

Major Depressive Disorder–It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy beyond response to the acute episode. Systematic evaluation of sertraline hydrochloride has demonstrated that its antidepressant efficacy is maintained for periods of up to 44 weeks following 8 weeks of initial treatment at a dose of 50 to 200 mg/day (mean dose of 70 mg/day) (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline hydrochloride needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment.

Posttraumatic Stress Disorder–It is generally agreed that PTSD requires several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of sertraline hydrochloride has demonstrated that its efficacy in PTSD is maintained for periods of up to 28 weeks following 24 weeks of treatment at a dose of 50 to 200 mg/day (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline hydrochloride needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment.

Social Anxiety Disorder–Social anxiety disorder is a chronic condition that may require several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of sertraline hydrochloride has demonstrated that its efficacy in social anxiety disorder is maintained for periods of up to 24 weeks following 20 weeks of treatment at a dose of 50 to 200 mg/day (see Clinical Trials under CLINICAL PHARMACOLOGY). Dosage adjustments should be made to maintain patients on the lowest effective dose and patients should be periodically reassessed to determine the need for long-term treatment.

Obsessive-Compulsive Disorder and Panic Disorder–It is generally agreed that OCD and Panic Disorder require several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of continuing sertraline hydrochloride for periods of up to 28 weeks in patients with OCD and Panic Disorder who have responded while taking sertraline hydrochloride during initial treatment phases of 24 to 52 weeks of treatment at a dose range of 50 to 200 mg/day has demonstrated a benefit of such maintenance treatment (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline needed for maintenance treatment is identical to the dose needed to achieve an initial response. Nevertheless, patients should be periodically reassessed to determine the need for maintenance treatment.

Premenstrual Dysphoric Disorder-The effectiveness of sertraline hydrochloride in long-term use, that is, for more than 3 menstrual cycles, has not been systematically evaluated in controlled trials. However, as women commonly report that symptoms worsen with age until relieved by the onset of menopause, it is reasonable to consider continuation of a responding patient. Dosage adjustments, which may include changes between dosage regimens (e.g., daily throughout the menstrual cycle versus during the luteal phase of the menstrual cycle), may be needed to maintain the patient on the lowest effective dosage and patients should be periodically reassessed to determine the need for continued treatment.

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

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

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

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

Special Populations

Dosage for Hepatically Impaired Patients–The use of sertraline in patients with liver disease should be approached with caution. The effects of sertraline in patients with moderate and severe hepatic impairment have not been studied. If sertraline is administered to patients with liver impairment, a lower or less frequent dose should be used (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Treatment of Pregnant Women During the Third Trimester–Neonates exposed to sertraline hydrochloride and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with sertraline hydrochloride during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

Discontinuation of Treatment with Sertraline Hydrochloride

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

Oxcarbazepine Suspension

All dosing should be given in a twice-a-day regimen. Oxcarbazepine oral suspension and oxcarbazepine film-coated tablets may be interchanged at equal doses.

Oxcarbazepine oral suspension should be kept out of the reach and sight of children.

Before using oxcarbazepine oral suspension, shake the bottle well and prepare the dose immediately afterwards. The prescribed amount of oral suspension should be withdrawn from the bottle using the oral dosing syringe supplied. Oxcarbazepine oral suspension can be mixed in a small glass of water just prior to administration or, alternatively, may be swallowed directly from the syringe. After each use, close the bottle and rinse the syringe with warm water and allow it to dry thoroughly.

Oxcarbazepine oral suspension can be taken with or without food [ see Clinical Pharmacology (12.3)].

2.1 Adjunctive Therapy for Adults

Treatment with oxcarbazepine should be initiated with a dose of 600 mg/day, given in a twice-a-day regimen. If clinically indicated, the dose may be increased by a maximum of 600 mg/day at approximately weekly intervals; the recommended daily dose is 1200 mg/day. Daily doses above 1200 mg/day show somewhat greater effectiveness in controlled trials, but most patients were not able to tolerate the 2400 mg/day dose, primarily because of CNS effects. It is recommended that the patient be observed closely and plasma levels of the concomitant AEDs be monitored during the period of oxcarbazepine titration, as these plasma levels may be altered, especially at oxcarbazepine doses greater than 1200 mg/day [ see Drug Interactions (7.1)].

2.2 Conversion to Monotherapy for Adults

Patients receiving concomitant AEDs may be converted to monotherapy by initiating treatment with oxcarbazepine at 600 mg/day (given in a twice-a-day regimen) while simultaneously initiating the reduction of the dose of the concomitant AEDs. The concomitant AEDs should be completely withdrawn over 3 to 6 weeks, while the maximum dose of oxcarbazepine should be reached in about 2 to 4 weeks. Oxcarbazepine may be increased as clinically indicated by a maximum increment of 600 mg/day at approximately weekly intervals to achieve the recommended daily dose of 2400 mg/day. A daily dose of 1200 mg/day has been shown in one study to be effective in patients in whom monotherapy has been initiated with oxcarbazepine. Patients should be observed closely during this transition phase.

2.3 Initiation of Monotherapy for Adults

Patients not currently being treated with AEDs may have monotherapy initiated with oxcarbazepine. In these patients, oxcarbazepine should be initiated at a dose of 600 mg/day (given in a twice-a-day regimen); the dose should be increased by 300 mg/day every third day to a dose of 1200 mg/day. Controlled trials in these patients examined the effectiveness of a 1200 mg/day dose; a dose of 2400 mg/day has been shown to be effective in patients converted from other AEDs to oxcarbazepine monotherapy (see above).

2.4 Adjunctive Therapy for Pediatric Patients (Aged 2 to 16 Years)

In pediatric patients aged 4 to 16 years, treatment should be initiated at a daily dose of 8 to 10 mg/kg generally not to exceed 600 mg/day, given in a twice-a-day regimen. The target maintenance dose of oxcarbazepine should be achieved over two weeks, and is dependent upon patient weight, according to the following chart:

20 to 29 kg - 900 mg/day

29.1 to 39 kg - 1200 mg/day

> 39 kg - 1800 mg/day

In the clinical trial, in which the intention was to reach these target doses, the median daily dose was 31 mg/kg with a range of 6 to 51 mg/kg.

In pediatric patients aged 2 to < 4 years, treatment should also be initiated at a daily dose of 8 to 10 mg/kg generally not to exceed 600 mg/day, given in a twice-a-day regimen. For patients under 20 kg, a starting dose of 16 to 20 mg/kg may be considered [ see Clinical Pharmacology (12.3)]. The maximum maintenance dose of oxcarbazepine should be achieved over 2 to 4 weeks and should not exceed 60 mg/kg/day in a twice-a-day regimen.

In the clinical trial in pediatric patients (2 to 4 years of age) in which the intention was to reach the target dose of 60 mg/kg/day, 50% of patients reached a final dose of at least 55 mg/kg/day.

Under adjunctive therapy (with and without enzyme-inducing AEDs), when normalized by body weight, apparent clearance (L/hr/kg) decreased when age increased such that children 2 to < 4 years of age may require up to twice the oxcarbazepine dose per body weight compared to adults; and children 4 to ≤ 12 years of age may require a 50% higher oxcarbazepine dose per body weight compared to adults.

2.5 Conversion to Monotherapy for Pediatric Patients (Aged 4 to 16 Years)

Patients receiving concomitant antiepileptic drugs may be converted to monotherapy by initiating treatment with oxcarbazepine at approximately 8 to 10 mg/kg/day given in a twice-a-day regimen, while simultaneously initiating the reduction of the dose of the concomitant antiepileptic drugs. The concomitant antiepileptic drugs can be completely withdrawn over 3 to 6 weeks while oxcarbazepine may be increased as clinically indicated by a maximum increment of 10 mg/kg/day at approximately weekly intervals to achieve the recommended daily dose. Patients should be observed closely during this transition phase.

The recommended total daily dose of oxcarbazepine is shown in the table below.

2.6 Initiation of Monotherapy for Pediatric Patients (Aged 4 to 16 Years)

Patients not currently being treated with antiepileptic drugs may have monotherapy initiated with oxcarbazepine. In these patients, oxcarbazepine should be initiated at a dose of 8 to 10 mg/kg/day given in a twice-a-day regimen. The dose should be increased by 5 mg/kg/day every third day to the recommended daily dose shown in the table below.
Table 1 Range of Maintenance Doses of Oxcarbazepine for Children by Weight During Monotherapy From To Weight in kg Dose (mg/day) Dose (mg/day)
20

600

900

25

900

1200

30

900

1200

35

900

1500

40

900

1500

45

1200

1500

50

1200

1800

55

1200

1800

60

1200

2100

65

1200

2100

70

1500

2100

2.7 Patients with Hepatic Impairment

In general, dose adjustments are not required in patients with mild-to-moderate hepatic impairment [ see Clinical Pharmacology (12.3).]

2.8 Patients with Renal Impairment

In patients with impaired renal function (creatinine clearance < 30 mL/min) oxcarbazepine therapy should be initiated at one-half the usual starting dose (300 mg/day) and increased slowly to achieve the desired clinical response [ see Clinical Pharmacology (12.3)]
Lorazepam

Lorazepam

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

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

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

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

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

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

Fenofibrate

Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibrate tablets, and should continue this diet during treatment with fenofibrate tablets. Fenofibrate tablets should be given with meals, thereby optimizing the bioavailability of the medication.

For the treatment of adult patients with primary hypercholesterolemia or mixed hyperlipidemia, the initial dose of fenofibrate tablets is 160 mg per day.

For adult patients with hypertriglyceridemia, the initial dose is 54 to 160 mg per day. Dosage should be individualized according to patient response, and should be adjusted if necessary following repeat lipid determinations at 4 to 8 week intervals. The maximum dose is 160 mg per day.

Treatment with fenofibrate tablets should be initiated at a dose of 54 mg/day in patients having impaired renal function, and increased only after evaluation of the effects on renal function and lipid levels at this dose. In the elderly, the initial dose should likewise be limited to 54 mg/day.

Lipid levels should be monitored periodically and consideration should be given to reducing the dosage of fenofibrate tablets if lipid levels fall significantly below the targeted range.
Extra Strength Pain Rel...

Extra Strength Pain Reliever

Hypertension

Monotherapy: The recommended initial dosage of quinapril tablets in patients not on diuretics is 10 or 20 mg once daily. Dosage should be adjusted according to blood pressure response measured at peak (2 to 6 hours after dosing) and trough (predosing). Generally, dosage adjustments should be made at intervals of at least 2 weeks. Most patients have required dosages of 20, 40, or 80 mg/day, given as a single dose or in two equally divided doses. In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval. In such patients an increase in dosage or twice daily administration may be warranted. In general, doses of 40 to 80 mg and divided doses give a somewhat greater effect at the end of the dosing interval.

Concomitant Diuretics: If blood pressure is not adequately controlled with quinapril tablets monotherapy, a diuretic may be added. In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of quinapril tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued 2 to 3 days prior to beginning therapy with quinapril tablets (see WARNINGS). Then, if blood pressure is not controlled with quinapril tablets alone, diuretic therapy should be resumed.

If the diuretic cannot be discontinued, an initial dose of 5 mg quinapril tablets should be used with careful medical supervision for several hours and until blood pressure has stabilized.

The dosage should subsequently be titrated (as described above) to the optimal response (see WARNINGS, PRECAUTIONS, and Drug Interactions).

Renal Impairment: Kinetic data indicate that the apparent elimination half-life of quinaprilat increases as creatinine clearance decreases. Recommended starting doses, based on clinical and pharmacokinetic data from patients with renal impairment, are as follows:
Creatinine Clearance Maximum Recommended Initial Dose
> 60 mL/min

10 mg

30 to 60 mL/min

5 mg

10 to 30 mL/min

2.5 mg

< 10 mL/min

Insufficient data for dosage recommendation

Patients should subsequently have their dosage titrated (as described above) to the optimal response.

Following the initial dose of quinapril tablets, the patient should be observed under medical supervision for at least two hours for the presence of hypotension or orthostasis and, if present, until blood pressure stabilizes. The appearance of hypotension, orthostasis, or azotemia early in dose titration should not preclude further careful dose titration. Consideration should be given to reducing the dose of concomitant diuretics.

Elderly (≥ 65 years): The recommended initial dosage of quinapril tablets in elderly patients is 10 mg given once daily followed by titration (as described above) to the optimal response.

DOSE ADJUSTMENTS IN PATIENTS WITH HEART FAILURE AND RENAL IMPAIRMENT OR HYPONATREMIA

Pharmacokinetic data indicate that quinapril elimination is dependent on level of renal function. In patients with heart failure and renal impairment, the recommended initial dose of quinapril tablets is 5 mg in patients with a creatinine clearance above 30 mL/min and 2.5 mg in patients with a creatinine clearance of 10 to 30 mL/min. There is insufficient data for dosage recommendation in patients with a creatinine clearance less than 10 mL/min (see WARNINGS, and PRECAUTIONS, Drug Interactions).

If the initial dose is well tolerated, quinapril tablets may be administered the following day as a twice daily regimen. In the absence of excessive hypotension or significant deterioration of renal function, the dose may be increased at weekly intervals based on clinical and hemodynamic response.
Pioglitazone

Pioglitazone

2.1 Recommendations for all patients

Pioglitazone tablets should be taken once daily and can be taken without regard to meals. The recommended starting dose for patients without congestive heart failure is 15 mg or 30 mg once daily. The recommended starting dose for patients with congestive heart failure (NYHA Class I or II) is 15 mg once daily. The dose can be titrated in increments of 15 mg up to a maximum of 45 mg once daily based on glycemic response as determined by HbA1c. After initiation of pioglitazone hydrochloride or with dose increase, monitor patients carefully for adverse reactions related to fluid retention such as weight gain, edema, and signs and symptoms of congestive heart failure [see Boxed Warning and Warnings and Precautions (5.2)]. Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating pioglitazone tablets. Routine periodic monitoring of liver tests during treatment with pioglitazone tablets is not recommended in patients without liver disease. Patients who have liver test abnormalities prior to initiation of pioglitazone hydrochloride or who are found to have abnormal liver tests while taking pioglitazone tablets should be managed as described under Warnings and Precautions [see Warnings andPrecautions (5.3) and Clinical Pharmacology (12.3)].

2.2 Concomitant use with an insulin secretagogue or insulin

If hypoglycemia occurs in a patient co-administered pioglitazone hydrochloride and an insulin secretagogue (e.g., sulfonylurea), the dose of the insulin secretagogue should be reduced.If hypoglycemia occurs in a patient co-administered pioglitazone hydrochloride and insulin, the dose of insulin should be decreased by 10% to 25%. Further adjustments to the insulin dose should be individualized based on glycemic response

2.3 Coadministration with strong CYP2C8 inhibitors

Coadministration of pioglitazone hydrochloride and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure approximately 3-fold. Therefore, the maximum recommended dose of pioglitazone tablet is 15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Clindamycin Hydrochlori...

Clindamycin Hydrochloride

If significant diarrhea occurs during therapy, this antibiotic should be discontinued (see WARNING box).

Adults: Serious infections—150 to 300 mg every 6 hours. More severe infections - 300 to 450 mg every 6 hours. Pediatric Patients: Serious infections - 8 to 16 mg/kg/day (4 to 8 mg/lb/day) divided into three or four equal doses. More severe infections - 16 to 20 mg/kg/day (8 to 10 mg/lb/day) divided into three or four equal doses.

To avoid the possibility of esophageal irritation, clindamycin hydrochloride capsules should be taken with a full glass of water.

Serious infections due to anaerobic bacteria are usually treated with clindamycin injection. However, in clinically appropriate circumstances, the physician may elect to initiate treatment or continue treatment with clindamycin hydrochloride capsules.

In cases of β-hemolytic streptococcal infections, treatment should continue for at least 10 days.
Cyclobenzaprine Hydroch...

Cyclobenzaprine Hydrochloride

For most patients, the recommended dose of cyclobenzaprine hydrochloride tablets is 5 mg three times a day. Based on individual patient response, the dose may be increased to either 7.5 or 10 mg three times a day. Use of cyclobenzaprine hydrochloride tablets for periods longer than two or three weeks is not recommended. (see INDICATIONS AND USAGE).

Less frequent dosing should be considered for hepatically impaired or elderly patients (see PRECAUTIONS, Impaired Hepatic Function, and Use in the Elderly).
Allopurinol

Allopurinol

The dosage of allopurinol tablets to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease. The average is 200 to 300 mg/day for patients with mild gout and 400 to 600 mg/day for those with moderately severe tophaceous gout. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. Dosage requirements in excess of 300 mg should be administered in divided doses. The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily. To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the patient start with a low dose of allopurinol tablets (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage.

Normal serum urate levels are usually achieved in 1 to 3 weeks. The upper limit of normal is about 7 mg/dL for men and postmenopausal women and 6 mg/dL for premenopausal women. Too much reliance should not be placed on a single serum uric acid determination since, for technical reasons, estimation of uric acid may be difficult. By selecting the appropriate dosage and, in certain patients, using uricosuric agents concurrently, it is possible to reduce serum uric acid to normal or, if desired, to as low as 2 to 3 mg/dL and keep it there indefinitely.

While adjusting the dosage of allopurinol tablets in patients who are being treated with colchicine and/or anti-inflammatory agents, it is wise to continue the latter therapy until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months.

In transferring a patient from a uricosuric agent to allopurinol tablets, the dose of the uricosuric agent should be gradually reduced over a period of several weeks and the dose of allopurinol tablets gradually increased to the required dose needed to maintain a normal serum uric acid level.

It should also be noted that allopurinol tablets are generally better tolerated if taken following meals. A fluid intake sufficient to yield a daily urinary output of at least 2 liters and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.

Since allopurinol tablets and its metabolites are primarily eliminated only by the kidney, accumulation of the drug can occur in renal failure, and the dose of allopurinol tablets should consequently be reduced. With a creatinine clearance of 10 to 20 mL/min, a daily dosage of 200 mg of allopurinol tablets is suitable. When the creatinine clearance is less than 10 mL/min, the daily dosage should not exceed 100 mg. With extreme renal impairment (creatinine clearance less than 3 mL/min) the interval between doses may also need to be lengthened.

The correct size and frequency of dosage for maintaining the serum uric acid just within the normal range is best determined by using the serum uric acid level as an index.

For the prevention of uric acid nephropathy during the vigorous therapy of neoplastic disease, treatment with 600 to 800 mg daily for 2 or 3 days is advisable together with a high fluid intake. Otherwise similar considerations to the above recommendations for treating patients with gout govern the regulation of dosage for maintenance purposes in secondary hyperuricemia.

The dose of allopurinol tablets recommended for management of recurrent calcium oxalate stones in hyperuricosuric patients is 200 to 300 mg/day in divided doses or as the single equivalent. This dose may be adjusted up or down depending upon the resultant control of the hyperuricosuria based upon subsequent 24 hour urinary urate determinations. Clinical experience suggests that patients with recurrent calcium oxalate stones may also benefit from dietary changes such as the reduction of animal protein, sodium, refined sugars, oxalate-rich foods, and excessive calcium intake, as well as an increase in oral fluids and dietary fiber.

Children, 6 to 10 years of age, with secondary hyperuricemia associated with malignancies may be given 300 mg allopurinol tablets daily while those under 6 years are generally given 150 mg daily. The response is evaluated after approximately 48 hours of therapy and a dosage adjustment is made if necessary.
Cefadroxil

Cefadroxil

Cefadroxil monohydrate is acid-stable and may be administered orally without regard to meals. Administration with food may be helpful in diminishing potential gastrointestinal complaints occasionally associated with oral cephalosporin therapy.

Adults

Urinary Tract Infections: For uncomplicated lower urinary tract infections (i.e., cystitis) the usual dosage is 1 or 2 g per day in a single (q.d.) or divided doses (b.i.d.).

For all other urinary tract infections the usual dosage is 2 g per day in divided doses (b.i.d.).

Skin and Skin Structure Infections: For skin and skin structure infections the usual dosage is 1 g per day in single (q.d.) or divided doses (b.i.d.).

Pharyngitis and Tonsillitis: Treatment of group A beta-hemolytic streptococcal pharyngitis and tonsillitis — 1 g per day in single (q.d.) or divided doses (b.i.d.) for 10 days.

Children

For urinary tract infections, the recommended daily dosage for children is 30 mg/kg/day in divided doses every 12 hours. For pharyngitis, tonsillitis, and impetigo, the recommended daily dosage for children is 30 mg/kg/day in a single dose or in equally divided doses every 12 hours. For other skin and skin structure infections, the recommended daily dosage is 30 mg/kg/day in equally divided doses every 12 hours. In the treatment of beta-hemolytic streptococcal infections, a therapeutic dosage of cefadroxil monohydrate should be administered for at least 10 days.
See chart for total daily dosage for children. DAILY DOSAGE OF CEFADROXIL FOR ORAL SUSPENSION Child’s Weight lbs kg 125 mg/5mL 250 mg/5mL 500mg/5mL 10 4.5 1 tsp ½ tsp 20 9.1 2 tsp 1 tsp 30 13.6 3 tsp 1 ½ tsp 40 18.2 4 tsp 2 tsp 1 tsp 50 22.7 5 tsp 2 ½ tsp 1 ¼ tsp 60 27.3 6 tsp 3 tsp 1 ½ tsp 70 & above 31.8+ — — 2 tsp
Renal Impairment:

In patients with renal impairment, the dosage of cefadroxil monohydrate should be adjusted according to creatinine clearance rates to prevent drug accumulation. The following schedule is suggested. In adults, the initial dose is 1000 mg of cefadroxil monohydrate and the maintenance dose (based on the creatinine clearance rate [mL/min/1.73 M2]) is 500 mg at the time intervals listed below.
Creatinine Clearances Dosage Interval 0 to 10 mL/min 36 hours 10 to 25 mL/min 24 hours 25 to 50 mL/min 12 hours
Patients with creatinine clearance rates over 50 mL/min may be treated as if they were patients having normal renal function.

Reconstitution Directions for Oral Suspension
Bottle Size Reconstitution Directions 100 mL Suspend in a total of 70mL of water. Method: Tap bottle lightly to loosen powder. Add 70 mL of water in two portions. Shake well after each addition. 75 mL Suspend in a total of 53 mL of water. Method: Tap bottle lightly to loosen powder. Add 53 mL of water in two portions. Shake well after each addition. 50 mL Suspend in a total of 35 mL of water. Method: Tap bottle lightly to loosen powder. Add 35 mL of water in two portions. Shake well after each addition. After reconstitution, store in refrigerator. Shake well before using. Keep container tightly closed. Discard unused portion after 14 days.
Adults

Urinary Tract Infections: For uncomplicated lower urinary tract infections (i.e., cystitis) the usual dosage is 1 or 2 g per day in a single (q.d.) or divided doses (b.i.d.).

For all other urinary tract infections the usual dosage is 2 g per day in divided doses (b.i.d.).

Skin and Skin Structure Infections: For skin and skin structure infections the usual dosage is 1 g per day in single (q.d.) or divided doses (b.i.d.).

Pharyngitis and Tonsillitis: Treatment of group A beta-hemolytic streptococcal pharyngitis and tonsillitis — 1 g per day in single (q.d.) or divided doses (b.i.d.) for 10 days.

Children

For urinary tract infections, the recommended daily dosage for children is 30 mg/kg/day in divided doses every 12 hours. For pharyngitis, tonsillitis, and impetigo, the recommended daily dosage for children is 30 mg/kg/day in a single dose or in equally divided doses every 12 hours. For other skin and skin structure infections, the recommended daily dosage is 30 mg/kg/day in equally divided doses every 12 hours. In the treatment of beta-hemolytic streptococcal infections, a therapeutic dosage of cefadroxil monohydrate should be administered for at least 10 days.
See chart for total daily dosage for children. DAILY DOSAGE OF CEFADROXIL FOR ORAL SUSPENSION Child’s Weight lbs kg 125 mg/5mL 250 mg/5mL 500mg/5mL 10 4.5 1 tsp ½ tsp 20 9.1 2 tsp 1 tsp 30 13.6 3 tsp 1 ½ tsp 40 18.2 4 tsp 2 tsp 1 tsp 50 22.7 5 tsp 2 ½ tsp 1 ¼ tsp 60 27.3 6 tsp 3 tsp 1 ½ tsp 70 & above 31.8+ — — 2 tsp
Renal Impairment:

In patients with renal impairment, the dosage of cefadroxil monohydrate should be adjusted according to creatinine clearance rates to prevent drug accumulation. The following schedule is suggested. In adults, the initial dose is 1000 mg of cefadroxil monohydrate and the maintenance dose (based on the creatinine clearance rate [mL/min/1.73 M2]) is 500 mg at the time intervals listed below.
Creatinine Clearances Dosage Interval 0 to 10 mL/min 36 hours 10 to 25 mL/min 24 hours 25 to 50 mL/min 12 hours
Patients with creatinine clearance rates over 50 mL/min may be treated as if they were patients having normal renal function.

Reconstitution Directions for Oral Suspension
Bottle Size Reconstitution Directions 100 mL Suspend in a total of 70mL of water. Method: Tap bottle lightly to loosen powder. Add 70 mL of water in two portions. Shake well after each addition. 75 mL Suspend in a total of 53 mL of water. Method: Tap bottle lightly to loosen powder. Add 53 mL of water in two portions. Shake well after each addition. 50 mL Suspend in a total of 35 mL of water. Method: Tap bottle lightly to loosen powder. Add 35 mL of water in two portions. Shake well after each addition. After reconstitution, store in refrigerator. Shake well before using. Keep container tightly closed. Discard unused portion after 14 days.
Cefuroxime Axetil For O...

Cefuroxime Axetil For Oral Suspension

NOTE: CEFUROXIME AXETIL TABLETS AND CEFUROXIME AXETIL FOR ORAL SUSPENSION ARE NOT BIOEQUIVALENT AND ARE NOT SUBSTITUTABLE ON A MILLIGRAM-PER-MILLIGRAM BASIS (SEE CLINICAL PHARMACOLOGY).

Cefuroxime axetil for oral suspension may be administered to pediatric patients ranging in age from 3 months to 12 years, according to dosages in Table 4:
Table 4: Cefuroxime Axetil For Oral Suspension(Must be administered with food. Shake well each time before using.) Population/Infection Dosage Daily Maximum Dose Duration (days) Pediatric Patients (3 months to 12 years) Pharyngitis/tonsillitis 20 mg/kg/day divided b.i.d. 500 mg 10 Acute otitis media 30 mg/kg/day divided b.i.d. 1,000 mg 10 Acute bacterial maxillary sinusitis 30 mg/kg/day divided b.i.d. 1,000 mg 10 Impetigo 30 mg/kg/day divided b.i.d. 1,000 mg 10
Patients With Renal Failure: The safety and efficacy of cefuroxime axetil in patients with renal failure have not been established. Since cefuroxime is renally eliminated, its half-life will be prolonged in patients with renal failure.

Directions for Mixing Cefuroxime Axetil For Oral Suspension: Prepare a suspension at the time of dispensing as follows:

1. Shake the bottle to loosen the powder.

2. Remove the cap.

3. Add the total amount of water for reconstitution (see Table 5) and replace the cap.

4. Vigorously shake in a diagonal direction to form suspension.
Table 5: Amount of Water Required for Reconstitution of Labeled Volumes of Cefuroxime Axetil For Oral Suspension Cefuroxime Axetil for Oral Suspension Labeled Volume After Reconstitution Amount of Water Required for Reconstitution 125 mg/5 mL 50 mL 23 mL 100 mL 44 mL 250 mg/5 mL 50 mL 22 mL 100 mL 43 mL
NOTE: SHAKE THE ORAL SUSPENSION WELL BEFORE EACH USE. Replace cap securely after each opening. Store the reconstituted suspension between 2 and 8°C (36 and 46°F) (in the refrigerator). DISCARD AFTER 10 DAYS.
Daliresp

Daliresp

2.1 Recommended Dosing Schedule

Pantoprazole sodium is supplied as delayed-release tablets. The recommended dosages are outlined in Table 1.

Table 1: Recommended Dosing Schedule for Pantoprazole Sodium Delayed-Release Tablets

Indication

Dose

Frequency

Short-Term Treatment of Erosive Esophagitis Associated With GERD

Adults

40 mg

Once daily for up to 8 weeks*

Children (5 years and older)

≥ 15 kg to < 40 kg

20 mg

Once daily for up to 8 weeks

≥ 40 kg

40 mg

Maintenance of Healing of Erosive Esophagitis

Adults

40 mg

Once daily***

Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

Adults

40 mg

Twice daily**

* For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium delayed-release tablets may be considered.

** Dosage regimens should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 240 mg daily have been administered.

***Controlled studies did not extend beyond 12 months

2.2 Administration Instructions

Directions for method of administration for each dosage form are presented in Table 2.
Table 2: Administration Instructions
Formulation

Route

Instructions*

Delayed-Release Tablets

Oral

Swallowed whole, with or without food

* Patients should be cautioned that pantoprazole sodium delayed-release tablets should not be split, chewed, or crushed.

Pantoprazole sodium delayed-release tablets should be swallowed whole, with or without food in the stomach. If patients are unable to swallow a 40 mg tablet, two 20 mg tablets may be taken. Concomitant administration of antacids does not affect the absorption of pantoprazole sodium delayed-release tablets.
Amoxicillin And Clavula...

Amoxicillin And Clavulanate Potassium

Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, does not contain the same amount of clavulanic acid (as the potassium salt) as any of the other suspensions of amoxicillin and clavulanate potassium.

Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL contains 42.9 mg of clavulanic acid per 5 mL, whereas the 200 mg/5 mL suspension of amoxicillin and clavulanate potassium contains 28.5 mg of clavulanic acid per 5 mL and the 400 mg/5 mL suspension contains 57 mg of clavulanic acid per 5 mL. Therefore, the 200 mg/5 mL and 400 mg/5 mL suspensions of amoxicillin and clavulanate potassium should not be substituted for amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, as they are not interchangeable.

Dosage: Pediatric patients 3 months and older: Based on the amoxicillin component (600 mg/5 mL), the recommended dose of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL is 90 mg/kg/day divided every 12 hours, administered for 10 days (see chart below).
Body Weight (kg) Volume of Amoxicillin and Clavulanate Potassium for Oral Suspension,600 mg/42.9 mg per 5 mLproviding 90 mg/kg/day 8 3 mL twice daily 12 4.5 mL twice daily 16 6 mL twice daily 20 7.5 mL twice daily 24 9 mL twice daily 28 10.5 mL twice daily 32 12 mL twice daily 36 13.5 mL twice daily
Pediatric patients weighing 40 kg and more: Experience with amoxicillin and clavulanate potassium for oral suspension (600 mg/42.9 mg per 5 mL formulation) in this group is not available.

Adults: Experience with amoxicillin and clavulanate potassium for oral suspension (600 mg/42.9 mg per 5 mL formulation) in adults is not available and adults who have difficulty swallowing should not be given amoxicillin and clavulanate potassium for oral suspension (600 mg/42.9 mg per 5 mL) in place of the 500 mg or 875 mg tablet of amoxicillin and clavulanate potassium .

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals (See WARNINGS).

Directions for Mixing Oral Suspension: Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Add approximately 2/3 of the total amount of water for reconstitution (see table below) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.
Amoxicillin and Clavulanate Potassium for Oral Suspension (600 mg/42.9 mg per 5 mL) Bottle Size Amount of Water Required for Suspension 50 mL 44 mL 75 mL 65 mL 100 mL 87 mL 125 mL 112 mL 150 mL 129 mL 200 mL 174 mL
Each teaspoonful (5 mL) will contain 600 mg amoxicillin as the trihydrate and 42.9 mg of clavulanic acid as the potassium salt.

NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING.

Administration: To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL should be taken at the start of a meal. Absorption of clavulanate potassium may be enhanced when amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mLis administered at the start of a meal.
Ciprofloxacin

Ciprofloxacin

Adults

Ciprofloxacin tablets should be administered orally to adults as described in the Dosage Guidelines table.

The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative organism, the integrity of the patient’s host-defense mechanisms, and the status of renal function and hepatic function.

The duration of treatment depends upon the severity of infection. The usual duration is 7 to 14 days; however, for severe and complicated infections more prolonged therapy may be required. Ciprofloxacin should be administered at least 2 hours before or 6 hours after magnesium/aluminum antacids, polymeric phosphate binders (for example, sevelamer, lanthanum carbonate) or sucralfate, Videx® (didanosine) chewable/buffered tablets or pediatric powder for oral solution, other highly buffered drugs, or other products containing calcium, iron or zinc.
ADULT DOSAGE GUIDELINES
* Used in conjunction with metronidazole

† Generally ciprofloxacin should be continued for at least 2 days after the signs and symptoms of infection have disappeared, except for inhalational anthrax (post-exposure).

** Drug administration should begin as soon as possible after suspected or confirmed exposure.
Infection Severity Dose Frequency Usual Durations† Urinary Tract Acute Uncomplicated 250 mg q 12 h 3 days Mild/Moderate 250 mg q 12 h 7 to 14 days Severe/Complicated 500 mg q 12 h 7 to 14 days Chronic Bacterial Prostatitis Mild/Moderate 500 mg q 12 h 28 days Lower Respiratory Tract Mild/Moderate 500 mg q 12 h 7 to 14 days Severe/Complicated 750 mg q 12 h 7 to 14 days Acute Sinusitis Mild/Moderate 500 mg q 12 h 10 days Skin and Skin Structure Mild/Moderate 500 mg q 12 h 7 to 14 days Severe/Complicated 750 mg q 12 h 7 to 14 days Bone and Joint Mild/Moderate 500 mg q 12 h ≥ 4 to 6 weeks Severe/Complicated 750 mg q 12 h ≥ 4 to 6 weeks Intra-Abdominal* Complicated 500 mg q 12 h 7 to 14 days Infectious Diarrhea Mild/Moderate/Severe 500 mg q 12 h 5 to 7 days Typhoid Fever Mild/Moderate 500 mg q 12 h 10 days Urethral and Cervical Gonococcal Infections Uncomplicated 250 mg single dose single dose Inhalational anthrax (post-exposure)** 500 mg q h 12 60 days
This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit.6 For a discussion of ciprofloxacin serum concentrations in various human populations, see Inhalational Anthrax, Additional Information.

Conversion of IV to Oral Dosing in Adults:

Patients whose therapy is started with ciprofloxacin IV may be switched to ciprofloxacin tablets when clinically indicated at the discretion of the physician (See CLINICAL PHARMACOLOGY and table below for the equivalent dosing regimens).
Equivalent AUC Dosing Regimens Ciprofloxacin Oral Dosage Equivalent Ciprofloxacin IV Dosage 250 mg Tablet q 12 h 200 mg IV q 12 h 500 mg Tablet q 12 h 400 mg IV q 12 h 750 mg Tablet q 12 h 400 mg IV q   8 h
Adults with Impaired Renal Function: Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction. The following table provides dosage guidelines for use in patients with renal impairment:

RECOMMENDED STARTING AND MAINTENANCE DOSES

FOR PATIENTS WITH IMPAIRED RENAL FUNCTION
Creatinine Clearance (mL/min) Dose > 50 See Usual Dosage. 30 to 50 250 to 500 mg q 12 h 5 to 29 250 to 500 mg q 18 h Patients on hemodialysis or Peritoneal dialysis 250 to 500 mg q 24 h (after dialysis)
When only the serum creatinine concentration is known, the following formula may be used to estimate creatinine clearance.

Men: Creatinine clearance (mL/min) =   Weight (kg) x (140 - age)

                                                             72 x serum creatinine (mg/dL)

Women: 0.85 x the value calculated for men.

The serum creatinine should represent a steady state of renal function.

In patients with severe infections and severe renal impairment, a unit dose of 750 mg may be administered at the intervals noted above. Patients should be carefully monitored.

Pediatrics

Ciprofloxacin tablets should be administered orally as described in the Dosage Guidelines table. An increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues, has been observed (See ADVERSE REACTIONS and CLINICAL STUDIES).

Dosing and initial route of therapy (that is, IV or oral) for complicated urinary tract infection or pyelonephritis should be determined by the severity of the infection. In the clinical trial, pediatric patients with moderate to severe infection were initiated on 6 to 10 mg/kg IV every 8 hours and allowed to switch to oral therapy (10 to 20 mg/kg every 12 hours), at the discretion of the physician.
PEDIATRIC DOSAGE GUIDELINES Infection Route of Administration Dose (mg/kg) Frequency Total Duration
* The total duration of therapy for complicated urinary tract infection and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days).

** Drug administration should begin as soon as possible after suspected or confirmed exposure to Bacillus anthracis spores. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit.6 For a discussion of ciprofloxacin serum concentrations in various human populations, see Inhalational Anthrax In Adults and Pediatrics, Additional Information.
Complicated Urinary Tract or Pyelonephritis (patients from 1 to 17 years of age) Intravenous 6 to 10 mg/kg (maximum 400 mg per dose; not to be exceeded even in patients weighing > 51 kg) Every 8 hours 10 to 21 days* Oral 10 mg/kg to 20 mg/kg (maximum 750 mg per dose; not to be exceeded even in patients weighing > 51 kg) Every 12 hours Inhalational Anthrax (Post-Exposure)** Intravenous 10 mg/kg (maximum 400 mg per dose) Every 12 hours 60 days Oral 15 mg/kg (maximum 500 mg per dose) Every 12 hours
Clarithromycin

Clarithromycin

Clarithromycin immediate-release tablets and clarithromycin for oral suspension may be given with or without food.

Clarithromycin may be administered without dosage adjustment in the presence of hepatic impairment if there is normal renal function. In patients with severe renal impairment (CLCR < 30 mL/min), the dose of clarithromycin should be reduced by 50%. However, when patients with moderate or severe renal impairment are taking clarithromycin concomitantly with atazanavir or ritonavir, the dose of clarithromycin should be reduced by 50% or 75% for patients with CLCR of 30 to 60 mL/min or < 30 mL/min, respectively.
ADULT DOSAGE GUIDELINES Clarithromycin Immediate-Release Tablets Infection Dosage (q12h) Duration (days) Pharyngitis/Tonsillitis due to S. pyogenes 250 mg 10 Acute maxillary sinusitis due to H. influenzae 500 mg 14 M. catarrhalis S. pneumoniae Acute exacerbation of chronic bronchitis due to H. influenzae 500 mg 7 to 14 H. parainfluenzae 500 mg 7 M. catarrhalis 250 mg 7 to 14 S. pneumoniae 250 mg 7 to 14 Community-Acquired Pneumonia due to H. influenzae 250 mg 7 H. parainfluenzae - - M. catarrhalis - - S. pneumoniae 250 mg 7 to 14 C. pneumoniae 250 mg 7 to 14 M. pneumoniae 250 mg 7 to 14 Uncomplicated skin and skin structure 250 mg 7 to14 S. aureus S. pyogenes
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

Triple therapy: clarithromycin/lansoprazole/amoxicillin

The recommended adult dose is 500 mg clarithromycin, 30 mg lansoprazole, and 1 gram amoxicillin, all given twice daily (q12h) for 10 or 14 days (see INDICATIONS AND USAGE and CLINICAL STUDIES sections).

Triple therapy: clarithromycin/omeprazole/amoxicillin

The recommended adult dose is 500 mg clarithromycin, 20 mg omeprazole, and 1 gram amoxicillin, all given twice daily (q12h) for 10 days (see INDICATIONS AND USAGE and CLINICAL STUDIES sections). In patients with an ulcer present at the time of initiation of therapy, an additional 18 days of omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.

Dual therapy: clarithromycin/omeprazole

The recommended adult dose is 500 mg clarithromycin given three times daily (q8h) and 40 mg omeprazole given once daily (qAM) for 14 days (see INDICATIONS AND USAGE and CLINICAL STUDIES sections). An additional 14 days of omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.

Dual therapy: clarithromycin/ranitidine bismuth citrate

The recommended adult dose is 500 mg clarithromycin given twice daily (q12h) or three times daily (q8h) and 400 mg ranitidine bismuth citrate given twice daily (q12h) for 14 days. An additional 14 days of 400 mg twice daily is recommended for ulcer healing and symptom relief. Clarithromycin and ranitidine bismuth citrate combination therapy is not recommended in patients with creatinine clearance less than 25 mL/min (see INDICATIONS AND USAGE and CLINICAL STUDIES sections).

Children

The usual recommended daily dosage is 15 mg/kg/day divided q12h for 10 days.
PEDIATRIC DOSAGE GUIDELINES Based on Body Weight Dosing Calculated on 7.5 mg/kg q12h Weight Dose kg lbs (q12h) 125 mg/5 mL 250 mg/5 mL 9 20 62.5 mg 2.5 mL q12h 1.25 mL q12h 17 37 125 mg 5 mL q12h 2.5 mL q12h 25 55 187.5 mg 7.5 mL q12h 3.75 mL q12h 33 73 250 mg 10 mL q12h 5 mL q12h
Mycobacterial Infections

Prophylaxis

The recommended dose of clarithromycin for the prevention of disseminated Mycobacterium avium disease is 500 mg b.i.d. In children, the recommended dose is 7.5 mg/kg b.i.d. up to 500 mg b.i.d. No studies of clarithromycin for MAC prophylaxis have been performed in pediatric populations and the doses recommended for prophylaxis are derived from MAC treatment studies in children. Dosing recommendations for children are in the table above.

Treatment

Clarithromycin is recommended as the primary agent for the treatment of disseminated infection due to Mycobacterium avium complex. Clarithromycin should be used in combination with other antimycobacterial drugs that have shown in vitro activity against MAC or clinical benefit in MAC treatment (see CLINICAL STUDIES). The recommended dose for mycobacterial infections in adults is 500 mg b.i.d. In children, the recommended dose is 7.5 mg/kg b.i.d. up to 500 mg b.i.d. Dosing recommendations for children are in the table above.

Clarithromycin therapy should continue if clinical response is observed. Clarithromycin can be discontinued when the patient is considered at low risk of disseminated infection.

Constituting Instructions

The table below indicates the volume of water to be added when constituting:
Total volume After Constitution Clarithromycin Concentration After Constitution Amount of water to be Added* 50 mL 125 mg/5 mL 32 mL 100 mL 125 mg/5 mL 64 mL 50 mL 250 mg/5 mL 32 mL 100 mL 250 mg/5 mL 64 mL *see instructions below.
Add half the volume of water to the bottle and shake vigorously. Add the remainder of water to the bottle and shake.

Shake well before each use. Oversize bottle provides shake space. Keep tightly closed. Do not refrigerate. After mixing, store at 20 - 25° C (68 - 77° F) (see USP Controlled Room Temperature) and use within 14 days.
Donepezil Hydrochloride...

Donepezil Hydrochloride

Donepezil hydrochloride tablets should be taken in the evening, just prior to retiring.

Donepezil hydrochloride tablets can be taken with or without food.

2.1 Mild to Moderate Alzheimer’s Disease

The dosages of donepezil hydrochloride tablets shown to be effective in controlled clinical trials are 5 mg and 10 mg administered once per day.

The higher dose of 10 mg did not provide a statistically significantly greater clinical benefit than 5 mg. There is a suggestion, however, based upon order of group mean scores and dose trend analyses of data from these clinical trials, that a daily dose of 10 mg of donepezil hydrochloride tablets might provide additional benefit for some patients. Accordingly, whether or not to employ a dose of 10 mg is a matter of prescriber and patient preference.

2.2 Severe Alzheimer’s Disease

Donepezil hydrochloride tablets have been shown to be effective in controlled clinical trials at a dose of 10 mg administered once daily.

2.3 Titration

The recommended starting dose of donepezil hydrochloride tablets is 5 mg once daily. Evidence from the controlled trials in mild to moderate Alzheimer’s disease indicates that the 10 mg dose, with a one week titration, is likely to be associated with a higher incidence of cholinergic adverse events compared to the 5 mg dose. In open-label trials using a 6 week titration, the type and frequency of these same adverse events were similar between the 5 mg and 10 mg dose groups. Therefore, because donepezil hydrochloride tablets steady state is achieved about 15 days after it is started and because the incidence of untoward effects may be influenced by the rate of dose escalation, a dose of 10 mg should not be administered until patients have been on a daily dose of 5 mg for 4 to 6 weeks.
Lisinopril And Hydrochl...

Lisinopril And Hydrochlorothiazide

Lisinopril monotherapy is an effective treatment of hypertension in once-daily doses of 10 to 80 mg, while hydrochlorothiazide monotherapy is effective in doses of 12.5 to 50 mg per day. In clinical trials of lisinopril/hydrochlorothiazide combination therapy using lisinopril doses of 10 to 80 mg and hydrochlorothiazide doses of 6.25 to 50 mg, the antihypertensive response rates generally increased with increasing dose of either component.

The side effects (see WARNINGS) of lisinopril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (eg, pancreatitis), the former much more common than the latter. Therapy with any combination of lisinopril and hydrochlorothiazide may be associated with either or both dose-independent or dose-dependent side effects, but addition of lisinopril in clinical trials blunted the hypokalemia normally seen with diuretics.

To minimize dose-dependent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Dose Titration Guided by Clinical Effect: A patient whose blood pressure is not adequately controlled with either lisinopril or hydrochlorothiazide monotherapy may be switched to lisinopril/HCTZ 10/12.5 or lisinopril/HCTZ 20/12.5, depending on current monotherapy dose. Further increases of either or both components should depend on clinical response with blood pressure measured at the interdosing interval to ensure that there is an adequate antihypertensive effect at that time. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. After addition of the diuretic it may be possible to reduce the dose of lisinopril. Patients whose blood pressures are adequately controlled with 25 mg of daily hydrochlorothiazide, but who experience significant potassium loss with this regimen may achieve similar or greater blood-pressure control without electrolyte disturbance if they are switched to lisinopril/HCTZ 10/12.5.

In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally may occur following the initial dose of lisinopril. The diuretic should, if possible, be discontinued for two to three days before beginning therapy with lisinopril to reduce the likelihood of hypotension (See WARNINGS). If the patient's blood pressure is not controlled with lisinopril alone, diuretic therapy may be resumed.

If the diuretic cannot be discontinued, an initial dose of 5 mg of lisinopril should be used under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour (See WARNINGS and PRECAUTIONS, Drug Interactions).

Concomitant administration of lisinopril and hydrochlorothiazide tablets with potassium supplements, potassium salt substitutes or potassium-sparing diuretics may lead to increases of serum potassium (See PRECAUTIONS).

Replacement Therapy: The combination may be substituted for the titrated individual components.

Use in Renal Impairment: Regimens of therapy with lisinopril/HCTZ need not take account of renal function as long as the patient’s creatinine clearance is > 30 mL/min/1.7 m2 (serum creatinine roughly ≤ 3 mg/dL or 265 µmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so lisinopril/HCTZ is not recommended (see WARNINGS, Anaphylactoid Reactions During Membrane Exposure).
Doxycycline

Doxycycline

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours or 50 mg every 6 hours) followed by a maintenance dose of 100 mg/day. The maintenance dose may be administered as a single dose or as 50 mg every 12 hours. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

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

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose.

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

Primary and secondary syphilis: 300 mg a day in divided doses for at least 10 days.

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

Nongonococcal urethritis caused by C. trachomatis and U. urealyticum: 100 mg, by mouth, twice a day for at least 7 days.

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

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

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

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS.) If gastric irritation occurs, doxycycline may be given with food. Ingestion of a high fat meal has been shown to delay the time to peak plasma concentrations by an average of one hour and 20 minutes. However, in the same study, food enhanced the average peak concentration by 7.5% and the area under the curve by 5.7%.
Healthy Accents Infants...

Healthy Accents Infants Pain And Fever

2.1 Dosage in Adults

Use the lowest effective dose for the patient. The recommended initial dose is 5 mg for women and either 5 or 10 mg for men, taken only once per night immediately before bedtime with at least 7 to 8 hours remaining before the planned time of awakening. If the 5 mg dose is not effective, the dose can be increased to 10 mg. In some patients, the higher morning blood levels following use of the 10 mg dose increase the risk of next day impairment of driving and other activities that require full alertness [see Warnings and Precautions (5.1)]. The total dose of zolpidem tartrate tablets should not exceed 10 mg once daily immediately before bedtime.

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

2.2 Special Populations

Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate. Patients with hepatic insufficiency do not clear the drug as rapidly as normal subjects. The recommended dose of zolpidem tartrate tablets in both of these patient populations is 5 mg once daily immediately before bedtime [see Warnings and Precautions (5.1); Use in Specific Populations (8.5)].

2.3 Use with CNS Depressants

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

2.4 Administration

The effect of zolpidem tartrate tablets may be slowed by ingestion with or immediately after a meal.
Lisinopril

Lisinopril

Hypertension

Initial Therapy: In patients with uncomplicated essential hypertension not on diuretic therapy, the recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 to 40 mg per day administered in a single daily dose. The antihypertensive effect may diminish toward the end of the dosing interval regardless of the administered dose, but most commonly with a dose of 10 mg daily. This can be evaluated by measuring blood pressure just prior to dosing to determine whether satisfactory control is being maintained for 24 hours. If it is not, an increase in dose should be considered. Doses up to 80 mg have been used but do not appear to give greater effect. If blood pressure is not controlled with lisinopril tablets alone, a low dose of a diuretic may be added. Hydrochlorothiazide, 12.5 mg has been shown to provide an additive effect. After the addition of a diuretic, it may be possible to reduce the dose of lisinopril tablets.

Diuretic Treated Patients: In hypertensive patients who are currently being treated with a diuretic, symptomatic hypotension may occur occasionally following the initial dose of lisinopril tablets. The diuretic should be discontinued, if possible, for two to three days before beginning therapy with lisinopril tablets to reduce the likelihood of hypotension (See WARNINGS). The dosage of lisinopril tablets should be adjusted according to blood pressure response. If the patient's blood pressure is not controlled with lisinopril tablets alone, diuretic therapy may be resumed as described above.

If the diuretic cannot be discontinued, an initial dose of 5 mg should be used under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour (See WARNINGS and PRECAUTIONS, Drug Interactions).

Concomitant administration of lisinopril tablets with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics may lead to increases of serum potassium (See PRECAUTIONS).

Dosage Adjustment in Renal Impairment: The usual dose of lisinopril tablets (10 mg) is recommended for patients with creatinine clearance > 30 mL/min (serum creatinine of up to approximately 3 mg/dL). For patients with creatinine clearance ≥ 10 mL/min ≤ 30 mL/min (serum creatinine ≥ 3 mg/dL), the first dose is 5 mg once daily. For patients with creatinine clearance < 10 mL/min (usually on hemodialysis) the recommended initial dose is 2.5 mg. The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.
Renal Status CreatinineClearancemL/min InitialDosemg/day Normal Renal Function to Mild Impairment > 30 10 Moderate to Severe Impairment ≥ 10 ≤ 30 5 Dialysis Patients1 < 10 2.52
1. See WARNINGS, Anaphylactoid Reactions During Membrane Exposure

2. Dosage or dosing interval should be adjusted depending on the blood pressure response.

Heart Failure

Lisinopril tablets are indicated as adjunctive therapy with diuretics and (usually) digitalis. The recommended starting dose is 5 mg once a day. When initiating treatment with lisinopril in patients with heart failure, the initial dose should be administered under medical observation, especially in those patients with low blood pressure (systolic blood pressure below 100 mmHg). The mean peak blood pressure lowering occurs six to eight hours after dosing. Observation should continue until blood pressure is stable. The concomitant diuretic dose should be reduced, if possible, to help minimize hypovolemia which may contribute to hypotension (See WARNINGS and PRECAUTIONS, Drug Interactions). The appearance of hypotension after the initial dose of lisinopril tablets does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

The usual effective dosage range is 5 to 40 mg per day administered as a single daily dose. The dose of lisinopril tablets can be increased by increments of no greater than 10 mg, at intervals of no less than 2 weeks to the highest tolerated dose, up to a maximum of 40 mg daily. Dose adjustment should be based on the clinical response of individual patients.

Dosage Adjustment in Patients with Heart Failure and Renal Impairment or Hyponatremia: In patients with heart failure who have hyponatremia (serum sodium < 130 mEq/L) or moderate to severe renal impairment (creatinine clearance ≤ 30 mL/min or serum creatinine > 3 mg/dL), therapy with lisinopril tablets should be initiated at a dose of 2.5 mg once a day under close medical supervision (See WARNINGS and PRECAUTIONS, Drug Interactions).

Acute Myocardial Infarction

In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, the first dose of lisinopril tablets are 5 mg given orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg of lisinopril tablets once daily. Dosing should continue for six weeks. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin, and beta-blockers.

Patients with a low systolic blood pressure (≤ 120 mmHg) when treatment is started or during the first 3 days after the infarct should be given a lower 2.5 mg oral dose of lisinopril tablets (See WARNINGS). If hypotension occurs (systolic blood pressure ≤ 100 mmHg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure < 90 mmHg for more than 1 hour) lisinopril tablets should be withdrawn. For patients who develop symptoms of heart failure, see DOSAGE AND ADMINISTRATION, Heart Failure.

Dosage Adjustment in Patients With Myocardial Infarction with Renal Impairment: In acute myocardial infarction, treatment with lisinopril tablets should be initiated with caution in patients with evidence of renal dysfunction, defined as serum creatinine concentration exceeding 2 mg/dL. No evaluation of dosing adjustments in myocardial infarction patients with severe renal impairment has been performed.

Use in Elderly

In general, the clinical response was similar in younger and older patients given similar doses of lisinopril tablets. Pharmacokinetic studies, however indicate that maximum blood levels and area under the plasma concentration time curve (AUC) are doubled in older patients, so that dosage adjustments should be made with particular caution.

Pediatric Hypertensive Patients ≥6 years of age

The usual recommended starting dose is 0.07 mg/kg once daily (up to 5 mg total). Dosage should be adjusted according to blood pressure response. Doses above 0.61 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients (See CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism and Pharmacodynamics and Clinical Effects).

Lisinopril tablets are not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m2 (See CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism and Pharmacodynamics and Clinical Effects and PRECAUTIONS).

Preparation of Suspension (for 200 mL of a 1 mg/mL suspension): Add 10 mL of Purified Water USP to a polyethylene terephthalate (PET) bottle containing ten 20 mg tablets of lisinopril and shake for at least one minute. Add 30 mL of Bicitra®3 diluent and 160 mL of Ora-Sweet SF™4 to the concentrate in the PET bottle and gently shake for several seconds to disperse the ingredients. The suspension should be stored at or below 25º C (77º F) and can be stored for up to four weeks. Shake the suspension before each use.

3Registered trademark of Alza Corporation

4Trademark of Paddock Laboratories, Inc.
Sumatriptan

Sumatriptan

2.1 Dosing Information

The recommended dose of sumatriptan tablets is 25 mg, 50 mg, or 100 mg. Doses of 50 mg and 100 mg may provide a greater effect than the 25 mg dose, but doses of 100 mg may not provide a greater effect than the 50 mg dose. Higher doses may have a greater risk of adverse reactions [see Clinical Studies (14)].

If the migraine has not resolved by 2 hours after taking sumatriptan tablets, or returns after a transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose is 200 mg in a 24-hour period.

Use after sumatriptan injection: If the migraine returns following an initial treatment with sumatriptan succinate injection, additional single sumatriptan tablets (up to 100 mg/day) may be given with an interval of at least 2 hours between tablet doses.

The safety of treating an average of more than 4 headaches in a 30-day period has not been established.

2.2 Dosing in Patients With Hepatic Impairment

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

Atenolol

Hypertension

The initial dose of atenolol is 50 mg given as one tablet a day either alone or added to diuretic therapy. The full effect of this dose will usually be seen within one to two weeks. If an optimal response is not achieved, the dosage should be increased to atenolol 100 mg given as one tablet a day. Increasing the dosage beyond 100 mg a day is unlikely to produce any further benefit.

Atenolol may be used alone or concomitantly with other antihypertensive agents including thiazide-type diuretics, hydralazine, prazosin, and alpha-methyldopa.

Angina Pectoris

The initial dose of atenolol is 50 mg given as one tablet a day. If an optimal response is not achieved within one week, the dosage should be increased to atenolol 100 mg given as one tablet a day. Some patients may require a dosage of 200 mg once a day for optimal effect.

Twenty-four hour control with once daily dosing is achieved by giving doses larger than necessary to achieve an immediate maximum effect. The maximum early effect on exercise tolerance occurs with doses of 50 to 100 mg, but at these doses the effect at 24 hours is attenuated, averaging about 50% to 75% of that observed with once a day oral doses of 200 mg.

Acute Myocardial Infarction

In patients with definite or suspected acute myocardial infarction, treatment with atenolol I.V. injection should be initiated as soon as possible after the patient’s arrival in the hospital and after eligibility is established. Such treatment should be initiated in a coronary care or similar unit immediately after the patient’s hemodynamic condition has stabilized. Treatment should begin with the intravenous administration of 5 mg atenolol over 5 minutes followed by another 5 mg intravenous injection 10 minutes later. Atenolol I.V. injection should be administered under carefully controlled conditions including monitoring of blood pressure, heart rate, and electrocardiogram. Dilutions of atenolol I.V. injection in Dextrose Injection USP, Sodium Chloride Injection USP, or Sodium Chloride and Dextrose Injection may be used. These admixtures are stable for 48 hours if they are not used immediately.

In patients who tolerate the full intravenous dose (10 mg), atenolol tablets 50 mg should be initiated 10 minutes after the last intravenous dose followed by another 50 mg oral dose 12 hours later. Thereafter, atenolol can be given orally either 100 mg once daily or 50 mg twice a day for a further 6 to 9 days or until discharge from the hospital. If bradycardia or hypotension requiring treatment or any other untoward effects occur, atenolol should be discontinued. (See full prescribing information prior to initiating therapy with atenolol tablets.)

Data from other beta-blocker trials suggest that if there is any question concerning the use of IV beta-blocker or clinical estimate that there is a contraindication, the IV beta-blocker may be eliminated and patients fulfilling the safety criteria may be given atenolol tablets 50 mg twice daily or 100 mg once a day for at least seven days (if the IV dosing is excluded).

Although the demonstration of efficacy of atenolol is based entirely on data from the first seven postinfarction days, data from other beta-blocker trials suggest that treatment with beta-blockers that are effective in the postinfarction setting may be continued for one to three years if there are no contraindications.

Atenolol is an additional treatment to standard coronary care unit therapy.

Elderly Patients or Patients with Renal Impairment

Atenolol is excreted by the kidneys; consequently dosage should be adjusted in cases of severe impairment of renal function. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Evaluation of patients with hypertension or myocardial infarction should always include assessment of renal function. Atenolol excretion would be expected to decrease with advancing age.

No significant accumulation of atenolol occurs until creatinine clearance falls below 35 mL/min/1.73 m2.Accumulation of atenolol and prolongation of its half-life were studied in subjects with creatinine clearance between 5 and 105 mL/min. Peak plasma levels were significantly increased in subjects with creatinine clearances below 30 mL/min.

The following maximum oral dosages are recommended for elderly, renally-impaired patients and for patients with renal impairment due to other causes:
Creatinine Clearance(mL/min/1.73 m2) AtenololElimination Half-Life(h) Maximum Dosage 15 to 35 16 to 27 50 mg daily < 15 > 27 25 mg daily
Some renally-impaired or elderly patients being treated for hypertension may require a lower starting dose of atenolol: 25 mg given as one tablet a day. If this 25 mg dose is used, assessment of efficacy must be made carefully. This should include measurement of blood pressure just prior to the next dose ("trough" blood pressure) to ensure that the treatment effect is present for a full 24 hours.

Although a similar dosage reduction may be considered for elderly and/or renally-impaired patients being treated for indications other than hypertension, data are not available for these patient populations.

Patients on hemodialysis should be given 25 mg or 50 mg after each dialysis; this should be done under hospital supervision as marked falls in blood pressure can occur.

Cessation of Therapy in Patients with Angina Pectoris

If withdrawal of atenolol therapy is planned, it should be achieved gradually and patients should be carefully observed and advised to limit physical activity to a minimum.
Acetaminophen And Codei...

Acetaminophen And Codeine Phosphate

Dosage should be adjusted according to severity of pain and response of the patient.

It should be kept in mind, however, that tolerance to codeine can develop with continued use and that the incidence of untoward effects is dose related. Adult doses of codeine higher than 60 mg fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of undesirable side effects.

Equivalently high doses in children would have similar effects.

The usual adult dosage for tablets is:
Single Doses Maximum (Range) 24 Hour Dose Codeine Phosphate 15 mg to 60 mg 360 mg Acetaminophen 300 mg to 1000 mg 4000 mg
Doses may be repeated up to every 4 hours.

The prescriber must determine the number of tablets per dose, and the maximum number of tablets per 24 hours, based upon the above dosage guidance. This information should be conveyed in the prescription.

For children, the dose of codeine phosphate is 0.5 mg/kg.
Fosinopril Sodium And H...

Fosinopril Sodium And Hydrochlorothiazide

Fosinopril is an effective treatment of hypertension in once-daily doses of 10 to 80 mg, while hydrochlorothiazide is effective in doses of 12.5 to 50 mg per day. In clinical trials of fosinopril/hydrochlorothiazide combination therapy using fosinopril doses of 2.5 to 40 mg and hydrochlorothiazide doses at 5 to 37.5 mg, the antihypertensive effects increased with increasing dose of either component.

The hazards (see WARNINGS) of fosinopril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of fosinopril and hydrochlorothiazide will be associated with both sets of dose-independent hazards. To minimize dose-independent hazards, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Dose Titration by Clinical Effect

A patient whose blood pressure is not adequately controlled with fosinopril or hydrochlorothiazide monotherapy may be switched to combination therapy with fosinopril sodium and hydrochlorothiazide tablets, USP. Dosage must be guided by clinical response; controlled clinical trials showed that the addition of 12.5 mg of hydrochlorothiazide to 10 to 20 mg of fosinopril will typically be associated with additional reduction in seated diastolic blood pressure at 24 hours after dosing. On average, the effect of the combination of 10 mg of fosinopril with 12.5 mg of hydrochlorothiazide was similar to the effect seen with monotherapy using either 40 mg of fosinopril or 37.5 mg of hydrochlorothiazide.

Use in Renal Impairment

In patients with severe renal impairment (creatinine clearance is < 30 mL/min/1.73 m2, serum creatine roughly ≥ 3 mg/dL or 265 µmol/L), loop diuretics are preferred to thiazides, so fosinopril sodium and hydrochlorothiazide tablets, USP is not recommended. In patients with lesser degrees of renal impairment, fosinopril sodium and hydrochlorothiazide tablets, USP may be used with no change in dosage.
Valacyclovir

Valacyclovir

Valacyclovir tablets may be given without regard to meals. Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) may be prepared extemporaneously from 500 mg valacyclovir tablets for use in pediatric patients for whom a solid dosage form is not appropriate [see Dosage and Administration (2.3)].
2.1 Adult Dosing Recommendations

Cold Sores (Herpes Labialis): The recommended dosage of valacyclovir tablets for treatment of cold sores is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning).

Genital Herpes:Initial Episode: The recommended dosage of valacyclovir tablets for treatment of initial genital herpes is 1 gram twice daily for 10 days. Therapy was most effective when administered within 48 hours of the onset of signs and symptoms.

Recurrent Episodes: The recommended dosage of valacyclovir tablets for treatment of recurrent genital herpes is 500 mg twice daily for 3 days. Initiate treatment at the first sign or symptom of an episode.

Suppressive Therapy: The recommended dosage of valacyclovir tablets for chronic suppressive therapy of recurrent genital herpes is 1 gram once daily in patients with normal immune function. In patients with a history of 9 or fewer recurrences per year, an alternative dose is 500 mg once daily.

In HIV-infected patients with a CD4 + cell count ≥ 100 cells/mm 3, the recommended dosage of valacyclovir tablets for chronic suppressive therapy of recurrent genital herpes is 500 mg twice daily.

Reduction of Transmission: The recommended dosage of valacyclovir tablets for reduction of transmission of genital herpes in patients with a history of 9 or fewer recurrences per year is 500 mg once daily for the source partner.

Herpes Zoster: The recommended dosage of valacyclovir tablets for treatment of herpes zoster is 1 gram 3 times daily for 7 days. Therapy should be initiated at the earliest sign or symptom of herpes zoster and is most effective when started within 48 hours of the onset of rash.

2.2 Pediatric Dosing Recommendations

Cold Sores (Herpes Labialis): The recommended dosage of valacyclovir tablets for the treatment of cold sores in pediatric patients ≥ 12 years of age is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning).

Chickenpox: The recommended dosage of valacyclovir tablets for treatment of chickenpox in immunocompetent pediatric patients 2 to < 18 years of age is 20 mg/kg administered 3 times daily for 5 days. The total dose should not exceed 1 gram 3 times daily. Therapy should be initiated at the earliest sign or symptom [see Use in Specific Populations (8.4), Clinical Pharmacology (12.3), Clinical Studies (14.4)].

2.3 Extemporaneous Preparation of Oral Suspension

Ingredients and Preparation per USP-NF: Valacyclovir tablets 500 mg, cherry flavor, and Suspension Structured Vehicle USP-NF (SSV). Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) should be prepared in lots of 100 mL.

Prepare Suspension at Time of Dispensing as Follows:
Prepare SSV according to the USP-NF. Using a pestle and mortar, grind the required number of valacyclovir tablets 500 mg until a fine powder is produced (5 valacyclovir tablets for 25 mg/mL suspension; 10 valacyclovir tablets for 50 mg/mL suspension). Gradually add approximately 5 mL aliquots of SSV to the mortar and triturate the powder until a paste has been produced. Ensure that the powder has been adequately wetted. Continue to add approximately 5 mL aliquots of SSV to the mortar, mixing thoroughly between additions, until a concentrated suspension is produced, to a minimum total quantity of 20 mL SSV and a maximum total quantity of 40 mL SSV for both the 25 mg/mL and 50 mg/mL suspensions. Transfer the mixture to a suitable 100 mL measuring flask. Transfer the cherry flavor* to the mortar and dissolve in approximately 5 mL of SSV. Once dissolved, add to the measuring flask. Rinse the mortar at least 3 times with approximately 5 mL aliquots of SSV, transferring the rinsing to the measuring flask between additions. Make the suspension to volume (100 mL) with SSV and shake thoroughly to mix. Transfer the suspension to an amber glass medicine bottle with a child-resistant closure. The prepared suspension should be labeled with the following information “Shake well before using. Store suspension between 2° to 8° C (36° to 46° F) in a refrigerator. Discard after 28 days.”
*The amount of cherry flavor added is as instructed by the suppliers of the cherry flavor.

2.4 Patients With Renal Impairment

Dosage recommendations for adult patients with reduced renal function are provided in Table 1[see Use in Specific Populations (8.5, 8.6), Clinical Pharmacology (12.3)]. Data are not available for the use of valacyclovir tablets in pediatric patients with a creatinine clearance < 50 mL/min/1.73 m2.
Table 1. Valacyclovir Tablets Dosage Recommendations for Adults With Renal Impairment Indications Normal Dosage Regimen (Creatinine Clearance ≥ 50 mL/min) Creatinine Clearance (mL/min) 30 to 49 10 to 29 < 10 Cold sores (Herpes labialis) Do not exceed 1 day of treatment. Two 2 gram doses taken 12 hours apart Two 1 gram doses taken 12 hours apart Two 500 mg doses taken 12 hours apart 500 mg single dose Genital herpes: Initialepisode 1 gram every 12 hours no reduction 1 gram every 24 hours 500 mg every 24 hours Genital herpes: Recurrent episode 500 mg every 12 hours no reduction 500 mg every 24 hours 500 mg every 24 hours Genital herpes: Suppressive therapy Immuno competent patients 1 gram every 24 hours no reduction 500 mg every 24 hours 500 mg every 24 hours Alternate dose for immunocompetent patients with ≤ 9 recurrences/year 500 mg every 24 hours no reduction 500 mg every 48 hours 500 mg every 48 hours HIV-infected patients 500 mg every 12 hours no reduction 500 mg every 24 hours 500 mg every 24 hours Herpes zoster 1 gram every 8 hours 1 gram every 12 hours 1 gram every 24 hours 500 mg every 24 hours
Hemodialysis: Patients requiring hemodialysis should receive the recommended dose of valacyclovir tablets after hemodialysis. During hemodialysis, the half-life of acyclovir after administration of valacyclovir tablets is approximately 4 hours. About one third of acyclovir in the body is removed by dialysis during a 4-hour hemodialysis session.

Peritoneal Dialysis: There is no information specific to administration of valacyclovir tablets in patients receiving peritoneal dialysis. The effect of chronic ambulatory peritoneal dialysis (CAPD) and continuous arteriovenous hemofiltration/dialysis (CAVHD) on acyclovir pharmacokinetics has been studied. The removal of acyclovir after CAPD and CAVHD is less pronounced than with hemodialysis, and the pharmacokinetic parameters closely resemble those observed in patients with end-stage renal disease (ESRD) not receiving hemodialysis. Therefore, supplemental doses of valacyclovir tablets should not be required following CAPD or CAVHD.
Amlodipine Besylate And...

Amlodipine Besylate And Atorvastatin Calcium

Amlodipine besylate and atorvastatin calcium tablets

Dosage of amlodipine besylate and atorvastatin calcium tablets must be individualized on the basis of both effectiveness and tolerance for each individual component in the treatment of hypertension/angina and hyperlipidemia. Select doses of amlodipine and atorvastatin independently.

Amlodipine besylate and atorvastatin calcium tablets may be substituted for its individually titrated components. Patients may be given the equivalent dose of amlodipine besylate and atorvastatin calcium tablets or a dose of amlodipine besylate and atorvastatin calcium tablets with increased amounts of amlodipine, atorvastatin, or both for additional antianginal effects, blood pressure lowering, or lipid-lowering effect.

Amlodipine besylate and atorvastatin calcium tablets may be used to provide additional therapy for patients already on one of its components. Amlodipine besylate and atorvastatin calcium tablets may be used to initiate treatment in patients with hyperlipidemia and either hypertension or angina.

Amlodipine

The usual initial antihypertensive oral dose of amlodipine is 5 mg once daily, and the maximum dose is 10 mg once daily.

Pediatric (age > 6 years), small adult, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding amlodipine to other antihypertensive therapy.

Adjust dosage according to blood pressure goals. In general, wait 7 to 14 days between titration steps. Titration may proceed more rapidly, however, if clinically warranted, provided the patient is assessed frequently.

Angina: The recommended dose of amlodipine for chronic stable or vasospastic angina is 5–10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg for adequate effect.

Coronary artery disease: The recommended dose range of amlodipine for patients with coronary artery disease is 5–10 mg once daily. In clinical studies, the majority of patients required 10 mg [see Clinical Studies (14.4)].

Pediatrics: The effective antihypertensive oral dose of amlodipine in pediatric patients ages 6–17 years is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been studied in pediatric patients [see Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Atorvastatin (Hyperlipidemia)

Hyperlipidemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb): The recommended starting dose of atorvastatin is 10 or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range of atorvastatin is 10 to 80 mg once daily. Atorvastatin can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance doses of atorvastatin should be individualized according to patient characteristics such as goal of therapy and response (see current NCEP Guidelines). After initiation and/or upon titration of atorvastatin, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly.

Homozygous Familial Hypercholesterolemia: The dosage range of atorvastatin in patients with homozygous FH is 10 to 80 mg daily. Atorvastatin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

Concomitant Lipid-Lowering Therapy: Atorvastatin may be used with bile acid resins. Monitor for signs of myopathy in patients receiving the combination of HMG-CoA reductase inhibitors (statins) and fibrates [see Warnings and Precautions (5.1), Drug Interactions (7)].

Patients with Renal Impairment: Renal disease does not affect the plasma concentrations nor LDL-C reduction of atorvastatin; thus, dosage adjustment in patients with renal dysfunction is not necessary [see Warnings and Precautions (5.1), Clinical Pharmacology (12.3)].

Use with Cyclosporine, Clarithromycin, Itraconazole, or Certain Protease Inhibitors: In patients taking cyclosporine or the HIV protease inhibitors (tipranavir plus ritonavir) or the hepatitis C protease inhibitor (telaprevir), avoid therapy with atorvastatin. In patients with HIV taking lopinavir plus ritonavir, use the lowest necessary dose of atorvastatin. In patients taking clarithromycin, itraconazole, or in patients with HIV taking a combination of saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, limit therapy with atorvastatin to 20 mg, and make appropriate clinical assessment to ensure that the lowest dose necessary of atorvastatin is employed. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, limit therapy with atorvastatin to 40 mg, and make appropriate clinical assessment to ensure that the lowest dose necessary of atorvastatin is employed [see Warnings and Precautions (5.1), Drug Interactions (7.13)].

Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10–17 years of age): The recommended starting dose of atorvastatin is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy [see current NCEP Pediatric Panel Guidelines 1, (References (15), Clinical Pharmacology (12), and Indications and Usage (1.4)]. Adjustments should be made at intervals of 4 weeks or more.
Chloroquine Phosphate

Chloroquine Phosphate

The dosage of chloroquine phosphate is often expressed in terms of equivalent chloroquine base. Each 500 mg tablet of chloroquine phosphate tablets contains the equivalent of 300 mg chloroquine base. In infants and children the dosage is preferably calculated by body weight.

Malaria: Suppression—Adult Dose: 500 mg (= 300 mg base) on exactly the same day of each week.

Pediatric Dose: The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight.

If circumstances permit, suppressive therapy should begin two weeks prior to exposure. However, failing this in adults, an initial double (loading) dose of 1 g (= 600 mg base), or in children 10 mg base/kg may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area.

For Treatment of Acute Attack

Adults: An initial dose of 1 g (= 600 mg base) followed by an additional 500 mg (= 300 mg base) after six to eight hours and a single dose of 500 mg (= 300 mg base) on each of two consecutive days. This represents a total dose of 2.5 g chloroquine phosphate or 1.5 g base in three days.

The dosage for adults of low body weight and for infants and children should be determined as follows:

First dose: 10 mg base per kg (but not exceeding a single dose of 600 mg base).

Second dose: (6 hours after first dose) 5 mg base per kg (but not exceeding a single dose of 300 mg base).

Third dose: (24 hours after first dose) 5 mg base per kg.

Fourth dose: (36 hours after first dose) 5 mg base per kg.

For radical cure of vivax and malariae malaria concomitant therapy with an 8-aminoquinoline compound is necessary.

Extraintestinal Amebiasis: Adults, 1 g (600 mg base) daily for two days, followed by 500 mg (300 mg base) daily for at least two to three weeks. Treatment is usually combined with an effective intestinal amebicide.

Geriatric Use

See PRECAUTIONS, Geriatric Use.
Chloroquine Phosphate

Chloroquine Phosphate

The dosage of chloroquine phosphate is often expressed or calculated as the base. Each 250 mg tablet of chloroquine phosphate is equivalent to 150 mg base. In infants and children the dosage is preferably calculated on the body weight.

Malaria: Suppression— Adult Dose: 500 mg (= 300 mg base) on exactly the same day of each week.

Pediatric Dose: The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight.

If circumstances permit, suppressive therapy should begin two weeks prior to exposure. However, failing this in adults, an initial double (loading) dose of 1 g (= 600 mg base), or in children 10 mg base/kg may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area.

For Treatment of Acute Attack:

Adults: An initial dose of 1 g (= 600 mg base) followed by an additional 500 mg (= 300 mg base) after six to eight hours and a single dose of 500 mg (= 300 mg base) on each of two consecutive days. This represents a total dose of 2.5 g chloroquine phosphate or 1.5 g base in three days.

The dosage for adults of low body weight and for infants and children should be determined as follows:

First dose: 10 mg base per kg (but not exceeding a single dose of 600 mg base).

Second dose: (6 hours after first dose) 5 mg base per kg (but not exceeding a single dose of 300 mg base).

Third dose: (24 hours after first dose) 5 mg base per kg.

Fourth dose: (36 hours after first dose) 5 mg base per kg.

For radical cure of vivax and malariae malaria concomitant therapy with an 8-aminoquinoline compound is necessary.

Extraintestinal Amebiasis: Adults:1 g (600 mg base) daily for two days, followed by 500 mg (300 mg base) daily for at least two to three weeks. Treatment is usually combined with an effective intestinal amebicide.

Geriatric Use

See PRECAUTIONS, Geriatric Use.
Gabapentin

Gabapentin

Gabapentin capsules are given orally with or without food.

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

Postherpetic Neuralgia

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

Epilepsy

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

Patients > 12 years of age: The effective dose of gabapentin capsules is 900 to 1800 mg/day and given in divided doses (three times a day) using 300 or 400 mg capsules. The starting dose is 300 mg three times a day. If necessary, the dose may be increased using 300 or 400 mg capsules three times a day up to 1800 mg/day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. The maximum time between doses in the TID schedule should not exceed 12 hours.

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

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

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

Dosage in Renal Impairment

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

for females CCr = (0.85)(140-age)(weight)/[(72)(SCr)]

for males CCr = (140-age)(weight)/[(72)(SCr)]

in which age is in years, weight is in kilograms, and SCr is serum creatinine in mg/dL.

Dosage adjustment in patients ≥ 12 years of age with compromised renal function or undergoing hemodialysis is recommended as follows (see dosing recommendations above for effective doses in each indication).
TABLE 6. Gabapentin Capsules Dosage Based on Renal Function
a For patients with creatinine clearance < 15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table.
Renal FunctionCreatinine Clearance(mL/min) Total Daily Dose Range (mg/day) Dose Regimen(mg) ≥ 60 900 to 3600 300 TID 400 TID 600 TID 800 TID 1200 TID > 30 to 59 400 to 1400 200 BID 300 BID 400 BID 500 BID 700 BID > 15 to 29 200 to 700 200 QD 300 QD 400 QD 500 QD 700 QD 15a 100 to 300 100 QD 125 QD 150 QD 200 QD 300 QD Post-Hemodialysis Supplemental Dose (mg)b Hemodialysis 125b 150b 200b 250b 350b
The use of gabapentin in patients < 12 years of age with compromised renal function has not been studied.

Dosage in Elderly

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

Furosemide

Edema

Therapy should be individualized according to patient response to gain maximal therapeutic response and to determine the minimal dose needed to maintain that response.

Adults -- The usual initial dose of furosemide tablets, USP is 20 to 80 mg given as a single dose. Ordinarily a prompt diuresis ensues. If needed, the same dose can be administered 6 to 8 hours later or the dose may be increased. The dose may be raised by 20 or 40 mg and given not sooner than 6 to 8 hours after the previous dose until the desired diuretic effect has been obtained. The individually determined single dose should then be given once or twice daily (e.g., at 8 am and 2 pm). The dose of furosemide tablets, USP may be carefully titrated up to 600 mg/day in patients with clinically severe edematous states.

Edema may be most efficiently and safely mobilized by giving furosemide tablets, USP on 2 to 4 consecutive days each week.

When doses exceeding 80 mg/day are given for prolonged periods, careful clinical observation and laboratory monitoring are particularly advisable. (See PRECAUTIONS: Laboratory Tests)

Geriatric patients -- In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS: Geriatric Use).

Pediatric patients -- The usual initial dose of furosemide tablets, USP in pediatric patients is 2 mg/kg body weight, given as a single dose. If the diuretic response is not satisfactory after the initial dose, dosage may be increased by 1 or 2 mg/kg no sooner than 6 to 8 hours after the previous dose. Doses greater than 6 mg/kg body weight are not recommended. For maintenance therapy in pediatric patients, the dose should be adjusted to the minimum effective level.

Hypertension

Therapy should be individualized according to the patient’s response to gain maximal therapeutic response and to determine the minimal dose needed to maintain the therapeutic response.

Adults -- The usual initial dose of furosemide tablets, USP for hypertension is 80 mg, usually divided into 40 mg twice a day. Dosage should then be adjusted according to response. If response is not satisfactory, add other antihypertensive agents.

Changes in blood pressure must be carefully monitored when furosemide tablets, USP are used with other antihypertensive drugs, especially during initial therapy. To prevent excessive drop in blood pressure, the dosage of other agents should be reduced by at least 50 percent when furosemide tablets, USP are added to the regimen. As the blood pressure falls under the potentiating effect of furosemide tablets, USP a further reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary.

Geriatric patients -- In general, dose selection and dose adjustment for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS: Geriatric Use).
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 capsules 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 Warnings and Precautions (5.2) and Drug Interactions (7.7)].

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 capsules, OCD is a chronic condition and it is reasonable to consider continuation for a responding patient. Although the efficacy of fluoxetine capsules 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 capsules 60 mg/day for periods of up to 52 weeks in patients with bulimia who have responded while taking fluoxetine capsules 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 capsules, 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 Capsules and Olanzapine in Combination: Depressive Episodes Associated with Bipolar I Disorder

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

Adult— 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 of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies.

Information for pediatric patients (10 to 17 years) is approved for Eli Lilly and Company’s Fluoxetine Capsules. However due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

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 capsules 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 Correspondence Between Olanzapine and Fluoxetine Hydrochloride Capsules1 and the Combination of Fluoxetine Capsules and Olanzapine
1Olanzapine/fluoxetine HCl is a fixed-dose combination of fluoxetine capsules and olanzapine.
For Olanzapine and Fluoxetine Hydrochloride Capsules (mg/day) Use in Combination Olanzapine (mg/day) Fluoxetine capsules (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
While there is no body of evidence to answer the question of how long a patient treated with fluoxetine capsules 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.

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

Geriatric — 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 Capsules 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, non-smoking 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 capsules and olanzapine in combination have not been systematically studied in patients over 65 years of age or in patients less than 10 years of age [see Warnings and Precautions (5.14) and Drug Interactions (7.7)].

2.8 Discontinuation of Treatment

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

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

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

2.10 Use of Fluoxetine Capsules with Other MAOIs such as Linezolid or Methylene Blue

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

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

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

Hydrocodone Bitartrate And Acetaminophen

Dosage should be adjusted according to the severity of the pain and the response of the patient. However, it should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related.

The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets.
Hydroxychloroquine Sulf...

Hydroxychloroquine Sulfate

One tablet of 200 mg of hydroxychloroquine sulfate is equivalent to 155 mg base.

Malaria: Suppression: In adults, 400 mg (=310 mg base) on exactly the same day of each week. In infants and children, the weekly suppressive dosage is 5 mg, calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight.

If circumstances permit, suppressive therapy should begin two weeks prior to exposure. However, failing this, in adults an initial double (loading) dose of 800 mg (=620 mg base), or in children 10 mg base/kg may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area.

Treatment of the acute attack: In adults, an initial dose of 800 mg (=620 mg base) followed by 400 mg (=310 mg base) in six to eight hours and 400 mg (=310 mg base) on each of two consecutive days (total 2 g hydroxychloroquine sulfate or 1.55 g base). An alternative method, employing a single dose of 800 mg (=620 mg base), has also proved effective.

The dosage for adults may also be calculated on the basis of body weight; this method is preferred for infants and children. A total dose representing 25 mg of base per kg of body weight is administered in three days, as follows:

First dose: 10 mg base per kg (but not exceeding a single dose of 620 mg base).

Second dose: 5 mg base per kg (but not exceeding a single dose of 310 mg base) 6 hours after first dose.

Third dose: 5 mg base per kg 18 hours after second dose.

Fourth dose: 5 mg base per kg 24 hours after third dose.

For radical cure of vivax and malariae malaria concomitant therapy with an 8-aminoquinoline compound is necessary.
LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITIS
INDICATIONS AND USAGE

Hydroxychloroquine sulfate tablets are useful in patients with the following disorders who have not responded satisfactorily to drugs with less potential for serious side effects: lupus erythematosus (chronic discoid and systemic) and acute or chronic rheumatoid arthritis.

WARNINGS

PHYSICIANS SHOULD COMPLETELY FAMlLlARlZE THEMSELVES WITH THE COMPLETE CONTENTS OF THIS LEAFLET BEFORE PRESCRlBlNG HYDROXYCHLOROQUINE SULFATE TABLETS

Irreversible retinal damage has been observed in some patients who had received long-term or high-dosage 4-aminoquinoline therapy for discoid and systemic lupus erythematosus, or rheumatoid arthritis. Retinopathy has been reported to be dose-related.

When prolonged therapy with any antimalarial compound is contemplated, initial (base line) and periodic (every three months) ophthalmologic examinations (including visual acuity, expert slit-lamp, funduscopic, and visual field tests) should be performed.

If there is any indication of abnormality in the visual acuity, visual field, or retinal macular areas (such as pigmentary changes, loss of foveal reflex), or any visual symptoms (such as light flashes and streaks) which are not fully explainable by difficulties of accommodation or corneal opacities, the drug should be discontinued immediately and the patient closely observed for possible progression. Retinal changes (and visual disturbances) may progress even after cessation of therapy.

All patients on long-term therapy with this preparation should be questioned and examined periodically, including the testing of knee and ankle reflexes, to detect any evidence of muscular weakness. If weakness occurs, discontinue the drug.

In the treatment of rheumatoid arthritis, if objective improvement (such as reduced joint swelling, increased mobility) does not occur within six months, the drug should be discontinued. Safe use of the drug in the treatment of juvenile arthritis has not been established.

PRECAUTIONS

Dermatologic reactions to hydroxychloroquine sulfate tablets may occur and, therefore, proper care should be exercised when they were administered to any patient receiving a drug with a significant tendency to produce dermatitis.

The methods recommended for early diagnosis of "chloroquine retinopathy" consist of (1) funduscopic examination of the macula for fine pigmentary disturbances or loss of the foveal reflex and (2) examination of the central visual field with a small red test object for pericentral or paracentral scotoma or determination of retinal thresholds to red. Any unexplained visual symptoms, such as light flashes or streaks should also be regarded with suspicion as possible manifestations of retinopathy.

If serious toxic symptoms occur from overdosage or sensitivity, it has been suggested that ammonium chloride (8 g daily in divided doses for adults) be administered orally three or four days a week for several months after therapy has been stopped, as acidification of the urine increases renal excretion of the 4-aminoquinoline compounds by 20 to 90 percent. However, caution must be exercised in patients with impaired renal function and/or metabolic acidosis.

ADVERSE REACTIONS

Not all of the following reactions have been observed with every 4-aminoquinoline compound during long-term therapy, but they have been reported with one or more and should be borne in mind when drugs of this class are administered. Adverse effects with different compounds vary in type and frequency.

CNS Reactions: Irritability, nervousness, emotional changes, nightmares, psychosis, headache, dizziness, vertigo, tinnitus, nystagmus, nerve deafness, convulsions, ataxia.

Neuromuscular Reactions: Skeletal muscle palsies or skeletal muscle myopathy or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups which may be associated with mild sensory changes, depression of tendon reflexes and abnormal nerve conduction.

Ocular Reactions:

A.   Ciliary body: Disturbance of accommodation with symptoms of blurred vision. This reaction is dose-related and reversed with cessation of therapy

B.   Cornea:Transient edema, punctuate to lineal opacities, decreased corneal sensitivity. The corneal changes, with or without accompanying symptoms (blurred vision, halos around lights, photophobia), are fairly common, but reversible. Corneal deposits may appears as early as three weeks following initiation of therapy.

       The incidence of corneal changes and visual side effects appears to be considerably lower with hydroxychloroquine than with chloroquine.

C.   Retina:

      Macula: Edema, atrophy, abnormal pigmentation (mild pigment stippling to a "bull's-eye" appearance), loss of foveal reflex, increased macular recovery time following exposure to a bright light (photo-stress test), elevated retinal and prominent choroidal patterns in advanced retinal areas

     Other fundus changes include optic disc pallor and atrophy, attenuation of retinal arterioles, fine granular pigmentary disturbances in the peripheral retina and prominent choroidal patterns in advanced stage

D. Visual field defects: Pericentral or paracentral scotoma, central scotoma with decreased visual acuity, rarely field constriction, abnormal color vision.

The most common visual symptoms attributed to the retinopathy are: reading and seeing difficulties (words, letters, or parts of objects missing), photophobia, blurred distance vision, missing or blacked out areas in the central or peripheral visual field, light flashes and streaks.

Retinopathy appears to be dose related and has occurred within several months (rarely) to several years of daily therapy; a small number of cases have been reported several years after antimalarial drug therapy was discontinued. It has not been noted during prolonged use of weekly doses of the 4-aminoquinoline compounds for suppression of malaria.

Patients with retinal changes may have visual symptoms or may be asymptomatic (with or without visual field changes). Rarely scotomatous vision or field defects may occur without obvious retinal change.

Retinopathy may progress even after the drug is discontinued. In a number of patients, early retinopathy (macular pigmentation sometimes with central field defects) diminished or regressed completely after therapy was discontinued. Paracentral scotoma to red targets (sometimes called "premaculopathy") is indicative of early retinal dysfunction which is usually reversible with cessation of therapy.

A small number of cases of retinal changes have been reported as occurring in patients who received only hydroxychloroquine sulfate tablets. These usually consisted of alteration in retinal pigmentation which was detected on periodic ophthalmologic examination; visual field defects were also present in some instances. A case of delayed retinopathy has been reported with loss of vision starting one year after administration of hydroxychloroquine sulfate tablets had been discontinued.

Dermatologic Reactions: Bleaching of hair, alopecia, pruritus, skin and mucosal pigmentation, photosensitivity, and skin eruptions (urticarial, morbilliform, Iichenoid, maculopapular, purpuric, erythema annulare centrifugum, Stevens Johnson-syndrome, acute generalized exanthematous pustulosis, and exfoliative dermatitis).

Hematologic Reactions: Various blood dyscrasias such as aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia (hemolysis in individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency).

Gastrointestinal Reactions: Anorexia, nausea, vomiting, diarrhea, and abdominal cramps. Isolated cases of abnormal liver function and fulminant hepatic failure.

Allergic reactions: Urticaria, angioedema and bronchospam have been reported.

Miscellaneous Reactions: Weight loss, lassitude, exacerbation or precipitation of porphyria and nonlight-sensitive psoriasis.

Cardiomyopathy has been rarely reported with high daily dosages of hydroxychloroquine sulfate tablets.

DOSAGE AND ADMINISTRATION

One tablet of hydroxychloroquine sulfate 200 mg, is equivalent to 155 mg base.

Lupus erythematosus: Initially, the average adult dose is 400 mg (=310 mg base) once or twice daily. This may be continued for several weeks or months, depending on the response of the patient. For prolonged maintenance therapy, a smaller dose, from 200 mg to 400 mg (=155 mg to 310 mg base) daily will frequently suffice.

The incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded.

Rheumatoid arthritis: The compound is cumulative in action and will require several weeks to exert its beneficial therapeutic effects, whereas minor side effects may occur relatively early. Several months of therapy may be required before maximum effects can be obtained. If objective improvement (such as reduced joint swelling, increased mobility) does not occur within six months, the drug should be discontinued. Safe use of the drug in the treatment of juvenile rheumatoid arthritis has not been established.

Initial dosage - In adults, from 400 mg to 600 mg (=310 mg to 465 mg base) daily, each dose to be taken with a meal or a glass of milk. In a small percentage of patients, troublesome side effects may require temporary reduction of the initial dosage. Later (usually from five to ten days), the dose may gradually be increased to the optimum response level, often without return of side effects.

Maintenance dosage - When a good response is obtained (usually in four to twelve weeks), the dosage is reduced by 50 percent and continued at a usual maintenance level of 200 mg to 400 mg (=155 mg to 310 mg base) daily, each dose to be taken with a meal or a glass of milk. The incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded.

Should a relapse occur after medication is withdrawn, therapy may be resumed or continued on an intermittent schedule if there are no ocular contraindications.

Corticosteroids and salicylates may be used in conjunction with this compound, and they can generally be decreased gradually in dosage or eliminated after the drug has been used for several weeks. When gradual reduction of steroid dosage is indicated, it may be done by reducing every four to five days the dose of cortisone by no more than from 5 mg to 15 mg; of hydrocortisone from 5 mg to 10 mg; of prednisolone and prednisone from 1 mg to 2.5 mg; of methylprednisolone and triamcinolone from 1 mg to 2 mg; and of dexamethasone from 0.25 mg to 0.5 mg.
Simvastatin

Simvastatin

2.1 Recommended Dosing

The usual dosage range is 5 to 40 mg/day. In patients with CHD or at high risk of CHD, simvastatin tablets can be started simultaneously with diet. The recommended usual starting dose is 10 or 20 mg once a day in the evening. For patients at high risk for a CHD event due to existing CHD, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter.

2.2 Restricted Dosing for 80 mg

Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 80 mg dose of simvastatin tablets should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity [see Warnings and Precautions (5.1)].

Patients who are currently tolerating the 80 mg dose of simvastatin tablets who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for the drug-drug interaction.

Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80 mg dose of simvastatin tablets, patients unable to achieve their LDL-C goal utilizing the 40 mg dose of simvastatin tablets should not be titrated to the 80 mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering.

2.3 Coadministration with Other Drugs

Patients taking Verapamil,Diltiazem, or Dronedarone
The dose of simvastatin tablets should not exceed 10 mg/day [see Warnings and Precautions (5.1), Drug Interactions (7.3), and Clinical Pharmacology (12.3)].
Patients taking Amiodarone, Amlodipine or Ranolazine
The dose of simvastatin tablets should not exceed 20 mg/day [see Warnings and Precautions (5.1), Drug Interactions (7.3), and Clinical Pharmacology (12.3)].
2.4 Patients with Homozygous Familial Hypercholesterolemia

The recommended dosage is 40 mg/day in the evening [see Dosage and Administration, Restricted Dosing for 80 mg (2.2)]. Simvastatin tablets should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of simvastatin tablets should be reduced by 50% if initiating lomitapide. Simvastatin tablets dosage should not exceed 20 mg/day (or 40 mg/day for patients who have previously taken simvastatin tablets 80 mg/day chronically, e.g., for 12 months or more, without evidence of muscle toxicity) while taking lomitapide.

2.5 Adolescents (10 to 17 years of age) with Heterozygous Familial Hypercholesterolemia

The recommended usual starting dose is 10 mg once a day in the evening. The recommended dosing range is 10 to 40 mg/day; the maximum recommended dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy [see NCEP Pediatric Panel Guidelines1 and Clinical Studies (14.2)]. Adjustments should be made at intervals of 4 weeks or more.

1National Cholesterol Education Program (NCEP): Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics. 89(3):495-501. 1992.

2.6 Patients with Renal Impairment

Because simvastatin tablets do not undergo significant renal excretion, modification of dosage should not be necessary in patients with mild to moderate renal impairment. However, caution should be exercised when simvastatin tablets are administered to patients with severe renal impairment; such patients should be started at 5 mg/day and be closely monitored [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

2.7 Chinese Patients Taking Lipid-Modifying Doses (greater than or equal to 1 g/day Niacin) of Niacin-Containing Products

Because of an increased risk for myopathy in Chinese patients taking simvastatin 40 mg coadministered with lipid-modifying doses (greater than or equal to 1 g/day niacin) of niacin-containing products, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products. The cause of the increased risk of myopathy is not known. It is also unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients. [See Warnings and Precautions (5.1).]
Topiramate

Topiramate

2.1 Epilepsy

It is not necessary to monitor topiramate plasma concentrations to optimize topiramate tablets therapy.

On occasion, the addition of topiramate tablets to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. Addition or withdrawal of phenytoin and/or carbamazepine during adjunctive therapy with topiramate tablets may require adjustment of the dose of topiramate tablets.

Because of the bitter taste, tablets should not be broken.

Topiramate tablets can be taken without regard to meals.

Monotherapy Use

Adults and Pediatric Patients 10 Years and Older

The recommended dose for topiramate tablets monotherapy in adults and pediatric patients 10 years of age and older is 400 mg/day in two divided doses. Approximately 58% of patients randomized to 400 mg/day achieved this maximal dose in the monotherapy controlled trial; the mean dose achieved in the trial was 275 mg/day. The dose should be achieved by titration according to the following schedule (Table 1):
Table 1: Monotherapy Titration Schedule for Adults and Pediatric Patients 10 years and older
Morning Dose

Evening Dose

Week 1

25 mg

25 mg

Week 2

50 mg

50 mg

Week 3

75 mg

75 mg

Week 4

100 mg

100 mg

Week 5

150 mg

150 mg

Week 6

200 mg

200 mg

Children Ages 2 to < 10 Years

Dosing of topiramate as initial monotherapy in children 2 to < 10 years of age with partial onset or primary generalized tonic-clonic seizures was based on a pharmacometric bridging approach [see Clinical Studies (14.1)].

Dosing in patients 2 to < 10 years is based on weight. During the titration period, the initial dose of topiramate tablets should be 25 mg/day administered nightly for the first week. Based upon tolerability, the dosage can be increased to 50 mg/day (25 mg twice daily) in the second week. Dosage can be increased by 25 to 50 mg/day each subsequent week as tolerated. Titration to the minimum maintenance dose should be attempted over 5 to 7 weeks of the total titration period. Based upon tolerability and clinical response, additional titration to a higher dose (up to the maximum maintenance dose) can be attempted at 25 to 50 mg/day weekly increments. The total daily dose should not exceed the maximum maintenance dose for each range of body weight (Table 2).
Table 2: Monotherapy Target Total Daily Maintenance Dosing for Patients 2 to < 10 Years * Administered in two equally divided doses
Weight (kg)

Total Daily Dose (mg/day)*

Total Daily Dose (mg/day)*

Minimum Maintenance Dose

Maximum Maintenance Dose

Up to 11

150

250

12 to 22

200

300

23 to 31

200

350

32 to 38

250

350

Greater than 38

250

400

Adjunctive Therapy Use

Adults 17 Years of Age and Over - Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of topiramate tablets as adjunctive therapy in adults with partial onset seizures is 200 to 400 mg/day in two divided doses, and 400 mg/day in two divided doses as adjunctive treatment in adults with primary generalized tonic-clonic seizures. It is recommended that therapy be initiated at 25 to 50 mg/day followed by titration to an effective dose in increments of 25 to 50 mg/day every week. Titrating in increments of 25 mg/day every week may delay the time to reach an effective dose. Doses above 400 mg/day (600, 800 or 1,000 mg/day) have not been shown to improve responses in dose-response studies in adults with partial onset seizures. Daily doses above 1,600 mg have not been studied.

In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies; the assigned dose was reached at the end of 8 weeks [see Clinical Studies (14.1)].

Pediatric Patients Ages 2 to 16 Years – Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of topiramate tablets as adjunctive therapy for pediatric patients with partial onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome is approximately 5 to 9 mg/kg/day in two divided doses. Titration should begin at 25 mg/day (or less, based on a range of 1 to 3 mg/kg/day) nightly for the first week. The dosage should then be increased at 1- or 2-week intervals by increments of 1 to 3 mg/kg/day (administered in two divided doses), to achieve optimal clinical response. Dose titration should be guided by clinical outcome.

In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies; the assigned dose of 6 mg/kg/day was reached at the end of 8 weeks [see Clinical Studies (14.1)].

2.4 Patients with Renal Impairment

In renally impaired subjects (creatinine clearance less than 70 mL/min/1.73 m 2), one-half of the usual adult dose is recommended. Such patients will require a longer time to reach steady-state at each dose.

2.5 Geriatric Patients (Ages 65 Years and Over)

Dosage adjustment may be indicated in the elderly patient when impaired renal function (creatinine clearance rate < 70 mL/min/1.73 m 2) is evident [see Clinical Pharmacology (12.3)].

2.6 Patients Undergoing Hemodialysis

Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than a normal individual. Accordingly, a prolonged period of dialysis may cause topiramate concentration to fall below that required to maintain an anti-seizure effect. To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of topiramate may be required. The actual adjustment should take into account 1) the duration of dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed.

2.7 Patients with Hepatic Disease

In hepatically impaired patients, topiramate plasma concentrations may be increased. The mechanism is not well understood.
Morphine Sulfate

Morphine Sulfate

2.1 Initial Dosing

Morphine sulfate extended-release tablets should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with morphine sulfate extended-release tablets [see Warnings and Precautions (5.2)].

Morphine sulfate extended-release tablets must be taken whole. Crushing, chewing, or dissolving morphine sulfate extended-release tablets will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.1)].

Use of Morphine Sulfate Extended-Release Tablets as the First Opioid Analgesic

Initiate treatment with morphine sulfate extended-release tablets with 15 mg tablets orally every 8 or 12 hours.

Use of Morphine Sulfate Extended-Release Tablets in Patients who are not Opioid Tolerant

The starting dose for patients who are not opioid tolerant is morphine sulfate extended-release tablets 15 mg orally every 12 hours. Patients who are opioid are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mg mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from Other Oral Morphine to Morphine Sulfate Extended-Release Tablets

Patients receiving other oral morphine formulations may be converted to morphine sulfate extended-release tablets by administering one-half of the patient's 24-hour requirement as morphine sulfate extended-release tablets on an every-12-hour schedule or by administering one-third of the patient's daily requirement as morphine sulfate extended-release tablets on an every-8-hour schedule.

Conversion from Other Opioids to Morphine Sulfate Extended-Release Tablets

There are no established conversion ratios for conversion from other opioids to morphine sulfate extended-release tablets defined by clinical trials. Discontinue all other around-the-clock opioid drugs when morphine sulfate extended-release tablets therapy is initiated and initiate dosing using morphine sulfate extended-release tablets 15 mg orally every 8 to 12 hours.

It is safer to underestimate a patient’s 24-hour oral morphine requirements and provide rescue medication (e.g., immediate-release morphine) than to overestimate the 24-hour oral morphine requirements and manage an adverse reaction. While useful tables of opioid equivalents are readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products.

Conversion from Parenteral Morphine or Other Opioids (Parenteral or Oral) to Morphine Sulfate Extended-Release Tablets

When converting from parenteral morphine or other non-morphine opioids (parenteral or oral) to morphine sulfate extended-release tablets, consider the following general points:

Parenteral to oral morphine ratio: Between 2 to 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of morphine that is approximately three times the previous daily parenteral morphine requirement is sufficient.

Other parenteral or oral non-morphine opioids to oral morphine sulfate: Specific recommendations are not available because of a lack of systematic evidence for these types of analgesic substitutions. Published relative potency data are available, but such ratios are approximations. In general, begin with half of the estimated daily morphine requirement as the initial dose, managing inadequate analgesia by supplementation with immediate-release morphine.

Conversion from Methadone to Morphine Sulfate Extended-Release Tablets

Close monitoring is of particular importance when converting methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

2.2 Titration and Maintenance of Therapy

Individually titrate morphine sulfate extended-release tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving morphine sulfate extended-release tablets to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy periodically reassess the continued need for the use of opioid analgesics.

Patients who experience breakthrough pain may require a dose increase of morphine sulfate extended-release tablets, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the morphine sulfate dose. Because steady-state plasma concentrations are approximated in 1 day, morphine sulfate extended-release tablets dosage adjustments may be done every 1 to 2 days.

If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.3 Discontinuation of Morphine Sulfate Extended-Release Tablets

When the patient no longer requires therapy with morphine sulfate extended-release tablets, use a gradual downward titration of the dose to prevent signs and symptoms of withdrawal in the physically-dependent patient. Do not abruptly discontinue morphine sulfate extended-release tablets.

2.4 Administration of Morphine Sulfate Extended-Release Tablets

Morphine sulfate extended-release tablets must be taken whole. Crushing, chewing, or dissolving morphine sulfate extended-release tablets will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.1)].
Minocycline Hydrochlori...

Minocycline Hydrochloride

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF MINOCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Minocycline hydrochloride capsules may be taken with or without food (see CLINICAL PHARMACOLOGY).

Ingestion of adequate amounts of fluids along with capsule and tablet forms of drugs in the tetracycline-class is recommended to reduce the risk of esophageal irritation and ulceration. The capsules should be swallowed whole.

For Pediatric Patients Above 8 Years of Age

Usual pediatric dose: 4 mg/kg initially followed by 2 mg/kg every 12 hours, not to exceed the usual adult dose.

Adults

The usual dosage of minocycline hydrochloride capsules is 200 mg initially followed by 100 mg every 12 hours. Alternatively, if more frequent doses are preferred, two or four 50 mg capsules may be given initially followed by one 50 mg capsule 4 times daily.

Uncomplicated gonococcal infections other than urethritis and anorectal infections in men: 200 mg initially, followed by 100 mg every 12 hours for a minimum of 4 days, with post-therapy cultures within 2 to 3 days.

In the treatment of uncomplicated gonococcal urethritis in men, 100 mg every 12 hours for 5 days is recommended.

For the treatment of syphilis, the usual dosage of minocycline hydrochloride should be administered over a period of 10 to 15 days. Close follow-up, including laboratory tests, is recommended.

In the treatment of meningococcal carrier state, the recommended dosage is 100 mg every 12 hours for 5 days.

Mycobacterium marinum infections: Although optimal doses have not been established, 100 mg every 12 hours for 6 to 8 weeks have been used successfully in a limited number of cases.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis or Ureaplasma urealyticum: 100 mg orally, every 12 hours for at least 7 days.

Ingestion of adequate amounts of fluids along with capsule and tablet forms of drugs in the tetracycline-class is recommended to reduce the risk of esophageal irritation and ulceration.

The pharmacokinetics of minocycline in patients with renal impairment (CLCR < 80mL/min) have not been fully characterized. Current data are insufficient to determine if a dosage adjustment is warranted. The total daily dosage should not exceed 200 mg in 24 hours. However, due to the anti-anabolic effect of tetracyclines, BUN and creatinine should be monitored (see WARNINGS).
Lingerie De Peau Invisi...

Lingerie De Peau Invisible Skin-fusion Foundation With Sunscreen Broad Spectrum Spf 20 03 Beige Naturel

Levocetirizine dihydrochloride is available as 5 mg breakable (scored) tablets, allowing for the administration of 2.5 mg, if needed. Levocetirizine dihydrochloride tablets can be taken without regard to food consumption.

2.1 Adults and Children 12 Years of Age and Older

The recommended dose of levocetirizine dihydrochloride tablets is 5 mg (1 tablet) once daily in the evening. Some patients may be adequately controlled by 2.5 mg (1/2 tablet) once daily in the evening.

2.2 Children 6 to 11 Years of Age

The recommended dose of levocetirizine dihydrochloride tablets is 2.5 mg (1/2 tablet) once daily in the evening. The 2.5 mg dose should not be exceeded because the systemic exposure with 5 mg is approximately twice that of adults [see Clinical Pharmacology (12.3)].

2.4 Dose Adjustment for Renal and Hepatic Impairment

In adults and children 12 years of age and older with:
• Mild renal impairment (creatinine clearance [CL CR] = 50 to 80 mL/min): a dose of 2.5 mg once daily is recommended; • Moderate renal impairment (CL CR = 30 to 50 mL/min): a dose of 2.5 mg once every other day is recommended; • Severe renal impairment (CL CR = 10 to 30 mL/min): a dose of 2.5 mg twice weekly (administered once every 3 to 4 days) is recommended; • End-stage renal disease patients (CL CR < 10 mL/min) and patients undergoing hemodialysis should not receive levocetirizine dihydrochloride tablets.
No dose adjustment is needed in patients with solely hepatic impairment. In patients with both hepatic impairment and renal impairment, adjustment of the dose is recommended.
Risperidone

Risperidone

Table 1. Recommended Daily Dosage by Indication
Initial Dose Titration(Increments) Target Dose Effective Dose Range Schizophrenia: adults (2.1) 2 mg 1 to 2 mg 4 to 8 mg 4 to 16 mg Schizophrenia: adolescents (2.2) 0.5 mg 0.5 to 1 mg 3 mg 1 to 6 mg Bipolar mania: adults (2.2) 2 to 3 mg 1 mg 1 to 6 mg 1 to 6 mg Bipolar mania: children and adolescents (2.2) 0.5 mg 0.5 to 1 mg 1 to 2.5 mg 1 to 6 mg Irritability in autistic disorder (2.3) 0.25 mg Can increase to 0.5 mg by Day 4: (body weight less than 20 kg) 0.5 mg Can increase to 1 mg by Day 4: (body weight greater than or equal to 20 kg) After Day 4, at intervals of > 2 weeks: 0.25 mg (body weight less than 20 kg) 0.5 mg (body weight greater than or equal to 20 kg) 0.5 mg: (body weight less than 20 kg) 1 mg: (body weight greater than or equal to 20 kg) 0.5 to 3 mg
Severe Renal and Hepatic Impairment in Adults: use a lower starting dose of 0.5 mg twice daily.

May increase to dosages above 1.5 mg twice daily at intervals of one week or longer.

2.1 Schizophrenia

Adults

Usual Initial Dose

Risperidone orally disintegrating tablets can be administered once or twice daily. Initial dosing is 2 mg per day. May increase the dose at intervals of 24 hours or greater, in increments of 1 to 2 mg per day, as tolerated, to a recommended dose of 4 to 8 mg per day. In some patients, slower titration may be appropriate. Efficacy has been demonstrated in a range of 4 mg to 16 mg per day. However, doses above 6 mg per day for twice daily dosing were not demonstrated to be more efficacious than lower doses, were associated with more extrapyramidal symptoms and other adverse effects, and are generally not recommended. In a single study supporting once-daily dosing, the efficacy results were generally stronger for 8 mg than for 4 mg. The safety of doses above 16 mg per day has not been evaluated in clinical trials [see Clinical Studies (14.1)].

Adolescents

The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day, as tolerated, to a recommended dose of 3 mg per day. Although efficacy has been demonstrated in studies of adolescent patients with schizophrenia at doses between 1 mg to 6 mg per day, no additional benefit was observed above 3 mg per day, and higher doses were associated with more adverse events. Doses higher than 6 mg per day have not been studied.

Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.

Maintenance Therapy

While it is unknown how long a patient with schizophrenia should remain on risperidone orally disintegrating tablets, the effectiveness of risperidone orally disintegrating tablets 2 mg per day to 8 mg per day at delaying relapse was demonstrated in a controlled trial in adult patients who had been clinically stable for at least 4 weeks and were then followed for a period of 1 to 2 years [see Clinical Studies (14.1)]. Both adult and adolescent patients who respond acutely should generally be maintained on their effective dose beyond the acute episode. Patients should be periodically reassessed to determine the need for maintenance treatment.

Reinitiation of Treatment in Patients Previously Discontinued

Although there are no data to specifically address reinitiation of treatment, it is recommended that after an interval off risperidone orally disintegrating tablets, the initial titration schedule should be followed.

Switching From Other Antipsychotics

There are no systematically collected data to specifically address switching schizophrenic patients from other antipsychotics to risperidone orally disintegrating tablets, or treating patients with concomitant antipsychotics.

2.2 Bipolar Mania

Usual Dose

Adults

The initial dose range is 2 mg to 3 mg per day. The dose may be adjusted at intervals of 24 hours or greater, in increments of 1 mg per day. The effective dose range is 1 mg to 6 mg per day, as studied in the short-term, placebo-controlled trials. In these trials, short-term (3 week) anti-manic efficacy was demonstrated in a flexible dosage range of 1 mg to 6 mg per day [see Clinical Studies (14.2, 14.3)]. Risperidone orally disintegrating tablets doses higher than 6 mg per day were not studied.

Pediatrics

The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day, as tolerated, to the recommended target dose of 1 mg to 2.5 mg per day. Although efficacy has been demonstrated in studies of pediatric patients with bipolar mania at doses between 0.5 mg and 6 mg per day, no additional benefit was observed above 2.5 mg per day, and higher doses were associated with more adverse events. Doses higher than 6 mg per day have not been studied.

Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.

Maintenance Therapy

There is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during treatment of an acute manic episode with risperidone orally disintegrating tablets. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of risperidone orally disintegrating tablets in such longer-term treatment (i.e., beyond 3 weeks). The physician who elects to use risperidone orally disintegrating tablets for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

2.3 Irritability Associated with Autistic Disorder – Pediatrics (Children and Adolescents)

The dosage of risperidone orally disintegrating tablets should be individualized according to the response and tolerability of the patient. The total daily dose of risperidone orally disintegrating tablets can be administered once daily, or half the total daily dose can be administered twice daily.

For patients with body weight less than 20 kg, initiate dosing at 0.25 mg per day. For patients with body weight greater than or equal to 20 kg, initiate dosing at 0.5 mg per day. After a minimum of four days, the dose may be increased to the recommended dose of 0.5 mg per day for patients less than 20 kg and 1 mg per day for patients greater than or equal to 20 kg. Maintain this dose for a minimum of 14 days. In patients not achieving sufficient clinical response, the dose may be increased at intervals of 2 weeks or greater, in increments of 0.25 mg per day for patients less than 20 kg, or increments of 0.5 mg per day for patients greater than or equal to 20 kg. The effective dose range is 0.5 mg to 3 mg per day. No dosing data are available for children who weigh less than 15 kg.

Once sufficient clinical response has been achieved and maintained, consider gradually lowering the dose to achieve the optimal balance of efficacy and safety. The physician who elects to use risperidone orally disintegrating tablets for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

Patients experiencing persistent somnolence may benefit from a once-daily dose administered at bedtime or administering half the daily dose twice daily, or a reduction of the dose.

2.4 Dosing in Patients with Severe Renal or Hepatic Impairment

For patients with severe renal impairment (CLcr < 30 mL/min) or hepatic impairment (10 to 15 points on Child Pugh System), the initial starting dose is 0.5 mg twice daily. The dose may be increased in increments of 0.5 mg or less, administered twice daily. For doses above 1.5 mg twice daily, increase in intervals of one week or greater [see Use in Specific Populations (8.6 and 8.7)].

2.5 Dose Adjustments for Specific Drug Interactions

When risperidone orally disintegrating tablets is co-administered with enzyme inducers (e.g., carbamazepine), the dose of risperidone orally disintegrating tablets should be increased up to double the patient’s usual dose. It may be necessary to decrease the risperidone orally disintegrating tablets dose when enzyme inducers such as carbamazepine are discontinued [see Drug Interactions (7.1)]. Similar effect may be expected with co-administration of risperidone orally disintegrating tablets with other enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital).

When fluoxetine or paroxetine is co-administered with risperidone orally disintegrating tablets, the dose of risperidone orally disintegrating tablets should be reduced. The risperidone orally disintegrating tablets dose should not exceed 8 mg per day in adults when co-administered with these drugs. When initiating therapy, risperidone orally disintegrating tablets should be titrated slowly. It may be necessary to increase the risperidone orally disintegrating tablets dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued [see Drug Interactions (7.1)].

2.7 Directions for Use of Risperidone Orally Disintegrating Tablets

Tablet Accessing

Risperidone orally disintegrating tablets 0.5 mg, 1 mg, 2 mg, 3 mg and 4 mg

Risperidone orally disintegrating tablets 0.5 mg, 1 mg, and 2 mg are supplied in bottles and unit-dose pouch packs.

Risperidone orally disintegrating tablets 3 mg and 4 mg are supplied in bottles and blister or unit-dose pouch packs.

The child-resistant pouch should be torn open at the notch to access the blister. Do not open the blister until ready to administer. Peel back foil from the side to expose the tablet. DO NOT push the tablet through the foil, because this could damage the tablet.

Tablet Administration

Using dry hands, remove the tablet from the blister or pouch and immediately place the entire risperidone orally disintegrating tablet on the tongue. The risperidone orally disintegrating tablet should be consumed immediately, as the tablet cannot be stored once removed from the blister or pouch. Risperidone orally disintegrating tablets disintegrate in the mouth within seconds and can be swallowed subsequently with or without liquid. Patients should not attempt to split or to chew the tablet.
Vida Mia Hand Sanitizer...

Vida Mia Hand Sanitizer

As individual monotherapy, quinapril is an effective treatment of hypertension in once-daily doses of 10 to 80 mg and hydrochlorothiazide is effective in doses of 12.5 to 50 mg. In clinical trials of quinapril/hydrochlorothiazide combination therapy using quinapril doses of 2.5 to 40 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects increased with increasing dose of either component.

The side effects (see WARNINGS) of quinapril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of quinapril and hydrochlorothiazide will be associated with both sets of dose-independent side effects, but regimens that combine low doses of hydrochlorothiazide with quinapril produce minimal effects on serum potassium. In clinical trials of quinapril hydrochloride and hydrochlorothiazide, the average change in serum potassium was near zero in subjects who received HCTZ 6.25 mg in the combination, and the average subject who received 10 to 40/12.5 to 25 mg experienced a milder reduction in serum potassium than that experienced by the average subject receiving the same dose of hydrochlorothiazide monotherapy.

To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Therapy Guided by Clinical Effect

Patients whose blood pressures are not adequately controlled with quinapril monotherapy may instead be given quinapril hydrochloride and hydrochlorothiazide tablets 10 mg/12.5 mg or 20 mg/12.5 mg. Further increases of either or both components could depend on clinical response. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. Patients whose blood pressures are adequately controlled with 25 mg of daily hydrochloro-thiazide, but who experience significant potassium loss with this regimen, may achieve blood pressure control with less electrolyte disturbance if they are switched to quinapril hydrochloride and hydrochlorothiazide tablets 10 mg/12.5 mg or 20 mg/12.5 mg.

Replacement Therapy

For convenience, patients who are adequately treated with 20 mg of quinapril and 25 mg of hydrochlorothiazide and experience no significant electrolyte disturbances may instead wish to receive quinapril hydrochloride and hydrochlorothiazide tablets 20 mg/25 mg.

Use in Renal Impairment

Regimens of therapy with quinapril hydrochloride and hydrochlorothiazide tablets need not take account of renal function as long as the patient’s creatinine clearance is > 30 mL/min/1.73 m2 (serum creatinine roughly ≤ 3 mg/dL or 265 µmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides. Therefore, quinapril hydrochloride and hydrochlorothiazide tablets are not recommended for use in these patients.
Ganciclovir

Ganciclovir

Dosage: THE RECOMMENDED DOSE FOR GANCICLOVIR CAPSULES SHOULD NOT BE EXCEEDED.

For Treatment of CMV Retinitis in Patients WithNormal Renal Function:

1. Induction Treatmen t

Ganciclovir capsules should not be used for induction treatment.

2. Maintenance Treatment

Following induction treatment, the recommended maintenance dosage of ganciclovir capsules is 1000 mg tid with food. Alternatively, the dosing regimen of 500 mg 6 times daily every 3 hours with food, during waking hours, may be used.

For patients who experience progression of CMV retinitis while receiving maintenance treatment with either formulation of ganciclovir, reinduction treatment is recommended.

For the Prevention of CMV Disease in Patients With Advanced HIV Infection andNormalRenal Function:

The recommended prophylactic dose of ganciclovir capsules is 1000 mg tid with food.

For the Prevention of CMV Disease in Transplant Recipients With Normal Renal Function:

The recommended prophylactic dosage of ganciclovir capsules is 1000 mg tid with food.

The duration of treatment with ganciclovir capsules in transplant recipients is dependent upon the duration and degree of immunosuppression. In a controlled clinical trial of liver allograft recipients, treatment with ganciclovir capsules was continued through week 14 posttransplantation (see INDICATIONS AND USAGE section for a more detailed discussion).

Renal Impairment:

In patients with renal impairment, the dose of ganciclovir capsules should be modified as shown below:

*Creatinine clearance can be related to serum creatinine by the following formulas:
Creatinine Clearance* mL/min Ganciclovir capsule Doses ≥ 70 1000 mg tid or 500 mg q3h, 6x/day 50 to 69 1500 mg qd or 500 mg tid 25 to 49 1000 mg qd or 500 mg bid 10 to 24 500 mg qd < 10 500 mg 3 times per week, following hemodialysis Creatinine clearance for males = (140 - age [yrs]) (body wt [kg]) (72) (serum creatinine [mg/dL]
Creatinine clearance for females = 0.85 x male value

Patient Monitoring: Due to the frequency of granulocytopenia, anemia and thrombocytopenia in patients receiving ganciclovir (see ADVERSE EVENTS), it is recommended that complete blood counts and platelet counts be performed frequently, especially in patients in whom ganciclovir or other nucleoside analogues have previously resulted in cytopenia, or in whom neutrophil counts are less than 1000 cells/µL at the beginning of treatment. Patients should have serum creatinine or creatinine clearance values followed carefully to allow for dosage adjustments in renally impaired patients (see DOSAGE AND ADMINISTRATION).

Reduction of Dose: Dosage reductions in renally impaired patients should be considered for ganciclovir capsules (see Renal Impairment). Dosage reductions should also be considered for those with neutropenia, anemia and/or thrombocytopenia (see ADVERSE EVENTS). Ganciclovir should not be administered in patients with severe neutropenia (ANC less than 500/µL) or severe thrombocytopenia (platelets less than 25,000/µL).

Handling and Disposal: Caution should be exercised in the handling of ganciclovir capsules. Avoid direct contact with the skin or mucous membranes of the powder contained in ganciclovir capsules. If such contact occurs, wash thoroughly with soap and water; rinse eyes thoroughly with plain water. Ganciclovir capsules should not be opened or crushed.

Because ganciclovir shares some of the properties of antitumor agents (ie, carcinogenicity and mutagenicity), consideration should be given to handling and disposal according to guidelines issued for antineoplastic drugs. Several guidelines on this subject have been published.

There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
Desvenlafaxine

Desvenlafaxine

2.1 General Instruction for Use

The recommended dose for desvenlafaxine is 50 mg once daily, with or without food.

In clinical studies, doses of 50 mg to 400 mg per day were shown to be effective, although no additional benefit was demonstrated at doses greater than 50 mg per day and adverse reactions and discontinuations were more frequent at higher doses.

When discontinuing therapy, gradual dose reduction is recommended whenever possible to minimize discontinuation symptoms [see Dosage and Administration (2.4) and Warnings and Precautions (5.9)].

Desvenlafaxine should be taken at approximately the same time each day. Tablets must be swallowed whole with fluid and not divided, crushed, chewed, or dissolved.

2.2 Special Populations

Patients with renal impairment

The maximum recommended dose in patients with moderate renal impairment (24-hr creatinine clearance [CrCl] = 30 to 50 mL/min, Cockcroft-Gault [C-G]) is 50 mg per day. The maximum recommended dose in patients with severe renal impairment (24-hr CrCl less than 30 mL/min, C-G) or end-stage renal disease (ESRD) is 50 mg every other day. Supplemental doses should not be given to patients after dialysis [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Patients with hepatic impairment

The recommended dose in patients with moderate to severe hepatic impairment is 50 mg per day. Dose escalation above 100 mg per day is not recommended [see Clinical Pharmacology (12.3)].

2.3 Maintenance/Continuation/Extended Treatment

It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy. Patients should be periodically reassessed to determine the need for continued treatment.

2.4 Discontinuing Desvenlafaxine

Symptoms associated with discontinuation of desvenlafaxine, other SNRIs and SSRIs have been reported [see Warnings and Precautions (5.9)]. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.

2.5 Switching Patients From Other Antidepressants to Desvenlafaxine

Discontinuation symptoms have been reported when switching patients from other antidepressants, including venlafaxine, to desvenlafaxine. Tapering of the initial antidepressant may be necessary to minimize discontinuation symptoms.

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

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disordersand initiation of therapy with desvenlafaxine. Conversely, at least 7 days should be allowed after stopping desvenlafaxine before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4)].

Use of Desvenlafaxine with other MAOIs such as Linezolid or Methylene Blue

Do not start desvenlafaxine in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4)].

In some cases, a patient already receiving desvenlafaxine therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, desvenlafaxine should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with desvenlafaxine may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].

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

Imitrex

2.1 Hypertension

Initial Therapy in adults: The recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 to 40 mg per day administered in a single daily dose. Doses up to 80 mg have been used but do not appear to give greater effect.

Use with diuretics in adults

If blood pressure is not controlled with lisinopril alone, a low dose of a diuretic may be added (eg, hydrochlorothiazide, 12.5 mg). After the addition of a diuretic, it may be possible to reduce the dose of lisinopril.

The recommended starting dose in adult patients with hypertension taking diuretics is 5 mg once per day.

Pediatric Patients 6 years of age and older with hypertension

For pediatric patients with glomerular filtration rate > 30 mL/min/1.73m2, the recommended starting dose is 0.07 mg per kg once daily (up to 5 mg total). Dosage should be adjusted according to blood pressure response up to a maximum of 0.61 mg per kg (up to 40 mg) once daily. Doses above 0.61 mg per kg (or in excess of 40 mg) have not been studied in pediatric patients [see Clinical Pharmacology (12.3)].

Lisinopril is not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m2 [see Use in Specific Populations (8.4) and Clinical Studies (14.1)].

2.2 Heart Failure

The recommended starting dose for lisinopril, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg once daily. The recommended starting dose in these patients with hyponatremia (serum sodium < 130 mEq/L) is 2.5 mg once daily. Increase as tolerated to a maximum of 40 mg once daily.

Diuretic dose may need to be adjusted to help minimize hypovolemia, which may contribute to hypotension [see Warnings and Precautions (5.4), and Drug Interactions (7.1)]. The appearance of hypotension after the initial dose of lisinopril does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

2.3 Reduction of Mortality in Acute Myocardial Infarction

In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, give lisinopril 5 mg orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Dosing should continue for at least six weeks.

Initiate therapy with 2.5 mg in patients with a low systolic blood pressure (≤ 120 mmHg and > 100 mm Hg) during the first 3 days after the infarct [see Warnings and Precautions (5.4)]. If hypotension occurs (systolic blood pressure ≤ 100 mmHg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure < 90 mmHg for more than 1 hour) lisinopril should be withdrawn.

2.4 Dose in Patients with Renal Impairment

No dose adjustment of lisinopril is required in patients with creatinine clearance > 30 mL/min. In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of lisinopril to half of the usual recommended dose i.e., hypertension, 5 mg; systolic heart failure, 2.5 mg and acute MI, 2.5 mg. Up titrate as tolerated to a maximum of 40 mg daily. For patients on hemodialysis or creatinine clearance < 10 mL/min, the recommended initial dose is 2.5 mg once daily [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
Metoprolol Tartrate

Metoprolol Tartrate

Hypertension

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

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

Angina Pectoris

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

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

Myocardial Infarction

Early Treatment:

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

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

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

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

Late Treatment:

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

Special populations

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

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

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

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

Method of administration:

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

Mupirocin

2.1 Initial Dosing

To avoid medication errors, prescribers and pharmacists must be aware that oxymorphone is available as both immediate-release 5 mg and 10 mg tablets and extended-release 5 mg and 10 mg tablets [see Dosage Forms and Strengths].

Oxymorphone hydrochloride extended-release tablets should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Initiate the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with oxymorphone hydrochloride extended-release tablets [see Warnings and Precautions (5.2)].

Oxymorphone hydrochloride extended-release tablets must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving oxymorphone hydrochloride extended-release tablets will result in uncontrolled delivery of oxymorphone and can lead to overdose or death [see Warnings and Precautions (5.2)].

Oxymorphone hydrochloride extended-release tablets are administered at a frequency of twice daily (every 12 hours). Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

Use of Oxymorphone Hydrochloride Extended-Release Tablets as the First Opioid Analgesic

Initiate treatment with oxymorphone hydrochloride extended-release tablets with the 5 mg tablet orally every 12-hours.

Use of Oxymorphone Hydrochloride Extended-Release Tablets in Patients who are not Opioid Tolerant

The starting dose for patients who are not opioid tolerant is oxymorphone hydrochloride extended-release tablets 5 mg orally every 12 hours. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from Oxymorphone Hydrochloride Tablets to Oxymorphone Hydrochloride Extended-Release Tablets

Patients receiving oxymorphone hydrochloride tablets may be converted to oxymorphone hydrochloride extended-release tablets by administering half the patient's total daily oral oxymorphone hydrochloride dose as oxymorphone hydrochloride extended-release tablets, every 12 hours.

Conversion from Parenteral Oxymorphone to Oxymorphone Hydrochloride Extended-Release Tablets

The absolute oral bioavailability of oxymorphone hydrochloride extended-release tablets is approximately 10%. Convert patients receiving parenteral oxymorphone to oxymorphone hydrochloride extended-release tablets by administering 10 times the patient's total daily parenteral oxymorphone dose as oxymorphone hydrochloride extended-release tablets in two equally divided doses (e.g., [IV dose x 10] divided by 2). Due to patient variability with regards to opioid analgesic response, upon conversion monitor patients closely to evaluate for adequate analgesia and side effects.

Conversion from Other Oral Opioids to Oxymorphone Hydrochloride Extended-Release Tablets

Discontinue all other around-the-clock opioid drugs when oxymorphone hydrochloride extended-release tablets therapy is initiated.

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

Consider the following when using the information in Table 1:
• This is not a table of equianalgesic doses. • The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics to oxymorphone hydrochloride extended-release tablets. • This table cannot be used to convert from oxymorphone hydrochloride extended-release tablets to another opioid. Doing so will result in an over-estimation of the dose of the new opioid and may result in fatal overdose.
CONVERSION FACTORS TO OXYMORPHONE HYDROCHLORIDE EXTENDED-RELEASE TABLETS

Prior Oral Opioid

Approximate Oral Conversion Factor

Oxymorphone

1

Hydrocodone

0.5

Oxycodone

0.5

Methadone

0.5

Morphine

0.333

To calculate the estimated oxymorphone hydrochloride extended-release tablets dose using Table 1:
• For patients on a single opioid, sum the current total daily dose of the opioid and then multiply the total daily dose by the conversion factor to calculate the approximate oral (active opioid) daily dose. • For patients on a regimen of more than one opioid, calculate the approximate oral (active opioid) dose for each opioid and sum the totals to obtain the approximate total (active opioid) daily dose. • For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion
Always round the dose down, if necessary, to the appropriate oxymorphone hydrochloride extended-release tablets strength(s) available.

Example conversion from a single opioid to oxymorphone hydrochloride extended-release tablets:
• Step 1: Sum the total daily dose of the opioid oxycodone 20 mg BID 20 mg former opioid 2 times daily = 40 mg total daily dose of former opioid • Step 2: Calculate the approximate equivalent dose of oral (active opioid) based on the total daily dose of the current opioid using Table 1 40 mg total daily dose of former opioid x 0.5 mg Conversion Factor = 20 mg of oral (active opioid) daily • Step 3: Calculate the approximate starting dose of oxymorphone hydrochloride extended-release tablets to be given every 12 hours. Round down, if necessary, to the appropriate oxymorphone hydrochloride extended-release tablets strengths available. 10 mg oxymorphone hydrochloride extended-release tablets every 12 hours
Conversion from Methadone to Oxymorphone Hydrochloride Extended-Release Tablets

Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

2.2 Titration and Maintenance of Therapy

Individually titrate oxymorphone hydrochloride extended-release tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving oxymorphone hydrochloride extended-release tablets to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, and misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for the use of opioid analgesics.

If the level of pain increases, attempt to identify the source of increased pain, while adjusting the oxymorphone hydrochloride extended-release tablets dose to decrease the level of pain. Because steady-state plasma concentrations are approximated within 3 days, oxymorphone hydrochloride extended-release tablets dosage adjustments, preferably at increments of 5 to 10 mg every 12 hours, may be done every 3 to 7 days.

Patients who experience breakthrough pain may require a dose increase of oxymorphone hydrochloride extended-release tablets, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing oxymorphone hydrochloride extended-release tablets dose.

If unacceptable opioid-related adverse reactions are observed, the subsequent dose may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.3 Discontinuation of Oxymorphone Hydrochloride Extended-Release Tablets

When a patient no longer requires therapy with oxymorphone hydrochloride extended-release tablets, use a gradual downward titration of the dose every two to four days, to prevent signs and symptoms of withdrawal in the physically-dependent patient. Do not abruptly discontinue oxymorphone hydrochloride extended-release tablets.

2.4 Administration of Oxymorphone Hydrochloride Extended-Release Tablets

Instruct patients to swallow oxymorphone hydrochloride extended-release tablets intact. The tablets are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of oxymorphone [see Warnings and Precautions (5.2)]. Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

2.5 Patients with Hepatic Impairment

Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with moderate or severe hepatic impairment.

In opioid-naïve patients with mild hepatic impairment, initiate treatment with the 5 mg dose. For patients on prior opioid therapy, start oxymorphone hydrochloride extended-release tablets at 50% lower than the starting dose for a patient with normal hepatic function on prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.2), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.6 Patients with Renal Impairment

In patients with creatinine clearance rates less than 50 mL/min, start oxymorphone hydrochloride extended-release tablets in the opioid-naïve patient with the 5 mg dose. For patients on prior opioid therapy, start oxymorphone hydrochloride extended-release tablets at 50% lower than the starting dose for a patient with normal renal function on prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.2), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.7 Geriatric Patients

The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects. Initiate dosing with oxymorphone hydrochloride extended-release tablets in patients 65 years of age and over using the 5 mg dose and monitor closely for signs of respiratory and central nervous system depression when initiating and titrating oxymorphone hydrochloride extended-release tablets to adequate analgesia [see Warnings and Precautions (5.2), Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)]. For patients on prior opioid therapy, start oxymorphone hydrochloride extended-release tablets at 50% lower than the starting dose for a younger patient on prior opioids and titrate slowly.
Atorvastatin Calcium

Atorvastatin Calcium

2.1 Hyperlipidemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb)

The recommended starting dose of atorvastatin calcium tablets is 10 or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range of atorvastatin calcium tablets is 10 to 80 mg once daily. Atorvastatin calcium tablets can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance doses of atorvastatin calcium tablets should be individualized according to patient characteristics such as goal of therapy and response (see current NCEP Guidelines). After initiation and/or upon titration of atorvastatin calcium tablets, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly.

2.2 Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10 to 17 years of age)

The recommended starting dose of atorvastatin calcium tablets is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy [see current NCEP Pediatric Panel Guidelines, Clinical Pharmacology(12), and Indications and Usage (1.2)]. Adjustments should be made at intervals of 4 weeks or more.

2.3 Homozygous Familial Hypercholesterolemia

The dosage of atorvastatin calcium tablets in patients with homozygous FH is 10 to 80 mg daily. Atorvastatin calcium tablets should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

2.4 Concomitant Lipid-Lowering Therapy

Atorvastatin calcium tablets may be used with bile acid resins. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should generally be used with caution [see Warnings and Precautions, Skeletal Muscle (5.1), Drug Interactions (7)].

2.5 Dosage in Patients With Renal Impairment

Renal disease does not affect the plasma concentrations nor LDL-C reduction of atorvastatin calcium tablets; thus, dosage adjustment in patients with renal dysfunction is not necessary [see Warnings and Precautions, Skeletal Muscle (5.1), Clinical Pharmacology, Pharmacokinetics (12.3)].

2.6 Dosage in Patients Taking Cyclosporine, Clarithromycin, Itraconazole, or Certain Protease Inhibitors

In patients taking cyclosporine or the HIV protease inhibitors (tipranavir plus ritonavir) or the hepatitis C protease inhibitor (telaprevir), therapy with atorvastatin calcium tablets should be avoided. In patients with HIV taking lopinavir plus ritonavir, caution should be used when prescribing atorvastatin calcium tablets and the lowest dose necessary employed. In patients taking clarithromycin, itraconazole, or in patients with HIV taking a combination of saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, therapy with atorvastatin calcium tablets should be limited to 20 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin calcium tablets is employed. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, therapy with atorvastatin calcium tablets should be limited to 40 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin calcium tablets is employed [see Warnings and Precautions, Skeletal Muscle (5.1), Drug Interactions (7)].

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