Avkare, Inc.

Manufacturer Details

There are currently no manufacturer details available.

Avkare, Inc. Drugs

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 or two tablets every four to six hours as needed for pain. The total daily dose should not exceed 8 tablets.
Clindamycin Phosphate

Clindamycin Phosphate

Apply a thin film of Clindamycin Phosphate Topical Solution twice daily to affected area.

Keep all liquid dosage forms in containers tightly closed.
Signature Care Antifung...

Signature Care Antifungal

2.1    Dosing Information   Tizanidine Tablets, USP tablets may be prescribed with or without food. Once the formulation has been selected and the decision to take with or without food has been made, this regimen should not be altered.

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

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

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

2.2     Dosing in Patients with Renal Impairment

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

2.3 Dosing in Patients with Hepatic Impairment

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

2.4 Drug Discontinuation

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

Temazepam

While the recommended usual adult dose is 15 mg before retiring, 7.5 mg may be sufficient for some patients, and others may need 30 mg. In transient insomnia, a 7.5 mg dose may be sufficient to improve sleep latency. In elderly or debilitated patients, it is recommended that therapy be initiated with 7.5 mg until individual responses are determined.
Ergocalciferol

Ergocalciferol

THE RANGE BETWEEN THERAPEUTIC AND TOXIC DOSES IS NARROW.

Vitamin D Resistant Rickets

12,000 to 500,000 USP units daily.

Hypoparathyroidism

50,000 to 200,000 USP units daily concomitantly with calcium lactate 4 g, six times per day.

DOSAGE MUST BE INDIVIDUALIZED UNDER CLOSE MEDICAL SUPERVISION.

Calcium intake should be adequate. Blood calcium and phosphorous determinations must be made every 2 weeks or more frequently if necessary. X-rays of the bones should be taken every month until condition is corrected and stabilized.
Guanfacine

Guanfacine

2.1 General Instruction for Use

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

2.2 Dose Selection

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

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

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

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

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

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

2.4 Maintenance Treatment

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

2.5 Discontinuation

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

2.6 Missed Doses

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

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

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

L-methyl-mc-nac

Usual adult dose is one caplet daily under medical supervision.

L-Methyl-MC-NAC Tablets is not recommended for use with children under the age of twelve.

L-Methyl-MC-NAC Tablets must be administered under medical supervision.
Isometheptene-dichloral...

Isometheptene-dichloral-apap Oral

Do not exceed the recommended dosage because severe liver damage may occur.

Tell your doctor about all usage of pain relievers.

FOR RELIEF OF MIGRAINE HEADACHE: The usual adult dosage is two capsules at once, followed by one capsule every hour until relieved, up to 5 capsules within a twelve hour period.

FOR RELIEF OF TENSION HEADACHE: The usual adult dosage is one or two capsules every four hours up to 8 capsules a day.
Metaxalone

Metaxalone

The recommended dose for adults and children over 12 years of age is one 800 mg tablet three to four times a day.
Glycopyrrolate

Glycopyrrolate

The dosage of glycopyrrolate 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 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 for adults is one tablet two or three times daily at equally spaced intervals.

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

DRUG INTERACTIONS

There are no known drug interactions.
Potassium Chloride

Potassium Chloride

Dosage must be adjusted to the individual needs of each patient but is typically in the range of 20 mEq per day for the prevention of hypokalemia to 40-100 mEq per day or more for the treatment of potassium depletion.

The usual adult dose is 20-100 mEq of potassium per day (one Potassium Chloride 20 mEq packet 1 to 5 times daily after meals.

The contents of each Potassium Chloride packet should be dissolved in at least 4 ounces of cold water or other beverage. These preparations, like other potassium supplements, must be properly diluted to avoid the possibility of gastrointestinal irritation.
Omega-3-acid Ethyl Este...

Omega-3-acid Ethyl Esters

Assess triglyceride levels carefully before initiating therapy. Identify other causes (e.g., diabetes mellitus, hypothyroidism, medications) of high triglyceride levels and manage as appropriate [see Indications and Usage (1)]. Patients should be placed on an appropriate lipid-lowering diet before receiving omega-3-acid ethyl esters capsules, and should continue this diet during treatment with omega-3-acid ethyl esters capsules. In clinical studies, omega-3-acid ethyl esters capsules were administered with meals.
The daily dose of omega-3-acid ethyl esters capsules is 4 grams per day. The daily dose may be taken as a single 4-gram dose (4 capsules) or as two 2-gram doses (2 capsules given twice daily).

Patients should be advised to swallow omega-3-acid ethyl esters capsules whole. Do not break open, crush, dissolve, or chew omega-3-acid ethyl esters capsules.
Doxazosin

Doxazosin

DOSAGE MUST BE INDIVIDUALIZED. The initial dosage of doxazosin tablets in patients with hypertension and/or BPH is 1 mg given once daily in the a.m. or p.m. This starting dose is intended to minimize the frequency of postural hypotension and first-dose syncope associated with doxazosin. Postural effects are most likely to occur between 2 and 6 hours after a dose. Therefore, blood pressure measurements should be taken during this time period after the first dose and with each increase in dose. If doxazosin tablets administration is discontinued for several days, therapy should be restarted using the initial dosing regimen.

Concomitant administration of doxazosin with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension; therefore, PDE-5 inhibitor therapy should be initiated at the lowest dose in patients taking doxazosin.

A. BENIGN PROSTATIC HYPERPLASIA 1 to 8 mg once daily.

The initial dosage of doxazosin is 1 mg, given once daily in the a.m. or p.m. Depending on the individual patient’s urodynamics and BPH symptomatology, dosage may then be increased to 2 mg and thereafter to 4 mg and 8 mg once daily, the maximum recommended dose for BPH. The recommended titration interval is 1 to 2 weeks. Blood pressure should be evaluated routinely in these patients.

B. HYPERTENSION 1 to 16 mg once daily.

The initial dosage of doxazosin is 1 mg given once daily. Depending on the individual patient’s standing blood pressure response (based on measurements taken at 2 to 6 hours post-dose and 24 hours post-dose), dosage may then be increased to 2 mg and thereafter if necessary to 4 mg, 8 mg and 16 mg to achieve the desired reduction in blood pressure. Increases in dose beyond 4 mg increase the likelihood of excessive postural effects, including syncope, postural dizziness/vertigo and postural hypotension. At a titrated dose of 16 mg once daily, the frequency of postural effects is about 12% compared to 3% for placebo.
Calcium Acetate

Calcium Acetate

The recommended initial dose of calcium acetate, USP for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal.
Tramadol Hydrochloride ...

Tramadol Hydrochloride And Acetaminophen

For the short-term (five days or less) management of acute pain, the recommended dose of tramadol hydrochloride and acetaminophen tablets, USP is 2 tablets every 4 to 6 hours as needed for pain relief up to a maximum of 8 tablets per day.

Individualization of Dose

In patients with creatinine clearances of less than 30 mL/min, it is recommended that the dosing interval of tramadol hydrochloride and acetaminophen tablets, USP be increased not to exceed 2 tablets every 12 hours. Dose selection for an elderly patient should be cautious, in view of the potential for greater sensitivity to adverse events.
Naltrexone Hydrochlorid...

Naltrexone Hydrochloride

IF THERE IS ANY QUESTION OF OCCULT OPIOID DEPENDENCE, PERFORM A NALOXONE CHALLENGE TEST AND DO NOT INITIATE NALTREXONE THERAPY UNTIL THE NALOXONE CHALLENGE IS NEGATIVE.

Treatment of Alcoholism

A dose of 50 mg once daily is recommended for most patients (see CLINICAL PHARMACOLOGY, Clinical Trials, Individualization of Dosage). The placebo-controlled studies that demonstrated the efficacy of naltrexone as an adjunctive treatment of alcoholism used a dose regimen of naltrexone 50 mg once daily for up to 12 weeks. Other dose regimens or durations of therapy were not evaluated in these trials.

A patient is a candidate for treatment with naltrexone if:
the patient is willing to take a medicine to help with alcohol dependence the patient is opioid-free for 7 to 10 days the patient does not have severe or active liver or kidney problems (Typical guidelines suggest liver function tests no greater than 3 times the upper limits of normal, and bilirubin normal.) the patient is not allergic to naltrexone, and no other contraindications are present
Refer to CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS sections for additional information.

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

Treatment of Opioid Dependence

Initiate treatment with Naltrexone using the following guidelines
Treatment should not be attempted unless the patient has remained opioid-free for at least 7 to10 days. Self-reporting of abstinence from opioids in opioid addicts should be verified by analysis of the patient's urine for absence of opioids. The patient should not be manifesting withdrawal signs or reporting withdrawal symptoms. If there is any question of occult opioid dependence, perform a naloxone challenge test. If signs of opioid withdrawal are still observed following naloxone challenge, treatment with naltrexone should not be attempted. The naloxone challenge can be repeated in 24 hours. Treatment should be initiated carefully, with an initial dose of 25 mg of naltrexone hydrochloride. If no withdrawal signs occur, the patient may be started on 50 mg a day thereafter.
Naloxone Challenge Test

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

Intravenous

Inject 0.2 mg naloxone.

Observe for 30 seconds for signs or symptoms of withdrawal.

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

Observe for an additional 20 minutes.

Subcutaneous

Administer 0.8 mg naloxone.

Observe for 20 minutes for signs or symptoms of withdrawal.

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

Interpretation of the Challenge

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

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

Alternative Dosing Schedules

Once the patient has been started on naltrexone hydrochloride, 50 mg every 24 hours will produce adequate clinical blockade of the actions of parenterally administered opioids (i.e., this dose will block the effects of a 25 mg intravenous heroin challenge). A flexible approach to a dosing regimen may need to be employed in cases of supervised administration. Thus, patients may receive 50 mg of naltrexone hydrochloride every weekday with a 100 mg dose on Saturday, 100 mg every other day, or 150 mg every third day. The degree of blockade produced by naltrexone may be reduced by these extended dosing intervals.

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

Patient Compliance

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

Capecitabine

Capecitabine tablets should be swallowed whole with water within 30 minutes after a meal. Do not crush or cut capecitabine tablets. Capecitabine tablets dose is calculated according to body surface area.

2.1 Standard Starting Dose

Monotherapy (Metastatic Colorectal Cancer, Adjuvant Colorectal Cancer, Metastatic Breast Cancer)

The recommended dose of capecitabine tablets is 1250 mg/m2 administered orally twice daily (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 2 weeks followed by a 1-week rest period given as 3-week cycles (see Table 1).

Adjuvant treatment in patients with Dukes' C colon cancer is recommended for a total of 6 months [i.e., capecitabine tablets 1250 mg/m2 orally twice daily for 2 weeks followed by a 1-week rest period, given as 3-week cycles for a total of 8 cycles (24 weeks)].
Table 1: Capecitabine Tablets Dose Calculation According to Body Surface Area * Total Daily Dose divided by 2 to allow equal morning and evening doses
Dose Level 1250 mg/m2 Twice a Day

Number of Tablets to be Taken at Each Dose (Morning and Evening)

Surface Area (m2)

Total Daily Dose* (mg)

150 mg

500 mg

≤ 1.25

3000

0

3

1.26 to 1.37

3300

1

3

1.38 to 1.51

3600

2

3

1.52 to 1.65

4000

0

4

1.66 to 1.77

4300

1

4

1.78 to 1.91

4600

2

4

1.92 to 2.05

5000

0

5

2.06 to 2.17

5300

1

5

≥ 2.18

5600

2

5

In Combination With Docetaxel (Metastatic Breast Cancer)

In combination with docetaxel, the recommended dose of capecitabine tablets are 1250 mg/m2 twice daily for 2 weeks followed by a 1-week rest period, combined with docetaxel at 75 mg/m2 as a 1-hour intravenous infusion every 3 weeks. Pre-medication, according to the docetaxel labeling, should be started prior to docetaxel administration for patients receiving the capecitabine tablets plus docetaxel combination. Table 1 displays the total daily dose of capecitabine tablets by body surface area and the number of tablets to be taken at each dose.

2.2 Dose Management Guidelines

General

Capecitabine tablets dosage may need to be individualized to optimize patient management. Patients should be carefully monitored for toxicity and doses of capecitabine tablets should be modified as necessary to accommodate individual patient tolerance to treatment [see Clinical Studies (14)]. Toxicity due to capecitabine tablet administration may be managed by symptomatic treatment, dose interruptions and adjustment of capecitabine tablets dose. Once the dose has been reduced, it should not be increased at a later time. Doses of capecitabine tablets omitted for toxicity are not replaced or restored; instead the patient should resume the planned treatment cycles.

The dose of phenytoin and the dose of coumarin-derivative anticoagulants may need to be reduced when either drug is administered concomitantly with capecitabine tablets [see Drug Interactions (7.1)].

Monotherapy (Metastatic Colorectal Cancer, Adjuvant Colorectal Cancer, Metastatic Breast Cancer)

Capecitabine tablets dose modification scheme as described below (see Table 2) is recommended for the management of adverse reactions.
Table 2: Recommended Dose Modifications of Capecitabine Tablets * National Cancer Institute of Canada Common Toxicity Criteria were used except for the hand-and-foot syndrome [ see Warnings and Precautions (5)].
Toxicity NCIC Grades*

During a Course of Therapy

Dose Adjustment for Next Treatment (% of starting dose)

Grade 1

Maintain dose level

Maintain dose level

Grade 2

-1st appearance

Interrupt until resolved to grade 0 to 1

100%

-2nd appearance

75%

-3rd appearance

50%

-4th appearance

Discontinue treatment permanently

-

Grade 3

-1st appearance

Interrupt until resolved to grade 0 to 1

75%

-2nd appearance

50%

-3rd appearance

Discontinue treatment permanently

-

Grade 4

-1st appearance

Discontinue permanentlyORIf physician deems it to be in the patient's best interest to continue, interrupt until resolved to grade 0 to 1

50%

In Combination With Docetaxel (Metastatic Breast Cancer)

Dose modifications of capecitabine tablets for toxicity should be made according to Table 2 above for capecitabine tablets. At the beginning of a treatment cycle, if a treatment delay is indicated for either capecitabine tablets or docetaxel, then administration of both agents should be delayed until the requirements for restarting both drugs are met.

The dose reduction schedule for docetaxel when used in combination with capecitabine tablets for the treatment of metastatic breast cancer is shown in Table 3.
Table 3: Docetaxel Dose Reduction Schedule in Combination with Capecitabine Tablets * National Cancer Institute of Canada Common Toxicity Criteria were used except for hand-and-foot syndrome [ see Warnings and Precautions (5)].
Toxicity NCIC Grades*

Grade 2

Grade 3

Grade 4

1st appearance

Delay treatment until resolved to grade 0 to 1; Resume treatment with original dose of 75 mg/m2 docetaxel

Delay treatment until resolved to grade 0 to 1; Resume treatment at 55 mg/m2 of docetaxel.

Discontinue treatment with docetaxel

2nd appearance

Delay treatment until resolved to grade 0 to 1; Resume treatment at 55 mg/m2 of docetaxel.

Discontinue treatment with docetaxel

-

3rd appearance

Discontinue treatment with docetaxel

-

-

2.3 Adjustment of Starting Dose in Special Populations

Renal Impairment

No adjustment to the starting dose of capecitabine tablets is recommended in patients with mild renal impairment (creatinine clearance = 51 to 80 mL/min [Cockroft and Gault, as shown below]). In patients with moderate renal impairment (baseline creatinine clearance = 30 to 50 mL/min), a dose reduction to 75% of the capecitabine tablets starting dose when used as monotherapy or in combination with docetaxel (from 1250 mg/m2 to 950 mg/m2 twice daily) is recommended [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Subsequent dose adjustment is recommended as outlined in Table 2 and Table 3 (depending on the regimen) if a patient develops a grade 2 to 4 adverse event [see Warnings and Precautions (5.5)]. The starting dose adjustment recommendations for patients with moderate renal impairment apply to both capecitabine tablets monotherapy and capecitabine tablets in combination use with docetaxel.

Cockroft and Gault Equation:

(140 - age [yrs]) (body wt [kg])

Creatinine clearance for males =

—————————————

(72) (serum creatinine [mg/dL])

Creatinine clearance for females = 0.85 × male value

Geriatrics

Physicians should exercise caution in monitoring the effects of capecitabine tablets in the elderly. Insufficient data are available to provide a dosage recommendation.
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.

The 23 mg tablet should not be split, crushed or chewed because this may increase its rate of absorption.

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 Moderate to Severe Alzheimer’s Disease

Donepezil hydrochloride tablets have been shown to be effective in controlled clinical trials at doses of 10 mg and 23 mg administered once daily. Results of a controlled clinical trial in moderate to severe Alzheimer’s Disease that compared donepezil hydrochloride tablets 23 mg once daily to 10 mg once daily suggest that a 23 mg dose of donepezil hydrochloride tablets provided additional benefit.

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. A dose of 23 mg once daily can be administered once patients have been on a dose of 10 mg once daily for at least 3 months.
Pioglitazone And Metfor...

Pioglitazone And Metformin Hydrochloride

2.1 Recommendations for All Patients

Pioglitazone and metformin hydrochloride tablets should be taken with meals to reduce the gastrointestinal side effects associated with metformin.

If therapy with a combination tablet containing pioglitazone and metformin is considered appropriate the recommended starting dose is:
• 15 mg/500 mg twice daily or 15 mg/850 mg once daily and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability, • for patients with New York Heart Association (NYHA) Class I or Class II congestive heart failure: 15 mg/500 mg or 15 mg/850 mg once daily and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability, • for patients inadequately controlled on metformin monotherapy: 15 mg/500 mg twice daily or 15 mg/850 mg once or twice daily (depending on the dose of metformin already being taken) and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability, • for patients inadequately controlled on pioglitazone monotherapy: 15 mg/500 mg twice daily or 15 mg/850 mg once daily and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability. • for patients who are changing from combination therapy of pioglitazone plus metformin as separate tablets: pioglitazone and metformin hydrochloride tablets should be taken at doses that are as close as possible to the dose of pioglitazone and metformin already being taken.
Pioglitazone and metformin hydrochloride tablets may be titrated up to a maximum daily dose of 45 mg of pioglitazone and 2550 mg of metformin.

Metformin doses above 2000 mg may be better tolerated given three times a day.

After initiation of pioglitazone and metformin hydrochloride 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 (5.1)]. Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating pioglitazone and metformin hydrochloride tablets. Routine periodic monitoring of liver tests during treatment with pioglitazone and metformin hydrochloride tablets is not recommended in patients without liver disease. Patients who have liver test abnormalities prior to initiation of pioglitazone and metformin hydrochloride tablets or who are found to have abnormal liver tests while taking pioglitazone and metformin hydrochloride tablets should be managed as described under Warnings and Precautions [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)].

2.2 Concomitant Use With an Insulin Secretagogue or Insulin

If hypoglycemia occurs in a patient coadministered pioglitazone and metformin hydrochloride 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 and metformin hydrochloride 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 Concomitant Use With Strong CYP2C8 Inhibitors

Coadministration of pioglitazone (one of the ingredients in pioglitazone and metformin hydrochloride tablets) and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure approximately 3 fold. Therefore, the maximum recommended dose of pioglitazone and metformin hydrochloride tablets are 15 mg/850 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Acyclovir

Acyclovir

Apply sufficient quantity to adequately cover all lesions every 3 hours, 6 times per day for 7 days. The dose size per application will vary depending upon the total lesion area but should approximate a one-half inch ribbon of ointment per 4 square inches of surface area. A finger cot or rubber glove should be used when applying acyclovir ointment, USP 5% to prevent autoinoculation of other body sites and transmission of infection to other persons. Therapy should be initiated as early as possible following onset of signs and symptoms.
Valsartan

Valsartan

2.1 Adult Hypertension

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

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

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

Valsartan tablets may be administered with other antihypertensive agents.

Valsartan tablets may be administered with or without food.

2.2 Pediatric Hypertension 6 to 16 Years of Age

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

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

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

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

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

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

2.3 Heart Failure

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

Theophylline

Taking theophylline extended-release tablets immediately after a high-fat content meal may result in a somewhat higher Cmax and delayed Tmax, and somewhat greater extent of absorption. However, the differences are usually not great and this product may normally be administered without regard to meals (see CLINICAL PHARMACOLOGY, Drug Interactions, Drug-Food Interactions).

Theophylline extended-release tablets are recommended for chronic or long-term management and prevention of symptoms, and not for use in treating acute symptoms of asthma and reversible bronchospasm.

General Considerations

The steady-state peak serum theophylline concentration is a function of the dose, the dosing interval, and the rate of theophylline absorption and clearance in the individual patient. Because of marked individual differences in the rate of theophylline clearance, the dose required to achieve a peak serum theophylline concentration in the 10 to 20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter theophylline clearance (e.g., 400 to 1600 mg/day in adults <60 years old and 10 to 36 mg/kg/day in children 1 to 9 years old). For a given population there is no single theophylline dose that will provide both safe and effective serum concentrations for all patients. Administration of the median theophylline dose required to achieve a therapeutic serum theophylline concentration in a given population may result in either subtherapeutic or potentially toxic serum theophylline concentrations in individual patients. For example, at a dose of 900 mg/d in adults <60 years or 22 mg/kg/d in children 1 to 9 years, the steady-state peak serum theophylline concentration will be <10 mcg/mL in about 30% of patients, 10 to 20 mcg/mL in about 50% and 20 to 30 mcg/mL in about 20% of patients. The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects.

Transient caffeine-like adverse effects and excessive serum concentrations in slow metabolizers can be avoided in most patients by starting with a sufficiently low dose and slowly increasing the dose, if judged to be clinically indicated, in small increments (see Table V). Dose increases should only be made if the previous dosage is well tolerated and at intervals of no less than 3 days to allow serum theophylline concentrations to reach the new steady state. Dosage adjustment should be guided by serum theophylline concentration measurement (see PRECAUTIONS, Laboratory Tests and DOSAGE AND ADMINISTRATION, Table VI). Health care providers should instruct patients and care givers to discontinue any dosage that causes adverse effects, to withhold the medication until these symptoms are gone and to then resume therapy at a lower, previously tolerated dosage (see WARNINGS).

If the patient’s symptoms are well controlled, there are no apparent adverse effects, and no intervening factors that might alter dosage requirements (see WARNINGS and PRECAUTIONS), serum theophylline concentrations should be monitored at 6 month intervals for rapidly growing children and at yearly intervals for all others. In acutely ill patients, serum theophylline concentrations should be monitored at frequent intervals, e.g. every 24 hours.

Theophylline distributes poorly into body fat, therefore, mg/kg dose should be calculated on the basis of ideal body weight.

Table V contains theophylline dosing titration schema recommended for patients in various age groups and clinical circumstances. Table VI contains recommendations for theophylline dosage adjustment based upon serum theophylline concentrations. Application of these general dosing recommendations to individual patients must take into account the unique clinical characteristics of each patient. In general, these recommendations should serve as the upper limit for dosage adjustments in order to decrease the risk of potentially serious adverse events associated with unexpected large increases in serum theophylline concentration.
Table V. Dosing initiation and titration (as anhydrous theophylline).* * Patients with more rapid metabolism, clinically identified by higher than average dose requirements, should receive a smaller dose more frequently (every 8 hours) to prevent breakthrough symptoms resulting from low trough concentrations before the next dose. A. Children (6 to 15 years) and adults (16 to 60 years) without risk factors for impaired clearance.
Titration Step
Children <45 kg Children >45 kg and adults 1.
Starting Dosage

12 to 14 mg/kg/day up

to a maximum of

300 mg/day divided
Q12 hrs*   300 mg/day divided Q12 hrs*   2.
After 3 days,

if tolerated,
increase dose to:
16 mg/kg/day up

to a maximum of

400 mg/day divided
Q12 hrs*
400 mg/day divided
Q12 hrs*   3.
After 3 more days,

if tolerated,
increase dose to:
20 mg/kg/day up to

a maximum of

600 mg/day
divided Q12 hrs*
600 mg/day divided
Q12 hrs*    B.
Patients With Risk Factors For Impaired Clearance, The Elderly (>60 Years), And Those In Whom It Is Not Feasible To Monitor Serum Theophylline Concentrations:

In children 6 to 15 years of age, the final theophylline dose should not exceed 16 mg/kg/day up to a maximum of 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS) or if it is not feasible to monitor serum theophylline concentrations.

In adolescents ≥16 years and adults, including the elderly, the final theophylline dose should not exceed 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS) or if it is not feasible to monitor serum theophylline concentrations.
Table VI. Dosage adjustment guided by serum theophylline concentration. * Dose reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued (see WARNINGS).
Peak Serum

Concentration

Dosage Adjustment
<9.9 mcg/mL If symptoms are not controlled and current dosage is tolerated, increase dose about 25%. Recheck serum concentration after three days for further dosage adjustment. 10 to 14.9 mcg/mL
If symptoms are controlled and current dosage is tolerated, maintain dose and recheck serum concentration at 6 to 12 month intervals.*
If symptoms are not controlled and current dosage is tolerated consider adding additional medication(s) to treatment regimen. 15 to 19.9 mcg/mL Consider 10% decrease in dose to provide greater margin of safety even if current dosage is tolerated.* 20 to 24.9 mcg/mL Decrease dose by 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment. 25 to 30 mcg/mL Skip next dose and decrease subsequent doses at least 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment. If symptomatic, consider whether overdose treatment is indicated (see recommendations for chronic overdosage). >30 mcg/mL Treat overdose as indicated (see recommendations for chronic overdosage). If theophylline is subsequently resumed, decrease dose by at least 50% and recheck serum concentration after 3 days to guide further dosage adjustment.
Once-Daily Dosing

The slow absorption rate of this preparation may allow once-daily administration in adult non-smokers with appropriate total body clearance and other patients with low dosage requirements. Once-daily dosing should be considered only after the patient has been gradually and satisfactorily titrated to therapeutic levels with q12h dosing. Once-daily dosing should be based on twice the q12h dose and should be initiated at the end of the last q12h dosing interval. The trough concentration (Cmin) obtained following conversion to once-daily dosing may be lower (especially in high clearance patients) and the peak concentration (Cmax) may be higher (especially in low clearance patients) than that obtained with q12h dosing. If symptoms recur, or signs of toxicity appear during the once-daily dosing interval, dosing on the q12h basis should be reinstituted.

It is essential that serum theophylline concentrations be monitored before and after transfer to once-daily dosing.

Food and posture, along with changes associated with circadian rhythm, may influence the rate of absorption and/or clearance rates of theophylline from extended-release dosage forms administered at night. The exact relationship of these and other factors to nighttime serum concentrations and the clinical significance of such findings require additional study. Therefore, it is not recommended that theophylline extended-release once-daily dosing be administered at night.
Letrozole

Letrozole

2.1 Recommended Dose

The recommended dose of letrozole tablets USP is one 2.5 mg tablet administered once a day, without regard to meals.

2.2 Use in Adjuvant Treatment of Early Breast Cancer

In the adjuvant setting, the optimal duration of treatment with letrozole is unknown. The planned duration of treatment in the study was 5 years with 73% of the patients having completed adjuvant therapy. Treatment should be discontinued at relapse [see Clinical Studies (14.1)].

2.3 Use in Extended Adjuvant Treatment of Early Breast Cancer

In the extended adjuvant setting, the optimal treatment duration with letrozole tablets USP is not known. The planned duration of treatment in the study was 5 years. In the final updated analysis, conducted at a median follow-up of 62 months, the median treatment duration was 60 months. Seventy-one percent of patients were treated for at least 3 years and 58% of patients completed least 4.5 years of extended adjuvant treatment. The treatment should be discontinued at tumor relapse [seeClinical Studies (14.2)].

2.4 Use in First and Second-Line Treatment of Advanced Breast Cancer

In patients with advanced disease, treatment with letrozole tablets USP should continue until tumor progression is evident [see Clinical Studies (14.4, 14.5)].

2.5 Use in Hepatic Impairment

No dosage adjustment is recommended for patients with mild to moderate hepatic impairment, although letrozole blood concentrations were modestly increased in subjects with moderate hepatic impairment due to cirrhosis. The dose of letrozole tablets USP in patients with cirrhosis and severe hepatic dysfunction should be reduced by 50% [see Warnings and Precautions (5.3)]. The recommended dose of letrozole tablets USP for such patients is 2.5 mg administered every other day. The effect of hepatic impairment on letrozole exposure in noncirrhotic cancer patients with elevated bilirubin levels has not been determined.

2.6 Use in Renal Impairment

No dosage adjustment is required for patients with renal impairment if creatinine clearance is ≥ 10 mL/min [see Clinical Pharmacology (12.3)].
Torsemide

Torsemide

GeneralTorsemide tablets may be given at any time in relation to a meal, as convenient. Special dosage adjustment in the elderly is not necessary.Congestive Heart FailureThe usual initial dose is 10 mg or 20 mg of once-daily oral torsemide. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 200 mg have not been adequately studied.Chronic Renal Failure The usual initial dose of torsemide is 20 mg of once-daily oral torsemide. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 200 mg have not been adequately studied.Hepatic CirrhosisThe usual initial dose is 5 mg or 10 mg of once-daily oral torsemide tablets, administered together with an aldosterone antagonist or a potassium-sparing diuretic. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 40 mg have not been adequately studied.Chronic use of any diuretic in hepatic disease has not been studied in adequate and well-controlled trials.HypertensionThe usual initial dose is 5 mg once daily. If the 5 mg dose does not provide adequate reduction in blood pressure within 4 to 6 weeks, the dose may be increased to 10 mg once daily. If the response to 10 mg is insufficient, an additional antihypertensive agent should be added to the treatment regimen.
Antacid

Antacid

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

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

2.1 Osteoarthritis

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

2.2 Rheumatoid Arthritis

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

2.3 Juvenile Rheumatoid Arthritis

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

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

2.4 Ankylosing Spondylitis

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

2.5 Management of Acute Pain and Treatment of Primary Dysmenorrhea

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

2.6 Special Populations

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

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

Methotrexate

Neoplastic Diseases

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

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

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

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

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

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

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

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

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

Psoriasis, Rheumatoid Arthritis, and Juvenile Rheumatoid Arthritis

Adult Rheumatoid Arthritis: Recommended Starting Dosage Schedules

1. Single oral doses of 7.5 mg once weekly.

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

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

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

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

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

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

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

Psoriasis: Recommended Starting Dose Schedules

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

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

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

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

Onexton

The dosage of Donnatal® Elixir should be adjusted to the needs of the individual patient to assure symptomatic control with a minimum of adverse effects.

Donnatal® Elixir. Adults: One or two teaspoonfuls of elixir three or four times a day according to conditions and severity of symptoms.

Pediatric patients: may be dosed every 4 to 6 hours.

Starting dosage

Body weight q4h q6h

10 lb. (4.5 kg) 0.5 mL 0.75 mL

20 lb. (9.1 kg) 1.0 mL 1.5 mL

30 lb. (13.6 kg) 1.5 mL 2.0 mL

50 lb. (22.7 kg) ½ tsp ¾ tsp

75 lb. (34 kg) ¾ tsp 1 tsp

100 lb. (45.4 kg) 1 tsp 1½ tsp
Clonidine Hydrochloride...

Clonidine Hydrochloride Extended-release

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.
Raloxifene Hydrochlorid...

Raloxifene Hydrochloride

2.1 Recommended Dosing

The recommended dosage is one 60 mg raloxifene hydrochloride tablet USP daily, which may be administered any time of day without regard to meals [see Clinical Pharmacology (12.3)].

For the indications in risk of invasive breast cancer the optimum duration of treatment is not known [see Clinical Studies (14.3, 14.4)].

2.2 Recommendations for Calcium and Vitamin D Supplementation

For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. Postmenopausal women require an average of 1500 mg/day of elemental calcium. Total daily intake of calcium above 1500 mg has not demonstrated additional bone benefits while daily intake above 2000 mg has been associated with increased risk of adverse effects, including hypercalcemia and kidney stones. The recommended intake of vitamin D is 400 to 800 IU daily. Patients at increased risk for vitamin D insufficiency (e.g., over the age of 70 years, nursing home bound, or chronically ill) may need additional vitamin D supplements. Patients with gastrointestinal malabsorption syndromes may require higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.
Metformin Hydrochloride...

Metformin Hydrochloride

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with metformin HCl extended release tablets, USP or any other pharmacologic agent. Dosage of metformin HCl extended release tablets, USP must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses. The maximum daily dose of metformin hydrochloride extended release tablets, USP in adults is 2000 mg. Metformin HCl extended release tablets, USP should generally be given once daily with the evening meal. Metformin HCl extended release tablets, USP should be started at a low dose, with gradual dose escalation, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.

During treatment initiation and dose titration (see Recommended Dosing Schedule), fasting plasma glucose should be used to determine the therapeutic response to metformin HCL extended release tablets, USP and identify the minimum effective dose for the patient.

Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of metformin HCl extended release tablets, USP either when used as monotherapy or in combination with sulfonylurea or insulin. Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness.

Short-term administration of metformin HCl extended release tablets, USP may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.

Metformin HCl extended release tablets, USP must be swallowed whole and never crushed or chewed. Occasionally, the inactive ingredients of metformin HCl extended release tablets, USP will be eliminated in the feces as a soft, hydrated mass. (See Patient Information printed below.)

Recommended Dosing Schedule

Adults - In general, clinically significant responses are not seen at doses below 1500 mg per day.

However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms.

The usual starting dose of metformin HCl extended release tablets, USP is 500 mg once daily with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved on metformin HCl extended release tablets, USP 2000 mg once daily, a trial of metformin HCl extended release tablets, USP 1000 mg twice daily should be considered. (See CLINICAL PHARMACOLOGY, Clinical Studies.)

Pediatrics - Safety and effectiveness of metformin HCl extended release tablets, USP in pediatric patients have not been established.

Transfer From Other Antidiabetic Therapy

When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to metformin HCl extended release tablets, USP no transition period generally is necessary. When transferring patients from chlorpropamide, care should be exercised during the first two weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.

Concomitant Metformin HCl Extended Release Tablets, USP and Oral Sulfonylurea Therapy in Adult Patients

If patients have not responded to four weeks of the maximum dose of metformin HCl extended release tablets, USP monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing metformin HCl extended release tablets, USP at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. Clinical and pharmacokinetic drug-drug interaction data are currently available only for metformin plus glyburide (glibenclamide).

With concomitant metformin HCl extended release tablets, USP and sulfonylurea therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. With concomitant metformin HCl extended release tablets, USP and sulfonylurea therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken. (See Package Insert of the respective sulfonylurea.)

If patients have not satisfactorily responded to one to three months of concomitant therapy with the maximum dose of metformin HCl extended release tablets, USP and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without metformin HCl extended release tablets, USP.

Concomitant Metformin HCl Extended Release Tablets, USP and Insulin Therapy in Adult Patients

The current insulin dose should be continued upon initiation of metformin HCl extended release tablets, USP therapy. Metformin HCl extended release tablets, USP therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of metformin HCl extended release tablets, USP should be increased by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose is 2000 mg for metformin HCl extended release tablets, USP. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and metformin HCl extended release tablets, USP. Further adjustment should be individualized based on glucose-lowering response.

Specific Patient Populations

Metformin hydrochloride extended release tablets are not recommended for use in pregnancy. Metformin HCl extended release tablets, USP is not recommended in pediatric patients (below the age of 17 years).

The initial and maintenance dosing of metformin HCl extended release tablets, USP should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of metformin HCl extended release tablets, USP.

Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly. (See WARNINGS.)
Azithromycin

Azithromycin

2.1 General Instructions

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 and Precautions (5.4)].

After observing the response to initial therapy with meloxicam, adjust the dose to suit an individual patient's needs.

In adults, the maximum recommended daily oral dose of meloxicam is 15 mg regardless of formulation. In patients with hemodialysis, a maximum daily dosage of 7.5 mg is recommended [see Warnings and Precautions (5.6), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].

Meloxicam may be taken without regard to timing of meals.

2.2 Osteoarthritis

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.

2.3 Rheumatoid Arthritis

For the relief of the signs and symptoms of rheumatoid arthritis, 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.
Oxandrolone

Oxandrolone

2.1 General Dosing Information

Methylphenidate HCl Extended-Release Tablets should be administered orally once daily in the morning with or without food.

Methylphenidate HCl Extended-Release Tablets must be swallowed whole with the aid of liquids, and must not be chewed, divided, or crushed [see Patient Counseling Information (17)].

2.2 Patients New to Methylphenidate

The recommended starting dose of Methylphenidate HCl Extended-Release Tablets for patients who are not currently taking methylphenidate or stimulants other than methylphenidate is 18 mg once daily for children and adolescents and 18 or 36 mg once daily for adults (see Table 1).
TABLE 1. Methylphenidate HCl Extended-Release Tablets Recommended Starting Doses and Dose Ranges Patient Age Recommended Starting Dose Dose Range Children 6-12 years of age 18 mg/day 18 mg - 54 mg/day Adolescents 13-17 years of age 18 mg/day 18 mg - 72 mg/daynot to exceed 2 mg/kg/day Adults 18-65 years of age 18 or 36 mg/day 18 mg - 72 mg/day
2.3 Patients Currently Using Methylphenidate

The recommended dose of Methylphenidate HCl Extended-Release Tablets for patients who are currently taking methylphenidate twice daily or three times daily, at doses of 10 to 60 mg/day is provided in Table 2. Dosing recommendations are based on current dose regimen and clinical judgment. Conversion dosage should not exceed 72 mg daily.
TABLE 2. Recommended Dose Conversion from Methylphenidate Regimens to Methylphenidate HCl Extended-Release Tablets Previous Methylphenidate Daily Dose Recommended Methylphenidate HCl Extended-Release Tablets Starting Dose 5 mg Methylphenidate twice daily or three times daily 18 mg every morning 10 mg Methylphenidate twice daily or three times daily 36 mg every morning 15 mg Methylphenidate twice daily or three times daily 54 mg every morning 20 mg Methylphenidate twice daily or three times daily 72 mg every morning
Other methylphenidate regimens: Clinical judgment should be used when selecting the starting dose.

2.4 Dose Titration

Doses may be increased in 18 mg increments at weekly intervals for patients who have not achieved an optimal response at a lower dose. Daily dosages above 54 mg in children and 72 mg in adolescents have not been studied and are not recommended. Daily dosages above 72 mg in adults are not recommended.

A 27 mg dosage strength is available for physicians who wish to prescribe between the 18 mg and 36 mg dosages.

2.5 Maintenance/Extended Treatment

There is no body of evidence available from controlled trials to indicate how long the patient with ADHD should be treated with Methylphenidate HCl Extended-Release Tablets. It is generally agreed, however, that pharmacological treatment of ADHD may be needed for extended periods.

The effectiveness of Methylphenidate HCl Extended-Release Tablets for long-term use, i.e., for more than 7 weeks, has not been systematically evaluated in controlled trials. The physician who elects to use Methylphenidate HCl Extended-Release Tablets for extended periods in patients with ADHD should periodically re-evaluate the long-term usefulness of the drug for the individual patient with trials off medication to assess the patient's functioning without pharmacotherapy. Improvement may be sustained when the drug is either temporarily or permanently discontinued.

2.6 Dose Reduction and Discontinuation

If paradoxical aggravation of symptoms or other adverse events occur, the dosage should be reduced, or, if necessary, the drug should be discontinued.

If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.
Butalbital And Acetamin...

Butalbital And Acetaminophen

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

Extended and repeated use of this product is not recommended because of the potential for physical dependence.
Control Anti-dandrudff

Control Anti-dandrudff

Because of the wide range of clinical indications for Chlordiazepoxide Hydrochloride Capsule the optimum dosage varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects.
ADULTS USUAL DAILY DOSE Relief of Mild and Moderate Anxiety Disordersand Symptoms of Anxiety 5 mg or 10 mg, 3 or 4 times daily Relief of Severe AnxietyDisorders and Symptoms of Anxiety 20 mg or 25 mg, 3 or 4 times daily Geriatric Patients, or in the presence of debilitatingdisease. 5 mg, 2 to 4 times daily
Preoperative Apprehension and Anxiety: On days preceding surgery, 5 to 10 mg orally, 3 or 4 times daily. If used as preoperative medication, 50 to 100 mg IM* 1 hour prior to surgery.
PEDIATRIC PATIENTS USUAL DAILY DOSE Because of the varied response of pediatric patients to CNS-acting drugs, therapy should be initiated with the lowest dose and increased as required. Since clinical experience in pediatric patients under 6 years of age is limited, the use of the drug in this age group is not recommended. 5 mg, 2 to 4 times daily (may be increased in some pediatric patients to 10 mg, 2 to 3 times daily)
For the relief of withdrawal symptoms of acute alcoholism, the parenteral form* is usually used initially. If the drug is administered orally, the suggested initial dose is 50 to 100 mg, to be followed by repeated doses as needed until agitation is controlled - up to 300 mg per day. Dosage should then be reduced to maintenance levels.

*See package insert for Injectable. Chlordiazepoxide Hydrochloride.
Primidone

Primidone

Adult Dosage

Patients 8 years of age and older who have received no previous treatment may be started on primidone according to the following regimen using either 50 mg or scored 250 mg primidone tablets:

Days 1 to 3: 100 to 125 mg at bedtime.

Days 4 to 6: 100 to 125 mg b.i.d.

Days 7 to 9: 100 to 125 mg t.i.d.

Day 10 to Maintenance: 250 mg t.i.d.

For most adults and children 8 years of age and over, the usual maintenance dosage is three to four 250 mg primidone tablets daily in divided doses (250 mg t.i.d. or q.i.d.). If required, an increase to five or six 250 mg tablets daily may be made but daily doses should not exceed 500 mg q.i.d.
INITIAL: ADULTS AND CHILDREN OVER 8 KEY: • = 50 MG TABLET; ●= 250 MG TABLET DAY 1 2 3 4 5 6 AM •• •• •• NOON PM •• •• •• •• •• •• DAY 7 8 9 10 11 12 AM •• •• •• ● NOON •• •• •• ● Adjust to Maintenance PM •• •• •• ●
Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations of primidone may be necessary for optimal dosage adjustment. The clinically effective serum level for primidone is between 5 to 12 µg/mL.

In Patients Already Receiving Other Anticonvulsants

Primidone should be started at 100 to 125 mg at bedtime and gradually increased to maintenance level as the other drug is gradually decreased. This regimen should be continued until satisfactory dosage level is achieved for the combination, or the other medication is completely withdrawn. When therapy with primidone alone is the objective, the transition from concomitant therapy should not be completed in less than two weeks.

Pediatric Dosage

For children under 8 years of age, the following regimen may be used:

Days 1 to 3: 50 mg at bedtime.

Days 4 to 6: 50 mg b.i.d.

Days 7 to 9: 100 mg b.i.d.

Day 10 to maintenance: 125 mg t.i.d. to 250 mg t.i.d.

For children under 8 years of age, the usual maintenance dosage is 125 to 250

mg three times daily or 10 to 25 mg/kg/day in divided doses.
Olanzapine

Olanzapine

One tablet of 200 mg of hydroxychloroquine sulfate, USP 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, USP 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, USP.

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:
Ciliary body: Disturbance of accommodation with symptoms of blurred vision. This reaction is dose-related and reversible with cessation of therapy. Cornea: Transient edema, punctate 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 appear 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 threshold to red light in macular, paramacular, and peripheral 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, angiodema and bronchospasm 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, USP 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.
Aveeno Protect Plus Hyd...

Aveeno Protect Plus Hydrate Sunscreen Broad Spectrum Spf70

adults and children 12 years of age and over take one 60 mg tablet with water every 12 hours; do not take more than 2 tablets in 24 hours children under 12 years of age do not use adults 65 years of age and older ask a doctor consumers with kidney disease ask a doctor
For 180 mg:
adults and children 12 years of age and over take one 180 mg tablet with water once a day; do not take more than 1 tablet in 24 hours children under 12 years of age do not use adults 65 years of age and older ask a doctor consumers with kidney disease ask a doctor
Carisoprodol

Carisoprodol

The recommended dose of CARISOPRODOL is 250 to 350 mg three times a day and at bedtime. The recommended maximum duration of CARISOPRODOL use is up to two or three weeks.
Epinastine Hcl

Epinastine Hcl

The recommended dosage is one drop in each eye twice a day.

Treatment should be continued throughout the period of exposure (i.e., until the pollen season is over or until exposure to the offending allergen is terminated), even when symptoms are absent.
Terbinafine Hydrochlori...

Terbinafine Hydrochloride

Fingernail onychomycosis: One 250 mg tablet once daily for 6 weeks.

Toenail onychomycosis: One 250 mg tablet once daily for 12 weeks.

The optimal clinical effect is seen some months after mycological cure and cessation of treatment. This is related to the period required for outgrowth of healthy nail.
Propylthiouracil

Propylthiouracil

Propylthiouracil is administered orally. The total daily dosage is usually given in 3 equal doses at approximately 8-hour intervals.

Adults

The initial dose is 300 mg daily. In patients with severe hyper-thyroidism, very large goiters, or both, the initial dose may be increased to 400 mg daily, an occasional patient will require 600 to 900 mg/day initially. The usual maintenance dosage is 100 to 150 mg daily. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Pediatric Patients

Propylthiouracil is generally not recommended for use in the pediatric patient population except in rare instances in which other alternative therapies are not appropriate options. Studies evaluating appropriate dosing regimen have not been conducted in the pediatric population although general practice would suggest initiation of therapy in patients 6 years or older at a dosage of 50 mg daily with careful upward titration based on clinical response and evaluation of TSH and free T4 levels. Although cases of severe liver injury have been reported with doses as low as 50 mg/day, most cases were associated with doses of 300 mg/day and higher.

Geriatric Use

Clinical studies of propylthiouracil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Probenecid And Colchici...

Probenecid And Colchicine

Therapy with probenecid and colchicine should not be started until an acute gouty attack has subsided. However, if an acute attack is precipitated during therapy, probenecid and colchicine may be continued without changing the dosage, and additional colchicine or other appropriate therapy should be given to control the acute attack.

The recommended adult dosage is 1 tablet of probenecid and colchicine daily for one week, followed by 1 tablet twice a day thereafter.

Some degree of renal impairment may be present in patients with gout. A daily dosage of 2 tablets may be adequate. However, if necessary, the daily dosage may be increased by 1 tablet every four weeks within tolerance (and usually not above 4 tablets per day) if symptoms of gouty arthritis are not controlled or the 24 hour uric acid excretion is not above 700 mg. As noted, probenecid may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mL/minute or less.

Gastric intolerance may be indicative of overdosage, and may be corrected by decreasing the dosage.

As uric acid tends to crystallize out of an acid urine, a liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7.5 g daily) or potassium citrate (7.5 g daily) to maintain an alkaline urine (see PRECAUTIONS).

Alkalization of the urine is recommended until the serum urate level returns to normal limits and tophaceous deposits disappear, i.e., during the period when urinary excretion of uric acid is at a high level. Thereafter, alkalization of the urine and the usual restriction of purine-producing foods may be somewhat relaxed.

Probenecid and colchicine (or probenecid) should be continued at the dosage that will maintain normal serum urate levels. When acute attacks have been absent for six months or more and serum urate levels remain within normal limits, the daily dosage of probenecid and colchicine may be decreased by 1 tablet every six months. The maintenance dosage should not be reduced to the point where serum urate levels tend to rise.
Lovastatin

Lovastatin

The patient should be placed on a standard cholesterol-lowering diet before receiving lovastatin and should continue on this diet during treatment with lovastatin (see NCEP Treatment Guidelines for details on dietary therapy). Lovastatin should be given with meals.

Adult Patients

The usual recommended starting dose is 20 mg once a day given with the evening meal. The recommended dosing range is 10-80 mg/day in single or two divided doses; the maximum recommended dose is 80 mg/day. Doses should be individualized according to the recommended goal of therapy (see NCEP Guidelines and CLINICAL PHARMACOLOGY ). Patients requiring reductions in LDL-C of 20% or more to achieve their goal (see INDICATIONS AND USAGE) should be started on 20 mg/day of lovastatin. A starting dose of 10 mg may be considered for patients requiring smaller reductions. Adjustments should be made at intervals of 4 weeks or more.

Cholesterol levels should be monitored periodically and consideration should be given to reducing the dosage of lovastatin if cholesterol levels fall significantly below the targeted range.

Dosage in Patients taking Cyclosporine or Danazol

In patients taking cyclosporine or danazol concomitantly with lovastatin (see WARNINGS, Myopathy/Rhabdomyolysis ), therapy should begin with 10 mg of lovastatin and should not exceed 20 mg/day.

Dosage in Patients taking Amiodarone or Verapamil

In patients taking amiodarone or verapamil concomitantly with lovastatin, the dose should not exceed 40 mg/day (see WARNINGS , Myopathy/Rhabdomyolysis and PRECAUTIONS , Drug Interactions , Other drug interactions ).

Adolescent Patients (10-17 years of age) with Heterozygous Familial Hypercholesterolemia

The recommended dosing range is 10-40 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 Guidelines ††,CLINICAL PHARMACOLOGY , and INDICATIONS AND USAGE ). Patients requiring reductions in LDL-C of 20% or more to achieve their goal should be started on 20 mg/day of lovastatin. A starting dose of 10 mg may be considered for patients requiring smaller reductions. Adjustments should be made at intervals of 4 weeks or more.

†† National 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.

Concomitant Lipid-Lowering Therapy

Lovastatin is effective alone or when used concomitantly with bile-acid sequestrants. If lovastatin is used in combination with gemfibrozil, other fibrates or lipid-lowering doses (≥1g/day) of niacin, the dose of lovastatin should not exceed 20 mg/day (see WARNINGS, Myopathy/Rhabdomyolysis and PRECAUTIONS , Drug Interactions ).

Dosage in Patients with Renal Insufficiency

In patients with severe renal insufficiency (creatinine clearance <30 mL/min), dosage increases above 20 mg/day should be carefully considered and, if deemed necessary, implemented cautiously (see CLINICAL PHARMACOLOGY and WARNINGS, Myopathy/Rhabdomyolysis ).
Sulindac

Sulindac

Carefully consider the potential benefits and risks of sulindac and other treatment options before deciding to use sulindac. 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 Sulindac Tablets USP, the dose and frequency should be adjusted to suit an individual patient’s needs.

Sulindac Tablets should be administered orally twice a day with food. The maximum dosage is 400 mg per day. Dosages above 400 mg per day are not recommended.

In osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, the recommended starting dosage is 150 mg twice a day. The dosage may be lowered or raised depending on the response.

A prompt response (within one week) can be expected in about one-half of patients with osteoarthritis, ankylosing spondylitis, and rheumatoid arthritis. Others may require longer to respond.

In acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis) and acute gouty arthritis, the recommended dosage is 200 mg twice a day. After a satisfactory response has been achieved, the dosage may be reduced according to the response. In acute painful shoulder, therapy for 7-14 days is usually adequate. In acute gouty arthritis, therapy for 7 days is usually adequate.
Midodrine Hydrochloride...

Midodrine Hydrochloride

The recommended dose of midodrine hydrochloride tablets is 10 mg, 3 times daily. Dosing should take place during the daytime hours when the patient needs to be upright, pursuing the activities of daily living. A suggested dosing schedule of approximately 4-hour intervals is as follows: shortly before or upon arising in the morning, midday, and late afternoon (not later than 6 PM). Doses may be given in 3-hour intervals, if required, to control symptoms, but not more frequently. Single doses as high as 20 mg have been given to patients, but severe and persistent systolic supine hypertension occurs at a high rate (about 45%) at this dose. In order to reduce the potential for supine hypertension during sleep, midodrine HCl tablets should not be given after the evening meal or less than 4 hours before bedtime. Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been studied systematically or established. Because of the risk of supine hypertension, midodrine HCl tablets should be continued only in patients who appear to attain symptomatic improvement during initial treatment.

The supine and standing blood pressure should be monitored regularly, and the administration of midodrine HCl tablets should be stopped if supine blood pressure increases excessively.

Because desglymidodrine is excreted renally, dosing in patients with abnormal renal function should be cautious; although this has not been systematically studied, it is recommended that treatment of these patients be initiated using 2.5 mg doses.

Dosing in children has not been adequately studied.

Blood levels of midodrine and desglymidodrine were similar when comparing levels in patients 65 or older vs. younger than 65 and when comparing males vs. females, suggesting dose modifications for these groups are not necessary.
Ropinirole Hydrochlorid...

Ropinirole Hydrochloride

2.1 General Dosing Considerations
Ropinirole extended-release tablets are taken once daily, with or without food. Taking ropinirole extended-release tablets with food may reduce the occurrence of nausea; this has not been established in controlled clinical trials [see Clinical Pharmacology (12.3)]. Tablets must be swallowed whole and must not be chewed, crushed, or divided. If a significant interruption in therapy with ropinirole extended-release tablets has occurred, retitration of therapy may be warranted.
2.2 Dosing for Parkinson’s Disease

The starting dose is 2 mg taken once daily for 1 to 2 weeks, followed by increases of 2 mg/day at 1-week or longer intervals as appropriate, depending on therapeutic response and tolerability, up to a maximally recommended dose of 24 mg/day.

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

When ropinirole extended-release tablets are administered as adjunct therapy to L-dopa, the concurrent dose of L-dopa may be decreased gradually as tolerated. In the placebo-controlled advanced Parkinson's disease study, the L-dopa dose was reduced once patients reached a dose of ropinirole extended-release tablets of 8 mg/day. Overall, L-dopa dose reduction was sustained in 93% of patients treated with ropinirole extended-release tablets and in 72% of patients on placebo. On average the L-dopa dose was reduced by 34% in patients treated with ropinirole extended-release tablets [see Clinical Studies (14)]. Ropinirole extended-release tablets should be discontinued gradually over a 7–day period.

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

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

Levetiracetam

Levetiracetam is indicated as adjunctive treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.

Partial Onset Seizures

Adults 16 Years And Older

In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing, were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose (see CLINICAL STUDIES), a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Pediatric Patients Ages 4 To <16 Years

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 52 mg/kg. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. Table 13 below provides a guideline for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.

Levetiracetam is given orally with or without food.
Table 13: Levetiracetam Tablet Weight-Based Dosing Guide For Children Daily Dose Patient Weight 20 mg/kg/day (BID dosing) 40 mg/kg/day(BID dosing) 60 mg/kg/day (BID dosing) 20.1-40 kg 500 mg/day(1 x 250 mgtablet BID) 1000 mg/day(1 x 500 mgtablet BID) 1500 mg/day(1 x 750 mgtablet BID) >40 kg 1000 mg/day(1 x 500 mgtablet BID) 2000 mg/day(2 x 500 mgtablets BID) 3000 mg/day(2 x 750 mgtablets BID)
The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients based on a daily dose of 20 mg/kg/day, 40 mg/kg/day or 60 mg/kg/day:
Total daily dose (mL/day) = Daily dose (mg/kg/day) x patient weight (kg) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 100 mg/mL
A household teaspoon or tablespoon is not an adequate measuring device. It is recommended that a calibrated measuring device be obtained and used. Healthcare providers should recommend a device that can measure and deliver the prescribed dose accurately, and provide instructions for measuring the dosage.

Myoclonic Seizures In Patients 12 Years Of Age And Older With Juvenile Myoclonic Epilepsy

Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.

Adult Patients With Impaired Renal Function

Levetiracetam dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 14. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the following formula:
CLcr = [140-age (years)] x weight (kg) (x 0.85 for female patients) 72 x serum creatinine (mg/dL) Table 14: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance(mL/min) Dosage(mg) Frequency 1 Following dialysis, a 250 to 500 mg supplemental dose is recommended. Normal > 80 500 to 1,500 Every 12 h Mild 50 – 80 500 to 1,000 Every 12 h Moderate 30 – 50 250 to 750 Every 12 h Severe < 30 250 to 500 Every 12 h ESRD patients using dialysis ---- 500 to 1,000 1 Every 24 h
Triamterene And Hydroch...

Triamterene And Hydrochlorothiazide

The usual dose of triamterene and hydrochlorothiazide capsules, USP is one or two capsules given once daily, with appropriate monitoring of serum potassium and of the clinical effect (see WARNINGS, Hyperkalemia).
Fluoxetine Hydrochlorid...

Fluoxetine Hydrochloride

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 B.I.D. 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 TRIALS). 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.

As with many other medications, a lower or less frequent dosage should be used in patients with hepatic impairment. A lower or less frequent dosage should also be considered for the elderly (see Geriatric Use under PRECAUTIONS), and for patients with concurrent disease or on multiple concomitant medications. Dosage adjustments for renal impairment are not routinely necessary (see Liver disease and Renal disease under CLINICAL PHARMACOLOGY, and Use in Patients with Concomitant Illness under PRECAUTIONS).

Maintenance/Continuation/Extended Treatment

It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy. Whether the dose needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.

Daily Dosing

Systematic evaluation of fluoxetine in adult patients has shown that its efficacy in major depressive disorder is maintained for periods of up to 38 weeks following 12 weeks of open-label acute treatment (50 weeks total) at a dose of 20 mg/day (see CLINICAL TRIALS).

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 Other drugs effective in the treatment of major depressive disorder under PRECAUTIONS, Drug Interactions).

Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI)

At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with fluoxetine. In addition, at least 5 weeks, perhaps longer, should be allowed after stopping fluoxetine before starting an MAOI (see CONTRAINDICATIONS and PRECAUTIONS).

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 TRIALS). 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-a-day (i.e., morning) or B.I.D. 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 TRIALS). 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.

All Patients

As with the use of fluoxetine in the treatment of major depressive disorder, a lower or less frequent dosage should be used in patients with hepatic impairment. A lower or less frequent dosage should also be considered for the elderly (see Geriatric Use under PRECAUTIONS), and for patients with concurrent disease or on multiple concomitant medications. Dosage adjustments for renal impairment are not routinely necessary (see Liver disease and Renal disease under CLINICAL PHARMACOLOGY, and Use in Patients with Concomitant Illness under PRECAUTIONS).

Maintenance/Continuation Treatment

While there are no systematic studies that answer the question of how long to continue fluoxetine, OCD is a chronic condition and it is reasonable to consider continuation for a responding patient. Although the efficacy of fluoxetine after 13 weeks has not been documented in controlled trials, adult patients have been continued in therapy under double-blind conditions for up to an additional 6 months without loss of benefit. However, dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for treatment.

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 TRIALS). 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.

As with the use of fluoxetine in the treatment of major depressive disorder and OCD, a lower or less frequent dosage should be used in patients with hepatic impairment. A lower or less frequent dosage should also be considered for the elderly (see Geriatric Use under PRECAUTIONS), and for patients with concurrent disease or on multiple concomitant medications. Dosage adjustments for renal impairment are not routinely necessary (see Liver disease and Renal disease under CLINICAL PHARMACOLOGY, and Use in Patients with Concomitant Illness under PRECAUTIONS).

Maintenance/Continuation Treatment

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

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 TRIALS). Treatment should be initiated with a dose of 10 mg/day. After 1 week, the dose should be increased to 20 mg/day. The most frequently administered dose in the two 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.

As with the use of fluoxetine in other indications, a lower or less frequent dosage should be used in patients with hepatic impairment. A lower or less frequent dosage should also be considered for the elderly (see Geriatric Use under PRECAUTIONS), and for patients with concurrent disease or on multiple concomitant medications. Dosage adjustments for renal impairment are not routinely necessary (see Liver disease and Renal disease under CLINICAL PHARMACOLOGY, and Use in Patients with Concomitant Illness under PRECAUTIONS).

Maintenance/Continuation Treatment

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

Special Populations

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to fluoxetine 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 fluoxetine during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering fluoxetine in the third trimester.

Discontinuation of Treatment with Fluoxetine

Symptoms associated with discontinuation of fluoxetine 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. Plasma fluoxetine and norfluoxetine concentration decrease gradually at the conclusion of therapy which may minimize the risk of discontinuation symptoms with this drug.
Doxepin Hydrochloride

Doxepin Hydrochloride

For most patients with illness of mild to moderate severity, a starting daily dose of 75 mg is recommended. Dosage may subsequently be increased or decreased at appropriate intervals and according to individual response. The usual optimum dose range is 75 mg/day to 150 mg/day.

In more severely ill patients higher doses may be required with subsequent gradual increase to 300 mg/day if necessary. Additional therapeutic effect is rarely to be obtained by exceeding a dose of 300 mg/day.

In patients with very mild symptomatology or emotional symptoms accompanying organic disease, lower doses may suffice. Some of these patients have been controlled on doses as low as 25 to 50 mg/day.

The total daily dosage of doxepin (as the hydrochloride) may be given on a divided or once a day dosage schedule. If the once a day schedule is employed the maximum recommended dose is 150 mg/day. This dose may be given at bedtime. The 150 mg capsule strength is intended for maintenance therapy only and is not recommended for initiation of treatment.

Antianxiety effect is apparent before the antidepressant effect. Optimal antidepressant effect may not be evident for 2 to 3 weeks.
Quinapril Hydrochloride...

Quinapril Hydrochloride And Hydrochlorothiazide

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 and 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 (eg, 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 HCl and hydrochlorothiazide tablets, 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 HCl and hydrochlorothiazide tablets 10/12.5 or 20/12.5. 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 hydrochlorothiazide, but who experience significant potassium loss with this regimen, may achieve blood pressure control with less electrolyte disturbance if they are switched to quinapril HCl and hydrochlorothiazide tablets 10/12.5 or 20/12.5.

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 HCl and hydrochlorothiazide tablets 20/25.

Use in Renal Impairment

Regimens of therapy with quinapril HCl 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 HCl and hydrochlorothiazide tablets are not recommended for use in these patients.
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 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. 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 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 (CLCR < 80 mL/min) have not been fully characterized. Current data are insufficient to determine if a dosage adjustment is warranted. The total daily dosage should not exceed 200 mg in 24 hours. However, due to the anti-anabolic effect of tetracyclines, BUN and creatinine should be monitored (see WARNINGS).
Danazol

Danazol

Endometriosis

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

Fibrocystic Breast Disease

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

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

Hereditary Angioedema

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

Indomethacin

Lisinopril is an effective treatment of hypertension in once-daily doses of 10 mg to 80 mg, while hydrochlorothiazide is effective in doses of 12.5 mg to 50 mg. In clinical trials of lisinopril and hydrochlorothiazide combination therapy using lisinopril doses of 10 mg to 80 mg and hydrochlorothiazide doses of 6.25 mg 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 (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of lisinopril and hydrochlorothiazide will be associated with both sets of dose-independent side effects, but addition of lisinopril in clinical trials blunted the hypokalemia normally seen with diuretics.

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.

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 and hydrochlorothiazide tablet 10 mg/12.5 mg or lisinopril and hydrochlorothiazide tablet 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 hydrochlorothiazide, but who experience significant potassium loss with this regimen, may achieve similar or greater blood pressure control with less potassium loss if they are switched to lisinopril and hydrochlorothiazide tablet 10 mg/12.5 mg. Dosage higher than lisinopril 80 mg and hydrochlorothiazide 50 mg should not be used.

Replacement Therapy

The combination may be substituted for the titrated individual components.

Use in Renal Impairment

The usual regimens of therapy with lisinopril and hydrochlorothiazide tablets need not be adjusted as long as the patient's creatinine clearance is >30 mL/min/1.73 m2 (serum creatinine approximately ≤3 mg/dL or 265 mcmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so lisinopril and hydrochlorothiazide tablet is not recommended (see WARNINGS, Anaphylactoid Reactions During Membrane Exposure).
Cold Multi-symptom Dayt...

Cold Multi-symptom Daytime

As a dietary adjunct before, during and after pregnancy, take one tablet daily with a meal, or as directed by a physician.
Maximum Strength Flu Hb...

Maximum Strength Flu Hbp

Hypertension

The initial dose of atenolol tablets USP 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 tablets USP 100 mg given as one tablet a day. Increasing the dosage beyond 100 mg a day is unlikely to produce any further benefit.

Atenolol tablets USP 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 tablets USP 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 tablets USP 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 USP, 50 mg should be initiated 10 minutes after the last intravenous dose followed by another 50 mg oral dose 12 hours later. Thereafter, atenolol tablets USP 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 tablets USP should be discontinued (see full prescribing information prior to initiating therapy with atenolol tablets USP).

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 USP, 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 tablets USP 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 tablets USP is an additional treatment to standard coronary care unit therapy.

Elderly Patients or Patients With Renal Impairment

Atenolol tablets USP are 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 tablets USP 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) Atenolol Elimination 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 tablets USP: 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 tablet USP therapy is planned, it should be achieved gradually and patients should be carefully observed and advised to limit physical activity to a minimum.
High Blood Pressure Che...

High Blood Pressure Chest Congestion And Cough

Amiloride HCl tablets should be administered with food.

Amiloride HCl tablets, one 5 mg tablet daily, should be added to the usual antihypertensive or diuretic dosage of a kaliuretic diuretic. The dosage may be increased to 10 mg per day, if necessary. More than two 5 mg tablets of amiloride HCl daily usually are not needed, and there is little controlled experience with such doses. If persistent hypokalemia is documented with 10 mg, the dose can be increased to 15 mg, then 20 mg, with careful monitoring of electrolytes.

In treating patients with congestive heart failure after an initial diuresis has been achieved, potassium loss may also decrease and the need for amiloride HCl tablets should be re-evaluated. Dosage adjustment may be necessary. Maintenance therapy may be on an intermittent basis.

If it is necessary to use amiloride HCl tablets alone (see INDICATIONS), the starting dosage should be one 5 mg tablet daily. This dosage may be increased to 10 mg per day, if necessary. More than two 5 mg tablets usually are not needed, and there is little controlled experience with such doses. If persistent hypokalemia is documented with 10 mg, the dose can be increased to 15 mg, then 20 mg, with careful monitoring of electrolytes.
Desloratadine

Desloratadine

Desloratadine Tablets may be taken without regard to meals.

2.1 Adults and adolescents 12 years of age and over

The recommended dose of Desloratadine Tablets is one 5-mg tablet once daily.

2.5 Adults with Hepatic or Renal Impairment

In adult patients with liver or renal impairment, a starting dose of one 5 mg tablet every other day is recommended based on pharmacokinetic data. Dosing recommendation for children with liver or renal impairment cannot be made due to lack of data [see Clinical Pharmacology (12.3)].
Diclofenac Sodium And M...

Diclofenac Sodium And Misoprostol

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

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

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

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

Note: See SPECIAL DOSING CONSIDERATIONS section below.

Osteoarthritis: The recommended dosage for maximal GI mucosal protection is diclofenac sodium and misoprostol delayed-release tablets 50 mg/0.2 mg tid. For patients who experience intolerance, diclofenac sodium and misoprostol delayed-release tablets 75 mg/0.2 mg bid or diclofenac sodium and misoprostol delayed-release tablets 50 mg/0.2 mg bid can be used, but are less effective in preventing ulcers. This fixed combination product, diclofenac sodium and misoprostol delayed-release tablets, is not recommended for patients who would not receive the appropriate dose of both ingredients. Doses of the components delivered with these regimens are as follows:
OA regimen Diclofenac sodium (mg/day) Misoprostol (mcg/day) Diclofenac Sodium and Misoprostol Delayed-Release Tablets 50 mg/0.2 mg tidbid 150100 600400 Diclofenac Sodium and Misoprostol Delayed-Release Tablets 75 mg/0.2 mg bid 150 400
Rheumatoid Arthritis: The recommended dosage is diclofenac sodium and misoprostol delayed-release tablets 50 mg/0.2 mg tid or qid. For patients who experience intolerance, diclofenac sodium and misoprostol delayed-release tablets 75 mg/0.2 mg bid or diclofenac sodium and misoprostol delayed-release tablets 50 mg/0.2 mg bid can be used, but are less effective in preventing ulcers. This fixed combination product, diclofenac sodium and misoprostol delayed-release tablets, is not recommended for patients who would not receive the appropriate dose of both ingredients. Doses of the components delivered with these regimens are as follows:
RA regimen Diclofenac sodium (mg/day) Misoprostol (mcg/day) Diclofenac Sodium and Misoprostol Delayed-Release Tablets 50 mg/0.2 mg qidtidbid 200150100 800600400 Diclofenac Sodium and Misoprostol Delayed-Release Tablets 75 mg/0.2 mg bid 150 400
SPECIAL DOSING CONSIDERATIONS: Diclofenac sodium and misoprostol delayed-release tablets contain misoprostol, which provides protection against gastric and duodenal ulcers (see CLINICAL STUDIES). For gastric ulcer prevention, the 200 mcg qid and tid regimens are therapeutically equivalent, but more protective than the bid regimen. For duodenal ulcer prevention, the qid regimen is more protective than the tid or bid regimens. However, the qid regimen is less well tolerated than the tid regimen because of usually self-limited diarrhea related to the misoprostol dose (see ADVERSE REACTIONS— Gastrointestinal), and the bid regimen may be better tolerated than tid in some patients.

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

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

Nitroglycerin Er

As noted above (CLINICAL PHARMACOLOGY) careful studies with other formulations of nitroglycerin have shown that maintenance of continuous 24-hour plasma levels of nitroglycerin results in tolerance (i.e., loss of clinical response). Every dosing regimen for Nitroglycerin Extended-Release Capsules should provide a daily nitrate-free interval to avoid the development of this tolerance. The minimum necessary length of such an interval has not been defined, but studies with other nitroglycerin formulations have shown that 10 to 12 hours is sufficient. Large controlled studies with other formulations of nitroglycerin show that no dosing regimen with Nitroglycerin Extended-Release Capsules should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.

The pharmacokinetics of Nitroglycerin capsules, and the clinical effects of multiple-dose regimens, have not been well studied. In clinical trials, the initial regimen of Nitroglycerin has been 2.5 to 6.5 mg three to four times a day, with subsequent upward dose adjustment guided by symptoms and side effects. In one trial, 5 of the 18 subjects were titrated up to a dose of 26 mg four times a day.
Hydroxychloroquine Sulf...

Hydroxychloroquine Sulfate

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

Dipyridamole

Adjunctive Use in Prophylaxis of Thromboembolism after Cardiac Valve Replacement. The recommended dose is 75 to 100 mg four times daily as an adjunct to the usual warfarin therapy. Please note that aspirin is not to be administered concomitantly with coumarin anticoagulants.
Ibuprofen

Ibuprofen

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

After observing the response to initial therapy with ibuprofen tablets the dose and frequency should be adjusted to suit an individual patient's needs.

Do not exceed 3200 mg total daily dose. If gastrointestinal complaints occur, administer Ibuprofen Tablets, USP with meals or milk.

Rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease:

Suggested Dosage: 1200 mg-3200 mg daily (300 mg qid; 400 mg, 600 mg or 800 mg tid or qid).

Individual patients may show a better response to 3200 mg daily, as compared with 2400 mg, although in well-controlled clinical trials patients on 3200 mg did not show a better mean response in terms of efficacy. Therefore, when treating patients with 3200 mg/day, the physician should observe sufficient increased clinical benefits to offset potential increased risk.

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

In general, patients with rheumatoid arthritis seem to require higher doses of ibuprofen tablets than do patients with osteoarthritis.

The smallest dose of ibuprofen tablets that yields acceptable control should be employed. A linear blood level dose-response relationship exists with single doses up to 800 mg (See CLINICAL PHARMACOLOGY for effects of food on rate of absorption). The availability of four tablet strengths facilitates dosage adjustment.

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

Mild to moderate pain: 400 mg every 4 to 6 hours as necessary for relief of pain.

In controlled analgesic clinical trials, doses of ibuprofen tablets greater than 400 mg were no more effective than the 400 mg dose.

Dysmenorrhea: For the treatment of dysmenorrhea, beginning with the earliest onset of such pain, ibuprofen tablets should be given in a dose of 400 mg every 4 hours as necessary for the relief of pain.
Orphenadrine Citrate

Orphenadrine Citrate

TABLETS: Adults-Two tablets per day; one in the morning and one in the evening.
Hydroxyzine Pamoate

Hydroxyzine Pamoate

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

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

As a sedative when used as a premedication and following general anesthesia: 50 mg to 100 mg in adults, and 0.6 mg/kg in children. When treatment is initiated by the intramuscular route of administration, subsequent doses may be administered orally.

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

Famciclovir

Famciclovir tablets may be taken with or without food.

2.1 Dosing Recommendation in Immunocompetent Adult Patients

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

Genital herpes:

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

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

Herpes zoster (shingles): The recommended dosage of famciclovir tablets for the treatment of herpes zoster is 500 mg every 8 hours for 7 days. Therapy should be initiated as soon as herpes zoster is diagnosed.

2.2 Dosing Recommendation in HIV-Infected Adult Patients

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

2.3 Dosing Recommendation in Patients With Renal Impairment

Dosage recommendations for adult patients with renal impairment are provided in Table 1 [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Table 1: Dosage Recommendations for Adult Patients With Renal Impairment * Hemodialysis Indication and Normal Dosage Regimen Creatinine Clearance (mL/min) Adjusted Dosage Regimen Dose (mg) Dosing Interval Single-Day Dosing Regimens Recurrent Genital Herpes 1000 mg every 12 hours for 1 day ≥ 60 1000 every 12 hours for 1 day 40 to 59 500 every 12 hours for 1 day 20 to 39 500 single dose < 20 250 single dose HD* 250 single dose following dialysis Recurrent Herpes Labialis 1500 mg single dose ≥ 60 1500 single dose 40 to 59 750 single dose 20 to 39 500 single dose < 20 250 single dose HD* 250 single dose following dialysis Multiple-Day Dosing Regimens Herpes Zoster 500 mg every 8 hours ≥ 60 500 every 8 hours 40 to 59 500 every 12 hours 20 to 39 500 every 24 hours < 20 250 every 24 hours HD* 250 following each dialysis Suppression of Recurrent Genital Herpes 250 mg every 12 hours ≥ 40 250 every 12 hours 20 to 39 125 every 12 hours < 20 125 every 24 hours HD* 125 following each dialysis Recurrent Orolabial or Genital Herpes in HIV-Infected Patients 500 mg every 12 hours ≥ 40 500 every 12 hours 20 to 39 500 every 24 hours < 20 250 every 24 hours HD* 250 following each dialysis
Terbutaline Sulfate

Terbutaline Sulfate

Adults

The usual oral dose of terbutaline sulfate tablets, USP for adults is 5 mg administered at approximately six-hour intervals, three times daily, during the hours the patient is usually awake. If side effects are particularly disturbing, the dose may be reduced to 2.5 mg three times daily, and still provide a clinically significant improvement in pulmonary function. The total dose within 24 hours should not exceed 15 mg.

Children

Terbutaline sulfate tablets, USP is not recommended for use in children below the age of 12 years. A dosage of 2.5 mg three times daily is recommended for children 12-15 years of age. The total dose within 24 hours should not exceed 7.5 mg.

If a previously effective dosage regimen fails to provide the usual relief, medical advice should be sought immediately as this is often a sign of seriously worsening asthma that would require reassessment of therapy.
Quinapril

Quinapril

Hypertension

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

If the diuretic cannot be discontinued, an initial dose of 5 mg quinapril hydrochloride 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 30-60 mL/min 5 mg 10-30 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.

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

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

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 hydrochloride 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 DOSAGE AND ADMINISTRATION, Heart Failure, WARNINGS, and PRECAUTIONS, Drug Interactions).

If the initial dose is well tolerated, quinapril hydrochloride 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.
Potassium Chloride

Potassium Chloride

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

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

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

Trimethoprim

The usual oral adult dosage is 100 mg of trimethoprim every 12 hours or 200 mg of trimethoprim every 24 hours, each for 10 days. The use of trimethoprim in patients with a creatinine clearance of less than 15 mL/min is not recommended. For patients with a creatinine clearance of 15 to 30 mL/min, the dose should be 50 mg every 12 hours.
Guaifenesin

Guaifenesin

adults and children 12 years of age and older, take 1 tablet every 4 hours with a full glass of water while symptoms persist.Do not exceed 6 doses in 24 hours. children under 12 years of age do not use.
Alprazolam

Alprazolam

Alprazolam extended-release tablets may be administered once daily, preferably in the morning. The tablets should be taken intact; they should not be chewed, crushed, or broken.

The suggested total daily dose ranges between 3 to 6 mg/day. Dosage should be individualized for maximum beneficial effect. While the suggested total daily dosages given will meet the needs of most patients, there will be some patients who require doses greater than 6 mg/day. In such cases, dosage should be increased cautiously to avoid adverse effects.

Dosing in Special Populations

In elderly patients, in patients with advanced liver disease, or in patients with debilitating disease, the usual starting dose of alprazolam extended-release tablets is 0.5 mg once daily. This may be gradually increased if needed and tolerated (see Dose Titration). The elderly may be especially sensitive to the effects of benzodiazepines.

Dose Titration

Treatment with alprazolam extended-release tablets may be initiated with a dose of 0.5 mg to 1 mg once daily. Depending on the response, the dose may be increased at intervals of 3 to 4 days in increments of no more than 1 mg/day. Slower titration to the dose levels may be advisable to allow full expression of the pharmacodynamic effect of alprazolam extended-release tablets.

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

Dose Maintenance

In controlled trials conducted to establish the efficacy of alprazolam extended-release tablets in panic disorder, doses in the range of 1 to 10 mg/day were used. Most patients showed efficacy in the dose range of 3 to 6 mg/day. Occasional patients required as much as 10 mg/day to achieve a successful response.

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

Dose Reduction

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

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

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

Switch from alprazolam (immediate-release) tablets to alprazolam extended-release tablets

Patients who are currently being treated with divided doses of alprazolam (immediate-release) tablets, for example 3 to 4 times a day, may be switched to alprazolam extended-release tablets at the same total daily dose taken once daily. If the therapeutic response after switching is inadequate, the dosage may be titrated as outlined above.
Norethindrone Acetate

Norethindrone Acetate

Therapy with norethindrone acetate tablets, USP must be adapted to the specific indications and therapeutic response of the individual patient.

Secondary amenorrhea, abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology: 2.5 to 10 mg norethindrone acetate, USP may be given daily for 5 to 10 days to produce secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen.

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

Endometriosis: Initial daily dosage of 5 mg norethindrone acetate, USP for two weeks. Dosage should be increased by 2.5 mg per day every two weeks until 15 mg per day of norethindrone acetate, USP is reached. Therapy may be held at this level for six to nine months or until annoying breakthrough bleeding demands temporary termination.
Piroxicam

Piroxicam

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

For the relief of rheumatoid arthritis and osteoarthritis, the recommended dose is 20 mg given orally once per day. If desired, the daily dose may be divided. Because of the long half-life of piroxicam capsules USP, steady-state blood levels are not reached for 7 to 12 days. Therefore, although the therapeutic effects of piroxicam are evident early in treatment, there is a progressive increase in response over several weeks and the effect of therapy should not be assessed for two weeks.
Glipizide And Metformin...

Glipizide And Metformin Hydrochloride

General Considerations

Dosage of glipizide and metformin hydrochloride tablets USP must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended daily dose of 20 mg glipizide/2000 mg metformin. Glipizide and metformin hydrochloride tablets USP should be given with meals and should be initiated at a low dose, with gradual dose escalation as described below, in order to avoid hypoglycemia (largely due to glipizide), reduce GI side effects (largely due to metformin), and permit determination of the minimum effective dose for adequate control of blood glucose for the individual patient.

With initial treatment and during dose titration, appropriate blood glucose monitoring should be used to determine the therapeutic response to glipizide and metformin hydrochloride tablets USP and to identify the minimum effective dose for the patient. Thereafter, HbA1c should be measured at intervals of approximately 3 months to assess the effectiveness of therapy. The therapeutic goal in all patients with type 2 diabetes is to decrease FPG, PPG, and HbA1c to normal or as near normal as possible. Ideally, the response to therapy should be evaluated using HbA1c, which is a better indicator of long-term glycemic control than FPG alone.

No studies have been performed specifically examining the safety and efficacy of switching to glipizide and metformin hydrochloride tablet therapy in patients taking concomitant glipizide (or other sulfonylurea) plus metformin. Changes in glycemic control may occur in such patients, with either hyperglycemia or hypoglycemia possible. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring.

Glipizide and Metformin Hydrochloride Tablets USP in Patients With Inadequate Glycemic Control on Diet and Exercise Alone

For patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone, the recommended starting dose of glipizide and metformin hydrochloride tablets USP is 2.5 mg/250 mg once a day with a meal. For patients whose FPG is 280 mg/dL to 320 mg/dL a starting dose of glipizide and metformin hydrochloride tablets USP, 2.5 mg/500 mg twice daily should be considered. The efficacy of glipizide and metformin hydrochloride tablets USP in patients whose FPG exceeds 320 mg/dL has not been established. Dosage increases to achieve adequate glycemic control should be made in increments of 1 tablet per day every 2 weeks up to maximum of 10 mg/1000 mg or 10 mg/2000 mg glipizide and metformin hydrochloride tablets USP per day given in divided doses. In clinical trials of glipizide and metformin hydrochloride tablets USP as initial therapy, there was no experience with total daily doses > 10 mg/2000 mg per day.

Glipizide and Metformin Hydrochloride Tablets USP in Patients With Inadequate Glycemic Control on a Sulfonylurea and/or Metformin

For patients not adequately controlled on either glipizide (or another sulfonylurea) or metformin alone, the recommended starting dose of glipizide and metformin hydrochloride tablets USP is 2.5 mg/500 mg or 5 mg/500 mg twice daily with the morning and evening meals. In order to avoid hypoglycemia, the starting dose of glipizide and metformin hydrochloride tablets USP should not exceed the daily doses of glipizide or metformin already being taken. The daily dose should be titrated in increments of no more than 5 mg/500 mg up to the minimum effective dose to achieve adequate control of blood glucose or to a maximum dose of 20 mg/2000 mg per day.

Patients previously treated with combination therapy of glipizide (or another sulfonylurea) plus metformin may be switched to glipizide and metformin hydrochloride tablets USP, 2.5 mg/500 mg or 5 mg/500 mg; the starting dose should not exceed the daily dose of glipizide (or equivalent dose of another sulfonylurea) and metformin already being taken. The decision to switch to the nearest equivalent dose or to titrate should be based on clinical judgment. Patients should be monitored closely for signs and symptoms of hypoglycemia following such a switch and the dose of glipizide and metformin hydrochloride tablets USP should be titrated as described above to achieve adequate control of blood glucose.

Specific Patient Populations

Glipizide and metformin hydrochloride tablets USP are not recommended for use during pregnancy or for use in pediatric patients. The initial and maintenance dosing of glipizide and metformin hydrochloride tablets USP should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment requires a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of glipizide and metformin hydrochloride tablets USP to avoid the risk of hypoglycemia. Monitoring of renal function is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in the elderly (see WARNINGS).
Ketoprofen

Ketoprofen

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

Concomitant use of ketoprofen capsules and ketoprofen extended-release capsules is not recommended.

If minor side effects appear, they may disappear at a lower dose which may still have an adequate therapeutic effect. If well tolerated but not optimally effective, the dosage may be increased. Individual patients may show a better response to 300 mg of ketoprofen capsules daily as compared to 200 mg, although in well-controlled clinical trials patients on 300 mg did not show greater mean effectiveness. They did, however, show an increased frequency of upper- and lower-GI distress and headaches. It is of interest that women also had an increased frequency of these adverse effects compared to men. When treating patients with 300 mg/day, the physician should observe sufficient increased clinical benefit to offset potential increased risk.

In patients with mildly impaired renal function, the maximum recommended total daily dose of ketoprofen capsules is 150 mg. In patients with a more severe renal impairment (GFR less than 25 mL/min/1.73 m2 or end-stage renal impairment), the maximum total daily dose of ketoprofen capsules should not exceed 100 mg.

In elderly patients, renal function may be reduced with apparently normal serum creatinine and/or BUN levels. Therefore, it is recommended that the initial dosage of ketoprofen capsules should be reduced for patients over 75 years of age (see Geriatric Use).

It is recommended that for patients with impaired liver function and serum albumin concentration less than 3.5 g/dL, the maximum initial total daily dose of ketoprofen capsules should be 100 mg. All patients with metabolic impairment, particularly those with both hypoalbuminemia and reduced renal function, may have increased levels of free (biologically active) ketoprofen and should be closely monitored. The dosage may be increased to the range recommended for the general population, if necessary, only after good individual tolerance has been ascertained.

Because hypoalbuminemia and reduced renal function both increase the fraction of free drug (biologically active form), patients who have both conditions may be at greater risk of adverse effects. Therefore, it is recommended that such patients also be started on lower doses of ketoprofen capsules and closely monitored.

Rheumatoid Arthritis and Osteoarthritis

The recommended starting dose of ketoprofen capsules in otherwise healthy patients is 75 mg three times or 50 mg four times a day. Smaller doses of ketoprofen capsules should be utilized initially in small individuals or in debilitated or elderly patients. The recommended maximum daily dose of ketoprofen capsules is 300 mg/day.

Dosages higher than 300 mg/day of ketoprofen capsules are not recommended because they have not been studied. Concomitant use of ketoprofen capsules and ketoprofen extended-release capsules is not recommended. Relatively smaller people may need smaller doses.

As with other non-steroidal anti-inflammatory drugs, the predominant adverse effects of ketoprofen are gastrointestinal. To attempt to minimize these effects, physicians may wish to prescribe that ketoprofen capsules be taken with antacids, food, or milk. Although food delays the absorption of ketoprofen capsules (see CLINICAL PHARMACOLOGY), in most of the clinical trials ketoprofen was taken with food or milk.

Physicians may want to make specific recommendations to patients about when they should take ketoprofen capsules in relation to food and/or what patients should do if they experience minor GI symptoms associated with ketoprofen capsules.

Management of Pain and Dysmenorrhea

The usual dose of ketoprofen capsules recommended for mild-to-moderate pain and dysmenorrhea is 25 to 50 mg every 6 to 8 hours as necessary. A smaller dose should be utilized initially in small individuals, in debilitated or elderly patients, or in patients with renal or liver disease (see PRECAUTIONS). A larger dose may be tried if the patient’s response to a previous dose was less than satisfactory, but doses above 75 mg have not been shown to give added analgesia. Daily doses above 300 mg are not recommended because they have not been adequately studied. Because of its typical non-steroidal anti-inflammatory drug-side-effect profile, including as its principal adverse effect GI side effects (see WARNINGS and ADVERSE REACTIONS), higher doses of ketoprofen capsules should be used with caution and patients receiving them observed carefully.
Venlafaxine Hydrochlori...

Venlafaxine Hydrochloride

Venlafaxine hydrochloride extended-release capsules should be administered in a single dose with food either in the morning or in the evening at approximately the same time each day. Each capsule should be swallowed whole with fluid and not divided, crushed, chewed, or placed in water, or it may be administered by carefully opening the capsule and sprinkling the entire contents on a spoonful of applesauce. This drug/food mixture should be swallowed immediately without chewing and followed with a glass of water to ensure complete swallowing of the pellets.

Initial Treatment

Major Depressive Disorder

For most patients, the recommended starting dose for venlafaxine hydrochloride extended-release capsules is 75 mg/day, administered in a single dose. In the clinical trials establishing the efficacy of venlafaxine hydrochloride extended-release capsules in moderately depressed outpatients, the initial dose of venlafaxine was 75 mg/day. For some patients, it may be desirable to start at 37.5 mg/day for 4 to 7 days, to allow new patients to adjust to the medication before increasing to 75 mg/day. While the relationship between dose and antidepressant response for venlafaxine hydrochloride extended-release capsules has not been adequately explored, patients not responding to the initial 75 mg/day dose may benefit from dose increases to a maximum of approximately 225 mg/day. Dose increases should be in increments of up to 75 mg/day, as needed, and should be made at intervals of not less than 4 days, since steady state plasma levels of venlafaxine and its major metabolites are achieved in most patients by day 4. In the clinical trials establishing efficacy, upward titration was permitted at intervals of 2 weeks or more; the average doses were about 140 to 180 mg/day (see CLINICAL PHARMACOLOGY, Clinical Trials).

It should be noted that, while the maximum recommended dose for moderately depressed outpatients is also 225 mg/day for venlafaxine hydrochloride tablets (immediate release), more severely depressed inpatients in one study of the development program for that product responded to a mean dose of 350 mg/day (range of 150 to 375 mg/day). Whether or not higher doses of venlafaxine hydrochloride extended-release capsules are needed for more severely depressed patients is unknown; however, the experience with venlafaxine hydrochloride extended-release capsule doses higher than 225 mg/day is very limited (see PRECAUTIONS, General, Use in Patients With Concomitant Illness).

Switching Patients From Venlafaxine Hydrochloride Tablets

Depressed patients who are currently being treated at a therapeutic dose with venlafaxine hydrochloride tablets (immediate release) may be switched to venlafaxine hydrochloride extended-release capsules at the nearest equivalent dose (mg/day), e.g., 37.5 mg venlafaxine two-times-a-day to 75 mg venlafaxine hydrochloride extended-release capsules once daily. However, individual dosage adjustments may be necessary.

Special Populations

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to venlafaxine hydrochloride extended-release capsules, other SNRIs, or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with venlafaxine hydrochloride extended-release capsules during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering venlafaxine hydrochloride extended-release capsules in the third trimester.

Patients With Hepatic Impairment

Given the decrease in clearance and increase in elimination half-life for both venlafaxine and ODV that is observed in patients with hepatic cirrhosis and mild and moderate hepatic impairment compared with normal subjects (see CLINICAL PHARMACOLOGY), it is recommended that the total daily dose be reduced by 50% in patients with mild to moderate hepatic impairment. Since there was much individual variability in clearance between subjects with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.

Patients With Renal Impairment

Given the decrease in clearance for venlafaxine and the increase in elimination half-life for both venlafaxine and ODV that is observed in patients with renal impairment (GFR = 10 to 70 mL/min) compared with normal subjects (see CLINICAL PHARMACOLOGY), it is recommended that the total daily dose be reduced by 25% to 50%. In patients undergoing hemodialysis, it is recommended that the total daily dose be reduced by 50%. Because there was much individual variability in clearance between patients with renal impairment, individualization of dosage may be desirable in some patients.

Elderly Patients

No dose adjustment is recommended for elderly patients solely on the basis of age. As with any drug for the treatment of major depressive disorder, however, caution should be exercised in treating the elderly. When individualizing the dosage, extra care should be taken when increasing the dose.

Maintenance Treatment

There is no body of evidence available from controlled trials to indicate how long patients with major depressive disorder should be treated with venlafaxine hydrochloride extended-release capsules.

It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. In one study, in which patients responding during 8 weeks of acute treatment with venlafaxine hydrochloride extended-release capsules were assigned randomly to placebo or to the same dose of venlafaxine hydrochloride extended-release capsules (75, 150, or 225 mg/day, qAM) during 26 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated. A second longer-term study has demonstrated the efficacy of venlafaxine hydrochloride tablets in maintaining a response in patients with recurrent major depressive disorder who had responded and continued to be improved during an initial 26 weeks of treatment and were then randomly assigned to placebo or venlafaxine hydrochloride tablets for periods of up to 52 weeks on the same dose (100 to 200 mg/day, on a b.i.d. schedule) (see CLINICAL PHARMACOLOGY, Clinical Trials). Based on these limited data, it is not known whether or not the dose of venlafaxine hydrochloride tablets/venlafaxine hydrochloride extended-release capsules needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Discontinuing Venlafaxine Hydrochloride Extended-Release Capsules

Symptoms associated with discontinuation of venlafaxine hydrochloride extended-release capsules, other SNRIs, and SSRIs, 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. In clinical trials with venlafaxine hydrochloride extended-release capsules, tapering was achieved by reducing the daily dose by 75 mg at 1 week intervals. Individualization of tapering may be necessary.

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 venlafaxine hydrochloride extended-release capsules. In addition, at least 7 days should be allowed after stopping venlafaxine hydrochloride extended-release capsules before starting an MAOI (see CONTRAINDICATIONS and WARNINGS).
Acyclovir

Acyclovir

Acute Treatment of Herpes Zoster: 800 mg every 4 hours orally, 5 times daily for 7 to 10 days.

Genital Herpes:Treatment of Initial Genital Herpes: 200 mg every 4 hours, 5 times daily for 10 days.

Chronic Suppressive Therapy for Recurrent Disease:

400 mg 2 times daily for up to 12 months, followed by reevaluation. Alternative regimens have included doses ranging from 200 mg 3 times daily to 200 mg 5 times daily.

The frequency and severity of episodes of untreated genital herpes may change over time. After 1 year of therapy, the frequency and severity of the patient's genital herpes infection should be re-evaluated to assess the need for continuation of therapy with acyclovir.

Intermittent Therapy: 200 mg every 4 hours, 5 times daily for 5 days. Therapy should be initiated at the earliest sign or symptom (prodrome) of recurrence.

Treatment of Chickenpox:Children (2 years of age and older): 20 mg/kg per dose orally 4 times daily (80 mg/kg/day) for 5 days. Children over 40 kg should receive the adult dose for chickenpox.

Adults and Children over 40 kg: 800 mg 4 times daily for 5 days.

Intravenous acyclovir is indicated for the treatment of varicella-zoster infections in immunocompromised patients.

When therapy is indicated, it should be initiated at the earliest sign or symptom of chickenpox. There is no information about the efficacy of therapy initiated more than 24 hours after onset of signs and symptoms.

Patients With Acute or Chronic Renal Impairment: In patients with renal impairment, the dose of acyclovir capsules should be modified as shown in Table 3:
Table 3. Dosage Modification for Renal Impairment Normal Dosage Creatinine Clearance Adjusted Dosage Regimen Regimen mL/min/1.73 m2) Dose (mg) Dosing Interval 200 mg every >10 200 every 4 hours, 4 hours 5x daily 0-10 200 every 12 hours 400 mg every >10 400 every 12 hours 12 hours 0-10 200 every 12 hours 800 mg every >25 800 every 4 hours, 4 hours 5x daily 10-25 800 every 8 hours 0-10 800 every 12 hours
Hemodialysis: For patients who require hemodialysis, the mean plasma half-life of acyclovir during hemodialysis is approximately 5 hours. This results in a 60% decrease in plasma concentrations following a 6-hour dialysis period. Therefore, the patient's dosing schedule should be adjusted so that an additional dose is administered after each dialysis.

Peritoneal Dialysis: No supplemental dose appears to be necessary after adjustment of the dosing interval.

Bioequivalence of Dosage Forms: acyclovir Suspension was shown to be bioequivalent to acyclovir Capsules (n = 20) and 1 acyclovir 800-mg capsule was shown to be bioequivalent to 4 acyclovir 200-mg capsules (n = 24).
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 (10-17 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)].
Valacyclovir Hydrochlor...

Valacyclovir Hydrochloride

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

Cold Sores (Herpes Labialis): The recommended dosage of valacyclovir hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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/mm3, the recommended dosage of valacyclovir hydrochloride tablets for chronic suppressive therapy of recurrent genital herpes is 500 mg twice daily.

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

2.4 Patients With Renal Impairment

Dosage recommendations for adult patients with reduced renal function are provided in Table 1 [see Use in Specific Populations (8.5, 8.6), Clinical Pharmacology (12.3)]. Data are not available for the use of valacyclovir hydrochloride tablets in pediatric patients with a creatinine clearance < 50 mL/min/1.73 m2.
Table 1. Valacyclovir Hydrochloride 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:

   Initial episode
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
   Immunocompetent 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 hydrochloride tablets after hemodialysis. During hemodialysis, the half-life of acyclovir after administration of valacyclovir hydrochloride 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 hydrochloride 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 hydrochloride tablets should not be required following CAPD or CAVHD.
Mexiletine Hydrochlorid...

Mexiletine Hydrochloride

The dosage of mexiletine hydrochloride must be individualized on the basis of response and tolerance, both of which are dose-related. Administration with food or antacid is recommended. Initiate mexiletine therapy with 200 mg every eight hours when rapid control of arrhythmia is not essential. A minimum of two to three days between dose adjustments is recommended. Dose may be adjusted in 50 or 100 mg increments up or down.

As with any antiarrhythmic drug, clinical and electrocardiographic evaluation (including Holter monitoring if necessary for evaluation) are needed to determine whether the desired antiarrhythmic effect has been obtained and to guide titration and dose adjustment.

Satisfactory control can be achieved in most patients by 200 to 300 mg given every eight hours with food or antacid. If satisfactory response has not been achieved at 300 mg q8h, and the patient tolerates mexiletine well, a dose of 400 mg q8h may be tried. As the severity of CNS side effects increases with total daily dose, the dose should not exceed 1200 mg/day.

In general, patients with renal failure will require the usual doses of mexiletine hydrochloride. Patients with severe liver disease, however, may require lower doses and must be monitored closely. Similarly, marked right-sided congestive heart failure can reduce hepatic metabolism and reduce the needed dose. Plasma level may also be affected by certain concomitant drugs (see PRECAUTIONS, Drug Interactions).

Loading Dose

When rapid control of ventricular arrhythmia is essential, an initial loading dose of 400 mg of mexiletine hydrochloride may be administered, followed by a 200 mg dose in eight hours. Onset of therapeutic effect is usually observed within 30 minutes to two hours.

Q12H Dosage Schedule

Some patients responding to mexiletine may be transferred to a 12 hour dosage schedule to improve convenience and compliance. If adequate suppression is achieved on a mexiletine hydrochloride dose of 300 mg or less every eight hours, the same total daily dose may be given in divided doses every 12 hours while carefully monitoring the degree of suppression of ventricular ectopy. This dose may be adjusted up to a maximum of 450 mg every 12 hours to achieve the desired response.

Transferring to Mexiletine Hydrochloride

The following dosage schedule, based on theoretical considerations rather than experimental data, is suggested for transferring patients from other Class I oral antiarrhythmic agents to mexiletine: mexiletine hydrochloride treatment may be initiated with a 200 mg dose, and titrated to response as described above, 6 to 12 hours after the last dose of quinidine sulfate, 3 to 6 hours after the last dose of procainamide, 6 to 12 hours after the last dose of disopryramide or 8 to 12 hours after the last dose of tocainide.

In patients in whom withdrawal of the previous antiarrhythmic agent is likely to produce life-threatening arrhythmias, hospitalization of the patient is recommended.

When transferring from lidocaine to mexiletine, the lidocaine infusion should be stopped when the first oral dose of mexiletine hydrochloride is administered. The infusion line should be left open until suppression of the arrhythmia appears to be satisfactorily maintained. Consideration should be given to the similarity of the adverse effects of lidocaine and mexiletine and the possibility that they may be additive.
Enalapril Maleate And H...

Enalapril Maleate And Hydrochlorothiazide

Enalapril and hydrochlorothiazide are effective treatments for hypertension. The usual dosage range of enalapril is 10 to 40 mg per day administered in a single or two divided doses; hydrochlorothiazide is effective in doses of 12.5 to 50 mg daily. The side effects (see WARNINGS) of enalapril 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 enalapril and hydrochlorothiazide will be associated with both sets of dose-independent side effects but the addition of enalapril in clinical trials blunted the hypokalemia normally seen with diuretics. 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.

Dose Titration Guided by Clinical Effect

A patient whose blood pressure is not adequately controlled with either enalapril or hydrochlorothiazide monotherapy may be given enalapril maleate and hydrochlorothiazide tablets, 5 mg/12.5 mg or enalapril maleate and hydrochlorothiazide tablets, 10 mg/25 mg. Further increases of enalapril, hydrochlorothiazide or both depend on clinical response. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. In general, patients do not require doses in excess of 20 mg of enalapril or 50 mg of hydrochlorothiazide. The daily dosage should not exceed four tablets of enalapril maleate and hydrochlorothiazide 5 mg/12.5 mg or two tablets of enalapril maleate and hydrochlorothiazide 10 mg/25 mg.

Replacement Therapy

The combination may be substituted for the titrated components.

Use in Renal Impairment

The usual regimens of therapy with enalapril maleate and hydrochlorothiazide need not be adjusted as long as the patient’s creatinine clearance is > 30 mL/min/1.73 m2 (serum creatinine approximately ≤ 3 mg/dL or 265 µmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so enalapril maleate and hydrochlorothiazide is not recommended (see WARNINGS, General, Enalapril Maleate,Anaphylactoid and Possibly Related Reactions,Anaphylactoid Reactions During Membrane Exposure).
Hydroxyurea

Hydroxyurea

Procedures for proper handling and disposal of cytotoxic drugs should be considered. Several guidelines on this subject have been published.1-4

To minimize the risk of dermal exposure, always wear impervious gloves when handling bottles containing hydroxyurea capsules. Hydroxyurea capsules should not be opened. Personnel should avoid exposure to crushed or opened capsules. If contact with crushed or opened capsules occurs, wash immediately and thoroughly. More information is available in the references listed below.

Because of the rarity of melanoma, resistant chronic myelocytic leukemia, carcinoma of the ovary, and carcinomas of the head and neck in pediatric patients, dosage regimens have not been established.

All dosage should be based on the patient’s actual or ideal weight, whichever is less. Concurrent use of hydroxyurea capsules with other myelosuppressive agents may require adjustment of dosages.

Since hydroxyurea may raise the serum uric acid level, dosage adjustment of uricosuric medication may be necessary.

Solid Tumors

Intermittent Therapy

80 mg/kg administered orally as a single dose every third day

Continuous Therapy

20 to 30 mg/kg administered orally as a single dose daily

Concomitant Therapy with Irradiation

Carcinoma of the head and neck

80 mg/kg administered orally as a single dose every third day

Administration of hydroxyurea should begin at least seven days before initiation of irradiation and continued during radiotherapy as well as indefinitely afterwards provided that the patient may be kept under adequate observation and evidences no unusual or severe reactions.

Resistant Chronic Myelocytic Leukemia

Until the intermittent therapy regimen has been evaluated, CONTINUOUS therapy (20 to 30 mg/kg administered orally as a single dose daily) is recommended.

An adequate trial period for determining the antineoplastic effectiveness of hydroxyurea is six weeks of therapy. When there is regression in tumor size or arrest in tumor growth, therapy should be continued indefinitely. Therapy should be interrupted if the white blood cell count drops below 2500/mm3, or the platelet count below 100,000/mm3. In these cases, the counts should be reevaluated after three days, and therapy resumed when the counts return to acceptable levels. Since the hematopoietic rebound is prompt, it is usually necessary to omit only a few doses. If prompt rebound has not occurred during combined hydroxyurea capsules and irradiation therapy, irradiation may also be interrupted. However, the need for postponement of irradiation has been rare; radiotherapy has usually been continued using the recommended dosage and technique. Severe anemia, if it occurs, should be corrected without interrupting hydroxyurea therapy. Because hematopoiesis may be compromised by extensive irradiation or by other antineoplastic agents, it is recommended that hydroxyurea be administered cautiously to patients who have recently received extensive radiation therapy or chemotherapy with other cytotoxic drugs.

Pain or discomfort from inflammation of the mucous membranes at the irradiated site (mucositis) is usually controlled by measures such as topical anesthetics and orally administered analgesics. If the reaction is severe, hydroxyurea therapy may be temporarily interrupted; if it is extremely severe, irradiation dosage may, in addition, be temporarily postponed. However, it has rarely been necessary to terminate these therapies.

Severe gastric distress, such as nausea, vomiting, and anorexia, resulting from combined therapy may usually be controlled by temporary interruption of hydroxyurea administration.

Renal Insufficiency

As renal excretion is a pathway of elimination, consideration should be given to decreasing the dosage of hydroxyurea capsules in patients with renal impairment (see PRECAUTIONS and CLINICAL PHARMACOLOGY). Close monitoring of hematologic parameters is advised in these patients.

Hepatic Insufficiency

There are no data that support specific guidance for dosage adjustment in patients with hepatic impairment. Close monitoring of hematologic parameters is advised in these patients.
Cimetidine

Cimetidine

Duodenal Ulcer

Active Duodenal Ulcer

Clinical studies have indicated that suppression of nocturnal acid is the most important factor in duodenal ulcer healing (see CLINICAL PHARMACOLOGY, Acid Secretion). This is supported by recent clinical trials (see Clinical Trials, Active duodenal ulcer). Therefore, there is no apparent rationale, except for familiarity with use, for treating with anything other than a once-daily at bedtime oral dosage regimen.

In a U.S. oral dose-ranging study of 400 mg at bedtime, 800 mg at bedtime and 1600 mg at bedtime, a continuous dose response relationship for ulcer healing was demonstrated.

However, 800 mg at bedtime is the dose of choice for most patients, as it provides a high healing rate (the difference between 800 mg at bedtime and 1600 mg at bedtime being small), maximal pain relief, a decreased potential for drug interactions (see PRECAUTIONS, Drug Interactions) and maximal patient convenience. Patients unhealed at four weeks, or those with persistent symptoms, have been shown to benefit from two to four weeks of continued therapy.

It has been shown that patients who both have an endoscopically demonstrated ulcer larger than 1 cm and are also heavy smokers (i.e., smoke one pack of cigarettes or more per day) are more difficult to heal. There is some evidence which suggests that more rapid healing can be achieved in this subpopulation with cimetidine 1600 mg at bedtime. While early pain relief with either 800 mg at bedtime or 1600 mg at bedtime is equivalent in all patients, 1600 mg at bedtime provides an appropriate alternative when it is important to ensure healing within four weeks for this subpopulation. Alternatively, approximately 94% of all patients will also heal in eight weeks with cimetidine 800 mg at bedtime.

Other cimetidine oral regimens in the U.S. which have been shown to be effective are: 300 mg four times daily, with meals and at bedtime, the original regimen with which U.S. physicians have the most experience, and 400 mg twice daily, in the morning and at bedtime (see Clinical Trials, Active duodenal ulcer).

Concomitant antacids should be given as needed for relief of pain. However, simultaneous administration of oral cimetidine and antacids is not recommended, since antacids have been reported to interfere with the absorption of cimetidine.

While healing with cimetidine often occurs during the first week or two, treatment should be continued for 4 to 6 weeks unless healing has been demonstrated by endoscopic examination.

Maintenance Therapy for Duodenal Ulcer

In those patients requiring maintenance therapy, the recommended adult oral dose is 400 mg at bedtime.

Active Benign Gastric Ulcer

The recommended adult oral dosage for short-term treatment of active benign gastric ulcer is 800 mg at bedtime, or 300 mg four times a day with meals and at bedtime. Controlled clinical studies were limited to six weeks of treatment (see Clinical Trials). 800 mg at bedtime is the preferred regimen for most patients based upon convenience and reduced potential for drug interactions. Symptomatic response to cimetidine dose not preclude the presence of a gastric malignancy. It is important to follow gastric ulcer patients to assure rapid progress to complete healing.

Erosive Gastroesophageal Reflux Disease (GERD)

The recommended adult oral dosage for the treatment of erosive esophagitis that has been diagnosed by endoscopy is 1600 mg daily in divided doses (800 mg twice daily or 400 mg four times daily) for 12 weeks. The use of cimetidine beyond 12 weeks has not been established.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison Syndrome)

Recommended adult oral dosage: 300 mg four times a day with meals at bedtime. In some patients it may be necessary to administer higher doses more frequently. Doses should be adjusted to individual patient needs, but should not usually exceed 2400 mg per day and should continue as long as clinically needed.

Dosage Adjustments for Patients with Impaired Renal Function

Patients with severely impaired renal function have been treated with cimetidine. However, such dosage has been very limited. On the basis of this experience the recommended dosage is 300 mg every 12 hours orally. Should the patient’s condition require, the frequency of dosing may be increased to every 8 hours or even further with caution. In severe renal failure, accumulation may occur and the lower frequency of dosing comparable with an adequate patient response should be used. When liver impairment is also present, further reductions in dosage may be necessary. Hemodialysis reduces the level of circulating cimetidine. Ideally, the dosage schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis.
Trandolapril

Trandolapril

Hypertension

The recommended initial dosage of trandolapril tablets for patients not receiving a diuretic is 1 mg once daily in non-black patients and 2 mg in black patients. Dosage should be adjusted according to the blood pressure response. Generally, dosage adjustments should be made at intervals of at least 1 week. Most patients have required dosages of 2 to 4 mg once daily. There is little clinical experience with doses above 8 mg.

Patients inadequately treated with once-daily dosing at 4 mg may be treated with twice-daily dosing. If blood pressure is not adequately controlled with trandolapril 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 trandolapril tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued two to three days prior to beginning therapy with trandolapril tablets. (See WARNINGS.) Then, if blood pressure is not controlled with trandolapril tablets alone, diuretic therapy should be resumed. If the diuretic cannot be discontinued, an initial dose of 0.5 mg trandolapril tablets should be used with careful medical supervision for several hours until blood pressure has stabilized. The dosage should subsequently be titrated (as described above) to the optimal response. (See WARNINGS and PRECAUTIONS, Drug Interactions.)

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

Dosage Adjustment in Renal Impairment or Hepatic Cirrhosis

For patients with a creatinine clearance < 30 mL/min. or with hepatic cirrhosis, the recommended starting dose, based on clinical and pharmacokinetic data, is 0.5 mg daily. Patients should subsequently have their dosage titrated (as described above) to the optimal response.
Levofloxacin

Levofloxacin

2.1 Dosage in Adult Patients With Normal Renal Function

The usual dose of levofloxacin tablets is 250 mg, 500 mg, or 750 mg administered orally every 24 hours, as indicated by infection and described in Table 1.

These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance < 50 mL/min, adjustments to the dosing regimen are required [see Dosage and Administration (2.3)].
Table 1: Dosage in Adult Patients With Normal Renal Function (Creatinine Clearance ≥ 50 mL/min) * Due to the designated pathogens [ see Indications and Usage (1)]. † Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. ‡ Due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [ see Indications and Usage (1.2)]. § Due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [ see Indications and Usage (1.3)]. ¶ This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia. # This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; and for AP due to E. coli. Þ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [ see Clinical Studies (14.9)]. ß The safety of levofloxacin tablets in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [ see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged levofloxacin tablet therapy should only be used when the benefit outweighs the risk. à Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Higher doses of levofloxacin tablets typically used for treatment of pneumonia can be used for treatment of plague, if clinically indicated. Type of Infection* Dosed Every 24 Hours Duration (Days)† Nosocomial Pneumonia 750 mg 7 to 14 Community Acquired Pneumonia‡ 500 mg 7 to 14 Community Acquired Pneumonia§ 750 mg 5 Acute Bacterial Sinusitis 750 mg 5 500 mg 10 to 14 Acute Bacterial Exacerbation of Chronic Bronchitis 500 mg 7 Complicated Skin and Skin Structure Infections (SSSI) 750 mg 7 to 14 Uncomplicated SSSI 500 mg 7 to 10 Chronic Bacterial Prostatitis 500 mg 28 Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)¶ 750 mg 5 Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)# 250 mg 10 Uncomplicated Urinary Tract Infection 250 mg 3 Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kgÞ,ß 500 mg 60ß Pediatric patients < 50 kg and ≥ 6 months of ageÞ,ß see Table 2 below(2.2) 60ß Plague, adult and pediatric patients > 50 kgà 500 mg 10 to 14 Pediatric patients < 50 kg and ≥ 6 months of age see Table 2 below 10 to 14
2.2 Dosage in Pediatric Patients

The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.
Table 2: Dosage in Pediatric Patients ≥ 6 Months of Age * Due to Bacillus anthracis [ see Indications and Usage (1.13)] and Yersinia pestis [see Indications and Usage ( 1.14)]. † Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. ‡ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [ see Clinical Studies (14.9)]. § The safety of levofloxacin tablets in pediatric patients for durations of therapy beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [ see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged levofloxacin tablet therapy should only be used when the benefit outweighs the risk. ¶ Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Type of Infection* Dose Freq. Once Every Duration† Inhalational Anthrax (post-exposure)‡,§ Pediatric patients > 50 kg 500 mg 24 hr 60 days§ Pediatric patients < 50 kg and ≥ 6 months of age 8 mg/kg (not to exceed 250 mg per dose) 12 hr 60 days§ Plague¶ Pediatric patients > 50 kg 500 mg 24 hr 10 to 14 days Pediatric patients < 50 kg and ≥ 6 months of age 8 mg/kg(not to exceed 250 mg per dose) 12 hr 10 to 14 days
2.3 Dosage Adjustment in Adults With Renal Impairment

Administer levofloxacin tablets with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.

No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.

In patients with impaired renal function (creatinine clearance < 50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance [see Use in Specific Populations (8.6)].

Table 3 shows how to adjust dose based on creatinine clearance.
Table 3: Dosage Adjustment in Adult Patients With Renal Impairment (Creatinine Clearance < 50 mL/min) Dosage in Normal Renal Function Every 24 Hours Creatinine Clearance 20 to 49 mL/min Creatinine Clearance 10 to 19 mL/min Hemodialysis or Chronic Ambulatory Peritoneal Dialysis (CAPD) 750 mg 750 mg every 48 hours 750 mg initial dose, then 500 mg every 48 hours 750 mg initial dose, then 500 mg every 48 hours 500 mg 500 mg initial dose, then 250 mg every 24 hours 500 mg initial dose, then 250 mg every 48 hours 500 mg initial dose, then 250 mg every 48 hours 250 mg No dosage adjustment required 250 mg every 48 hours. If treating uncomplicated UTI, then no dosage adjustment is required No information on dosing adjustment is available
2.4 Drug Interaction With Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

Levofloxacin Tablets

Levofloxacin tablets should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine chewable/buffered tablets or the pediatric powder for oral solution [see Drug Interactions (7.1) and Patient Counseling Information (17.2)].

2.5 Administration Instructions

Food and Levofloxacin Tablets

Levofloxacin tablets can be administered without regard to food.

Hydration for Patients Receiving Levofloxacin Tablets

Adequate hydration of patients receiving oral levofloxacin should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones [see Adverse Reactions (6.1) and Patient Counseling Information (17.2)].
Lansoprazole

Lansoprazole

Lansoprazole delayed-release capsules are available in 15 mg and 30 mg strengths. Directions for use specific to the route and available methods of administration for this dosage form is presented below. Lansoprazole delayed-release capsules should be taken before eating. Lansoprazole delayed-release capsules SHOULD NOT BE CRUSHED OR CHEWED. In the clinical trials, antacids were used concomitantly with lansoprazole.

2.1 Recommended Dose
* Please refer to amoxicillin and clarithromycin full prescribing information for CONTRAINDICATIONS and WARNINGS, and for information regarding dosing in elderly and renally-impaired patients. † Controlled studies did not extend beyond indicated duration. ‡ For patients who do not heal with lansoprazole delayed-release capsules for 8 weeks (5 to 10%), it may be helpful to give an additional 8 weeks of treatment. If there is a recurrence of erosive esophagitis, an additional 8 week course of lansoprazole delayed-release capsules may be considered. § The lansoprazole dose was increased (up to 30 mg twice daily) in some pediatric patients after 2 or more weeks of treatment if they remained symptomatic. For pediatric patients unable to swallow an intact capsule please see Administration Options. ¶ Controlled studies did not extend beyond 12 months. # Varies with individual patient. Recommended adult starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Dosages up to 90 mg twice daily have been administered. Daily dose of greater than 120 mg should be administered in divided doses. Some patients with Zollinger-Ellison syndrome have been treated continuously with lansoprazole for more than 4 years. Indication Recommended Dose Frequency Duodenal Ulcers Short-Term Treatment 15 mg Once daily for 4 weeks Maintenance of Healed 15 mg Once daily H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence* Triple Therapy: Lansoprazole Delayed-Release Capsules 30 mg Twice daily (q12h) for 10 or 14 days Amoxicillin 1 gram Twice daily (q12h) for 10 or 14 days Clarithromycin 500 mg Twice daily (q12h) for 10 or 14 days Dual Therapy: Lansoprazole Delayed-Release Capsules 30 mg Three times daily (q8h) for 14 days Amoxicillin 1 gram Three times daily (q8h) for 14 days Benign Gastric Ulcer Short-Term Treatment 30 mg Once daily for up to 8 weeks NSAID-associated Gastric Ulcer Healing 30 mg Once daily for 8 weeks† Risk Reduction 15 mg Once daily for up to 12 weeks† Gastroesophageal Reflux Disease (GERD) Short-Term Treatment of Symptomatic GERD 15 mg Once daily for up to 8 weeks Short-Term Treatment of Erosive Esophagitis 30 mg Once daily for up to 8 weeks‡ Pediatric (1 to 11 years of age) Short-Term Treatment of Symptomatic GERD and Short-Term Treatment of Erosive Esophagitis ≤ 30 kg 15 mg Once daily for up to 12 weeks§ > 30 kg 30 mg Once daily for up to 12 weeks§ (12 to 17 years of age) Short-Term Treatment of Symptomatic GERD Nonerosive GERD 15 mg Once daily for up to 8 weeks Erosive Esophagitis 30 mg Once daily for up to 8 weeks Maintenance of Healing of Erosive Esophagitis 15 mg Once daily¶ Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome 60 mg Once daily#
Patients should be instructed that if a dose is missed, it should be taken as soon as possible. However, if the next scheduled dose is due, the patient should not take the missed dose, and should be instructed to take the next dose on time. Patients should be instructed not to take 2 doses at one time to make up for a missed dose.

2.2 Special Populations

Renal impairment patients and geriatric patients do not require dosage adjustment. However, consider dose adjustment in patients with severe liver impairment [see Use in Specific Populations (8.5, 8.6 and 8.7)].

2.3 Important Administration Information

Administration Options

Lansoprazole Delayed-Release Capsules - Oral Administration
Lansoprazole delayed-release capsules should be swallowed whole. Alternatively, for patients who have difficulty swallowing capsules, lansoprazole delayed-release capsules can be opened and administered as follows: Open capsule. Sprinkle intact granules on one tablespoon of either applesauce, ENSURE® pudding, cottage cheese, yogurt or strained pears. Swallow immediately. Lansoprazole delayed-release capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice and administered as follows: Open capsule. Sprinkle intact granules into a small volume of either apple juice, orange juice or tomato juice (60 mL — approximately 2 ounces). Mix briefly. Swallow immediately. To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately.
Lansoprazole Delayed-Release Capsules - Nasogastric Tube (≥ 16 French) Administration
For patients who have a nasogastric tube in place, lansoprazole delayed-release capsules can be administered as follows: Open capsule. Mix intact granules into 40 mL of apple juice. DO NOT USE OTHER LIQUIDS. Inject through the nasogastric tube into the stomach. Flush with additional apple juice to clear the tube.
USE IN OTHER FOODS AND LIQUIDS HAS NOT BEEN STUDIED CLINICALLY AND IS THEREFORE NOT RECOMMENDED.
Cetirizine Hydrochlorid...

Cetirizine Hydrochloride

adults and children 6 years and over: one 10 mg tablet once daily; do not take more than one 10 mg tablet in 24 hours. A 5 mg product may be appropriate for less severe symptoms.

adults 65 years and over: ask a doctor

children under 6 years of age: ask a doctor

consumers with liver or kidney disease: ask a doctor
Ergocalciferol

Ergocalciferol

THE RANGE BETWEEN THERAPEUTIC AND TOXIC DOSES IS NARROW.
Vitamin D Resistant Rickets:
12,000 to 500,000 USP Units daily.
Hypoparathyroidism:
50,000 to 200,000 USP Units daily concomitantly with calcium lactate 4 g, six times per day.

DOSAGE MUST BE INDIVIDUALIZED UNDER CLOSE MEDICAL SUPERVISION.

Calcium intake should be adequate. Blood calcium and phosphorus determinations must be made every 2 weeks or more frequently if necessary. X-rays of the bones should be taken every month until condition is corrected and stabilized.
Bethanechol Chloride

Bethanechol Chloride

Dosage must be individualized, depending on the type and severity of the condition to be treated.

Preferably give the drug when the stomach is empty. If taken soon after eating, nausea and vomiting may occur.

The usual adult oral dose ranges from 10 to 50 mg three or four times a day. The minimum effective dose is determined by giving 5 to 10 mg initially and repeating the same amount at hourly intervals until satisfactory response occurs, or until a maximum of 50 mg has been given. The effects of the drug sometimes appear within 30 minutes and are usually maximal within 60 to 90 minutes. The drug effects persist for about one hour.

If necessary, the effects of the drug can be abolished promptly by atropine (see OVERDOSAGE).
Buspirone Hydrochloride...

Buspirone Hydrochloride

The recommended initial dose is 15 mg daily (7.5 mg b.i.d.). To achieve an optimal therapeutic response, at intervals of 2 to 3 days the dosage may be increased 5 mg per day, as needed. The maximum daily dosage should not exceed 60 mg per day. In clinical trials allowing dose titration, divided doses of 20 mg to 30 mg per day were commonly employed.

The bioavailability of buspirone is increased when given with food as compared to the fasted state (see CLINICAL PHARMACOLOGY). Consequently, patients should take buspirone in a consistent manner with regard to the timing of dosing; either always with or always without food.

When buspirone is to be given with a potent inhibitor of CYP3A4 the dosage recommendations described in the PRECAUTIONS: Drug Interactionssection should be followed.
Nicardipine Hydrochlori...

Nicardipine Hydrochloride

Angina

The dose should be individually titrated for each patient beginning with 20 mg three times daily. Doses in the range of 20 to 40 mg three times a day have been shown to be effective. At least three days should be allowed before increasing the nicardipine hydrochloride dose to ensure achievement of steady state plasma drug concentrations.

Concomitant Use With Other Antianginal Agents
Sublingual NTG - may be taken as required to abort acute anginal attacks during nicardipine therapy. Prophylactic Nitrate Therapy - nicardipine may be safely coadministered with short- and long-acting nitrates Beta-blockers - (See PRECAUTIONS, Drug Interactions.)
Hypertension

The dose of nicardipine hydrochloride should be individually adjusted according to the blood pressure response beginning with 20 mg three times daily. The effective doses in clinical trials have ranged from 20 mg to 40 mg three times daily. The maximum blood pressure lowering effect occurs approximately 1 to 2 hours after dosing. To assess the adequacy of blood pressure response, the blood pressure should be measured at trough (8 hours after dosing). Because of the prominent peak effects of nicardipine, blood pressure should be measured 1 to 2 hours after dosing, particularly during initiation of therapy. (See PRECAUTIONS: Blood Pressure, INDICATIONS AND USAGE, CLINICAL PHARMACOLOGY, Effects in Hypertension.) At least three days should be allowed before increasing the nicardipine dose to ensure achievement of steady state plasma drug concentrations.

Concomitant use with other Antihypertensive Agents, Beta-blockers.

(See PRECAUTIONS, Drug Interactions.)

Special Patient Population

Renal Insufficiency

Although there is no evidence that nicardipine impairs renal function, careful dose titration beginning with 20 mg TID is advised. (See PRECAUTIONS)

Hepatic Insufficiency

Nicardipine should be administered cautiously in patients with severely impaired hepatic function. A suggested starting dose of 20 mg twice a day is advised with individual titration based on clinical findings maintaining the twice a day schedule. (See PRECAUTIONS.)

Congestive Heart Failure

Caution is advised when titrating nicardipine dosage in patients with congestive heart failure. (See WARNINGS.)
Pramipexole Dihydrochlo...

Pramipexole Dihydrochloride

2.1 General Dosing Considerations

Pramipexole dihydrochloride tablets are taken orally, with or without food.

If a significant interruption in therapy with pramipexole dihydrochloride tablets has occurred, re-titration of therapy may be warranted.

2.2 Parkinson's Disease

In all clinical studies, dosage was initiated at a subtherapeutic level to avoid intolerable adverse effects and orthostatic hypotension. Pramipexole dihydrochloride tablets should be titrated gradually in all patients. The dose should be increased to achieve a maximum therapeutic effect, balanced against the principal side effects of dyskinesia, hallucinations, somnolence, and dry mouth.

Dosing in Patients with Normal Renal Function

Initial Treatment Doses should be increased gradually from a starting dose of 0.375 mg/day given in three divided doses and should not be increased more frequently than every 5 to 7 days. A suggested ascending dosage schedule that was used in clinical studies is shown in the following table:
Table 1 Ascending Dosage Schedule of Pramipexole Dihydrochloride Tablets for Parkinson's Disease Week Dosage (mg) Total Daily Dose (mg) 1 0.125 TID 0.375 2 0.25 TID 0.75 3 0.5 TID 1.50 4 0.75 TID 2.25 5 1 TID 3.0 6 1.25 TID 3.75 7 1.5 TID 4.50
Maintenance Treatment Pramipexole dihydrochloride tablets were effective and well tolerated over a dosage range of 1.5 to 4.5 mg/day administered in equally divided doses three times per day with or without concomitant levodopa (approximately 800 mg/day).

In a fixed-dose study in early Parkinson's disease patients, doses of 3 mg, 4.5 mg, and 6 mg per day of pramipexole dihydrochloride tablets were not shown to provide any significant benefit beyond that achieved at a daily dose of 1.5 mg/day. However, in the same fixed-dose study, the following adverse events were dose related: postural hypotension, nausea, constipation, somnolence, and amnesia. The frequency of these events was generally 2-fold greater than placebo for pramipexole doses greater than 3 mg/day. The incidence of somnolence reported with pramipexole at a dose of 1.5 mg/day was comparable to placebo.

When pramipexole dihydrochloride tablets are used in combination with levodopa, a reduction of the levodopa dosage should be considered. In a controlled study in advanced Parkinson's disease, the dosage of levodopa was reduced by an average of 27% from baseline.

Dosing in Patients with Renal Impairment
Table 2 Dosing of Pramipexole Dihydrochloride Tablets in Parkinson’s Disease Patients with Renal Impairment Renal Status Starting Dose (mg) Maximum Dose (mg) Normal to mild impairment(creatinine Cl > 50 mL/min) 0.125 TID 1.5 TID Moderate impairment(creatinine Cl = 30 to 50 mL/min) 0.125 BID 0.75 TID Severe impairment(creatinine Cl = 15 to <30 mL/min) 0.125 QD 1.5 QD Very severe impairment(creatinine Cl < 15 mL/minand hemodialysis patients) The use of pramipexole dihydrochloride tablets has not been adequately studied in this group of patients.
Discontinuation of Treatment

Pramipexole dihydrochloride tablets should be tapered off at a rate of 0.75 mg per day until the daily dose has been reduced to 0.75 mg. Thereafter, the dose should be reduced by 0.375 mg per day. In some studies, however, abrupt discontinuation was uneventful.
Famotidine

Famotidine

Duodenal Ulcer

Acute Therapy: The recommended adult oral dosage for active duodenal ulcer is 40 mg once a day at bedtime. Most patients heal within 4 weeks; there is rarely reason to use famotidine at full dosage for longer than 6 to 8 weeks. A regimen of 20 mg b.i.d. is also effective.

Maintenance Therapy: The recommended adult oral dose is 20 mg once a day at bedtime.

Benign Gastric Ulcer

Acute Therapy: The recommended adult oral dosage for active benign gastric ulcer is 40 mg once a day at bedtime.

Gastroesophageal Reflux Disease (GERD)

The recommended oral dosage for treatment of adult patients with symptoms of GERD is 20 mg b.i.d. for up to 6 weeks. The recommended oral dosage for the treatment of adult patients with esophagitis including erosions and ulcerations and accompanying symptoms due to GERD is 20 or 40 mg b.i.d. for up to 12 weeks (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical Studies).

Dosage for Pediatric Patients <1 year of age Gastroesophageal Reflux Disease (GERD)

See PRECAUTIONS , Pediatric Patients <1 year of age.

The studies described in PRECAUTIONS , Pediatric Patients <1 year of age suggest the following starting doses in pediatric patients <1 year of age: Gastroesophageal Reflux Disease (GERD) - 0.5 mg/kg/dose of famotidine oral suspension for the treatment of GERD for up to 8 weeks once daily in patients <3 months of age and 0.5 mg/kg/dose twice daily in patients 3 months to <1 year of age. Patients should also be receiving conservative measures (e.g., thickened feedings). The use of intravenous famotidine in pediatric patients <1 year of age with GERD has not been adequately studied.

Dosage for Pediatric Patients 1-16 years of age

See PRECAUTIONS , Pediatric Patients 1-16 years of age .

The studies described in PRECAUTIONS , Pediatric Patients 1-16 years of age suggest the following starting doses in pediatric patients 1-16 years of age:

Peptic ulcer — 0.5 mg/kg/day p.o. at bedtime or divided b.i.d. up to 40 mg/day.

Gastroesophageal Reflux Disease with or without esophagitis including erosions and ulcerations — 1.0 mg/kg/day p.o. divided b.i.d. up to 40 mg b.i.d.

While published uncontrolled studies suggest effectiveness of famotidine in the treatment of gastroesophageal reflux disease and peptic ulcer, data in pediatric patients are insufficient to establish percent response with dose and duration of therapy. Therefore, treatment duration (initially based on adult duration recommendations) and dose should be individualized based on clinical response and/or pH determination (gastric or esophageal) and endoscopy. Published uncontrolled clinical studies in pediatric patients 1-16 years of age have employed doses up to 1 mg/kg/day for peptic ulcer and 2 mg/kg/day for GERD with or without esophagitis including erosions and ulcerations.

Pathological Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome, Multiple Endocrine Adenomas)

The dosage of famotidine in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult oral starting dose for pathological hypersecretory conditions is 20 mg q 6 h. In some patients, a higher starting dose may be required. Doses should be adjusted to individual patient needs and should continue as long as clinically indicated. Doses up to 160 mg q 6 h have been administered to some adult patients with severe Zollinger-Ellison Syndrome.

Concomitant Use of Antacids

Antacids may be given concomitantly if needed.

Dosage Adjustment for Patients with Moderate or Severe Renal Insufficiency

In adult patients with moderate (creatinine clearance <50 mL/min) or severe (creatinine clearance <10 mL/min) renal insufficiency, the elimination half-life of famotidine is increased. For patients with severe renal insufficiency, it may exceed 20 hours, reaching approximately 24 hours in anuric patients. Since CNS adverse effects have been reported in patients with moderate and severe renal insufficiency, to avoid excess accumulation of the drug in patients with moderate or severe renal insufficiency, the dose of famotidine may be reduced to half the dose or the dosing interval may be prolonged to 36-48 hours as indicated by the patient's clinical response.

Based on the comparison of pharmacokinetic parameters for famotidine in adults and pediatric patients, dosage adjustment in pediatric patients with moderate or severe renal insufficiency should be considered.
Ropinirole Hydrochlorid...

Ropinirole Hydrochloride

2.1 General Dosing Considerations
Ropinirole extended-release tablets are taken once daily, with or without food. Taking ropinirole extended-release tablets with food may reduce the occurrence of nausea; this has not been established in controlled clinical trials [see Clinical Pharmacology (12.3)]. Tablets must be swallowed whole and must not be chewed, crushed, or divided. If a significant interruption in therapy with ropinirole extended-release tablets has occurred, retitration of therapy may be warranted.
2.2 Dosing for Parkinson’s Disease

The starting dose is 2 mg taken once daily for 1 to 2 weeks, followed by increases of 2 mg/day at 1-week or longer intervals as appropriate, depending on therapeutic response and tolerability, up to a maximally recommended dose of 24 mg/day.

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

When ropinirole extended-release tablets are administered as adjunct therapy to L-dopa, the concurrent dose of L-dopa may be decreased gradually as tolerated. In the placebo-controlled advanced Parkinson's disease study, the L-dopa dose was reduced once patients reached a dose of ropinirole extended-release tablets of 8 mg/day. Overall, L-dopa dose reduction was sustained in 93% of patients treated with ropinirole extended-release tablets and in 72% of patients on placebo. On average the L-dopa dose was reduced by 34% in patients treated with ropinirole extended-release tablets [see Clinical Studies (14)]. Ropinirole extended-release tablets should be discontinued gradually over a 7–day period.

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

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

Sildenafil

2.1 Sildenafil Tablets

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

In the clinical trial no greater efficacy was achieved with the use of higher doses. Treatment with doses higher than 20 mg TID is not recommended.
Irbesartan And Hydrochl...

Irbesartan And Hydrochlorothiazide

2.1 General Considerations

The side effects of irbesartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter [see Adverse Reactions (6)].

Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.

Irbesartan and hydrochlorothiazide tablets USP may be administered with or without food.

Irbesartan and hydrochlorothiazide tablets USP may be administered with other antihypertensive agents.

Renal impairment. The usual regimens of therapy with irbesartan and hydrochlorothiazide tablets USP may be followed as long as the patient’s creatinine clearance is > 30 mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so irbesartan and hydrochlorothiazide tablets USP are not recommended.

Hepatic impairment. No dosage adjustment is necessary in patients with hepatic impairment.

2.2 Add-On Therapy

In patients not controlled on monotherapy with irbesartan or hydrochlorothiazide, the recommended doses of irbesartan and hydrochlorothiazide tablets USP, in order of increasing mean effect, are (irbesartan-hydrochlorothiazide) 150/12.5 mg, 300/12.5 mg, and 300/25 mg. The largest incremental effect will likely be in the transition from monotherapy to 150/12.5 mg [see Clinical Studies (14.2)].

2.3 Replacement Therapy

Irbesartan and hydrochlorothiazide tablets USP may be substituted for the titrated components.

2.4 Initial Therapy

The usual starting dose is irbesartan and hydrochlorothiazide tablets USP 150/12.5 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 300/25 mg tablet once daily as needed to control blood pressure [see Clinical Studies (14.2)]. Irbesartan and hydrochlorothiazide tablets USP are not recommended as initial therapy in patients with intravascular volume depletion [see Warnings and Precautions (5.2)].
Buprenorphine Hcl And N...

Buprenorphine Hcl And Naloxone Hcl

Buprenorphine HCl and naloxone HCl sublingual tablets are administered sublingually as a single daily dose. Buprenorphine HCl and naloxone HCl sublingual tablets should be used in patients who have been initially inducted using buprenorphine sublingual tablets.

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

2.1 Maintenance
Buprenorphine HCl and naloxone HCl sublingual tablets are indicated for maintenance treatment. The recommended target dosage of buprenorphine HCl and naloxone HCl sublingual tablets are 16 mg/4 mg buprenorphine/naloxone/day as a single daily dose. The dosage of buprenorphine HCl and naloxone HCl sublingual tablets should be progressively adjusted in increments/decrements of 2 mg/0.5 mg or 4 mg/1 mg buprenorphine/naloxone to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms. The maintenance dose of buprenorphine HCl and naloxone HCl sublingual tablets is generally in the range of 4 mg/1 mg buprenorphine/naloxone to 24 mg/6 mg buprenorphine/naloxone per day depending on the individual patient. Dosages higher than this have not been demonstrated to provide any clinical advantage.
2.2 Method of Administration

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

Proper administration technique should be demonstrated to the patient.

2.3 Clinical Supervision

Treatment should be initiated with supervised administration, progressing to unsupervised administration as the patient’s clinical stability permits. Buprenorphine HCl and naloxone HCl sublingual tablets are subject to diversion and abuse. When determining the prescription quantity for unsupervised administration, consider the patient’s level of stability, the security of his or her home situation, and other factors likely to affect the ability to manage supplies of take-home medication.

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

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

2.4 Unstable Patients

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

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

2.5 Stopping Treatment

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

2.6 Switching between Buprenorphine and Naloxone Sublingual Film and Buprenorphine HCl and Naloxone HCl Sublingual Tablets

Patients being switched between buprenorphine HCl and naloxone HCl sublingual tablets and buprenorphine and naloxone sublingual film should be started on the same dosage as the previously administered product. However, dosage adjustments may be necessary when switching between products. Because of the potentially greater relative bioavailability of buprenorphine and naloxone sublingual film compared to buprenorphine HCl and naloxone HCl sublingual tablets, patients switching from buprenorphine HCl and naloxone HCl sublingual tablets to buprenorphine and naloxone sublingual film should be monitored for over-medication. Those switching from buprenorphine and naloxone sublingual film to buprenorphine HCl and naloxone HCl sublingual tablets should be monitored for withdrawal or other indications of underdosing. In clinical studies, pharmacokinetics of buprenorphine and naloxone sublingual film was similar to the respective dosage strengths of buprenorphine HCl and naloxone HCl sublingual tablets, although not all doses and dose combinations met bioequivalence criteria.
Naproxen

Naproxen

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

After observing the response to initial therapy with naproxen tablets, USP, the dose and frequency should be adjusted to suit an individual patient’s needs.

Different dose strengths and formulations (i.e., tablets, suspension) of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation.

Although naproxen tablets, naproxen suspension, naproxen delayed-release tablets, and naproxen sodium tablets all circulate in the plasma as naproxen, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 1 hour in patients taking naproxen.

The recommended strategy for initiating therapy is to choose a formulation and a starting dose likely to be effective for the patient and then adjust the dosage based on observation of benefit and/or adverse events. A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see WARNINGS and PRECAUTIONS).

Geriatric Patients

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Patients With Moderate to Severe Renal Impairment

Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 mL/min) (see WARNINGS: Renal Effects).

Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis
Naproxen Tablets, USP 250 mg twice daily or 375 mg twice daily or 500 mg twice daily
During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.

In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk. The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response (see CLINICAL PHARMACOLOGY).

Acute Gout

The recommended starting dose is 750 mg of naproxen tablets, USP followed by 250 mg every 8 hours until the attack has subsided.
Lamivudine And Zidovudi...

Lamivudine And Zidovudine

2.1 Adults and Adolescents Weighing ≥ 30 kg

The recommended oral dose of lamivudine and zidovudine tablets USP in HIV-1-infected adults and adolescents weighing greater than or equal to 30 kg is 1 tablet (containing 150 mg of lamivudine and 300 mg of zidovudine) twice daily.

2.2 Pediatric Patients

The recommended oral dosage of scored lamivudine and zidovudine tablets USP for pediatric patients who weigh greater than or equal to 30 kg and for whom a solid oral dosage form is appropriate is 1 tablet administered twice daily.

Before prescribing lamivudine and zidovudine tablets USP, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a lamivudine and zidovudine tablet USP, the liquid oral formulations should be prescribed: EPIVIR® (lamivudine) Oral Solution and RETROVIR® (zidovudine) Syrup.

2.3 Patients Requiring Dosage Adjustment

Because lamivudine and zidovudine tablets USP are a fixed-dose combination tablet, they should not be prescribed for pediatric patients weighing less than 30 kg or patients requiring dosage adjustment, such as those with reduced renal function (creatinine clearance less than 50 mL/min), patients with hepatic impairment, or patients experiencing dose-limiting adverse reactions. Liquid and solid oral formulations of the individual components of lamivudine and zidovudine tablets USP are available for these populations.
Guaifenesin

Guaifenesin

do not exceed 6 doses in 24 hours take with a full glass of water adults and children 12 years of age and over 1 to 2 tablets every4 hours children 6 to under 12 yearsof age
½ to 1 tablet every

4 hours
children under 6 years of age consult a physician
Naproxen Delayed Releas...

Naproxen Delayed Release

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

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

Different dose strengths and formulations (ie, tablets, suspension) of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation.

Although all naproxen-containing products circulate in the plasma as naproxen, they have pharmacokinetic differences that may affect onset of action. Because naproxen delayed-release tablets dissolves in the small intestine rather than in the stomach, the absorption of the drug is delayed compared to the other naproxen formulations (see CLINICAL PHARMACOLOGY).

The recommended strategy for initiating therapy is to choose a formulation and a starting dose likely to be effective for the patient and then adjust the dosage based on observation of benefit and/or adverse events. A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see WARNINGS and PRECAUTIONS).

Geriatric Patients

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Patients With Moderate to Severe Renal Impairment

Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 mL/min) (see WARNINGS: Renal Effects).

Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis
Naproxen Delayed-release Tablets 375 mg or 500 mg twice dailytwice daily
To maintain the integrity of the enteric coating, the naproxen delayed-release tablets should not be broken, crushed, or chewed during ingestion.

During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.

In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk. The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response (see CLINICAL PHARMACOLOGY).

Juvenile Arthritis

The recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses (ie, 5 mg/kg given twice a day). Naproxen delayed-release tablets are not well suited to this dosage so use of naproxen oral suspension is recommended for this indication.

Management of Pain, Primary Dysmenorrhea, and Acute Tendonitis and Bursitis

Naproxen delayed-release tablets are not recommended for initial treatment of acute pain because absorption of naproxen is delayed compared to other naproxen-containing products (see CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE).

Acute Gout

Naproxen delayed-release tablets are not recommended because of the delay in absorption (see CLINICAL PHARMACOLOGY)
Acyclovir

Acyclovir

Acute Treatment of Herpes Zoster

800 mg every 4 hours orally, 5 times daily for 7 to 10 days.

Genital Herpes

Treatment of Initial Genital Herpes

200 mg every 4 hours, 5 times daily for 10 days.

Chronic Suppressive Therapy for Recurrent Disease

400 mg 2 times daily for up to 12 months, followed by re-evaluation. Alternative regimens have included doses ranging from 200 mg 3 times daily to 200 mg 5 times daily.

The frequency and severity of episodes of untreated genital herpes may change over time. After 1 year of therapy, the frequency and severity of the patient’s genital herpes infection should be re-evaluated to assess the need for continuation of therapy with acyclovir.

Intermittent Therapy

200 mg every 4 hours, 5 times daily for 5 days. Therapy should be initiated at the earliest sign or symptom (prodrome) of recurrence.

Treatment of Chickenpox

Children (2 Years of age and Older)

20 mg/kg per dose orally 4 times daily (80 mg/kg/day) for 5 days. Children over 40 kg should receive the adult dose for chickenpox.

Adults and Children Over 40 kg

800 mg 4 times daily for 5 days.

Intravenous acyclovir is indicated for the treatment of varicella-zoster infections in immunocompromised patients.

When therapy is indicated, it should be initiated at the earliest sign or symptom of chickenpox. There is no information about the efficacy of therapy initiated more than 24 hours after onset of signs and symptoms.

Patients With Acute or Chronic Renal Impairment

In patients with renal impairment, the dose of acyclovir capsules and tablets should be modified as shown in Table 3:
Table 3: Dosage Modification for Renal Impairment Normal Dosage Regimen Creatinine Clearance (mL/min/1.73 m2) Adjusted Dosage Regimen Dose (mg) Dosing Interval 200 mg every 4 hours > 10 200 every 4 hours, 5x daily 0 to 10 200 every 12 hours 400 mg every 12 hours > 10 400 every 12 hours 0 to 10 200 every 12 hours 800 mg every 4 hours > 25 800 every 4 hours, 5x daily 10 to 25 800 every 8 hours 0 to 10 800 every 12 hours
Hemodialysis

For patients who require hemodialysis, the mean plasma half-life of acyclovir during hemodialysis is approximately 5 hours. This results in a 60% decrease in plasma concentrations following a 6 hour dialysis period. Therefore, the patient’s dosing schedule should be adjusted so that an additional dose is administered after each dialysis.

Peritoneal Dialysis

No supplemental dose appears to be necessary after adjustment of the dosing interval.

Bioequivalence of Dosage Forms

Acyclovir suspension was shown to be bioequivalent to acyclovir capsules (n = 20) and 1 acyclovir 800 mg tablet was shown to be bioequivalent to 4 acyclovir 200 mg capsules (n = 24).
Acebutolol Hydrochlorid...

Acebutolol Hydrochloride

HYPERTENSION: The initial dosage of acebutolol in uncomplicated mild-to-moderate hypertension is 400 mg. This can be given as a single daily dose, but in occasional patients twice daily dosing may be required for adequate 24-hour blood-pressure control. An optimal response is usually achieved with dosages of 400 to 800 mg per day, although some patients have been maintained on as little as 200 mg per day. Patients with more severe hypertension or who have demonstrated inadequate control may respond to a total of 1200 mg daily (administered b.i.d.), or to the addition of a second antihypertensive agent. Beta-1 selectivity diminishes as dosage is increased.

VENTRICULAR ARRHYTHMIA: The usual initial dose of acebutolol is 400 mg daily given as 200 mg b.i.d. Dosage should be increased gradually until an optimal clinical response is obtained, generally at 600 to 1200 mg per day. If treatment is to be discontinued, the dosage should be reduced gradually over a period of about two weeks.

USE IN OLDER PATIENTS: Older patients have an approximately 2-fold increase in bioavailability and may require lower maintenance doses. Doses above 800 mg/day should be avoided in the elderly.
Benefit Dream Screen Br...

Benefit Dream Screen Broad Spectrum Spf 45 Sunscreen For Face

Dosage should be individualized with careful monitoring of patient response.

Oral Administration

The usual total daily dosage of bumetanide is 0.5 to 2 mg and in most patients is given as a single dose.

If the diuretic response to an initial dose of bumetanide is not adequate, in view of its rapid onset and short duration of action, a second or third dose may be given at 4- to 5-hour intervals up to a maximum daily dose of 10 mg. An intermittent dose schedule, whereby bumetanide is given on alternate days or for 3 to 4 days with rest periods of 1 to 2 days in between, is recommended as the safest and most effective method for the continued control of edema. In patients with hepatic failure, the dosage should be kept to a minimum, and if necessary, dosage increased very carefully. Because cross-sensitivity with furosemide has rarely been observed, bumetanide can be substituted at approximately a 1:40 ratio of bumetanide to furosemide in patients allergic to furosemide.

Parenteral Administration

Bumetanide Injection may be administered parenterally (IV or IM) to patients in whom gastrointestinal absorption may be impaired or in whom oral administration is not practical.

Parenteral treatment should be terminated and oral treatment instituted as soon as possible.
Chlordiazepoxide Hydroc...

Chlordiazepoxide Hydrochlorideclidinium Bromide

Because of the varied individual responses to tranquilizers and anticholinergics, the optimum dosage of Chlordiazepoxide Hydrochloride/Clidinium Bromide varies with the diagnosis and response of the individual patient. The dosage therefore should be individualized for maximum beneficial effects. The usual maintenance dose is 1 or 2 capsules, 3 or 4 times a day administered before meals and at bedtime.

Geriatric Use

Geriatric Dosing

Dosage should be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion. The initial dose should not exceed 2 Chlordiazepoxide Hydrochloride/Clidinium Bromide capsules per day, to be increased gradually as needed and tolerated.
Buspirone Hydrochloride...

Buspirone Hydrochloride

The recommended initial dose is 15 mg daily (7.5 mg b.i.d.). To achieve an optimal therapeutic response, at intervals of 2 to 3 days the dosage may be increased 5 mg per day, as needed. The maximum daily dosage should not exceed 60 mg per day. In clinical trials allowing dose titration, divided doses of 20 to 30 mg per day were commonly employed.

The bioavailability of buspirone is increased when given with food as compared to the fasted state (see CLINICAL PHARMACOLOGY). Consequently, patients should take buspirone in a consistent manner with regard to the timing of dosing; either always with or always without food.

When buspirone is to be given with a potent inhibitor of CYP3A4, the dosage recommendations described in the PRECAUTIONS, Drug Interactions section should be followed.
Pentoxifylline

Pentoxifylline

The usual dosage of Pentoxifylline Extended-release Tablet form is one tablet (400 mg) three times a day with meals.

While the effect of Pentoxifylline may be seen within 2 to 4 weeks, it is recommended that treatment be continued for at least 8 weeks. Efficacy has been demonstrated in double-blind clinical studies of 6 months duration.

Digestive and central nervous system side effects are dose related. If patients develop these effects it is recommended that the dosage be lowered to one tablet twice a day (800 mg/day). If side effects persist at this lower dosage, the administration of Pentoxifylline Extended-release Tablet should be discontinued.
Repaglinide

Repaglinide

There is no fixed dosage regimen for the management of type 2 diabetes with Repaglinide.

The patient's blood glucose should be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of an adequate blood glucose-lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels are of value in monitoring the patient's longer term response to therapy.

Short-term administration of Repaglinide may be sufficient during periods of transient loss of control in patients usually well controlled on diet.

Repaglinide doses are usually taken within 15 minutes of the meal but time may vary from immediately preceding the meal to as long as 30 minutes before the meal.

Starting Dose

For patients not previously treated or whose HbA1c is < 8%, the starting dose should be 0.5 mg with each meal. For patients previously treated with blood glucose-lowering drugs and whose HbA1c is ≥ 8%, the initial dose is 1 or 2 mg with each meal preprandially (see previous paragraph).

Dose Adjustment

Dosing adjustments should be determined by blood glucose response, usually fasting blood glucose. Postprandial glucose levels testing may be clinically helpful in patients whose pre-meal blood glucose levels are satisfactory but whose overall glycemic control (HbA1c) is inadequate. The preprandial dose should be doubled up to 4 mg with each meal until satisfactory blood glucose response is achieved. At least one week should elapse to assess response after each dose adjustment.

The recommended dose range is 0.5 mg to 4 mg taken with meals. Repaglinide may be dosed preprandially 2, 3, or 4 times a day in response to changes in the patient’s meal pattern. The maximum recommended daily dose is 16 mg.

Patient Management

Long-term efficacy should be monitored by measurement of HbA1c levels approximately every 3 months. Failure to follow an appropriate dosage regimen may precipitate hypoglycemia or hyperglycemia. Patients who do not adhere to their prescribed dietary and drug regimen are more prone to exhibit unsatisfactory response to therapy including hypoglycemia. When hypoglycemia occurs in patients taking a combination of Repaglinide and a thiazolidinedione or Repaglinide and metformin, the dose of Repaglinide should be reduced.

Patients Receiving Other Oral Hypoglycemic Agents

When Repaglinide is used to replace therapy with other oral hypoglycemic agents, Repaglinide may be started on the day after the final dose is given. Patients should then be observed carefully for hypoglycemia due to potential overlapping of drug effects. When transferred from longer half-life sulfonylurea agents (e.g., chlorpropamide) to repaglinide, close monitoring may be indicated for up to one week or longer.

Combination Therapy

If Repaglinide monotherapy does not result in adequate glycemic control, metformin or a thiazolidinedione may be added. If metformin or thiazolidinedione monotherapy does not provide adequate control, Repaglinide may be added. The starting dose and dose adjustments for Repaglinide combination therapy is the same as for Repaglinide monotherapy. The dose of each drug should be carefully adjusted to determine the minimal dose required to achieve the desired pharmacologic effect. Failure to do so could result in an increase in the incidence of hypoglycemic episodes. Appropriate monitoring of FPG and HbA1c measurements should be used to ensure that the patient is not subjected to excessive drug exposure or increased probability of secondary drug failure.
Nefazodone Hydrochlorid...

Nefazodone Hydrochloride

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

Initial Treatment

The recommended starting dose for nefazodone hydrochloride tablets 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.
Fluocinolone Acetonide ...

Fluocinolone Acetonide Oil

For the treatment of chronic eczematous external otitis, using the supplied ear-dropper, apply 5 drops of fluocinolone acetonide oil 0.01% into the affected ear. To apply, tilt head to one side so that the ear is facing up. Then gently pull the ear lobe backward and upward and apply 5 drops of fluocinolone acetonide oil 0.01% into the ear. Keep head tilted for about a minute to allow fluocinolone acetonide oil 0.01% to penetrate lower into the ear canal. Gently pat excess material dripping out of the ear using a clean cotton ball. Follow these instructions twice each day for 7 to 14 days.
Acarbose

Acarbose

There is no fixed dosage regimen for the management of diabetes mellitus with acarbose tablets or any other pharmacologic agent. Dosage of acarbose tablets must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dose of 100 mg t.i.d. Acarbose tablets should be taken three times daily at the start (with the first bite) of each main meal. Acarbose tablets should be started at a low dose, with gradual dose escalation as described below, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient. If the prescribed diet is not observed, the intestinal side effects may be intensified. If strongly distressing symptoms develop in spite of adherence to the diabetic diet prescribed, the doctor must be consulted and the dose temporarily or permanently reduced.

During treatment initiation and dose titration (see below), one-hour postprandial plasma glucose may be used to determine the therapeutic response to acarbose tablets and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both postprandial plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of acarbose tablets, either as monotherapy or in combination with sulfonylureas, insulin or metformin.

Initial Dosage:

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

Maintenance Dosage:

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

Maximum Dosage:

The maximum recommended dose for patient's ≤ 60 kg is 50 mg t.i.d. The maximum recommended dose for patients > 60 kg is 100 mg t.i.d.

Patients Receiving Sulfonylureas or Insulin:

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

Quinapril

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

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

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

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

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

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

Riluzole

The recommended dose for Riluzole is 50 mg every 12 hours. No increased benefit can be expected from higher daily doses, but adverse events are increased.

Riluzole tablets should be taken at least an hour before, or two hours after, a meal to avoid a food-related decrease in bioavailability.

Special Populations

Patients with Impaired Hepatic Function:

see WARNINGS, PRECAUTIONS, CLINICAL PHARMACOLOGY.
Nystatin

Nystatin

The usual therapeutic dosage is one to two tablets (500,000 to 1,000,000 units nystatin) three times daily. Treatment should generally be continued for at least 48 hours after clinical cure to prevent relapse.
Nabumetone

Nabumetone

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

Osteoarthritis and Rheumatoid Arthritis

The recommended starting dose is 1,000 mg taken as a single dose with or without food. Some patients may obtain more symptomatic relief from 1,500 mg to 2,000 mg per day. Nabumetone tablets USP can be given in either a single or twice-daily dose. Dosages greater than 2,000 mg per day have not been studied. The lowest effective dose should be used for chronic treatment (see WARNINGS, Renal Effects). Patients weighing under 50 kg may be less likely to require dosages beyond 1,000 mg; therefore, after observing the response to initial therapy, the dose should be adjusted to meet individual patients’ requirements.
Sucralfate

Sucralfate

Active Duodenal Ulcer

The recommended adult oral dosage for duodenal ulcer is 1 g four times per day on an empty stomach.

Antacids may be prescribed as needed for relief of pain but should not be taken within one-half hour before or after sucralfate.

While healing with sucralfate may occur during the first week or two, treatment should be continued for 4 to 8 weeks unless healing has been demonstrated by x-ray or endoscopic examination.

Maintenance Therapy

The recommended adult oral dosage is 1 g twice a day.

Elderly

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy (see PRECAUTIONS, Geriatric Use).

Call your doctor for medical advice about side effects. You may report side effects to AvKARE Customer Response Line at 1-855-361-3993 or drugsafety@avkare.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Bicalutamide

Bicalutamide

The recommended dose for bicalutamide therapy in combination with an LHRH analog is one 50 mg tablet once daily (morning or evening), with or without food. It is recommended that bicalutamide tablets USP be taken at the same time each day. Treatment with bicalutamide tablets USP should be started at the same time as treatment with an LHRH analog.

2.1 Dosage Adjustment in Renal Impairment

No dosage adjustment is necessary for patients with renal impairment [see Use in Specific Populations (8.7)].

2.2 Dosage Adjustment in Hepatic Impairment

No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. In patients with severe liver impairment (n = 4), although there was a 76% increase in the half-life (5.9 and 10.4 days for normal and impaired patients, respectively) of the active enantiomer of bicalutamide no dosage adjustment is necessary [see Use in Specific Populations (8.6)].
Ribavirin

Ribavirin

Under no circumstances should ribavirin capsules be opened, crushed, or broken. Ribavirin capsules should be taken with food [see Clinical Pharmacology (12.3)]. Ribavirin capsules should not be used in patients with creatinine clearance < 50 mL/min.

2.2 Ribavirin/INTRON A Combination Therapy

Adults

Duration of Treatment – Interferon Alpha-naïve Patients

The recommended dose of INTRON A is 3 million IU three times weekly subcutaneously. The recommended dose of ribavirin capsules depends on the patient’s body weight (refer to Table 3). The recommended duration of treatment for patients previously untreated with interferon is 24 to 48 weeks. The duration of treatment should be individualized to the patient depending on baseline disease characteristics, response to therapy, and tolerability of the regimen [see Indications and Usage (1.1) and Clinical Studies (14)]. After 24 weeks of treatment, virologic response should be assessed. Treatment discontinuation should be considered in any patient who has not achieved an HCV-RNA below the limit of detection of the assay by 24 weeks. There are no safety and efficacy data on treatment for longer than 48 weeks in the previously untreated patient population.
Duration of Treatment – Re-treatment with INTRON A/Ribavirin in Relapse Patients In patients who relapse following nonpegylated interferon monotherapy, the recommended duration of treatment is 24 weeks. Table 3: Recommended Dosing Body Weight Ribavirin Capsules ≤ 75 kg
2 x 200 mg capsules AM
3 x 200 mg capsules PM daily orally > 75 kg
3 x 200 mg capsules AM
3 x 200 mg capsules PM daily orally
Pediatrics

The recommended dose of ribavirin is 15 mg/kg per day orally (divided dose AM and PM). Refer to Table 5 for Pediatric Dosing of ribavirin in combination with INTRON A. INTRON A for injection by body weight of 25 kg to 61 kg is 3 million IU/m2 three times weekly subcutaneously. Refer to adult dosing table for > 61 kg body weight.

The recommended duration of treatment is 48 weeks for pediatric patients with genotype 1. After 24 weeks of treatment, virologic response should be assessed. Treatment discontinuation should be considered in any patient who has not achieved an HCV-RNA below the limit of detection of the assay by this time. The recommended duration of treatment for pediatric patients with genotype 2/3 is 24 weeks.

2.3 Laboratory Tests

The following laboratory tests are recommended for all patients treated with ribavirin, prior to beginning treatment and then periodically thereafter.
Standard hematologic tests - including hemoglobin (pretreatment, Week 2 and Week 4 of therapy, and as clinically appropriate [see Warnings and Precautions (5.2, 5.7)], complete and differential white blood cell counts, and platelet count. Blood chemistries - liver function tests and TSH. Pregnancy - including monthly monitoring for women of childbearing potential. ECG [see Warnings and Precautions (5.2)].
2.4 Dose Modifications

If severe adverse reactions or laboratory abnormalities develop during combination ribavirin/INTRON A therapy, modify or discontinue the dose until the adverse reaction abates or decreases in severity [see Warnings and Precautions (5)]. If intolerance persists after dose adjustment, combination therapy should be discontinued.

Ribavirin should not be used in patients with creatinine clearance < 50 mL/min. Subjects with impaired renal function and those over the age of 50 should be carefully monitored with respect to development of anemia [see Warnings and Precautions (5.2), Use in Specific Populations (8.5), and Clinical Pharmacology (12.3)].

Ribavirin should be administered with caution to patients with preexisting cardiac disease. Patients should be assessed before commencement of therapy and should be appropriately monitored during therapy. If there is any deterioration of cardiovascular status, therapy should be stopped [see Warnings and Precautions (5.2)].

For patients with a history of stable cardiovascular disease, a permanent dose reduction is required if the hemoglobin decreases by ≥ 2 g/dL during any 4 week period. In addition, for these cardiac history patients, if the hemoglobin remains < 12 g/dL after 4 weeks on a reduced dose, the patient should discontinue combination therapy.

It is recommended that a patient whose hemoglobin level falls below 10 g/dL have his/her ribavirin dose modified or discontinued per Table 5 [see Warnings and Precautions (5.2)].
Table 5: Guidelines for Dose Modification and Discontinuation of INTRON A/Ribavirin Based on Laboratory Parameters in Adults and Pediatrics * For adult patients with a history of stable cardiac disease receiving INTRON A in combination with ribavirin, the INTRON A dose should be reduced by half and the ribavirin dose by 200 mg/day if a > 2 g/dL decrease in hemoglobin is observed during any 4 week period. INTRON A and ribavirin should be permanently discontinued if patients have hemoglobin levels < 12 g/dL after this ribavirin dose reduction. Pediatric patients who have preexisting cardiac conditions and experience a hemoglobin decrease ≥ 2 g/dL during any 4 week period during treatment should have weekly evaluations and hematology testing. † 1 st dose reduction of ribavirin is by 200 mg/day, except in patients receiving the 1400 mg dose it is by 400 mg/day; 2 nd dose reduction of ribavirin (if needed) is by an additional 200 mg/day. ‡ For patients on ribavirin/INTRON A combination therapy, reduce INTRON A dose by 50%. Laboratory Values Adults Pediatrics Adults Pediatrics INTRON A Ribavirin Hgb < 10 g/dL For patients with cardiac disease, reduce by 50%* See footnote* Adjust Dose†
1st reduction to 12 mg/kg/day

2nd reduction to 8 mg/kg/day
WBC < 1.5 x 109/L Adjust Dose‡ Reduce by 50% No Dose Change No Dose Change Neutrophils < 0.75 x 109/L Platelets < 50 x 109/L (Adults) < 70 x 109/L (Pediatrics) Hgb < 8.5 g/dL Permanently Discontinue Permanently Discontinue Permanently Discontinue Permanently Discontinue WBC < 1 x 109/L Neutrophils < 0.5 x 109/L Creatinine > 2 mg/dL (Pediatrics) Platelets < 25 x 109/L (Adults) < 50 x 109/L (Pediatrics)
Refer to the INTRON A Package Insert for additional information about how to reduce an INTRON A dose.

2.5 Discontinuation of Dosing

Adults

Regardless of genotype, previously treated patients who have detectable HCV-RNA at week 12 or 24 are highly unlikely to achieve SVR and discontinuation of therapy should be considered.
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 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 HCl alone, a diuretic can be added.

Total daily doses above 80 mg have not been evaluated.

Concomitant administration of Benazepril HCl 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 HCl. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued two to three days prior to beginning therapy with Benazepril hydrochloride (see WARNINGS). Then, if blood pressure is not controlled with Benazepril hydrochloride alone, diuretic therapy should be resumed.

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

Pediatrics

In children, doses of Benazepril HCl 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 HCl in 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 HCl, follow the suspension preparation instructions below to administer benazepril HCl as a suspension.

Treatment with benazepril HCl 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 HCl 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 HCl 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 to 8°C (36 to 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 citric acid, berry citrus flavorant, glycerin, methylparaben, potassium sorbate, sodium phosphate monobasic, sorbitol, sucrose, and water.
Hydroxychloroquine Sulf...

Hydroxychloroquine Sulfate

DOSAGE AND ADMINISTRATION

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.
Carvedilol

Carvedilol

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

2.2 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.

2.3 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.

2.4 Hepatic Impairment

Carvedilol should not be given to patients with severe hepatic impairment (see CONTRAINDICATIONS [4]).
Disopyramide Phosphate

Disopyramide Phosphate

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

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

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

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

Transferring to Disopyramide Phosphate

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

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

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

Pediatric Dosage

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

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

Finasteride

Finasteride tablets may be administered with or without meals.

2.1 Monotherapy

The recommended dose of finasteride tablets is one tablet (5 mg) taken once a day [see Clinical Studies (14.1)].

2.2 Combination With Alpha-Blocker

The recommended dose of finasteride tablets is one tablet (5 mg) taken once a day in combination with the alpha-blocker doxazosin [see Clinical Studies (14.2)].
Doxycycline Hyclate

Doxycycline Hyclate

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

For prophylaxis of malaria: For adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up to the adult dose. Prophylaxis should begin 1–2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area.

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

Venlafaxine Hydrochloride

Initial Treatment

The recommended starting dose for venlafaxine tablets, USP is 75 mg/day, administered in two or three divided doses, taken with food. Depending on tolerability and the need for further clinical effect, the dose may be increased to 150 mg/day. If needed, the dose should be further increased up to 225 mg/day. When increasing the dose, increments of up to 75 mg/day should be made at intervals of no less than 4 days. In outpatient settings there was no evidence of usefulness of doses greater than 225 mg/day for moderately depressed patients, but more severely depressed inpatients responded to a mean dose of 350 mg/day. Certain patients, including more severely depressed patients, may therefore respond more to higher doses, up to a maximum of 375 mg/day, generally in three divided doses (see PRECAUTIONS, General, Use in Patients with Concomitant Illness).

Special Populations

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to venlafaxine tablets, USP, other SNRIs, or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with venlafaxine tablets, USP during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

Dosage for Patients with Hepatic Impairment

Given the decrease in clearance and increase in elimination half-life for both venlafaxine and ODV that is observed in patients with hepatic cirrhosis and mild and moderate hepatic impairment compared to normal subjects (see CLINICAL PHARMACOLOGY), it is recommended that the total daily dose be reduced by 50% in patients with mild to moderate hepatic impairment. Since there was much individual variability in clearance between subjects with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.

Dosage for Patients with Renal Impairment

Given the decrease in clearance for venlafaxine and the increase in elimination half-life for both venlafaxine and ODV that is observed in patients with renal impairment (GFR=10 to 70 mL/min) compared to normals (see CLINICAL PHARMACOLOGY), it is recommended that the total daily dose be reduced by 25% in patients with mild to moderate renal impairment. It is recommended that the total daily dose be reduced by 50% in patients undergoing hemodialysis. Since there was much individual variability in clearance between patients with renal impairment, individualization of dosing may be desirable in some patients.

Dosage for Elderly Patients

No dose adjustment is recommended for elderly patients on the basis of age. As with any antidepressant, however, caution should be exercised in treating the elderly. When individualizing the dosage, extra care should be taken when increasing the dose.

Maintenance Treatment

It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. In one study, in which patients responding during 8 weeks of acute treatment with venlafaxine HCI extended-release capsules were assigned randomly to placebo or to the same dose of venlafaxine HCI extended-release capsules (75, 150, or 225 mg/day, qAM) during 26 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated. A second longer-term study has demonstrated the efficacy of venlafaxine tablets, USP immediate-release in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then randomly assigned to placebo or venlafaxine tablets,USP immediate-release for periods of up to 52 weeks on the same dose (100 to 200 mg/day, on a b.i.d. schedule) (see CLINICAL TRIALS). Based on these limited data, it is not known whether or not the dose of venlafaxine tablets,USP immediate-release/ venlafaxine HCI extended-release capsules needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Discontinuing Venlafaxine Tablets, USP

Symptoms associated with discontinuation of venlafaxine tablets, USP, other SNRIs, and SSRIs, 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.

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 venlafaxine tablets, USP. In addition, at least 7 days should be allowed after stopping Venlafaxine Hydrochloride Tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).Use of Venlafaxine Tablets, USP With Other MAOIs, Such as Linezolid or Methylene Blue: Do not start venlafaxine tablets, USP in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).In some cases, a patient already receiving therapy with venlafaxine tablets, USP 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, venlafaxine tablets, USP 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 venlafaxine tablets, USP 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 venlafaxine tablets, USP is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).
Sotalol Hydrochloride

Sotalol Hydrochloride

Dosing and Administration in Adults
Therapy with sotalol hydrochloride tablets (AF) must be initiated (and, if necessary, titrated) in a setting that provides continuous electrocardiographic (ECG) monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Patients should continue to be monitored in this way for a minimum of 3 days on the maintenance dose. In addition, patients should not be discharged within 12 hours of electrical or pharmacological conversion to normal sinus rhythm. The QT interval is used to determine patient eligibility for sotalol hydrochloride tablets (AF) treatment and for monitoring safety during treatment. The baseline QT interval must be ≤450 msec in order for a patient to be started on sotalol hydrochloride tablets (AF) therapy. During initiation and titration, the QT interval should be monitored 2 to 4 hours after each dose. If the QT interval prolongs to 500 msec or greater, the dose must be reduced or the drug discontinued. The dose of sotalol hydrochloride tablets, USP (AF) must be individualized according to calculated creatinine clearance. In patients with a creatinine clearance >60 mL/min sotalol hydrochloride tablets (AF) are administered twice daily (BID) while in those with a creatinine clearance between 40 and 60 mL/min, the dose is administered once daily (QD) or half the dose is administered twice daily (BID). In patients with a creatinine clearance less than 40 mL/min sotalol hydrochloride tablets (AF) are contraindicated. The recommended initial dose of sotalol hydrochloride tablets (AF) is 80 mg and is initiated as shown in the dosing algorithm described below. The 80 mg dose can be titrated upward to 100 mg or 120 mg during initial hospitalization or after discharge on 80 mg in the event of recurrence, by rehospitalization and repeating the same steps used during the initiation of therapy (see DOSAGE AND ADMINISTRATION,Upward Titration of Dose). Patients with atrial fibrillation should be anticoagulated according to usual medical practice. Hypokalemia should be corrected before initiation of sotalol hydrochloride tablets (AF) therapy (see WARNINGS, Ventricular Arrhythmia). Patients to be discharged on sotalol hydrochloride tablets (AF) therapy from an in-patient setting should have an adequate supply of sotalol hydrochloride tablets (AF), to allow uninterrupted therapy until the patient can fill a sotalol hydrochloride tablets (AF) prescription.
Initiation of Sotalol Hydrochloride Tablets, USP (AF) Therapy

Step 1. Electrocardiographic assessment: Prior to administration of the first dose, the QT interval must be determined using an average of 5 beats. If the baseline QT is greater than 450 msec (JT ≥330 msec if QRS over 100 msec), sotalol hydrochloride tablets (AF) are contraindicated.

Step 2. Calculation of creatinine clearance: Prior to the administration of the first dose, the patient's creatinine clearance should be calculated using the following formula:
creatinine clearance (male) = (140-age)x body weight in kg 72 x serum creatinine (mg/dL) creatinine clearance (female) = (140-age)x body weight in kg x 0.85 72 x serum creatinine (mg/dL)
When serum creatinine is given in μmol/L, divide the value by 88.4 (1 mg/dL = 88.4 mcmol/L).

Step 3. Starting Dose: The starting dose of sotalol hydrochloride tablets (AF) is 80 mg twice daily (BID) if the creatinine clearance is >60 mL/min, and 80 mg once daily (QD) if the creatinine clearance is 40 to 60 mL/min. If the creatinine clearance is <40 mL/min sotalol hydrochloride tablets (AF) are contraindicated.

Step 4. Administer the appropriate daily dose of sotalol hydrochloride tablets (AF) and begin continuous ECG monitoring with QT interval measurements 2 to 4 hours after each dose.

Step 5. In patients with a creatinine clearance >60 mL/min, if the 80 mg dose level is tolerated and the QT interval remains <500 msec after at least 3 days (after 5 or 6 doses if patient receiving QD dosing), the patient can be discharged. Alternatively, during hospitalization, the dose can be increased to 100 mg or 120 mg BID and the patient followed for 3 days on this dose (followed for 5 or 6 doses if patient receiving QD doses).

The steps described above are summarized in the following diagram:

Place Patient on Telemetry

Check Baseline QT

If QT >450 msec sotalol hydrochloride tablets (AF) are CONTRAINDICATED

If QT ≤450 msec, proceed

Calculate Creatine Clearance (Clcr)

If Clcr is <40 mL/min sotalol hydrochloride tablets (AF) are CONTRAINDICATED

If Clcr is 40-60 mL/min start sotalol hydrochloride tablets (AF) 80 mg QD

If Clcr is >60 mL/min start sotalol hydrochloride tablets (AF) 80 mg BID

Monitor QT 2 to 4 hours after each dose.

If QT ≥500 msec discontinue sotalol hydrochloride tablets (AF)

If QT <500 msec after 3 days (after 5th or 6th dose if

patient receiving QD dosing)

discharge patient on current treatment. Alternatively, during

hospitalization, the dose can be increased to 120 mg BID

and the patient followed for 3 days on this dose (followed for 5 or

6 doses if patient receiving QD doses).

Upward Titration of Dose

If the 80 mg dose level (given BID or QD depending upon the creatinine clearance) does not reduce the frequency of relapses of AFIB/AFL and is tolerated without excessive QT interval prolongation (i.e., ≥520 msec), the dose level may be increased to 120 mg (BID or QD depending upon the creatinine clearance). As proarrhythmic events can occur not only at initiation of therapy, but also with each upward dosage adjustment, Steps 2 through 5 used during initiation of sotalol hydrochloride tablet (AF) therapy should be followed when increasing the dose level. In the U.S. multicenter dose-response study, the 120 mg dose (BID or QD) was found to be the most effective in prolonging the time to ECG documented symptomatic recurrence of AFIB/AFL. If the 120 mg dose does not reduce the frequency of early relapse of AFIB/AFL and is tolerated without excessive QT interval prolongation (≥520 msec), an increase to 160 mg (BID or QD depending upon the creatinine clearance), can be considered. Steps 2 through 5 used during the initiation of therapy should be used again to introduce such an increase.

Maintenance of Sotalol Hydrochloride Tablets, USP (AF) Therapy

Renal function and QT should be re-evaluated regularly if medically warranted. If QT is 520 msec or greater (JT 430 msec or greater if QRS is > 100 msec), the dose of sotalol hydrochloride tablets (AF) therapy should be reduced and patients should be carefully monitored until QT returns to less than 520 msec. If the QT interval is ≥520 msec while on the lowest maintenance dose level (80 mg) the drug should be discontinued. If renal function deteriorates, reduce the daily dose in half by administering the drug once daily as described in Initiation of sotalol hydrochloride tablets (AF) Therapy, Step 3.

Special Considerations

The maximum recommended dose in patients with a calculated creatinine clearance greater than 60 mL/min is 160 mg BID, doses greater than 160 mg BID have been associated with an increased incidence of Torsade de Pointes and are not recommended.

A patient who misses a dose should NOT double the next dose. The next dose should be taken at the usual time.

Dosing and Administration in Children

As in adults the following precautionary measures should be considered when initiating sotalol treatment in children: initiation of treatment in the hospital after appropriate clinical assessment; individualized regimen as appropriate; gradual increase of doses if required; careful assessment of therapeutic response and tolerability; and frequent monitoring of the QTc interval and heart rate.

For children aged about 2 years and greater

For children aged about 2 years and greater, with normal renal function, doses normalized for body surface area are appropriate for both initial and incremental dosing. Since the Class III potency in children (see CLINICAL PHARMACOLOGY) is not very different from that in adults, reaching plasma concentrations that occur within the adult dose range is an appropriate guide. From pediatric pharmacokinetic data the following is recommended.

For initiation of treatment, 30 mg/m2 three times a day (90 mg/m2 total daily dose) is approximately equivalent to the initial 160 mg total daily dose for adults. Subsequent titration to a maximum of 60 mg/m2 (approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be guided by clinical response, heart rate and QTc, with increased dosing being preferably carried out in-hospital. At least 36 hours should be allowed between dose increments to attain steady-state plasma concentrations of sotalol in patients with age-adjusted normal renal function.

For children aged about 2 years or younger

For children aged about 2 years or younger the above pediatric dosage should be reduced by a factor that depends heavily upon age, as shown in the following graph, age plotted on a logarithmic scale in months.

For a child aged 20 months, the dosing suggested for children with normal renal function aged 2 years or greater should be multiplied by about 0.97; the initial starting dose would be (30 X 0.97)=29.1 mg/m2, administered three times daily. For a child aged 1 month, the starting dose should be multiplied by 0.68; the initial starting dose would be (30 X 0.68)=20 mg/m2, administered three times daily. For a child aged about 1 week, the initial starting dose should be multiplied by 0.3; the starting dose would be (30 X 0.3)=9 mg/m2. Similar calculations should be made for increased doses as titration proceeds. Since the half-life of sotalol decreases with decreasing age (below about 2 years), time to steady-state will also increase. Thus, in neonates the time to steady-state may be as long as a week or longer.

In all children, individualization of dosage is required. As in adults sotalol hydrochloride tablets (AF) should be used with particular caution in children if the QTc is greater than 500 msec on therapy and serious consideration should be given to reducing the dose or discontinuing therapy when QTc exceeds 550 msec.

The use of sotalol hydrochloride tablets (AF) in children with renal impairment has not been investigated. Sotalol elimination is predominantly via the kidney in the unchanged form. Use of sotalol in any age group with decreased renal function should be at lower doses or at increased intervals between doses. Monitoring of heart rate and QTc is more important and it will take much longer to reach steady-state with any dose and/or frequency of administration.

Transfer to Sotalol Hydrochloride Tablets (AF) from Sotalol Hydrochloride Tablets

Patients with a history of symptomatic AFIB/AFL who are currently receiving sotalol hydrochloride for the maintenance of normal sinus should be transferred to sotalol hydrochloride tablets (AF) because of the significant differences in labeling (i.e., patient package insert, dosing administration, and safety information).

Transfer to Sotalol Hydrochloride Tablets (AF) from Other Antiarrhythmic Agents

Before starting sotalol hydrochloride tablets (AF), previous antiarrhythmic therapy should generally be withdrawn under careful monitoring for a minimum of 2 to 3 plasma half-lives if the patient's clinical condition permits (see DRUG INTERACTIONS). Treatment has been initiated in some patients receiving I.V. lidocaine without ill effect. After discontinuation of amiodarone, sotalol hydrochloride tablets (AF) should not be initiated until the QT interval is normalized (see WARNINGS).

Preparation of Extemporaneous Oral Solution

Sotalol hydrochloride (AF) Syrup 5 mg/mL can be compounded using Simple Syrup containing 0.1% sodium benzoate (Syrup, NF) available from Humco Laboratories as follows:
Measure 120 mL of Simple Syrup Transfer the syrup to a 6-ounce amber plastic (polyethylene terephthalate [PET]) prescription bottle. NOTE: An oversized bottle is used to allow for a headspace, so that there will be more effective mixing during shaking of the bottle. Add five (5) sotalol hydrochloride (AF) 120 mg tablets to the bottle. These tablets are added intact; it is not necessary to crush the tablets. NOTE: The addition of the tablets can also be done first. The tablets can also be crushed if preferred. If the tablets are crushed, care should be taken to transfer the entire quantity of tablet powder into the bottle containing the syrup. Shake the bottle to wet the entire surface of the tablets. If the tablets have been crushed, shake the bottle until the endpoint is achieved. Allow the tablets to hydrate for approximately two hours. After at least two hours have elapsed, shake the bottle intermittently over the course of at least another two hours until the tablets are completely disintegrated. NOTE: The tablets can be allowed to hydrate overnight to simplify the disintegration process.
The endpoint is achieved when a dispersion of fine particles in the syrup is obtained.

This compounding procedure results in a solution containing 5 mg/mL of sotalol HCl. The fine solid particles are the water-insoluble inactive ingredients of the tablets.

This extemporaneously prepared oral solution of sotalol HCl (with suspended inactive particles) must be shaken well prior to administration. This is to ensure that the amount of inactive solid particles per dose remains constant throughout the duration of use.

Stability studies indicate that the suspension is stable when stored at controlled room temperature (15° to 30°C/59° to 86°F) and ambient humidity for three (3) months.
Rabeprazole Sodium

Rabeprazole Sodium

2.1 Healing of Erosive or Ulcerative GERD in Adults

The recommended adult oral dose is one rabeprazole sodium 20 mg delayed-release tablet to be taken once daily for four to eight weeks [see Indications and Usage (1.1)]. For those patients who have not healed after 8 weeks of treatment, an additional 8 week course of rabeprazole sodium delayed-release tablets may be considered.

2.2 Maintenance of Healing of Erosive or Ulcerative GERD in Adults

The recommended adult oral dose is one rabeprazole sodium 20 mg delayed-release tablet to be taken once daily [see Indications and Usage (1.2)].

2.3 Treatment of Symptomatic GERD in Adults

The recommended adult oral dose is one rabeprazole sodium 20 mg delayed-release tablet to be taken once daily for 4 weeks [see Indications and Usage (1.3)]. If symptoms do not resolve completely after 4 weeks, an additional course of treatment may be considered. The recommended adolescent dosing is one rabeprazole sodium 20 mg delayed-release tablet to be taken once daily for 8 weeks.

2.4 Healing of Duodenal Ulcers in Adults

The recommended adult oral dose is one rabeprazole sodium 20 mg delayed-release tablet to be taken once daily after the morning meal for a period up to four weeks [see Indications and Usage (1.5)]. Most patients with duodenal ulcer heal within four weeks. A few patients may require additional therapy to achieve healing.

2.5 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence in Adults
TABLE 1: THREE DRUG REGIMEN* * It is important that patients comply with the full 7 day regimen [ see Clinical Studies (14.5)]. Rabeprazole Sodium Delayed-Release Tablet 20 mg Twice Daily for 7 Days Amoxicillin 1000 mg Twice Daily for 7 Days Clarithromycin 500 mg Twice Daily for 7 Days All three medications should be taken twice daily with the morning and evening meals.
2.6 Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome in Adults

The dosage of rabeprazole sodium delayed-release tablets in patients with pathologic hypersecretory-conditions varies with the individual patient. The recommended adult oral starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Some patients may require divided doses. Doses up to 100 mg QD and 60 mg BID have been administered. Some patients with Zollinger-Ellison syndrome have been treated continuously with rabeprazole sodium delayed-release tablets for up to one year.

2.7 Short-Term Treatment of Symptomatic GERD in Adolescent Patients 12 Years of Age and Older

The recommended oral dose for adolescents 12 years of age and older is one 20 mg delayed-release tablet once daily for up to 8 weeks [see Use in Specific Populations (8.4) and Clinical Studies (14.7)].

2.9 Elderly, Renal and Hepatic Impaired Patients

No dosage adjustment is necessary in elderly patients, in patients with renal disease or in patients with mild to moderate hepatic impairment. Administration of rabeprazole to patients with mild to moderate liver impairment resulted in increased exposure and decreased elimination. Due to the lack of clinical data on rabeprazole in patients with severe hepatic impairment, caution should be exercised in those patients.

2.10 Administration Recommendations
TABLE 2: Administration Recommendations Formulation Population Instructions Delayed-Release Tablet Adults and adolescents 12 years of age and older
Swallow tablets whole. Do not chew, crush or split tablets.

Tablets can be taken with or without food.
Alfuzosin Hydrochloride...

Alfuzosin Hydrochloride Er

The recommended dosage is one 10 mg alfuzosin hydrochloride extended-release tablet once daily. The extent of absorption of alfuzosin is 50% lower under fasting conditions. Therefore, alfuzosin hydrochloride extended-release tablets should be taken with food and with the same meal each day. The tablets should not be chewed or crushed.
Quetiapine Fumarate

Quetiapine Fumarate

2.1 Important Administration Instructions

Quetiapine fumarate tablets can be taken with or without food.

2.2 Recommended Dosing

The recommended initial dose, titration, dose range and maximum quetiapine fumarate tablets dose for each approved indication is displayed in Table 1. After initial dosing, adjustments can be made upwards or downwards, if necessary, depending upon the clinical response and tolerability of the patient [see Clinical Studies (14.1 and 14.2)].
Table 1: Recommended Dosing for Quetiapine Fumarate Tablets *N/A Not applicable Indication Initial Dose and Titration
Recommended
Dose
Maximum Dose

Schizophrenia-Adults
(2.1)
Day 1: 25 mg twice daily.

Increase in increments of 25 mg to 50 mg divided two or three times on Days 2 and 3 to range of 300 to 400 mg by Day 4.

Further adjustments can be made in
increments of 25 to 50 mg twice a day, in intervals of not less than 2 days.
150 to 750
mg/day 750 mg/day
Schizophrenia-

Adolescents (13 to 17 years) (2.1)

Day 1: 25 mg twice daily.

Day 2: Twice daily dosing totaling 100 mg.

Day 3: Twice daily dosing totaling 200 mg.

Day 4: Twice daily dosing totaling 300 mg.

Day 5: Twice daily dosing totaling 400 mg.

Further adjustments should be in increments no greater than 100 mg/day within the recommended dose range of 400 to 800 mg/day.
Based on response and tolerability, may be administered three times daily.
400 to 800 mg/day

800 mg/day

Schizophrenia-

Maintenance
N/A*
400 to 800

mg/day

800 mg/day

Bipolar Mania- Adults Monotherapy or as an adjunct to lithium or divalproex (2.2)

Day 1: Twice daily dosing totaling 100 mg.

Day 2: Twice daily dosing totaling 200 mg.

Day 3: Twice daily dosing totaling 300 mg.

Day 4: Twice daily dosing totaling 400 mg.
Further dosage adjustments up to 800 mg/day by Day 6 should be in increments of no greater than 200 mg/day.
400 to 800

mg/day
800 mg/day
Bipolar Mania-Children and Adolescents (10 to 17 years),
Monotherapy
Day 1: 25 mg twice daily.

Day 2: Twice daily dosing totaling 100 mg.

Day 3: Twice daily dosing totaling 200 mg.

Day 4: Twice daily dosing totaling 300 mg.

Day 5: Twice daily dosing totaling 400 mg.

Further adjustments should be in increments no greater than 100 mg/day within the recommended dose range of 400 to 600 mg/day.

Based on response and tolerability, may be
administered three times daily.
400 to 600

mg/day
600 mg/day
Bipolar Depression-
Adults
Administer once daily at bedtime.

Day 1: 50 mg

Day 2: 100 mg

Day 3: 200 mg
Day 4: 300 mg 300 mg/day 300 mg/day
Bipolar I Disorder
Maintenance Therapy- Adults
Administer twice daily totaling 400 to 800

mg/day as adjunct to lithium or divalproex.
Generally, in the maintenance phase, patients continued on the same dose on which they were stabilized.
400 to 800
mg/day 800 mg/day

Maintenance Treatment for Schizophrenia and Bipolar I Disorder

Maintenance Treatment—Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.2)].

2.3 Dose Modifications in Elderly Patients

Consideration should be given to a slower rate of dose titration and a lower target dose in the elderly and in patients who are debilitated or who have a predisposition to hypotensive reactions [see Clinical Pharmacology (12.3)]. When indicated, dose escalation should be performed with caution in these patients.

Elderly patients should be started on quetiapine fumarate tablets 50 mg/day and the dose can be increased in increments of 50 mg/day depending on the clinical response and tolerability of the individual patient.

2.4 Dose Modifications in Hepatically Impaired Patients

Patients with hepatic impairment should be started on 25 mg/day. The dose should be increased daily in increments of 25 mg/day to 50 mg/day to an effective dose, depending on the clinical response and tolerability of the patient.

2.5 Dose Modifications when used with CYP3A4 Inhibitors

Quetiapine fumarate tablets dose should be reduced to one sixth of original dose when co-medicated with a potent CYP3A4 inhibitor (e.g. ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). When the CYP3A4 inhibitor is discontinued, the dose of quetiapine fumarate tablets should be increased by 6 fold [see Clinical Pharmacology (12.3) and Drug Interactions7.1)].

2.6 Dose Modifications when used with CYP3A4 Inducers

Quetiapine fumarate tablets dose should be increased up to 5 fold of the original dose when used in combination with a chronic treatment (e.g., greater than 7 to 14 days) of a potent CYP3A4 inducer (e.g. phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.). The dose should be titrated based on the clinical response and tolerability of the individual patient. When the CYP3A4 inducer is discontinued, the dose of quetiapine fumarate tablets should be reduced to the original level within 7 to 14 days [see Clinical Pharmacology (12.3) and Drug Interactions (7.1)].

2.7 Reinitiation of Treatment in Patients Previously Discontinued

Although there are no data to specifically address re-initiation of treatment, it is recommended that when restarting therapy of patients who have been off quetiapine fumarate tablets for more than one week, the initial dosing schedule should be followed. When restarting patients who have been off quetiapine fumarate tablets for less than one week, gradual dose escalation may not be required and the maintenance dose may be reinitiated.

2.8 Switching from Antipsychotics

There are no systematically collected data to specifically address switching patients with schizophrenia from antipsychotics to quetiapine fumarate tablets, or concerning concomitant administration with antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized. When switching patients with schizophrenia from depot antipsychotics, if medically appropriate, initiate quetiapine fumarate tablets therapy in place of the next scheduled injection. The need for continuing existing EPS medication should be re-evaluated periodically.
Naproxen Sodium

Naproxen Sodium

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

After observing the response to initial therapy with naproxen sodium tablets, USP, the dose and frequency should be adjusted to suit an individual patient's needs.

Different dose strengths and formulations (i.e., tablets, suspension) of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation.

Although naproxen tablets, USP, naproxen suspension, naproxen delayed-release tablets, USP and naproxen sodium tablets, USP all circulate in the plasma as naproxen, USP, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 30 minutes in patients taking naproxen sodium, USP and within 1 hour in patients taking naproxen, USP. (see CLINICAL PHARMACOLOGY).

The recommended strategy for initiating therapy is to choose a formulation and a starting dose likely to be effective for the patient and then adjust the dosage based on observation of benefit and/or adverse events. A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see WARNINGS and PRECAUTIONS).

Geriatric Patients

Studies indicate that although total plasma concentration of naproxen, USP is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Patients with Moderate to Severe Renal Impairment

Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 mL/min) (see WARNINGS: Renal Effects).

Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis
Naproxen sodium tablets, USP
275 mg (naproxen, USP 250 mg with 25 mg sodium)
twice daily Naproxen sodium tablets, USP
550 mg (naproxen, USP 500 mgwith 50 mg sodium)
twice daily
During long-term administration, the dose of naproxen, USP may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary. In patients who tolerate lower doses well, the dose may be increased to naproxen sodium, USP 1500 mg/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen sodium, USP 1500 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk. The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response (see CLINICAL PHARMACOLOGY).

Juvenile Arthritis

For the relief of juvenile arthritis, the recommended dose is approximately 10 mg/kg given orally in 2 divided doses (i.e., 5 mg/kg given twice a day). Naproxen sodium tablets, USP are not well suited to this dosage so use of naproxen oral suspension, USP is recommended for this indication.

Management of Pain, Primary Dysmenorrhea and Acute Tendonitis and Bursitis

The recommended starting dose is 550 mg of naproxen sodium, USP followed by 550 mg every 12 hours or 275 mg every 6 to 8 hours as required. The initial total daily dose should not exceed 1375 mg of naproxen sodium, USP. Thereafter, the total daily dose should not exceed 1100 mg of naproxen sodium. Because the sodium salt of naproxen, USP is more rapidly absorbed, naproxen sodium tablets, USP are recommended for the management of acute painful conditions when prompt onset of pain relief is desired.

Acute Gout

The recommended starting dose is 825 mg of naproxen sodium tablets, USP followed by 275 mg every 8 hours until the attack has subsided.
Oxaprozin

Oxaprozin

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

Rheumatoid arthritis: For relief of the signs and symptoms of rheumatoid arthritis, the usual recommended dose is 1200 mg (two 600-mg tablets) given orally once a day (see Individualization of dosage).

Osteoarthritis: For relief of the signs and symptoms of osteoarthritis, the usual recommended dose is 1200 mg (two 600-mg tablets) given orally once a day (see Individualization of dosage).

Juvenile rheumatoid arthritis: For the relief of the signs and symptoms of JRA in patients 6-16 years of age, the recommended dose given orally once per day should be based on body weight of the patient as given in Table 3 (see also Individualization of dosage).
Table 3 Body Weight Range (kg) Dose (mg) 22-31 600 32-54 900 ≥55 1200
(see CLINICAL PHARMACOLOGY: Special populations: Pediatric patients)
Ticlopidine Hydrochlori...

Ticlopidine Hydrochloride

Stroke

The recommended dose of ticlopidine hydrochloride is 250 mg bid taken with food. Other doses have not been studied in controlled trials for these indications.

Coronary Artery Stenting

The recommended dose of ticlopidine hydrochloride is 250 mg bid taken with food together with antiplatelet doses of aspirin for up to 30 days of therapy following successful stent implantation.
Good Sense Pain And Fev...

Good Sense Pain And Fever Infants

The dosage of Donnatal® should be adjusted to the needs of the dividual patient to assure symptomatic control with a minimum of adverse effects. Donnatal® Tablets. Adults: One or two Donnatal® tablets three or four times a day according to condition and severity of symptoms.
Trazodone Hydrochloride...

Trazodone Hydrochloride

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

Dose Selection

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

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

Important Administration Instructions

Trazodone hydrochloride tablets are scored to provide flexibility in dosing.

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

Milk Of Magnesia

The recommended initial dose of guanfacine tablets, USP when given alone or in combination with another antihypertensive drug is 1 mg daily given at bedtime to minimize somnolence. If after 3 to 4 weeks of therapy 1 mg does not give a satisfactory result, a dose of 2 mg may be given, although most of the effect of guanfacine is seen at 1 mg (see CLINICAL PHARMACOLOGY). Higher daily doses have been used, but adverse reactions increase significantly with doses above 3 mg/day.

The frequency of rebound hypertension is low, but it can occur. When rebound occurs, it does so after 2 to 4 days, which is delayed compared with clonidine hydrochloride. This is consistent with the longer half-life of guanfacine. In most cases, after abrupt withdrawal of guanfacine, blood pressure returns to pretreatment levels slowly (within 2 to 4 days) without ill effects.
Cyproheptadine Hydrochl...

Cyproheptadine Hydrochloride

DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND THE RESPONSE OF THE PATIENT.

Each tablet contains 4 mg of cyproheptadine hydrochloride.

Pediatric Patients: Age 2 to 6 years: The total daily dosage for pediatric patients may be calculated on the basis of body weight or body area using approximately 0.25 mg/kg/day or 8 mg per square meter of body surface (8 mg/m2).

The usual dose is 2 mg (1⁄2 tablet) two or three times a day, adjusted as necessary to the size and response of the patient. The dose is not to exceed 12 mg a day.

Age 7 to 14 years: The usual dose is 4 mg (1 tablet) two or three times a day adjusted as necessary to the size and response of the patient. The dose is not to exceed 16 mg a day.

Adults: The total daily dose for adults should not exceed 0.5 mg/kg/day. The therapeutic range is 4 to 20 mg a day, with the majority of patients requiring 12 to 16 mg a day. An occasional patient may require as much as 32 mg a day for adequate relief. It is suggested that dosage be initiated with 4 mg (1 tablet) three times a day and adjusted according to the size and response of the patient.
Phenazopyridine Hydroch...

Phenazopyridine Hydrochloride

100 mg Tablets: Average adult dosage is two tablets 3 times a day after meals.

200 mg Tablets: Average adult dosage is one tablet 3 times a day after meals.

When used concomitantly with an antibacterial agent for the treatment of a urinary tract infection, the administration of Phenazopyridine HCl should not exceed 2 days.
Pioglitazone And Metfor...

Pioglitazone And Metformin Hydrocholride

2.1 Recommendations for All Patients

Pioglitazone and metformin hydrochloride tablets should be taken with meals to reduce the gastrointestinal side effects associated with metformin. If therapy with a combination tablet containing pioglitazone and metformin is considered appropriate the recommended starting dose is:
• 15 mg/500 mg twice daily or 15 mg/850 mg once daily and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability, • for patients with New York Heart Association (NYHA) Class I or Class II congestive heart failure: 15 mg/500 mg or 15 mg/850 mg once daily and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability, • for patients inadequately controlled on metformin monotherapy: 15 mg/500 mg twice daily or 15 mg/850 mg once or twice daily (depending on the dose of metformin already being taken) and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability, • for patients inadequately controlled on pioglitazone monotherapy: 15 mg/500 mg twice daily or 15 mg/850 mg once daily and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability. • for patients who are changing from combination therapy of pioglitazone plus metformin as separate tablets: pioglitazone and metformin hydrochloride tablets should be taken at doses that are as close as possible to the dose of pioglitazone and metformin already being taken.
Pioglitazone and metformin hydrochloride tablets may be titrated up to a maximum daily dose of 45 mg of pioglitazone and 2550 mg of metformin.

Metformin doses above 2000 mg may be better tolerated given three times a day.

After initiation of pioglitazone and metformin hydrochloride 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 (5.1)]. Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating pioglitazone and metformin hydrochloride tablets. Routine periodic monitoring of liver tests during treatment with pioglitazone and metformin hydrochloride tablets are not recommended in patients without liver disease. Patients who have liver test abnormalities prior to initiation of pioglitazone and metformin hydrochloride tablets or who are found to have abnormal liver tests while taking pioglitazone and metformin hydrochloride tablets should be managed as described under Warnings and Precautions [see Warnings and Precautions (5.4) and Clinical Pharmacology (12.3)].

2.2 Concomitant Use with an Insulin Secretagogue or Insulin

If hypoglycemia occurs in a patient coadministered pioglitazone and metformin hydrochloride 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 and metformin hydrochloride 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 (one of the ingredients in pioglitazone and metformin hydrochloride tablets) and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure approximately 3-fold. Therefore, the maximum recommended dose of pioglitazone and metformin hydrochloride tablets is 15 mg/850 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Felodipine

Felodipine

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).
Eszopiclone

Eszopiclone

2.1 Dosage in Adults

The dose of eszopiclone tablets should be individualized. The recommended starting dose for eszopiclone tablets for most non-elderly adults is 2 mg immediately before bedtime. Dosing can be initiated at or raised to 3 mg if clinically indicated, since 3 mg is more effective for sleep maintenance [see Warnings and Precautions (5)].

Use in Geriatric Patients

The recommended starting dose of eszopiclone tablets for elderly patients whose primary complaint is difficulty falling asleep is 1 mg immediately before bedtime. In these patients, the dose may be increased to 2 mg if clinically indicated. For elderly patients whose primary complaint is difficulty staying asleep, the recommended dose is 2 mg immediately before bedtime [see Warnings and Precautions (5.7)].

Use in Patients with Hepatic Impairment

The starting dose of eszopiclone tablets should be 1 mg in patients with severe hepatic impairment. Eszopiclone tablets should be used with caution in these patients.

Use with CYP3A4 Inhibitors

The starting dose of eszopiclone tablets should not exceed 1 mg in patients coadministered eszopiclone tablets with potent CYP3A4 inhibitors. If needed, the dose can be raised to 2 mg.

Use with CNS Depressants

Dosage adjustments may be necessary when eszopiclone tablets are combined with other CNS depressant drugs because of the potentially additive effects [see Warnings and Precautions (5.5)].

Administration with Food

Taking eszopiclone tablets with or immediately after a heavy, high-fat meal results in slower absorption and would be expected to reduce the effect of eszopiclone tablets on sleep latency [see Clinical Pharmacology (12.3)].
Potassium Chloride

Potassium Chloride

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

Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40-100 mEq per day or more are used for the treatment of potassium depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose.

Each Potassium Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of potassium chloride.

Potassium Chloride Extended Release Tablets USP, 20 mEq should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS).

Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration:
Break the tablet in half, and take each half separately with a glass of water. Prepare an aqueous (water) suspension as follows: Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces). Allow approximately 2 minutes for the tablet(s) to disintegrate. Stir for about half a minute after the tablet(s) has disintegrated. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw. Add another 1 fluid ounce of water, swirl, and consume immediately. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.
Aqueous suspension of Potassium Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Potassium Chloride Extended Release Tablets USP, 20 mEq is not recommended.
Np Thyroid 30

Np Thyroid 30

DOSAGE AND ADMINISTRATION: The dosage of thyroid hormones is determined by the indication and must in every case be individualized according to patient response and laboratory findings. Thyroid hormones are given orally. In acute, emergency conditions, injectable levothyroxine sodium may be given intravenously when oral administration is not feasible or desirable, as in the treatment of myxedema coma, or during total parenteral nutrition. Intramuscular administration is not advisable because of reported poor absorption.Hypothyroidism—Therapy is usually instituted using low doses, with increments which depend on the cardiovascular status of the patient. The usual starting dose is 30 mg NP Thyroid, with increments of 15 mg every 2 to 3 weeks. A lower starting dosage, 15 mg/day, is recommended in patients with long standing myxedema, particularly if cardiovascular impairment is suspected, in which case extreme caution is recommended. The appearance of angina is an indication for a reduction in dosage. Most patients require 60 to 120 mg/day. Failure to respond to doses of 180 mg suggests lack of compliance or malabsorption. Maintenance dosages 60 to 120 mg/day usually result in normal serum levothyroxine (T4) and triiodothyronine (T3) levels. Adequate therapy usually results in normal TSH and T4 levels after 2 to 3 weeks of therapy. Readjustment of thyroid hormone dosage should be made within the first four weeks of therapy, after proper clinical and laboratory evaluations, including serum levels of T4, bound and free, and TSH. T3 may be used in preference to levothyroxine (T4) during radio-isotope scanning procedures, since induction of hypothyroidism in those cases is more abrupt and can be of shorter duration. It may also be preferred when impairment of peripheral conversion of T4 and T3 is suspected.Myxedema Coma—Myxedema coma is usually precipitated in the hypothyroid patient of longstanding by intercurrent illness or drugs such as sedatives and anesthetics and should be considered a medical emergency. Therapy should be directed at the correction of electrolyte disturbances and possible infection besides the administration of thyroid hormones. Corticosteroids should be administered routinely. T4 and T3 may be administered via a nasogastric tube but the preferred route of administration of both hormones is intravenous. Levothyroxine sodium (T4) is given at starting dose of 400 mcg (100 mcg/mL) given rapidly, and is usually well tolerated, even in the elderly. This initial dose is followed by daily supplements of 100 to 200 mcg given intravenously. Normal T4 levels are achieved in 24 hours followed in 3 days by threefold elevation of T3. Oral therapy with thyroid hormone would be resumed as soon as the clinical situation has been stabilized and the patient is able to take oral medication.Thyroid Cancer—Exogenous thyroid hormone may produce regression of metastases from follicular and papillary carcinoma of the thyroid and is used as ancillary therapy of these conditions with radioactive iodine. TSH should be suppressed to low or undetectable levels. Therefore, larger amounts of thyroid hormone than those used for replacement therapy are required. Medullary carcinoma of the thyroid is usually unresponsive to this therapy.Thyroid Suppression Therapy—Administration of thyroid hormone in doses higher than those produced physiologically by the gland results in suppression of the production of endogenous hormone. This is the basis for the thyroid suppression test and is used as an aid in the diagnosis of patients with signs of mild hyperthyroidism in whom base line laboratory tests appear normal, or to demonstrate thyroid gland autonomy in patients with Grave’s ophthalmopathy. 131I uptake is determined before and after the administration of the exogenous hormone. A 50 percent or greater suppression of uptake indicates a normal thyroid-pituitary axis and thus rules out thyroid gland autonomy. For adults, the usual suppressive dose of levothyroxine (T4) is 1.56 mcg/kg of body weight per day given for 7 to 10 days. These doses usually yield normal serum T4 and T3 levels and lack of response to TSH. Thyroid hormones should be administered cautiously to patients in whom there is strong suspicion of thyroid gland autonomy, in view of the fact that the exogenous hormone effects will be additive to the endogenous source.Pediatric Dosage—Pediatric dosage should follow the recommendations summarized in Table 1. In infants with congenital hypothyroidism, therapy with full doses should be instituted as soon as the diagnosis has been made.
Recommended Pediatric Dosage for Congenital Hypothyroidism NP Thyroid Tablets Age Dose per day Daily dose per kg of body weight 0 - 6 mos. 15 - 30 mg 4.8 - 6 mg 6 - 12 mos. 30 - 45 mg 3.6 - 4.8 mg 1 - 5 yrs. 45 - 60 mg 3 - 3.6 mg 6 - 12 yrs. 60 - 90 mg 2.4 - 3 mg Over 12 yrs. Over 90 mg 1.2 - 1.8 mg
Kimvent Q2 Oral Care Ki...

Kimvent Q2 Oral Care Kit

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

Addison's Disease

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

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

Salt-Losing Adrenogenital Syndrome

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

* 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.

This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit. 4 For a discussion of ciprofloxacin serum concentrations in various human populations, see INHALATIONAL ANTHRAX – ADDITIONAL INFORMATION.
ADULT DOSAGE GUIDELINES Infection Severity Dose Frequency Usual Durations† Urinary Tract Acute Uncomplicated 250 mg q 12 h 3 days Mild/Moderate 250 mg q 12 h 7 to 14 days Severe/Complicated 500mg q 12 h 7 to 14 days Chronic Bacterial Mild/Moderate 500 mg q 12 h 28 days Prostatitis 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 Mild/Moderate 500 mg q 12 h 7 to 14 days Skin Structure 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 week Intra-Abdominal* Complicated 500 mg q 12 h 7 to 14 daysInfectious Diarrhea Mild/Moderate/Severe 500 mg q 12 h 5 to 7 daysTyphoid Fever Mild/Moderate 500 mg q 12 h 10 daysUrethral and Cervical Uncomplicated 250 mg single dose single doseGonococcal InfectionsInhalational anthrax 500 mg q 12 h 60 days(post-exposure)**
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 – 50 250 – 500 mg q 12 h 5 – 29 250 – 500 mg q 18 h Patients on hemodialysisor Peritoneal dialysis 250 – 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.

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 (i.e., I.V. 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 I.V. every 8 hours and allowed to switch to oral therapy (10 to 20 mg/kg every 12 hours), at the discretion of the physician.

* 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.5 For a discussion of ciprofloxacin serum concentrations in various human populations, see INHALATIONAL ANTHRAX – ADDITIONAL INFORMATION.
PEDIATRIC DOSAGE GUIDELINES Infection Route of Administration Dose(mg/kg) Frequency TotalDuration Complicated Urinary TractorPyelonephritis(patients from1 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 10-21 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 12hours 60 days Oral 15 mg/kg (maximum 500 mg per dose) Every 12hours
Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of complicated urinary tract infection and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (i.e., creatinine clearance of < 50 mL/min/1.73m2).
Triamcinolone Acetonide...

Triamcinolone Acetonide Paste

Press a small dab (about 1/4 inch) to the lesion until a thin film develops. A larger quantity may be required for coverage of some lesions. For optimal results use only enough to coat the lesion with a thin film. Do not rub in. Attempting to spread this preparation may result in granular, gritty sensation and cause it to crumble. After application, however, a smooth, slippery film develops.

The preparation should be applied at bedtime to permit steroid contact with the lesion throughout the night. Depending on the severity of symptoms, it may be necessary to apply the preparation two or three times a day, preferably after meals. If significant repair or regeneration has not occurred in seven days, further investigation is advisable.
Oxcarbazepine Suspensio...

Oxcarbazepine Suspension

All dosing should be given in a twice-a-day regimen.

Oxcarbazepine 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 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 (12.4)]. 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 Oxcarbazepinefor 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)]
Polyethylene Glycol 335...

Polyethylene Glycol 3350

The usual dose is 17 grams (about 1 heaping tablespoonful) of powder per day (or as directed by physician) in 4 - 8 ounces of water, juice, soda, coffee, or tea. Each bottle of Polyethylene Glycol 3350, NF is supplied with a dosing cap marked to contain 17 grams of laxative powder when filled to the indicated line.

Two to 4 days (48 to 96 hours) may be required to produce a bowel movement.
Progesterone

Progesterone

Prevention of Endometrial Hyperplasia

Progesterone Capsules should be given as a single daily dose at bedtime, 200 mg orally for 12 days sequentially per 28-day cycle, to a postmenopausal woman with a uterus who is receiving daily conjugated estrogens tablets.

Treatment of Secondary Amenorrhea

Progesterone Capsules may be given as a single daily dose of 400 mg at bedtime for 10 days.

Some women may experience difficulty swallowing Progesterone Capsules. For these women, Progesterone Capsules should be taken with a glass of water while in the standing position.
Fluocinolone Acetonide ...

Fluocinolone Acetonide Oil

Fluocinolone acetonide 0.01% topical oil is not for oral, ophthalmic, or intravaginal use.

The dosing of fluocinolone acetonide 0.01% topical oil is different for adult and pediatric patients.

2.1. Adult Patients with Atopic Dermatitis

Apply fluocinolone acetonide 0.01% topical oil as a thin film to the affected areas three times daily.

2.2. Pediatric Patients with Atopic Dermatitis

Moisten skin and apply fluocinolone acetonide 0.01% topical oil as a thin film to the affected areas twice daily for up to four weeks.
Fluocinolone Acetonide ...

Fluocinolone Acetonide Oil

Fluocinolone Acetonide 0.01% Topical Oil for scalp psoriasis in adults (Scalp Oil):

For the treatment of scalp psoriasis, wet or dampen hair and scalp thoroughly. Apply a thin film of Fluocinolone Acetonide 0.01% Topical Oil on the scalp, massage well and cover scalp with the supplied shower cap. Leave on overnight, or for a minimum of 4 hours before washing off. Wash hair with regular shampoo and rinse thoroughly.
Entacapone

Entacapone

The recommended dose of Entacapone Tablets is one 200 mg tablet administered concomitantly with each levodopa and carbidopa dose to a maximum of 8 times daily (200 mg x 8 = 1,600 mg per day). Clinical experience with daily doses above 1,600 mg is limited. Entacapone Tablets should always be administered in association with levodopa and carbidopa. Entacapone has no antiparkinsonian effect of its own. In clinical trials, the majority of patients required a decrease in daily levodopa dose if their daily dose of levodopa had been greater than or equal to 800 mg or if patients had moderate or severe dyskinesias before beginning treatment. To optimize an individual patient’s response, reductions in daily levodopa dose or extending the interval between doses may be necessary. In clinical trials, the average reduction in daily levodopa dose was about 25% in those patients requiring a levodopa dose reduction. (More than 58% of patients with levodopa doses above 800 mg daily required such a reduction.) Entacapone Tablets can be combined with both the immediate and sustained-release formulations of levodopa and carbidopa. Entacapone Tablets may be taken with or without food (see CLINICAL PHARMACOLOGY).

Patients With Impaired Hepatic Function: Patients with hepatic impairment should be treated with caution. The AUC and Cmax of entacapone approximately doubled in patients with documented liver disease, compared to controls. However, these studies were conducted with single-dose entacapone without levodopa and dopa decarboxylase inhibitor coadministration, and therefore the effects of liver disease on the kinetics of chronically administered entacapone have not been evaluated (see CLINICAL PHARMACOLOGY, Pharmacokinetics of Entacapone).

Withdrawing Patients from Entacapone Tablets: Rapid withdrawal or abrupt reduction in the Entacapone Tablets dose could lead to emergence of signs and symptoms of Parkinson’s Disease (see CLINICAL PHARMACOLOGY, Clinical Studies), and may lead to Hyperpyrexia and Confusion, a symptom complex resembling the neuroleptic malignant syndrome (see PRECAUTIONS, Other Events Reported With Dopaminergic Therapy). This syndrome should be considered in the differential diagnosis for any patient who develops a high fever or severe rigidity. If a decision is made to discontinue treatment with Entacapone Tablets, patients should be monitored closely and other dopaminergic treatments should be adjusted as needed. Although tapering Entacapone Tablets have not been systematically evaluated, it seems prudent to withdraw patients slowly if the decision to discontinue treatment is made.
Tizanidine Hydrochlorid...

Tizanidine Hydrochloride

2.1 Dosing Information

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

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

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

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

2.2 Dosing in Patients with Renal Impairment

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

2.3 Dosing in Patients with Hepatic Impairment

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

2.4 Drug Discontinuation

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

Amoxicillin

Amoxicillin capsules may be given without regard to meals.

Neonates and Infants Aged ≤ 12 Weeks (≤ 3 Months)

Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin is 30 mg/kg/day divided q12h.

Adults and Pediatric Patients > 3 Months
* Dosing for infections caused by less susceptible organisms should follow the recommendations for severe infections.† The children’s dosage is intended for individuals whose weight is less than 40 kg. Children weighing 40 kg or more should be dosed according to the adult recommendations. Infection Severity* Usual Adult Dose Usual Dose for Children >3 Months† Ear/Nose/Throat Mild/ Moderate 500 mg every 12 hours or 250 mg every 8 hours 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hoursor 40 mg/kg/day in divided doses every 8 hours Lower Respiratory Tract Mild/ Moderate or Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hoursor 40 mg/kg/day in divided doses every 8 hours Skin/Skin Structure Mild/ Moderate 500 mg every 12 hours or 250 mg every 8 hours 25 mg/kg/day in divided doses every 12 hoursor 20 mg/kg/day in divided doses every 8 hours Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hoursor 40 mg/kg/day in divided doses every 8 hours Genitourinary Tract Mild/ Moderate 500 mg every 12 hours or 250 mg every 8 hours 25 mg/kg/day in divided doses every 12 hoursor 20 mg/kg/day in divided doses every 8 hours Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hoursor 40 mg/kg/day in divided doses every 8 hours Gonorrhea Acute, uncomplicated ano-genital and urethral infections in males and females 3 grams as single oral dose Prepubertal children:50 mg/kg Amoxicillin, combined with 25 mg/kg probenecid as a single dose.NOTE: SINCE PROBENECID IS CONTRAINDICATED IN CHILDREN UNDER 2 YEARS, DO NOT USE THIS REGIMEN IN THESE CASES.
All patients with gonorrhea should be evaluated for syphilis. (See PRECAUTIONS: Laboratory Tests section.)

Larger doses may be required for stubborn or severe infections.

General

It should be recognized that in the treatment of chronic urinary tract infections, frequent bacteriological and clinical appraisals are necessary. Smaller doses than those recommended above should not be used. Even higher doses may be needed at times. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy. Except for gonorrhea, treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever.

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

Triple Therapy

Amoxicillin/Clarithromycin/Lansoprazole

The recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (q12h) for 14 days. (See INDICATIONS AND USAGE section.)

Dual Therapy

Amoxicillin/Lansoprazole

The recommended adult oral dose is 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (q8h) for 14 days. (See INDICATIONS AND USAGE section.)

Please refer to clarithromycin and lansoprazole full prescribing information for CONTRAINDICATIONS and WARNINGS section, and for information regarding dosing in elderly and renally impaired patients.

Dosing Recommendations for Adults with Impaired Renal Function

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of < 30 mL/min should not receive the 875 mg tablet. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a less than 10 mL/min glomerular filtration rate should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection.

Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

There are currently no dosing recommendations for pediatric patients with impaired renal function.
Doctor Hoys Natural Pai...

Doctor Hoys Natural Pain Relief

2.1 Asthma

Montelukast sodium should be taken once daily in the evening. The following doses are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet.

Safety and effectiveness in pediatric patients less than 12 months of age with asthma have not been established.

There have been no clinical trials in patients with asthma to evaluate the relative efficacy of morning versus evening dosing. The pharmacokinetics of montelukast are similar whether dosed in the morning or evening. Efficacy has been demonstrated for asthma when montelukast was administered in the evening without regard to time of food ingestion.

2.2 Exercise-Induced Bronchoconstriction (EIB) in Patients 15 Years of Age and Older

For prevention of EIB, a single 10 mg dose of montelukast should be taken at least 2 hours before exercise. An additional dose of montelukast should not be taken within 24 hours of a previous dose. Patients already taking montelukast sodium daily for another indication (including chronic asthma) should not take an additional dose to prevent EIB. All patients should have available for rescue a short-acting β-agonist. Safety and effectiveness in patients younger than 15 years of age have not been established. Daily administration of montelukast sodium for the chronic treatment of asthma has not been established to prevent acute episodes of EIB.

Pediatric use information for patients ages 6 to 14 years of age for acute prevention of exercise-induced bronchoconstriction (EIB) is approved for Merck Sharp & Dohme Corp's montelukast tablet products. However, due to Merck Sharp & Dohme Corp's marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.3 Allergic Rhinitis

For allergic rhinitis, montelukast sodium should be taken once daily. Efficacy was demonstrated for seasonal allergic rhinitis when montelukast was administered in the morning or the evening without regard to time of food ingestion. The time of administration may be individualized to suit patient needs.

The following doses for the treatment of symptoms of seasonal allergic rhinitis are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet.

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet

Safety and effectiveness in pediatric patients younger than 2 years of age with seasonal allergic rhinitis have not been established.

The following doses for the treatment of symptoms of perennial allergic rhinitis are recommended:

For adults and adolescents 15 years of age and older: one 10-mg tablet

For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet

For pediatric patients 2 to 5 years of age: one 4-mg chewable tablet

Safety and effectiveness in pediatric patients younger than 2 years of age with perennial allergic rhinitis have not been established.

2.4 Asthma and Allergic Rhinitis

Patients with both asthma and allergic rhinitis should take only one montelukast sodium dose daily in the evening.
Cephalexin

Cephalexin

Cephalexin capsules are administered orally.

Adults — The adult dosage ranges from 1 to 4 g daily in divided doses. The 333 mg and the 750 mg strengths should be administered such that the daily dose is within 1 to 4 grams per day. 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.

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.
Duloxetine

Duloxetine

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

2.1 Initial Treatment

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

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

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

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

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

2.2 Maintenance/Continuation/Extended Treatment

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

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

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

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

2.3 Dosing in Special Populations

Hepatic Insufficiency - It is recommended that duloxetine delayed-release should ordinarily not be administered to patients with any hepatic insufficiency [see Warnings and Precautions (5.13) and Use in Specific Populations (8.9)].

Severe Renal Impairment - Duloxetine delayed-release is not recommended for patients with end-stage renal disease or severe renal impairment (estimated creatinine clearance <30 mL/min) [see Warnings and Precautions (5.13) and Use in Specific Populations (8.10)].

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

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

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

2.4 Discontinuing Duloxetine Delayed-Release

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

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

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

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

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

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

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

Olanzapine And Fluoxetine

2.1 Depressive Episodes Associated With Bipolar I Disorder

Adults - Olanzapine and fluoxetine capsules USP should be administered once daily in the evening, generally beginning with the 6 mg/25 mg capsule (mg equivalent olanzapine/mg equivalent fluoxetine) capsule. While food has no appreciable effect on the absorption of olanzapine and fluoxetine given individually, the effect of food on the absorption of olanzapine and fluoxetine capsules USP has not been studied. Dosage adjustments, if indicated, can be made according to efficacy and tolerability. Antidepressant efficacy was demonstrated with olanzapine and fluoxetine capsules USP in a dose range of olanzapine 6 mg to 12 mg and fluoxetine 25 mg to 50 mg [see Clinical Studies (14.1)]. The safety of doses above 18 mg of olanzapine and 75 mg of fluoxetine has not been evaluated in adult clinical studies.

There is no body of evidence to answer the question of how long a patient treated with olanzapine and fluoxetine capsules USP should remain on them beyond 8 weeks. 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 reexamine the need for continued pharmacotherapy.

2.3 Specific Populations

The starting dose of olanzapine and fluoxetine capsules USP, 3 mg/25 mg to 6 mg/25 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 and fluoxetine capsules USP (female gender, geriatric age, nonsmoking status) or those patients who may be pharmacodynamically sensitive to olanzapine. Dosing modification 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. Olanzapine and fluoxetine capsules USP have not been systematically studied in patients > 65 years of age or in patients < 10 years of age [see Warnings and Precautions (5.19), Use in Specific Populations (8.5), and Clinical Pharmacology (12.3, 12.4)].

Treatment of Pregnant Women — When treating pregnant women with fluoxetine, a component of olanzapine and fluoxetine capsules USP, 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 hospitalizations, respiratory support, and tube feeding [see Use in Specific Populations (8.1)].

2.4 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 olanzapine and fluoxetine capsules USP. Conversely, at least 5 weeks should be allowed after stopping olanzapine and fluoxetine capsules USP before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.1)].

2.5 Use of Olanzapine and Fluoxetine Capsules USP With Other MAOIs Such as Linezolid or Methylene Blue

Do not start olanzapine and fluoxetine capsules USP 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 olanzapine and fluoxetine capsule 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 are judged to outweigh the risks of serotonin syndrome in a particular patient, olanzapine and fluoxetine capsules USP 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 olanzapine and fluoxetine capsules USP may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.7)].

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 olanzapine and fluoxetine capsules USP is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.7)].

2.6 Discontinuation of Treatment With Olanzapine and Fluoxetine Capsules USP

Symptoms associated with discontinuation of fluoxetine, a component of olanzapine and fluoxetine capsules USP, SNRIs, and SSRIs, have been reported [see Warnings and Precautions (5.24)].
Minoxidil

Minoxidil

Patients over 12 years of age: The recommended initial dosage of minoxidil tablets is 5 mg of minoxidil given as a single daily dose. Daily dosage can be increased to 10, 20 and then to 40 mg in single or divided doses if required for optimum blood pressure control. The effective dosage range is usually 10 to 40 mg per day. The maximum recommended dosage is 100 mg per day.

Patients under 12 years of age: The initial dosage is 0.2 mg/kg minoxidil as a single daily dose. The dosage may be increased in 50 to 100% increments until optimum blood pressure control is achieved. The effective dosage range is usually 0.25 mg to 1 mg/kg/day. The maximum recommended dosage is 50 mg daily (see 9. Pediatric Use under PRECAUTIONS).

Dose frequency: The magnitude of within-day fluctuation of arterial pressure during therapy with minoxidil is directly proportional to the extent of pressure reduction. If supine diastolic pressure has been reduced less than 30 mm Hg, the drug need be administered only once a day; if supine diastolic pressure has been reduced more than 30 mm Hg, the daily dosage should be divided into two equal parts.

Frequency of dosage adjustment: Dosage must be titrated carefully according to individual response. Intervals between dosage adjustments normally should be at least 3 days since the full response to a given dose is not obtained for at least that amount of time. Where a more rapid management of hypertension is required, dose adjustments can be made every 6 hours if the patient is carefully monitored.

Concomitant therapy: Diuretic and beta-blocker or other sympathetic nervous system suppressant.

Diuretics: Minoxidil must be used in conjunction with a diuretic in patients relying on renal function for maintaining salt and water balance. Diuretics have been used at the following dosages when starting therapy with minoxidil: hydrochlorothiazide (50 mg, b.i.d.) or other thiazides at equieffective dosage; chlorthalidone (50 to 100 mg, once daily); furosemide (40 mg, b.i.d.). If excessive salt and water retention results in a weight gain of more than 5 pounds, diuretic therapy should be changed to furosemide; if the patient is already taking furosemide, dosage should be increased in accordance with the patient's requirements.

Beta-blocker or other sympathetic nervous system suppressants: When therapy with minoxidil is begun, the dosage of a beta-adrenergic receptor blocking drug should be the equivalent of 80 to 160 mg of propranolol per day in divided doses.

If beta-blockers are contraindicated, methyldopa (250 to 750 mg, b.i.d.) may be used instead. Methyldopa must be given for at least 24 hours before starting therapy with minoxidil because of the delay in the onset of methyldopa's action. Limited clinical experience indicates that clonidine may also be used to prevent tachycardia induced by minoxidil; the usual dosage is 0.1 to 0.2 mg twice daily.

Sympathetic nervous system suppressants may not completely prevent an increase in heart rate due to minoxidil but usually do prevent tachycardia. Typically, patients receiving a beta-blocker prior to initiation of therapy with minoxidil have a bradycardia and can be expected to have an increase in heart rate toward normal when minoxidil is added. When treatment with minoxidil and beta-blocker or other sympathetic nervous system suppressant are begun simultaneously, their opposing cardiac effects usually nullify each other, leading to little change in heart rate.
Day Night Cold And Flu

Day Night Cold And Flu

The dosage of Amantadine Hydrochloride Capsules may need to be reduced in patients with congestive heart failure, peripheral edema, orthostatic hypotension, or impaired renal function (see Dosage for Impaired Renal Function).

Dosage for Prophylaxis and Treatment of Uncomplicated Influenza A Virus Illness

Adult: The adult daily dosage of Amantadine Hydrochloride Capsules is 200 mg; two 100 mg capsules as a single daily dose. The daily dosage may be split into one capsule of 100 mg twice a day. If central nervous system effects develop in once-a-day dosage, a split dosage schedule may reduce such complaints. In persons 65 years of age or older, the daily dosage of Amantadine Hydrochloride Capsules is 100 mg.

A 100 mg daily dose has also been shown in experimental challenge studies to be effective as prophylaxis in healthy adults who are not at high risk for influenza-related complications. However, it has not been demonstrated that a 100 mg daily dose is as effective as a 200 mg daily dose for prophylaxis, nor has the 100 mg daily dose been studied in the treatment of acute influenza illness. In recent clinical trials, the incidence of central nervous system (CNS) side effects associated with the 100 mg daily dose was at or near the level of placebo. The 100 mg dose is recommended for persons who have demonstrated intolerance to 200 mg of Amantadine Hydrochloride Capsules daily because of CNS or other toxicities.

Pediatric Patients: 1 yr. to 9 yrs. of age: The total daily dose should be calculated on the basis of 2 to 4 mg/lb/day (4.4 to 8.8 mg/kg/day), but not to exceed 150 mg per day.

9 yrs.to12 yrs. of age: The total daily dose is 200 mg given as one capsule of 100 mg twice a day. The 100 mg daily dose has not been studied in this pediatric population. Therefore, there are no data which demonstrate that this dose is as effective as or is safer than the 200 mg daily dose in this patient population.

Prophylactic dosing should be started in anticipation of an influenza A outbreak and before or after contact with individuals with influenza A virus respiratory tract illness.

Amantadine Hydrochloride Capsules should be continued daily for at least 10 days following a known exposure. If Amantadine Hydrochloride Capsules are used chemoprophylactically in conjunction with inactivated influenza A virus vaccine until protective antibody responses develop, then it should be administered for 2 to 4 weeks after the vaccine has been given. When inactivated influenza A virus vaccine is unavailable or contraindicated, Amantadine Hydrochloride Capsules should be administered for the duration of known influenza A in the community because of repeated and unknown exposure.

Treatment of influenza A virus illness should be started as soon as possible, preferably within 24 to 48 hours after onset of signs and symptoms, and should be continued for 24 to 48 hours after the disappearance of signs and symptoms.

Dosage for Parkinsonism

Adult: The usual dose of Amantadine Hydrochloride Capsules is 100 mg twice a day when used alone. Amantadine Hydrochloride Capsules have an onset of action usually within 48 hours.

The initial dose of Amantadine Hydrochloride Capsules is 100 mg daily for patients with serious associated medical illnesses or who are receiving high doses of other antiparkinson drugs. After one to several weeks at 100 mg once daily, the dose may be increased to 100 mg twice daily, if necessary.

Occasionally, patients whose responses are not optimal with Amantadine Hydrochloride Capsules at 200 mg daily may benefit from an increase up to 400 mg daily in divided doses. However, such patients should be supervised closely by their physicians.

Patients initially deriving benefit from Amantadine Hydrochloride Capsules not uncommonly experience a fall-off of effectiveness after a few months. Benefit may be regained by increasing the dose to 300 mg daily. Alternatively, temporary discontinuation of Amantadine Hydrochloride Capsules for several weeks, followed by reinitiation of the drug, may result in regaining benefit in some patients. A decision to use other antiparkinson drugs may be necessary.

Dosage for Concomitant Therapy

Some patients who do not respond to anticholinergic antiparkinson drugs may respond to Amantadine Hydrochloride Capsules. When Amantadine Hydrochloride Capsules or anticholinergic antiparkinson drugs are each used with marginal benefit, concomitant use may produce additional benefit.

When Amantadine Hydrochloride Capsules and levodopa are initiated concurrently, the patient can exhibit rapid therapeutic benefits. Amantadine Hydrochloride Capsules, should be held constant at 100 mg daily or twice daily while the daily dose of levodopa is gradually increased to optimal benefit.

When Amantadine Hydrochloride Capsules are added to optimal well-tolerated doses of levodopa, additional benefit may result, including smoothing out the fluctuations in improvement which sometimes occur in patients on levodopa alone. Patients who require a reduction in their usual dose of levodopa because of development of side effects may possibly regain lost benefit with the addition of Amantadine Hydrochloride Capsules.

Dosage for Drug-Induced Extrapyramidal Reactions

Adult: The usual dose of Amantadine Hydrochloride Capsules is 100 mg twice a day. Occasionally, patients whose responses are not optimal with Amantadine Hydrochloride Capsules at 200 mg daily may benefit from an increase up to 300 mg daily in divided doses.

Dosage for Impaired Renal Function

Depending upon creatinine clearance, the following dosage adjustments are recommended:
CREATININE CLEARANCE (mL/min/1.73 m2) Amantadine Hydrochloride Capsules DOSAGE 30 to 50 200 mg 1st day and 100 mg each day thereafter 15 to 29 200 mg 1st day followed by 100 mg on alternate days <15 200 mg every 7 days
The recommended dosage for patients on hemodialysis is 200 mg every 7 days.
Salsalate

Salsalate

Carefully consider the potential benefits and risks of Salsalate tablet, USP and other treatment options before deciding to use Salsalate tablet, USP. 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 Salsalate tablet, USP, the dose and frequency should be adjusted to suit an individual patient's needs. Salsalate is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorder.

Adults: The usual dosage is 3000 mg daily, given in divided doses as follows: 1) two doses of two 750 mg tablets; 2) two doses of three 500 mg tablets; or 3) three doses of two 500 mg tablets. Some patients, e.g., the elderly, may require a lower dosage to achieve therapeutic blood concentrations and to avoid the more common side effects such as auditory.

Alleviation of symptoms is gradual, and full benefit may not be evident for 3 to 4 days, when plasma salicylate levels have achieved steady state. There is no evidence for development of tissue tolerance (tachyphylaxis), but salicylate therapy may induce increased activity of metabolizing liver enzymes, causing a greater rate of salicyluric acid production and excretion, with a resultant increase in dosage requirement for maintenance of therapeutic serum salicylate levels.

Children: Dosage recommendations and indications for salsalate use in children have not been established.
Equate Daytime Severe

Equate Daytime Severe

When Lidocaine Ointment USP, 5% is used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind.

Adult

A single application should not exceed 5 g of Lidocaine Ointment USP, 5% containing 250 mg of lidocaine base (equivalent chemically to approximately 300 mg of Lidocaine hydrochloride). This is roughly equivalent to squeezing a six (6) inch length of ointment from the tube. In a 70 kg adult this dose equals 3.6 mg/kg (1.6 mg/lb) lidocaine base. No more than 17-20 g of ointment or 850-1000 mg lidocaine base should be administered in any one day.

Although the incidence of adverse effects with Lidocaine Ointment USP, 5% is quite low, caution should be exercised, particularly when employing large amounts, since the incidence of adverse effects is directly proportional to the total dose of local anesthetic agent administered.

Dosage for children

It is difficult to recommend a maximum dose of any drug for children since this varies as a function of age and weight. For children less than ten years who have a normal lean body mass and a normal lean body development, the maximum dose may be determined by the application of one of the standard pediatric drug formulas (e.g., Clark's rule). For example, in a child of five years weighing 50 lbs., the dose of lidocaine should not exceed 75-100 mg when calculated according to Clark's rule. In any case, the maximum amount of lidocaine administered should not exceed 4.5 mg/kg (2.0 mg/lb) of body weight.

Administration

For medical use, apply topically for adequate control of symptoms. The use of a sterile gauze pad is suggested for application to broken skin tissue. Apply to the tube prior to intubation.

In dentistry, apply to previously dried oral mucosa. Subsequent removal of excess saliva with cotton rolls or saliva ejector minimizes dilution of the ointment, permits maximum penetration, and minimizes the possibility of swallowing the topical ointment.

For use in connection with the insertion of new dentures, apply to all denture surfaces contacting mucosa.

IMPORTANT: Patients should consult a dentist at intervals not exceeding 48 hours throughout the fitting period.
Ergoloid Mesylates

Ergoloid Mesylates

1 mg three times a day.

Alleviation of symptoms is usually gradual and results may not be observed for 3–4 weeks.
Gabapentin

Gabapentin

Gabapentin Capsules is given orally with or without food.

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

Patients >12 years of age: The effective dose of Gabapentin 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 3–12 years: The starting dose should range from 10-15 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 25–35 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, Pediatrics.) 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 is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.

Dosage in Renal Impairment

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

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

where 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. Gabapetin Capsules Dosage Based on Renal Function. Renal Function Creatinine Clearance (mL/min) Total Daily Dose Range (mg/day) Dose Regimen (mg) a For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive). b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table. ≥60 900-3600 300 TID 400 TID 600 TID 800 TID 1200 TID >30-59 400-1400 200 BID 300 BID 400 BID 500 BID 700 BID >15-29 200-700 200 QD 300 QD 400 QD 500 QD 700 QD 15a 100-300 100 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 Capsules 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.
Ranitidine

Ranitidine

Active Duodenal Ulcer: The current recommended adult oral dosage of Ranitidine Tablets, USP for duodenal ulcer is 150 mg twice daily. An alternative dosage of 300 mg once daily after the evening meal or at bedtime can be used for patients in whom dosing convenience is important. The advantages of one treatment regimen compared to the other in a particular patient population have yet to be demonstrated (see Clinical Trials: Active Duodenal Ulcer). Smaller doses have been shown to be equally effective in inhibiting gastric acid secretion in US studies, and several foreign trials have shown that 100 mg twice daily is as effective as the 150-mg dose.

Antacid should be given as needed for relief of pain (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

Maintenance of Healing of Duodenal Ulcers: The current recommended adult oral dosage is 150 mg at bedtime.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome):

The current recommended adult oral dosage is 150 mg twice a day. In some patients it may be necessary to administer Ranitidine Tablets, USP 150-mg doses more frequently. Dosages should be adjusted to individual patient needs, and should continue as long as clinically indicated. Dosages up to 6 g/day have been employed in patients with severe disease.

Benign Gastric Ulcer: The current recommended adult oral dosage is 150 mg twice daily.

Maintenance of Healing of Gastric Ulcers: The current recommended adult oral dosage is 150 mg at bedtime.

GERD: The current recommended adult oral dosage is 150 mg twice daily.

Erosive Esophagitis: The current recommended adult oral dosage is 150 mg four times daily.

Maintenance of Healing of Erosive Esophagitis: The current recommended adult oral dosage is 150 mg twice a day.

Pediatric Use: The safety and effectiveness of Ranitidine Tablets, USP have been established in the age-group of 1 month to 16 years. There is insufficient information about the pharmacokinetics of Ranitidine Tablets, USP in neonatal patients (less than 1 month of age) to make dosing recommendations.

The following 3 subsections provide dosing information for each of the pediatric indications.

Treatment of Duodenal and Gastric Ulcers: The recommended oral dose for the treatment of active duodenal and gastric ulcers is 2 to 4 mg/kg twice daily to a maximum of 300 mg/day. This recommendation is derived from adult clinical studies and pharmacokinetic data in pediatric patients.

Maintenance of Healing of Duodenal and Gastric Ulcers: The recommended oral dose for the maintenance of healing of duodenal and gastric ulcers is 2 to 4 mg/kg once daily to a maximum of 150 mg/day. This recommendation is derived from adult clinical studies and pharmacokinetic data in pediatric patients.

Treatment of GERD and Erosive Esophagitis: Although limited data exist for these conditions in pediatric patients, published literature supports a dosage of 5 to 10 mg/kg/day, usually given as two divided doses.

Dosage Adjustment for Patients With Impaired Renal Function: On the basis of experience with a group of subjects with severely impaired renal function treated with Ranitidine Tablets, USP, the recommended dosage in patients with a creatinine clearance <50 mL/min is 150 mg every 24 hours. Should the patient's condition require, the frequency of dosing may be increased to every 12 hours or even further with caution. Hemodialysis reduces the level of circulating ranitidine. Ideally, the dosing schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis.

Elderly patients are more likely to have decreased renal function, therefore caution should be exercised in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatrics andPRECAUTIONS: Geriatric Use).
Baclofen

Baclofen

The determination of optimal dosage requires individual titration. Start therapy at a low dosage and increase gradually until optimum effect is achieved (usually between 40 to 80 mg daily).

The following dosage titration schedule is suggested:

5 mg t.i.d. for 3 days 10 mg t.i.d. for 3 days 15 mg t.i.d. for 3 days 20 mg t.i.d. for 3 days

Thereafter additional increases may be necessary but the total daily dose should not exceed a maximum of 80 mg daily (20 mg q.i.d.).

The lowest dose compatible with an optimal response is recommended. If benefits are not evident after a reasonable trial period, patients should be slowly withdrawn from the drug (see WARNINGS, Abrupt Drug Withdrawal).
Valsartan And Hydrochlo...

Valsartan And Hydrochlorothiazide

2.1 General Considerations

The usual starting dose is valsartan and hydrochlorothiazide tablets 160 mg/12.5 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 320 mg/25 mg tablet once daily as needed to control blood pressure [see Clinical Studies (14.2)]. Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.

2.2 Add-On Therapy

A patient whose blood pressure is not adequately controlled with valsartan (or another ARB) alone or hydrochlorothiazide alone may be switched to combination therapy with valsartan and hydrochlorothiazide tablets.

A patient who experiences dose-limiting adverse reactions on either component alone may be switched to valsartan and hydrochlorothiazide tablets containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions. The clinical response to valsartan and hydrochlorothiazide tablets should be subsequently evaluated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dose may be titrated up to a maximum of 320 mg/25 mg.

2.3 Replacement Therapy

Valsartan and hydrochlorothiazide tablets may be substituted for the titrated components.

2.4 Initial Therapy

Valsartan and hydrochlorothiazide tablets are not recommended as initial therapy in patients with intravascular volume depletion [see Warnings and Precautions (5.2)].

2.5 Use with Other Antihypertensive Drugs

Valsartan and hydrochlorothiazide tablets may be administered with other antihypertensive agents.
Pravastatin Sodium

Pravastatin Sodium

2.1 General Dosing Information

The patient should be placed on a standard cholesterol-lowering diet before receiving pravastatin sodium tablets and should continue on this diet during treatment with pravastatin sodium tablets [see NCEP Treatment Guidelines for details on dietary therapy].

2.2 Adult Patients

The recommended starting dose is 40 mg once daily. If a daily dose of 40 mg does not achieve desired cholesterol levels, 80 mg once daily is recommended. In patients with significant renal impairment, a starting dose of 10 mg daily is recommended. Pravastatin sodium tablets can be administered orally as a single dose at any time of the day, with or without food. Since the maximal effect of a given dose is seen within 4 weeks, periodic lipid determinations should be performed at this time and dosage adjusted according to the patient’s response to therapy and established treatment guidelines.

2.3 Pediatric Patients

Children (Ages 8 to 13 Years, Inclusive)

The recommended dose is 20 mg once daily in children 8 to 13 years of age. Doses greater than 20 mg have not been studied in this patient population.

Adolescents (Ages 14 to 18 Years)

The recommended starting dose is 40 mg once daily in adolescents 14 to 18 years of age. Doses greater than 40 mg have not been studied in this patient population.

Children and adolescents treated with pravastatin should be reevaluated in adulthood and appropriate changes made to their cholesterol-lowering regimen to achieve adult goals for LDL-C [see Indications and Usage (1.2)].

2.4 Concomitant Lipid-Altering Therapy

Pravastatin sodium tablets may be used with bile acid resins. When administering a bile-acid-binding resin (e.g., cholestyramine, colestipol) and pravastatin, pravastatin sodium tablets should be given either 1 hour or more before or at least 4 hours following the resin [see Clinical Pharmacology (12.3)].

2.5 Dosage in Patients Taking Cyclosporine

In patients taking immunosuppressive drugs such as cyclosporine concomitantly with pravastatin, therapy should begin with 10 mg of pravastatin sodium once-a-day at bedtime and titration to higher doses should be done with caution. Most patients treated with this combination received a maximum pravastatin sodium dose of 20 mg/day. In patients taking cyclosporine, therapy should be limited to 20 mg of pravastatin sodium once daily [see Warnings and Precautions (5.1) and Drug Interactions (7.1)].

2.6 Dosage in Patients Taking Clarithromycin

In patients taking clarithromycin, therapy should be limited to 40 mg of pravastatin sodium once daily [see Drug Interactions (7.2)].
Metformin Hydrochloride...

Metformin Hydrochloride

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with Metformin HCL, USP or any other pharmacologic agent. Dosage of Metformin HCL, USP must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses. The maximum recommended daily dose of Metformin HCL, USP is 2550 mg in adults and 2000 mg in pediatric patients (10 to 16 years of age).

Metformin HCL, USP should be given in divided doses with meals. Metformin HCL, USP should be started at a low dose, with gradual dose escalation, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.

During treatment initiation and dose titration (see Recommended Dosing Schedule), fasting plasma glucose should be used to determine the therapeutic response to Metformin HCL, USP and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of Metformin HCL, USP either when used as monotherapy or in combination with sulfonylurea or insulin.

Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness.

Short-term administration of Metformin HCL, USP may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.

Recommended Dosing Schedule

Adults - In general, clinically significant responses are not seen at doses below 1500 mg per day. However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms.

The usual starting dose of Metformin HCL Tablets, USP is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. Patients can also be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks. For those patients requiring additional glycemic control, Metformin HCL, USP may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.

If higher doses of metformin are required, Metformin HCL, USP should be used at total daily doses up to 2550 mg administered in divided daily doses, as described above. (See CLINICAL PHARMACOLOGY, Clinical Studies.)

Pediatrics - The usual starting dose of Metformin HCL, USP is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Transfer From Other Antidiabetic Therapy

When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to Metformin HCL, USP, no transition period generally is necessary. When transferring patients from chlorpropamide, care should be exercised during the first two weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.

Concomitant Metformin HCL and Oral Sulfonylurea Therapy in Adult Patients

If patients have not responded to four weeks of the maximum dose of Metformin HCL, USP monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing Metformin HCL, USP at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. Clinical and pharmacokinetic drug-drug interaction data are currently available only for metformin plus glyburide (glibenclamide).

With concomitant Metformin HCL, USP and sulfonylurea therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. In a clinical trial of patients with type 2 diabetes and prior failure on glyburide, patients started on Metformin HCL, USP 500 mg and glyburide 20 mg were titrated to 1000/20 mg, 1500/20 mg, 2000/20 mg or 2500/20 mg of Metformin HCL, USP and glyburide, respectively, to reach the goal of glycemic control as measured by FPG, HbA1c and plasma glucose response (see CLINICAL PHARMACOLOGY: Clinical Studies). However, attempts should be made to identify the minimum effective dose of each drug to achieve this goal. With concomitant Metformin HCL, USP and sulfonylurea therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken. (See Package Insert of the respective sulfonylurea.)

If patients have not satisfactorily responded to one to three months of concomitant therapy with the maximum dose of Metformin HCL, USP and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without Metformin HCL, USP.

Concomitant Metformin HCL, USP and Insulin Therapy in Adult Patients

The current insulin dose should be continued upon initiation of Metformin HCL, USP therapy. Metformin HCL, USP therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of Metformin HCL, USP should be increased by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose is 2500 mg for Metformin HCL, USP. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and Metformin HCL, USP. Further adjustment should be individualized based on glucose-lowering response.

Specific Patient Populations

Metformin HCL, USP is not recommended for use in pregnancy. Metformin HCL, USP is not recommended in patients below the age of 10 years.

The initial and maintenance dosing of Metformin HCL, USP should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of Metformin HCL, USP.

Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly. (See WARNINGS.)
Diltiazem Hydrochloride...

Diltiazem Hydrochloride

Patients controlled on diltiazem alone or in combination with other medications may be switched to Diltiazem Hydrochloride Extended-release Capsules (Once-a-Day Dosage) at the nearest equivalent total daily dose. Higher doses of Diltiazem Hydrochloride Extended-release Capsules (Once-a-Day Dosage) may be needed in some patients. Patients should be closely monitored. Subsequent titration to higher or lower doses may be necessary and should be initiated as clinically warranted. There is limited general clinical experience with doses above 360 mg, but doses to 540 mg have been studied in clinical trials. The incidence of side effects increases as the dose increases with first-degree AV block, dizziness, and sinus bradycardia bearing the strongest relationship to dose.

Hypertension. Dosage needs to be adjusted by titration to individual patient needs. When used as monotherapy, reasonable starting doses are 180 to 240 mg once daily, although some patients may respond to lower doses. Maximum antihypertensive effect is usually observed by 14 days of chronic therapy; therefore, dosage adjustments should be scheduled accordingly. The usual dosage range studied in clinical trials was 240 to 360 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily.

Angina. Dosages for the treatment of angina should be adjusted to each patient's needs, starting with a dose of 120 or 180 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily. When necessary, titration may be carried out over a 7- to 14-day period.

Concomitant Use With Other Cardiovascular Agents

1. Sublingual NTG. May be taken as required to abort acute anginal attacks during Diltiazem Hydrochloride Extended-release (One-a-Day Dosage) therapy.

2. Prophylactic Nitrate Therapy. Diltiazem Hydrochloride Extended-release Capsules (Once-a-Day Dosage) may be safely coadministered with short-and long-acting nitrates.

3. Beta-blockers (see WARNINGS and PRECAUTIONS).

4. Antihypertensives. Diltiazem Hydrochloride Extended-release Capsules (Once-a-Day Dosage) have an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of Diltiazem Hydrochloride Extended-release Capsules (Once-a-Day Dosage) or the concomitant antihypertensives may need to be adjusted when adding one to the other.
Glyburide

Glyburide

Patients should be retitrated when transferred from glyburide (micronized) tablets or other oral hypoglycemic agents (see PRECAUTIONS).

There is no fixed dosage regimen for the management of diabetes mellitus with glyburide tablets or any other hypoglycemic agent. In addition to the usual monitoring of urinary glucose, the patient’s blood glucose must also be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of adequate blood glucose lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels may also be of value in monitoring the patient’s response to therapy.

Short-term administration of glyburide tablets may be sufficient during periods of transient loss of control in patients usually controlled well on diet.

Usual Starting Dose

The usual starting dose of glyburide tablets is 2.5 to 5 mg daily, administered with breakfast or the first main meal. Those patients who may be more sensitive to hypoglycemic drugs should be started at 1.25 mg daily. (See PRECAUTIONS section for patients at increased risk.) Failure to follow an appropriate dosage regimen may precipitate hypoglycemia. Patients who do not adhere to their prescribed dietary and drug regimen are more prone to exhibit unsatisfactory response to therapy.

Transfer From Other Hypoglycemic Therapy Patients Receiving Other Oral Antidiabetic Therapy

Transfer of patients from other oral antidiabetic regimens to glyburide tablets should be done conservatively and the initial daily dose should be 2.5 to 5 mg. When transferring patients from oral hypoglycemic agents other than chlorpropamide to glyburide tablets, no transition period and no initial or priming dose are necessary. When transferring patients from chlorpropamide, particular care should be exercised during the first two weeks because the prolonged retention of chlorpropamide in the body and subsequent overlapping drug effects may provoke hypoglycemia.

Patients Receiving Insulin

Some Type II diabetic patients being treated with insulin may respond satisfactorily to glyburide tablets. If the insulin dose is less than 20 units daily, substitution of glyburide tablets 2.5 to 5 mg as a single daily dose may be tried. If the insulin dose is between 20 and 40 units daily, the patient may be placed directly on glyburide tablets 5 mg daily as a single dose. If the insulin dose is more than 40 units daily, a transition period is required for conversion to glyburide tablets. In these patients, insulin dosage is decreased by 50% and glyburide tablets 5 mg daily is started. Please refer to Titration to Maintenance Dose for further explanation.

Patients Receiving Colesevelam

When colesevelam is coadministered with glyburide, maximum plasma concentration and total exposure to glyburide is reduced. Therefore, glyburide tablets should be administered at least 4 hours prior to colesevelam.

Titration to Maintenance Dose

The usual maintenance dose is in the range of 1.25 to 20 mg daily, which may be given as a single dose or in divided doses (see Dosage Interval). Dosage increases should be made in increments of no more than 2.5 mg at weekly intervals based upon the patient’s blood glucose response.

No exact dosage relationship exists between glyburide tablets and the other oral hypoglycemic agents. Although patients may be transferred from the maximum dose of other sulfonylureas, the maximum starting dose of 5 mg of glyburide tablets should be observed. A maintenance dose of 5 mg of glyburide tablets provides approximately the same degree of blood glucose control as 250 to 375 mg chlorpropamide, 250 to 375 mg tolazamide, 500 to 750 mg acetohexamide, or 1000 to 1500 mg tolbutamide.

When transferring patients receiving more than 40 units of insulin daily, they may be started on a daily dose of glyburide tablets 5 mg concomitantly with a 50% reduction in insulin dose. Progressive withdrawal of insulin and increase of glyburide tablets in increments of 1.25 to 2.5 mg every 2 to 10 days is then carried out. During this conversion period when both insulin and glyburide tablets are being used, hypoglycemia may rarely occur. During insulin withdrawal, patients should test their urine for glucose and acetone at least three times daily and report results to their physician. The appearance of persistent acetonuria with glycosuria indicates that the patient is a Type I diabetic who requires insulin therapy.

Concomitant Glyburide and Metformin Therapy

Glyburide tablets should be added gradually to the dosing regimen of patients who have not responded to the maximum dose of metformin monotherapy after four weeks (see Usual Starting Dose and Titration to Maintenance Dose). Refer to metformin package insert.

With concomitant glyburide and metformin therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. However, attempts should be made to identify the optimal dose of each drug needed to achieve this goal. With concomitant glyburide and metformin therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken (see PRECAUTIONS).

Maximum Dose

Daily doses of more than 20 mg are not recommended.

Dosage Interval

Once-a-day therapy is usually satisfactory. Some patients, particularly those receiving more than 10 mg daily, may have a more satisfactory response with twice-a-day dosage.

Specific Patient Populations

Glyburide is not recommended for use in pregnancy or for use in pediatric patients.

In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see PRECAUTIONS).
Progesterone

Progesterone

Prevention of Endometrial Hyperplasia

Progesterone capsules should be given as a single daily dose at bedtime, 200 mg orally for 12 days sequentially per 28-day cycle, to postmenopausal women with a uterus who are receiving daily conjugated estrogens tablets.

Treatment of Secondary Amenorrhea

Progesterone capsules may be given as a single daily dose of 400 mg at bedtime for 10 days.

Some women may experience difficulty swallowing progesterone capsules. For these women, progesterone capsules should be taken with a glass of water while in the standing position.
Metoclopramide

Metoclopramide

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

For the Relief of Symptomatic Gastroesophageal Reflux

Administer from 10 mg to 15 mg of metoclopramide tablet, 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, USP 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 tablet, USP 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 OVERDOSAGE section 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.
Losartan Potassium And ...

Losartan Potassium And Hydrochlorothiazide

Hypertension

Dosing must be individualized. The usual starting dose of losartan is 50 mg once daily, with 25 mg recommended for patients with intravascular volume depletion (e.g., patients treated with diuretics) (see WARNINGS, Hypotension — Volume-Depleted Patients) and patients with a history of hepatic impairment (see WARNINGS, Impaired Hepatic Function). Losartan can be administered once or twice daily at total daily doses of 25 to 100 mg. If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response.

Hydrochlorothiazide is effective in doses of 12.5 to 50 mg once daily and can be given at doses of 12.5 to 25 mg as losartan potassium and hydrochlorothiazide tablets USP.

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.

The side effects (see WARNINGS) of losartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of losartan and hydrochlorothiazide will be associated with both sets of dose-independent side effects.

Replacement Therapy

The combination may be substituted for the titrated components.

Dose Titration by Clinical Effect

A patient whose blood pressure is not adequately controlled with losartan monotherapy (see above) or hydrochlorothiazide alone may be switched to losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg (losartan 50 mg/hydrochlorothiazide 12.5 mg) once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets of losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg once daily or one tablet of losartan potassium and hydrochlorothiazide tablets USP, 100 mg/25 mg (losartan 100 mg/hydrochlorothiazide 25 mg) once daily. A patient whose blood pressure is not adequately controlled with losartan 100 mg monotherapy (see above) may be switched to losartan potassium and hydrochlorothiazide tablets USP, 100 mg/12.5 mg once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets of losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg once daily or one tablet of losartan potassium and hydrochlorothiazide tablets USP, 100 mg/25 mg (losartan 100 mg/hydrochlorothiazide 25 mg) once daily.

A patient whose blood pressure is inadequately controlled by 25 mg once daily of hydrochlorothiazide, or is controlled but who experiences hypokalemia with this regimen, may be switched to losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg, (losartan 50 mg/hydrochlorothiazide 12.5 mg) once daily, reducing the dose of hydrochlorothiazide without reducing the overall expected antihypertensive response. The clinical response to losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg should be subsequently evaluated, and if blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets of losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg once daily or one tablet of losartan potassium and hydrochlorothiazide tablets USP, 100 mg/25 mg (losartan 100 mg/hydrochlorothiazide 25 mg) once daily.

The usual dose of losartan potassium and hydrochlorothiazide tablets USP is one tablet of losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg once daily. More than two tablets of losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg once daily or more than one tablet of losartan potassium and hydrochlorothiazide tablets USP, 100 mg/25 mg once daily is not recommended. The maximal antihypertensive effect is attained about 3 weeks after initiation of therapy.

Use in Patients With Renal Impairment

The usual regimens of therapy with losartan potassium and hydrochlorothiazide tablets USP may be followed as long as the patient's creatinine clearance is greater than 30 mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so losartan potassium and hydrochlorothiazide tablets USP are not recommended.

Patients With Hepatic Impairment

Losartan potassium and hydrochlorothiazide tablets USP are not recommended for titration in patients with hepatic impairment (see WARNINGS, Impaired Hepatic Function) because the appropriate 25 mg starting dose of losartan cannot be given.

Severe Hypertension

The starting dose of losartan potassium and hydrochlorothiazide tablets USP for initial treatment of severe hypertension is one tablet of losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg once daily (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects). For patients who do not respond adequately to losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg after 2 to 4 weeks of therapy, the dosage may be increased to one tablet of losartan potassium and hydrochlorothiazide tablets USP, 100 mg/25 mg once daily. The maximum dose is one tablet of losartan potassium and hydrochlorothiazide tablets USP, 100 mg/25 mg once daily. Losartan potassium and hydrochlorothiazide tablets USP are not recommended as initial therapy in patients with hepatic impairment (see WARNINGS, Impaired Hepatic Function) because the appropriate 25 mg starting dose of losartan cannot be given. It is also not recommended for use as initial therapy in patients with intravascular volume depletion (e.g., patients treated with diuretics, see WARNINGS, Hypotension—Volume–Depleted Patients).

Hypertensive Patients With Left Ventricular Hypertrophy

Treatment should be initiated with losartan potassium 50 mg once daily. Hydrochlorothiazide 12.5 mg should be added or losartan potassium and hydrochlorothiazide tablets USP, 50 mg/12.5 mg substituted if the blood pressure reduction is inadequate. If additional blood pressure reduction is needed, losartan potassium 100 mg and hydrochlorothiazide 12.5 mg or losartan potassium and hydrochlorothiazide tablets USP, 100 mg/12.5 mg may be substituted, followed by losartan potassium 100 mg and hydrochlorothiazide 25 mg or losartan potassium and hydrochlorothiazide tablets USP, 100 mg/25 mg. For further blood pressure reduction other antihypertensives should be added (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, LosartanPotassium, Reduction in the risk of stroke).

Losartan potassium and hydrochlorothiazide tablets USP may be administered with other antihypertensive agents.

Losartan potassium and hydrochlorothiazide tablets USP may be administered with or without food.
Triamterene And Hydroch...

Triamterene And Hydrochlorothiazide

Note: 37.5 mg/25 mg = 37.5 mg triamterene and 25 mg hydrochlorothiazide

75 mg/50 mg = 75 mg triamterene and 50 mg hydrochlorothiazide

The usual dose of Triamterene and Hydrochlorothiazide 37.5 mg/25 mg is one or two tablets daily, given as a single dose, with appropriate monitoring of serum potassium (see WARNINGS). The usual dose of Triamterene and Hydrochlorothiazide 75 mg/50 mg is one tablet daily, with appropriate monitoring of serum potassium (see WARNINGS). There is no experience with the use of more than one 75 mg/50 mg tablet daily or more than two 37.5 mg/25 mg tablets daily. Clinical experience with the administration of two 37.5 mg/25 mg tablets daily in divided doses (rather than as a single dose) suggests an increased risk of electrolyte imbalance and renal dysfunction.

Patients receiving 50 mg of hydrochlorothiazide who become hypokalemic may be transferred to 75 mg/50 mg product directly. Patients receiving 25 mg hydrochlorothiazide who become hypokalemic may be transferred to a 37.5 mg triamterene/25 mg hydrochlorothiazide directly.

In patients requiring hydrochlorothiazide therapy and in whom hypokalemia cannot be risked, therapy may be initiated with 37.5 mg/25 mg of triamterene and hydrochlorothiazide. If an optimal blood pressure response is not obtained with 37.5 mg/25 mg of triamterene and hydrochlorothiazide, the dose should be increased to two 37.5 mg/25 mg tablets daily as a single dose, or one 75 mg/50 mg tablet daily. If blood pressure still is not controlled, another antihypertensive agent may be added (see PRECAUTIONS, Drug Interactions).

Clinical studies have shown that patients taking less bioavailable formulations of triamterene and hydrochlorothiazide in daily doses of 25 mg to 50 mg hydrochlorothiazide and 50 mg to 100 mg triamterene may be safely changed to one 37.5 mg/25 mg of triamterene and hydrochlorothiazide daily. All patients changed from less bioavailable formulations to triamterene and hydrochlorothiazide should be monitored clinically and for serum potassium after the transfer.

Avkare, Inc.

Manufacturer Details

Share This Page

Avkare, Inc. Drugs