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Matte Foundation Sunscr...

Matte Foundation Sunscreen Broad Spectrum Spf 20 Warm Nude No.34

The usual dosage and frequency of administration of doxycycline differs from that of the other tetracyclines. Exceeding the recommended dosage may result in an increased incidence of side effects. Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg/day.

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

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

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

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

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

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

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

Uncomplicated gonococcal infections in adults (except anorectal infections in men)

100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose. The dose may be administered with food, including milk or carbonated beverage, as required.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis

100 mg, by mouth twice a day for 7 days.

Nongonococcal urethritis (NGU) caused by C. trachomatis or U. urealyticum

100 mg by mouth, twice a day for 7 days.

Syphilis – early

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

Syphilis of more than one year's duration

Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 4 weeks.

Acute epididymo-orchitis caused by N. gonorrhoeae

100 mg, by mouth, twice a day for at least 10 days.

Acute epididymo-orchitis caused by C. trachomatis

100 mg, by mouth, twice a day for at least 10 days.

For prophylaxis of malaria

For adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up to the adult dose. Prophylaxis should begin 1–2 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.
Voriconazole

Voriconazole

2.1 Instructions for Use in All Patients

Voriconazole Tablets or Oral Suspension should be taken at least one hour before or after a meal.

2.2 Recommended Dosing in Adults

Invasive aspergillosis and serious fungal infections due to Fusarium spp. and Scedosporium apiospermum

See Table 1. Therapy must be initiated with the specified loading dose regimen of intravenous voriconazole on Day 1 followed by the recommended maintenance dose regimen. Intravenous treatment should be continued for at least 7 days. Once the patient has clinically improved and can tolerate medication given by mouth, the oral tablet form or oral suspension form of voriconazole may be utilized. The recommended oral maintenance dose of 200 mg achieves a voriconazole exposure similar to 3 mg/kg IV; a 300 mg oral dose achieves an exposure similar to 4 mg/kg IV. Switching between the intravenous and oral formulations is appropriate because of the high bioavailability of the oral formulation in adults [see Clinical Pharmacology (12)].

Candidemia in non-neutropenic patients and other deep tissue Candida infections

See Table 1. Patients should be treated for at least 14 days following resolution of symptoms or following last positive culture, whichever is longer.

Esophageal Candidiasis

See Table 1. Patients should be treated for a minimum of 14 days and for at least 7 days following resolution of symptoms.
Table 1: Recommended Dosing Regimen Infection Loading dose Maintenance Dose*,† IV IV Oral‡ * Increase dose when voriconazole is co-administered with phenytoin or efavirenz ( 7); Decrease dose in patients with hepatic impairment ( 2.5) † In healthy volunteer studies, the 200 mg oral q12h dose provided an exposure (AUC τ) similar to a 3 mg/kg IV q12h dose; the 300 mg oral q12h dose provided an exposure (AUC τ) similar to a 4 mg/kg IV q12h dose [see Clinical Pharmacology (12)]. ‡ Adult patients who weigh less than 40 kg should receive half of the oral maintenance dose. § In a clinical study of invasive aspergillosis, the median duration of IV voriconazole therapy was 10 days (range 2–85 days). The median duration of oral voriconazole therapy was 76 days (range 2–232 days) [see Clinical Studies (14.1)]. ¶ In clinical trials, patients with candidemia received 3 mg/kg IV q12h as primary therapy, while patients with other deep tissue Candida infections received 4 mg/kg q12h as salvage therapy. Appropriate dose should be based on the severity and nature of the infection. # Not evaluated in patients with esophageal candidiasis. Invasive Aspergillosis§ 6 mg/kg q12h for the first 24 hours 4 mg/kg q12h 200 mg q12h Candidemia in nonneutropenic patients and other deep tissue Candida infections 6 mg/kg q12h for the first 24 hours 3–4 mg/kg q12h¶ 200 mg q12h Esophageal Candidiasis # # 200 mg q12h Scedosporiosis and Fusariosis 6 mg/kg q12h for the first 24 hours 4 mg/kg q12h 200 mg q12h
2.3 Dosage Adjustment

If patient response is inadequate, the oral maintenance dose may be increased from 200 mg every 12 hours (similar to 3 mg/kg IV q12h) to 300 mg every 12 hours (similar to 4 mg/kg IV q12h). For adult patients weighing less than 40 kg, the oral maintenance dose may be increased from 100 mg every 12 hours to 150 mg every 12 hours. If patient is unable to tolerate 300 mg orally every 12 hours, reduce the oral maintenance dose by 50 mg steps to a minimum of 200 mg every 12 hours (or to 100 mg every 12 hours for adult patients weighing less than 40 kg).

If patient is unable to tolerate 4 mg/kg IV q12h, reduce the intravenous maintenance dose to 3 mg/kg q12h.

The maintenance dose of voriconazole should be increased when co-administered with phenytoin or efavirenz [see Drug Interactions (7)].

The maintenance dose of voriconazole should be reduced in patients with mild to moderate hepatic impairment, Child-Pugh Class A and B [see Dosage and Administration (2.5)]. There are no PK data to allow for dosage adjustment recommendations in patients with severe hepatic impairment (Child-Pugh Class C).

Duration of therapy should be based on the severity of the patient's underlying disease, recovery from immunosuppression, and clinical response.

2.4 Oral Suspension

Reconstitution

Tap the bottle to release the powder. Add 46 mL of water to the bottle. Shake the closed bottle vigorously for about 1 minute. Remove child-resistant cap and push bottle adaptor into the neck of the bottle. Replace the cap. Write the date of expiration of the reconstituted suspension on the bottle label (the shelf-life of the reconstituted suspension is 14 days at controlled room temperature 15-30°C [59-86°F]).

Instructions for use

Shake the closed bottle of reconstituted suspension for approximately 10 seconds before each use. The reconstituted oral suspension should only be administered using the oral dispenser supplied with each pack.

Incompatibilities

Voriconazole for Oral Suspension and the 40 mg/mL reconstituted oral suspension should not be mixed with any other medication or additional flavoring agent. It is not intended that the suspension be further diluted with water or other vehicles.

2.5 Use in Patients With Hepatic Impairment

In the clinical program, patients were included who had baseline liver function tests (ALT, AST) up to 5 times the upper limit of normal. No dose adjustment is necessary in patients with this degree of abnormal liver function, but continued monitoring of liver function tests for further elevations is recommended [see Warnings and Precautions (5.9)].

It is recommended that the standard loading dose regimens be used but that the maintenance dose be halved in patients with mild to moderate hepatic cirrhosis (Child-Pugh Class A and B) [see Clinical Pharmacology (12.3)].

Voriconazole has not been studied in patients with severe hepatic cirrhosis (Child-Pugh Class C) or in patients with chronic hepatitis B or chronic hepatitis C disease. Voriconazole has been associated with elevations in liver function tests and clinical signs of liver damage, such as jaundice, and should only be used in patients with severe hepatic impairment if the benefit outweighs the potential risk. Patients with hepatic insufficiency must be carefully monitored for drug toxicity.

2.6 Use in Patients With Renal Impairment

The pharmacokinetics of orally administered voriconazole are not significantly affected by renal impairment. Therefore, no adjustment is necessary for oral dosing in patients with mild to severe renal impairment [see Clinical Pharmacology (12.3)].

In patients with moderate or severe renal impairment (creatinine clearance <50 mL/min), accumulation of the intravenous vehicle, SBECD, occurs. Oral voriconazole should be administered to these patients, unless an assessment of the benefit/risk to the patient justifies the use of intravenous voriconazole. Serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral voriconazole therapy [see Warnings and Precautions (5.10)].

Voriconazole is hemodialyzed with clearance of 121 mL/min. The intravenous vehicle, SBECD, is hemodialyzed with clearance of 55 mL/min. A 4-hour hemodialysis session does not remove a sufficient amount of voriconazole to warrant dose adjustment.
Phenelzine Sulfate

Phenelzine Sulfate

Initial dose

The usual starting dose of phenelzine sulfate is one tablet (15 mg) three times a day.

Early phase treatment

Dosage should be increased to at least 60 mg per day at a fairly rapid pace consistent with patient tolerance. It may be necessary to increase dosage up to 90 mg per day to obtain sufficient MAO inhibition. Many patients do not show a clinical response until treatment at 60 mg has been continued for at least 4 weeks.

Maintenance dose

After maximum benefit from phenelzine sulfate is achieved, dosage should be reduced slowly over several weeks. Maintenance dose may be as low as one tablet, 15 mg, a day or every other day, and should be continued for as long as is required.
Nitroglycerin

Nitroglycerin

One tablet should be dissolved under the tongue or in the buccal pouch at the first sign of an acute anginal attack. The dose may be repeated approximately every 5 minutes, until relief is obtained. If the pain persists after a total of 3 tablets in a 15-minute period, prompt medical attention is recommended. Nitroglycerin tablets may be used prophylactically 5 to 10 minutes prior to engaging in activities which might precipitate an acute attack.

During administration the patient should rest, preferably in the sitting position.

No dosage adjustment is required in patients with renal failure.
Mycophenolate Mofetil

Mycophenolate Mofetil

Renal Transplantation

Adults

A dose of 1 g administered orally or intravenously (over NO LESS THAN 2 HOURS) twice a day (daily dose of 2 g) is recommended for use in renal transplant patients. Although a dose of 1.5 g administered twice daily (daily dose of 3 g) was used in clinical trials and was shown to be safe and effective, no efficacy advantage could be established for renal transplant patients. Patients receiving 2 g/day of mycophenolate mofetil demonstrated an overall better safety profile than did patients receiving 3 g/day of mycophenolate mofetil.

Pediatrics (3 months to 18 years of age)

The recommended dose of mycophenolate mofetil oral suspension is 600 mg/m2 administered twice daily (upto a maximum daily dose of 2 g/ 10mL oral suspension). Patients with a body surface area of 1.25 m2 to 1.5 m2 may be dosed with mycophenolate mofetil capsules at a dose of 750 mg twice daily (1.5 g daily dose). Patients with a body surface area >1.5 m2 may be dosed with mycophenolate mofetil capsules or tablets at a dose of 1 g twice daily (2 g daily dose).

Cardiac Transplantation

Adults

A dose of 1.5 g bid oral (daily dose of 3 g) is recommended for use in adult cardiac transplant patients.

Hepatic Transplantation

Adults

A dose of 1.5 g bid oral (daily dose of 3 g) is recommended for use in adult hepatic transplant patients.

Mycophenolate Mofetil Capsules and Tablets

The initial oral dose of mycophenolate mofetil should be given as soon as possible following renal, cardiac or hepatic transplantation. Food had no effect on MPA AUC, but has been shown to decrease MPA Cmax by 40%. Therefore, it is recommended that mycophenolate mofetil be administered on an empty stomach. However, in stable renal transplant patients, mycophenolate mofetil may be administered with food if necessary.

Patients With Hepatic Impairment

No dose adjustments are recommended for renal patients with severe hepatic parenchymal disease. However, it is not known whether dose adjustments are needed for hepatic disease with other etiologies (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

No data are available for cardiac transplant patients with severe hepatic parenchymal disease.

Geriatrics

The recommended oral dose of 1 g bid for renal transplant patients, 1.5 g bid for cardiac transplant patients, and 1.5 g bid administered orally in hepatic transplant patients is appropriate for elderly patients (see PRECAUTIONS: Geriatric Use).

Dosage Adjustments

In renal transplant patients with severe chronic renal impairment (GFR <25 mL/min/1.73 m2) outside the immediate posttransplant period, doses of mycophenolate mofetil greater than 1 g administered twice a day should be avoided. These patients should also be carefully observed. No dose adjustments are needed in renal transplant patients experiencing delayed graft function postoperatively (see CLINICAL PHARMACOLOGY: Pharmacokinetics and PRECAUTIONS: General ).

No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment. Mycophenolate mofetil may be used for cardiac or hepatic transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.

If neutropenia develops (ANC <1.3 x 103/mcL), dosing with mycophenolate mofetil should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately (see WARNINGS: Neutropenia , ADVERSE REACTIONS , and PRECAUTIONS: Laboratory Tests ).

HANDLING AND DISPOSAL

Mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbits (see WARNINGS: Pregnancy). Mycophenolate mofetil tablets should not be crushed and mycophenolate mofetil capsules should not be opened or crushed. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in mycophenolate mofetil capsules and mycophenolate mofetil Oral Suspension (before or after constitution). If such contact occurs, wash thoroughly with soap and water; rinse eyes with plain water. Should a spill occur, wipe up using paper towels wetted with water to remove spilled powder or suspension. Caution should be exercised in the handling and preparation of solutions of mycophenolate mofetil Intravenous. Avoid direct contact of the prepared solution of mycophenolate mofetil Intravenous with skin or mucous membranes. If such contact occurs, wash thoroughly with soap and water; rinse eyes with plain water.
Donepezil Hydrochloride...

Donepezil Hydrochloride

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

Donepezil HCl can be taken with or without food.

Allow Donepezil HCl ODT to dissolve on the tongue and follow with water.

2.1. Mild to Moderate Alzheimer's Disease

The dosages of donepezil HCl 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 HCl might provide additional benefit for some patients. Accordingly, whether or not to employ a dose of 10 mg is a matter of prescriber and patient preference.

2.2. Severe Alzheimer's Disease

Donepezil HCl has been shown to be effective in controlled clinical trials at doses of 10 mg.

2.3. Titration

The recommended starting dose of donepezil HCl 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 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.
Up And Up Junior Streng...

Up And Up Junior Strength Ibuprofen

Carefully consider the potential benefits and risks of piroxicam and other treatment options before deciding to use piroxicam. 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, 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, steady-state blood levels are not reached for 7–12 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.
Epirubicin Hydrochlorid...

Epirubicin Hydrochloride

When possible, to reduce the risk of developing cardiotoxicity in patients receiving Epirubicin HCl after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, Epirubicin HCl-based therapy should be delayed until the other agents have cleared from the circulation [see Warnings and Precautions (5.3)].

Administer Epirubicin HCl Injection by intravenous infusion. Give Epirubicin HCl in repeated 3- to 4-week cycles. The total dose of Epirubicin HCl may be given on Day 1 of each cycle or divided equally and given on Days 1 and 8 of each cycle. The recommended dosages of Epirubicin HCl are as follows:

2.1 Recommended Dose

The recommended dose of Epirubicin HCl is 100 to 120 mg/m2. The following regimens are recommended:
CEF-120: Cyclophosphamide 75 mg/m2 PO D 1–14 Epirubicin HCl 60 mg/m2 IV D 1, 8 5-Fluorouracil 500 mg/m2 IV D 1, 8 Repeated every 28 days for 6 cycles FEC-100: 5-Fluorouracil 500 mg/m2 Epirubicin HCl 100 mg/m2 Cyclophosphamide 500 mg/m2 All drugs administered intravenously on Day 1 and repeated every 21 days for 6 cycles
Patients administered the 120-mg/m2 regimen of Epirubicin HCl should receive prophylactic antibiotic therapy.

2.2 Dose Modifications

Epirubicin HCl dosage adjustments for hematologic and non-hematologic toxicities within a cycle of treatment, is based on nadir platelet counts <50,000/mm3, absolute neutrophil counts (ANC) <250/mm3, neutropenic fever, or Grades 3/4 nonhematologic toxicity. Reduce Epirubicin HCl Day 1 dose in subsequent cycles to 75% of the Day 1 dose given in the current cycle. Delay Day 1 chemotherapy in subsequent courses of treatment until platelet counts are ≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic toxicities have recovered to ≤ Grade 1.

Bone Marrow Dysfunction

Consider administering a lower starting dose (75–90 mg/m2) for heavily pretreated patients, patients with pre-existing bone marrow depression, or in the presence of neoplastic bone marrow infiltration [see Warnings and Precautions (5)]. For patients receiving a divided dose of Epirubicin HCl (Day 1 and Day 8), the Day 8 dose should be 75% of Day 1 if platelet counts are 75,000–100,000/mm3 and ANC is 1000 to 1499/mm3. If Day 8 platelet counts are <75,000/mm3, ANC <1000/mm3, or Grades 3/4 nonhematologic toxicity has occurred, omit the Day 8 dose.

Hepatic Impairment

Recommendations regarding use of Epirubicin HCl in patients with hepatic impairment are not available because patients with hepatic abnormalities were not included in the adjuvant trials [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]. In patients with elevated serum AST or serum total bilirubin concentrations, the following dose reductions are recommended:
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times upper limit of normal 1/2 of recommended starting dose Bilirubin > 3 mg/dL or AST > 4 times upper limit of normal 1/4 of recommended starting dose
Renal Impairment

While no specific dose recommendation can be made based on the limited available data in patients with renal impairment, consider lower doses in patients with severe renal impairment (serum creatinine > 5 mg/dL) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].

2.3 Preparation and Administration Precautions

Storage of the solution for injection at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after 2 to a maximum of 4 hours equilibration at controlled room temperature (15–25ºC).

Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Procedures for proper handling and disposal of anticancer drugs should be used when handling and preparing Epirubicin HCl. Several guidelines on this subject have been published.1–4 [see References (15)].

Protective Measures

Take the following protective measures when handling Epirubicin HCl:
Train personnel in appropriate techniques for reconstitution and handling. Exclude pregnant staff from working with this drug. Wear protective clothing: goggles, gowns, and disposable gloves and masks when handling Epirubicin HCl. Define a designated area for syringe preparation (preferably under a laminar flow system), with the work surface protected by disposable, plastic-backed, absorbent paper. Place all items used for reconstitution, administration, or cleaning (including gloves) in high-risk, waste-disposal bags for high temperature incineration. Treat spillage or leakage with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. Place all contaminated and cleaning materials in high-risk, waste-disposal bags for incineration. Treat accidental contact with the skin or eyes immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Seek medical attention. Always wash hands after removing gloves.
Incompatibilities

Avoid prolonged contact with any solution of an alkaline pH as it will result in hydrolysis of the drug. Do not mix Epirubicin HCl with heparin or fluorouracil due to chemical incompatibility that may lead to precipitation.

Epirubicin HCl can be used in combination with other antitumor agents, but do not mix with other drugs in the same syringe.

Preparation of Infusion Solution

Administer Epirubicin HCl into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution). Patients receiving initial therapy at the recommended starting doses of 100–120 mg/m2 should generally have Epirubicin HCl infused over 15–20 minutes. For patients who require lower Epirubicin HCl starting doses due to organ dysfunction or who require modification of Epirubicin HCl doses during therapy, the Epirubicin HCl infusion time may be proportionally decreased, but should not be less than 3 minutes. This technique is intended to minimize the risk of thrombosis or perivenous extravasation, which could lead to severe cellulitis, vesication, or tissue necrosis. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration. Venous sclerosis may result from injection into small vessels or repeated injections into the same vein [see Warnings and Precautions (5.9)]. Use Epirubicin HCl within 24 hours of first penetration of the rubber stopper. Discard any unused solution.
Trifluridine Solution

Trifluridine Solution

Instill one drop of Trifluridine Ophthalmic Solution, 1% onto the cornea of the affected eye every 2 hours while awake for a maximum daily dosage of nine drops until the corneal ulcer has completely re-epithelialized. Following re-epithelialization, treatment for an additional 7 days of one drop every 4 hours while awake for a minimum daily dosage of five drops is recommended.

If there are no signs of improvement after 7 days of therapy or complete re-epithelialization has not occurred after 14 days of therapy, other forms of therapy should be considered. Continuous administration of Trifluridine Ophthalmic Solution, 1% for periods exceeding 21 days should be avoided because of potential ocular toxicity.
Sertraline Hydrochlorid...

Sertraline Hydrochloride

Initial Treatment

Dosage for Adults

Major Depressive Disorder and Obsessive-Compulsive Disorder

Sertraline hydrochloride treatment should be administered at a dose of 50 mg once daily.

Panic Disorder, Posttraumatic Stress Disorder and Social Anxiety Disorder

Sertraline hydrochloride treatment should be initiated with a dose of 25 mg once daily. After one week, the dose should be increased to 50 mg once daily.

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

Premenstrual Dysphoric Disorder

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

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

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

Dosage for Pediatric Population (Children and Adolescents)

Obsessive-Compulsive Disorder

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

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

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

Maintenance/Continuation/Extended Treatment

Major Depressive Disorder

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

Posttraumatic Stress Disorder

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

Social Anxiety Disorder

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

Obsessive-Compulsive Disorder and Panic Disorder

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

Premenstrual Dysphoric Disorder

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

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

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

Use of Sertraline Hydrochloride With Other MAOIs Such as Linezolid or Methylene Blue

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

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

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

Special Populations

Dosage for Hepatically Impaired Patients

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

Treatment of Pregnant Women During the Third Trimester

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

Discontinuation of Treatment with Sertraline Hydrochloride

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

Sertraline Hydrochloride Oral Concentrate

Sertraline hydrochloride oral concentrate contains 20 mg/mL of sertraline (as the hydrochloride) as the active ingredient and 12% alcohol. Sertraline hydrochloride oral concentrate must be diluted before use. Just before taking, use the dropper provided to remove the required amount of sertraline hydrochloride oral concentrate and mix with 4 oz (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade or orange juice ONLY. Do not mix sertraline hydrochloride oral concentrate with anything other than the liquids listed. The dose should be taken immediately after mixing. Do not mix in advance. At times, a slight haze may appear after mixing; this is normal. Note that caution should be exercised for patients with latex sensitivity, as the dropper dispenser contains dry natural rubber.

Sertraline hydrochloride oral concentrate is contraindicated with ANTABUSE (disulfiram) due to the alcohol content of the concentrate.
Diphenoxylate Hydrochlo...

Diphenoxylate Hydrochloride And Atropine Sulfate

DO NOT EXCEED RECOMMENDED DOSAGE.

Adults

The recommended initial dosage is two diphenoxylate hydrochloride tablets four times daily . Most patients will require this dosage until initial control has been achieved, after which the dosage may be reduced to meet individual requirements. Control may often be maintained with as little as 5 mg (two tablets) daily.

Clinical improvement of acute diarrhea is usually observed within 48 hours. If clinical improvement of chronic diarrhea after treatment with a maximum daily dose of 20 mg of diphenoxylate hydrochloride is not observed within 10 days, symptoms are unlikely to be controlled by further administration.

Children

Diphenoxylate hydrochloride is not recommended in children under 2 years of age and should be used with special caution in young children (see Warnings and Precautions). The nutritional status and degree of dehydration must be considered. Do not use diphenoxylate hydrochloride tablets for children under 13 years of age .

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
Oxaprozin

Oxaprozin

Carefully consider the potential benefits and risks of oxaprozin and other treatment options before deciding to use oxaprozin. 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, 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 caplets) 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 caplets) 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) (see CLINICAL PHARMACOLOGY, Special populations: Pediatric patients) 22–31 600 32–54 900 ≥55 1200
Individualization of dosage

As with other NSAIDs, the lowest dose should be sought for each patient. Therefore, after observing the response to initial therapy with oxaprozin, the dose and frequency should be adjusted to suit an individual patient's needs. In osteoarthritis and rheumatoid arthritis and juvenile rheumatoid arthritis, the dosage should be individualized to the lowest effective dose of oxaprozin to minimize adverse effects. The maximum recommended total daily dose of oxaprozin in adults is 1800 mg (26 mg/kg, whichever is lower) in divided doses. In children, doses greater than 1200 mg have not been studied.

Patients of low body weight should initiate therapy with 600 mg once daily. Patients with severe renal impairment or on dialysis should also initiate therapy with 600 mg once daily. If there is insufficient relief of symptoms in such patients, the dose may be cautiously increased to 1200 mg, but only with close monitoring (see CLINICAL PHARMACOLOGY, Special populations).

In adults, in cases where a quick onset of action is important, the pharmacokinetics of oxaprozin allows therapy to be started with a one-time loading dose of 1200 to 1800 mg (not to exceed 26 mg/kg). Doses larger than 1200 mg/day on a chronic basis should be reserved for patients who weigh more than 50 kg, have normal renal and hepatic function, are at low risk of peptic ulcer, and whose severity of disease justifies maximal therapy. Physicians should ensure that patients are tolerating doses in the 600 to 1200 mg/day range without gastroenterologic, renal, hepatic, or dermatologic adverse effects before advancing to the larger doses. Most patients will tolerate once-a-day dosing with oxaprozin, although divided doses may be tried in patients unable to tolerate single doses.
Latanoprost Solution

Latanoprost Solution

The recommended dosage is one drop (1.5 μg) in the affected eye(s) once daily in the evening. If one dose is missed, treatment should continue with the next dose as normal.

The dosage of latanoprost ophthalmic solution should not exceed once daily; the combined use of two or more prostaglandins, or prostaglandin analogs including latanoprost ophthalmic solution is not recommended. It has been shown that administration of these prostaglandin drug products more than once daily may decrease the intraocular pressure lowering effect or cause paradoxical elevations in IOP.

Reduction of the intraocular pressure starts approximately 3 to 4 hours after administration and the maximum effect is reached after 8 to 12 hours.

Latanoprost ophthalmic solution may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.
Amlodipine Besylate

Amlodipine Besylate

2.1 Adults

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

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

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

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

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

2.2 Children

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

Azithromycin

2.1 Dosage for Postherpetic Neuralgia

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

2.2 Dosage for Epilepsy with Partial Onset Seizures

Patients 12 years of age and above

The starting dose is 300 mg three times a day. The recommended maintenance dose of gabapentin is 300 mg to 600 mg three times a day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. Administer gabapentin three times a day using 300 mg or 400 mg capsules, or 600 mg or 800 mg tablets. The maximum time between doses should not exceed 12 hours.

Pediatric Patients Age 3 to 11 years

The starting dose range is 10 mg/kg/day to 15 mg/kg/day, given in three divided doses, and the recommended maintenance dose reached by upward titration over a period of approximately 3 days. The recommended maintenance dose of gabapentin in patients 3 to 4 years of age is 40 mg/kg/day, given in three divided doses. The recommended maintenance dose of gabapentin in patients 5 to 11 years of age is 25 mg/kg/day to 35 mg/kg/day, given in three divided doses. Gabapentin may be administered as the oral solution, capsule, or tablet, or using combinations of these formulations. 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.

2.3 Dosage Adjustment in Patients with Renal Impairment

Dosage adjustment in patients 12 years of age and older with renal impairment or undergoing hemodialysis is recommended, as follows (see dosing recommendations above for effective doses in each indication):
TABLE 1. Gabapentin Dosage Based on Renal Function Renal Function Creatinine Clearance(mL/min) Total Daily Dose Range(mg/day) Dose Regimen(mg) TID = Three times a day; BID = Two times a day; QD = Single daily dose * 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). † Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table. ≥ 60 900 to 3600 300 TID 400 TID 600 TID 800 TID 1200 TID >30 to 59 400 to 1400 200 BID 300 BID 400 BID 500 BID 700 BID >15 to 29 200 to 700 200 QD 300 QD 400 QD 500 QD 700 QD 15* 100 to 300 100 QD 125 QD 150 QD 200 QD 300 QD Post-Hemodialysis Supplemental Dose (mg)† Hemodialysis 125† 150† 200† 250† 350†
Creatinine clearance (CLCr) is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance can be reasonably well estimated using the equation of Cockcroft and Gault:

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

2.4 Dosage in Elderly

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

2.5 Administration Information

Administer gabapentin orally with or without food.

Gabapentin capsules should be swallowed whole with water.

Inform patients that, should they divide the scored 600 mg or 800 mg gabapentin tablet in order to administer a half-tablet, they should take the unused half-tablet as the next dose. Half-tablets not used within 28 days of dividing the scored tablet should be discarded.

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

Spironolactone

Primary hyperaldosteronism

Spironolactone tablets may be employed as an initial diagnostic measure to provide presumptive evidence of primary hyperaldosteronism while patients are on normal diets.

Long test

Spironolactone tablets are administered at a daily dosage of 400 mg for three to four weeks. Correction of hypokalemia and of hypertension provides presumptive evidence for the diagnosis of primary hyperaldosteronism.

Short test

Spironolactone tablets are administered at a daily dosage of 400 mg for four days. If serum potassium increases during spironolactone administration but drops when spironolactone tablets are discontinued, a presumptive diagnosis of primary hyperaldosteronism should be considered.

After the diagnosis of hyperaldosteronism has been established by more definitive testing procedures, spironolactone tablets may be administered in doses of 100 to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, spironolactone tablets may be employed for long-term maintenance therapy at the lowest effective dosage determined for the individual patient.

Edema in adults (congestive heart failure, hepatic cirrhosis, or nephrotic syndrome)

An initial daily dosage of 100 mg of spironolactone tablets administered in either single or divided doses is recommended, but may range from 25 to 200 mg daily. When given as the sole agent for diuresis, spironolactone tablets should be continued for at least five days at the initial dosage level, after which it may be adjusted to the optimal therapeutic or maintenance level administered in either single or divided daily doses. If, after five days, an adequate diuretic response to spironolactone tablets has not occurred, a second diuretic that acts more proximally in the renal tubule may be added to the regimen. Because of the additive effect of spironolactone tablets when administered concurrently with such diuretics, an enhanced diuresis usually begins on the first day of combined treatment; combined therapy is indicated when more rapid diuresis is desired. The dosage of spironolactone tablets should remain unchanged when other diuretic therapy is added.

Essential hypertension

For adults, an initial daily dosage of 50 to 100 mg of spironolactone tablets administered in either single or divided doses is recommended. Spironolactone tablets may also be given with diuretics that act more proximally in the renal tubule or with other antihypertensive agents. Treatment with spironolactone tablets should be continued for at least two weeks, since the maximum response may not occur before this time. Subsequently, dosage should be adjusted according to the response of the patient.

Hypokalemia

Spironolactone tablets in a dosage ranging from 25 mg to 100 mg daily are useful in treating a diuretic-induced hypokalemia, when oral potassium supplements or other potassium-sparing regimens are considered inappropriate.

Severe heart failure in conjunction with standard therapy (NYHA class III – IV)

Treatment should be initiated with spironolactone 25 mg once daily if the patient's serum potassium is ≤5.0 mEq/L and the patient's serum creatinine is ≤ 2.5 mg/dL. Patients who tolerate 25 mg once daily may have their dosage increased to 50 mg once daily as clinically indicated. Patients who do not tolerate 25 mg once-daily dose may have their dosage reduced to 25 mg every other day. See Warnings: Hyperkalemia in patients with severe heart failure for advice on monitoring serum potassium and serum creatinine.
Ziprasidone

Ziprasidone

2.1 Schizophrenia

Dose Selection

Ziprasidone capsules should be administered at an initial daily dose of 20 mg twice daily with food. In some patients, daily dosage may subsequently be adjusted on the basis of individual clinical status up to 80 mg twice daily. Dosage adjustments, if indicated, should generally occur at intervals of not less than 2 days, as steady-state is achieved within 1 to 3 days. In order to ensure use of the lowest effective dose, patients should ordinarily be observed for improvement for several weeks before upward dosage adjustment.

Efficacy in schizophrenia was demonstrated in a dose range of 20 mg to 100 mg twice daily in short-term, placebo-controlled clinical trials. There were trends toward dose response within the range of 20 mg to 80 mg twice daily, but results were not consistent. An increase to a dose greater than 80 mg twice daily is not generally recommended. The safety of doses above 100 mg twice daily has not been systematically evaluated in clinical trials [see Clinical Studies (14.1)].

Maintenance Treatment

While there is no body of evidence available to answer the question of how long a patient treated with ziprasidone should remain on it, a maintenance study in patients who had been symptomatically stable and then randomized to continue ziprasidone or switch to placebo demonstrated a delay in time to relapse for patients receiving ziprasidone [see Clinical Studies (14.1)]. No additional benefit was demonstrated for doses above 20 mg twice daily. Patients should be periodically reassessed to determine the need for maintenance treatment.

2.2 Bipolar I Disorder (Acute Mixed or Manic Episodes and Maintenance Treatment as an Adjunct to Lithium or Valproate)

Acute Treatment of Manic or Mixed Episodes

Dose Selection-Oral ziprasidone should be administered at an initial daily dose of 40 mg twice daily with food. The dose may then be increased to 60 mg or 80 mg twice daily on the second day of treatment and subsequently adjusted on the basis of tolerance and efficacy within the range 40 mg–80 mg twice daily. In the flexible-dose clinical trials, the mean daily dose administered was approximately 120 mg [see Clinical Studies (14.2)].

Maintenance Treatment (as an adjunct to lithium or valproate)

Continue treatment at the same dose on which the patient was initially stabilized, within the range of 40 mg–80 mg twice daily with food. Patients should be periodically reassessed to determine the need for maintenance treatment [see Clinical Studies (14.2)].

2.3 Dosing in Special Populations

Oral: Dosage adjustments are generally not required on the basis of age, gender, race, or renal or hepatic impairment. Ziprasidone is not approved for use in children or adolescents.
Divalproex Sodium Exten...

Divalproex Sodium Extended-release

There is no fixed dosage regimen for the management of diabetes mellitus with Glipizide XL extended-release tablet or any other hypoglycemic agent. Glycemic control should be monitored with hemoglobin A1C and/or blood-glucose levels 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. Home blood-glucose monitoring may also provide useful information to the patient and physician. Short-term administration of Glipizide XL extended-release tablet may be sufficient during periods of transient loss of control in patients usually controlled on diet.

In general, Glipizide XL should be given with breakfast.

Recommended Dosing

The usual starting dose of Glipizide XL as initial therapy is 5 mg per day, given with breakfast. Those patients who may be more sensitive to hypoglycemic drugs may be started at a lower dose.

Dosage adjustment should be based on laboratory measures of glycemic control. While fasting blood-glucose levels generally reach steady-state following initiation or change in Glipizide XL dosage, a single fasting glucose determination may not accurately reflect the response to therapy. In most cases, hemoglobin A1C level measured at three month intervals is the preferred means of monitoring response to therapy.

Hemoglobin A1C should be measured as Glipizide XL therapy is initiated and repeated approximately three months later. If the result of this test suggests that glycemic control over the preceding three months was inadequate, the Glipizide XL dose may be increased. Subsequent dosage adjustments should be made on the basis of hemoglobin A1C levels measured at three month intervals. If no improvement is seen after three months of therapy with a higher dose, the previous dose should be resumed. Decisions which utilize fasting blood glucose to adjust Glipizide XL therapy should be based on at least two or more similar, consecutive values obtained seven days or more after the previous dose adjustment.

Most patients will be controlled with 5 mg to 10 mg taken once daily. However, some patients may require up to the maximum recommended daily dose of 20 mg. While the glycemic control of selected patients may improve with doses which exceed 10 mg, clinical studies conducted to date have not demonstrated an additional group average reduction of hemoglobin A1C beyond what was achieved with the 10 mg dose.

Based on the results of a randomized crossover study, patients receiving immediate release glipizide may be switched safely to Glipizide XL extended-release tablets once-a-day at the nearest equivalent total daily dose. Patients receiving immediate release glipizide tablets also may be titrated to the appropriate dose of Glipizide XL starting with 5 mg once daily. The decision to switch to the nearest equivalent dose or to titrate should be based on clinical judgment.

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 section).

Combination Use

When adding other blood-glucose-lowering agents to Glipizide XL for combination therapy, the agent should be initiated at the lowest recommended dose, and patients should be observed carefully for hypoglycemia. Refer to the product information supplied with the oral agent for additional information.

When adding Glipizide XL to other blood-glucose-lowering agents, Glipizide XL can be initiated at 5 mg. Those patients who may be more sensitive to hypoglycemic drugs may be started at a lower dose. Titration should be based on clinical judgment.

When colesevelam is coadministered with glipizide ER, maximum plasma concentration and total exposure to glipizide is reduced. Therefore, Glipizide XL should be administered at least 4 hours prior to colesevelam.

Patients Receiving Insulin

As with other sulfonylurea-class hypoglycemics, many patients with stable type 2 diabetes receiving insulin may be transferred safely to treatment with Glipizide XL extended-release tablets. When transferring patients from insulin to Glipizide XL, the following general guidelines should be considered:

For patients whose daily insulin requirement is 20 units or less, insulin may be discontinued and Glipizide XL therapy may begin at usual dosages. Several days should elapse between titration steps.

For patients whose daily insulin requirement is greater than 20 units, the insulin dose should be reduced by 50% and Glipizide XL therapy may begin at usual dosages. Subsequent reductions in insulin dosage should depend on individual patient response. Several days should elapse between titration steps.

During the insulin withdrawal period, the patient should test urine samples for sugar and ketone bodies at least three times daily. Patients should be instructed to contact the prescriber immediately if these tests are abnormal. In some cases, especially when the patient has been receiving greater than 40 units of insulin daily, it may be advisable to consider hospitalization during the transition period.

Patients Receiving Other Oral Hypoglycemic Agents

As with other sulfonylurea-class hypoglycemics, no transition period is necessary when transferring patients to Glipizide XL extended-release tablets. Patients should be observed carefully (1–2 weeks) for hypoglycemia when being transferred from longer half-life sulfonylureas (e.g., chlorpropamide) to Glipizide XL due to potential overlapping of drug effect.
Hydrocortisone

Hydrocortisone

The initial dosage of hydrocortisone tablets may vary from 20 mg to 240 mg of hydrocortisone per day depending on the specific disease entity being treated. In situations of less severity lower doses will generally suffice while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, hydrocortisone should be discontinued and the patient transferred to other appropriate therapy. IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF THE PATIENT. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation it may be necessary to increase the dosage of hydrocortisone for a period of time consistent with the patient's condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually, rather than abruptly.

Multiple Sclerosis

In treatment of acute exacerbations of multiple sclerosis, daily doses of 200 mg of prednisolone for a week followed by 80 mg every other day for 1 month have been shown to be effective (20 mg of hydrocortisone is equivalent to 5 mg of prednisolone).
Clindamycin Palmitate H...

Clindamycin Palmitate Hydrochloride Solution

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

Concomitant administration of food does not adversely affect the absorption of clindamycin palmitate HCl contained in clindamycin palmitate HCl pediatric flavored granules.

Serious infections: 8–12 mg/kg/day (4–6 mg/lb/day) divided into 3 or 4 equal doses.

Severe infections: 13–16 mg/kg/day (6.5–8 mg/lb/day) divided into 3 or 4 equal doses.

More severe infections: 17–25 mg/kg/day (8.5–12.5 mg/lb/day) divided into 3 or 4 equal doses.

In pediatric patients weighing 10 kg or less, ½ teaspoon (37.5 mg) three times a day should be considered the minimum recommended dose.

Serious infections due to anaerobic bacteria are usually treated with CLEOCIN PHOSPHATE® Sterile Solution. However, in clinically appropriate circumstances, the physician may elect to initiate treatment or continue treatment with clindamycin palmitate HCl.

NOTE: In cases of ß-hemolytic streptococcal infections, treatment should be continued for at least 10 days.

Reconstitution Instructions

When reconstituted with water as follows, each 5 mL (teaspoon) of solution contains clindamycin palmitate HCl equivalent to 75 mg clindamycin.

Reconstitute bottles of 100 mL with 75 mL of water. Add a large portion of the water and shake vigorously; add the remainder of the water and shake until the solution is uniform.

Storage Conditions

Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].

Do NOT refrigerate the reconstituted solution; when chilled, the solution may thicken and be difficult to pour. The solution is stable for 2 weeks at room temperature.
Clarithromycin For Susp...

Clarithromycin For Suspension

When given in equal doses, Phenytoin Infatabs yield higher plasma levels than Dilantin Kapseals®. For this reason serum concentrations should be monitored and care should be taken when switching a patient from the sodium salt to the free acid form.

Dilantin capsules is formulated with the sodium salt of phenytoin. The free acid form of phenytoin is used in Dilantin-125 Suspension and Phenytoin Infatabs. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa.

General

Not for once-a-day dosing.

Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum level is usually 10–20 mcg/mL. With recommended dosage, a period of seven to ten days may be required to achieve steady-state blood levels with phenytoin and changes in dosage (increase or decrease) should not be carried out at intervals shorter than seven to ten days.

Phenytoin Infatabs can be either chewed thoroughly before being swallowed or swallowed whole.

Adult Dosage

Patients who have received no previous treatment may be started on two Phenytoin Infatabs three times daily, and the dose is then adjusted to suit individual requirements. For most adults, the satisfactory maintenance dosage will be six to eight Phenytoin Infatabs daily; an increase to twelve Phenytoin Infatabs daily may be made, if necessary.

Dosing in Special Populations

Patients with Renal or Hepatic Disease

Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution. Unbound phenytoin concentrations may be more useful in these patient populations.

Elderly Patients

Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required.

Pediatric

Initially, 5 mg/kg/day in two or three equally divided doses, with subsequent dosage individualized to a maximum 300 mg daily. A recommended daily maintenance dosage is usually 4 to 8 mg/kg. Children over 6 years old and adolescents may require the minimum adult dose (300 mg/day). If the daily dosage cannot be divided equally, the larger dose should be given before retiring.
Childrens Pain And Feve...

Childrens Pain And Fever

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)].
Norethindrone

Norethindrone

To achieve maximum contraceptive effectiveness, norethindrone tablets must be taken exactly as directed. One tablet is taken every day, at the same time. Administration is continuous, with no interruption between pill packs. See PATIENT LABELING for detailed instructions.
Ampicillin And Sulbacta...

Ampicillin And Sulbactam

Sildenafil Tablets

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

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

Exemestane

2.1 Recommended Dose

The recommended dose of EXEMESTANE in early and advanced breast cancer is one 25 mg tablet once daily after a meal.
adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to EXEMESTANE for completion of a total of five consecutive years of adjuvant hormonal therapy . the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
2.2 Dose Modifications

For patients receiving EXEMESTANE with a potent CYP 3A4 inducer such as rifampicin or phenytoin, the recommended dose of EXEMESTANE is 50 mg once daily after a meal.

The safety of chronic dosing in patients with moderate or severe hepatic or renal impairment has not been studied. Based on experience with EXEMESTANE at repeated doses up to 200 mg daily that demonstrated a moderate increase in non life-threatening adverse events, dosage adjustment does not appear to be necessary [see Use In Specific Populations (8.6 and 8.7)].
Clindamycin Hydrochlori...

Clindamycin Hydrochloride

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

Adults

Serious infections - 150 to 300 mg every 6 hours. More severe infections - 300 to 450 mg every 6 hours.

Pediatric Patients

Serious infections - 8 to 16 mg/kg/day (4 to 8 mg/lb/day) divided into three or four equal doses. More severe infections - 16 to 20 mg/kg/day (8 to 10 mg/lb/day) divided into three or four equal doses.

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

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

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

Clindamycin Phosphate

The recommended dose is one applicatorful of clindamycin phosphate vaginal cream 2%, (5 grams containing approximately 100 mg of clindamycin phosphate) intravaginally, preferably at bedtime, for 3 or 7 consecutive days in non-pregnant patients and for 7 consecutive days in pregnant patients. (See CLINICAL STUDIES.)
Methylprednisolone

Methylprednisolone

The initial dosage of methylprednisolone tablets may vary from 4 mg to 48 mg of methylprednisolone per day, depending on the specific disease entity being treated. In situations of less severity, lower doses will generally suffice, while in selected patients, higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, methylprednisolone tablets should be discontinued and the patient transferred to other appropriate therapy.

IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF THE PATIENT.

After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation, it may be necessary to increase the dosage of methylprednisolone tablets for a period of time consistent with the patient's condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.

Multiple Sclerosis

In treatment of acute exacerbations of multiple sclerosis, daily doses of 200 mg of prednisolone for a week followed by 80 mg every other day for 1 month have been shown to be effective (4 mg of methylprednisolone is equivalent to 5 mg of prednisolone).

Alternate Day Therapy

Alternate day therapy is a corticosteroid dosing regimen in which twice the usual daily dose of corticoid is administered every other morning. The purpose of this mode of therapy is to provide the patient requiring long-term pharmacologic dose treatment with the beneficial effects of corticoids while minimizing certain undesirable effects, including pituitary-adrenal suppression, the Cushingoid state, corticoid withdrawal symptoms, and growth suppression in children.

The rationale for this treatment schedule is based on two major premises: (a) the anti-inflammatory or therapeutic effect of corticoids persists longer than their physical presence and metabolic effects and (b) administration of the corticosteroid every other morning allows for reestablishment of more nearly normal hypothalamic-pituitary-adrenal (HPA) activity on the off-steroid day.

A brief review of the HPA physiology may be helpful in understanding this rationale. Acting primarily through the hypothalamus, a fall in free cortisol stimulates the pituitary gland to produce increasing amounts of corticotropin (ACTH) while a rise in free cortisol inhibits ACTH secretion. Normally, the HPA system is characterized by diurnal (circadian) rhythm. Serum levels of ACTH rise from a low point at about 10 pm to a peak level at about 6 am. Increasing levels of ACTH stimulate adrenal cortical activity resulting in a rise in plasma cortisol with maximal levels occurring between 2 am and 8 am. This rise in cortisol dampens ACTH production and in turn adrenal cortical activity. There is a gradual fall in plasma corticoids during the day with lowest levels occurring about midnight.

The diurnal rhythm of the HPA axis is lost in Cushing's disease, a syndrome of adrenal cortical hyperfunction characterized by obesity with centripetal fat distribution, thinning of the skin with easy bruisability, muscle wasting with weakness, hypertension, latent diabetes, osteoporosis, electrolyte imbalance, etc. The same clinical findings of hyperadrenocorticism may be noted during long-term pharmacologic dose corticoid therapy administered in conventional daily divided doses. It would appear, then, that a disturbance in the diurnal cycle with maintenance of elevated corticoid values during the night may play a significant role in the development of undesirable corticoid effects. Escape from these constantly elevated plasma levels for even short periods of time may be instrumental in protecting against undesirable pharmacologic effects.

During conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited with subsequent suppression of cortisol production by the adrenal cortex. Recovery time for normal HPA activity is variable depending upon the dose and duration of treatment. During this time, the patient is vulnerable to any stressful situation. Although it has been shown that there is considerably less adrenal suppression following a single morning dose of prednisolone (10 mg) as opposed to a quarter of that dose administered every six hours, there is evidence that some suppressive effect on adrenal activity may be carried over into the following day when pharmacologic doses are used. Further, it has been shown that a single dose of certain corticosteroids will produce adrenal cortical suppression for two or more days. Other corticoids, including methylprednisolone, hydrocortisone, prednisone, and prednisolone, are considered to be short-acting (producing adrenal cortical suppression for 1¼ to 1½ days following a single dose) and thus are recommended for alternate day therapy.

The following should be kept in mind when considering alternate day therapy:
1) Basic principles and indications for corticosteroid therapy should apply. The benefits of alternate day therapy should not encourage the indiscriminate use of steroids. 2) Alternate day therapy is a therapeutic technique primarily designed for patients in whom long-term pharmacologic corticoid therapy is anticipated. 3) In less severe disease processes in which corticoid therapy is indicated, it may be possible to initiate treatment with alternate day therapy. More severe disease states usually will require daily divided high-dose therapy for initial control of the disease process. The initial suppressive dose level should be continued until satisfactory clinical response is obtained, which is usually four to ten days in the case of many allergic and collagen diseases. It is important to keep the period of initial suppressive dose as brief as possible, particularly when subsequent use of alternate day therapy is intended.
Once control has been established, two courses are available: (a) change to alternate day therapy and then gradually reduce the amount of corticoid given every other day or (b) following control of the disease process, reduce the daily dose of corticoid to the lowest effective level as rapidly as possible and then change over to an alternate day schedule. Theoretically, course (a) may be preferable.
4) Because of the advantages of alternate day therapy, it may be desirable to try patients on this form of therapy who have been on daily corticoids for long periods of time (e.g., patients with rheumatoid arthritis). Since these patients may already have a suppressed HPA axis, establishing them on alternate day therapy may be difficult and not always successful. However, it is recommended that regular attempts be made to change them over. It may be helpful to triple or even quadruple the daily maintenance dose and administer this every other day rather than just doubling the daily dose if difficulty is encountered. Once the patient is again controlled, an attempt should be made to reduce this dose to a minimum. 5) As indicated above, certain corticosteroids, because of their prolonged suppressive effect on adrenal activity, are not recommended for alternate day therapy (e.g., dexamethasone and betamethasone). 6) The maximal activity of the adrenal cortex is between 2 am and 8 am, and it is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocortical activity the least, when given at the time of maximal activity (am). 7) In using alternate day therapy, it is important, as in all therapeutic situations, to individualize and tailor the therapy to each patient. Complete control of symptoms will not be possible in all patients. An explanation of the benefits of alternate day therapy will help the patient to understand and tolerate the possible flare-up in symptoms which may occur in the latter part of the off-steroid day. Other symptomatic therapy may be added or increased at this time if needed. 8) In the event of an acute flare-up of the disease process, it may be necessary to return to a full suppressive daily divided corticoid dose for control. Once control is again established, alternate day therapy may be reinstituted. 9) Although many of the undesirable features of corticosteroid therapy can be minimized by alternate day therapy, as in any therapeutic situation, the physician must carefully weigh the benefit-risk ratio for each patient in whom corticoid therapy is being considered.
Amoxicillin

Amoxicillin

2.1 Dosing for Adult and Pediatric Patients > 3 Months of Age

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. In some 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.
Table 1. Dosing Recommendations for Adult and Pediatric Patients > 3 Months of Age Infection Severitya Usual Adult Dose Usual Dose for Children> 3 Monthsb a Dosing for infections caused by bacteria that are intermediate in their susceptibility to amoxicillin should follow the recommendations for severe infections. b 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. Ear/Nose/Throat Skin/Skin Structure Genitourinary Tract 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 hours or 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 hours or 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 tablets, 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 children under 2 years of age.
2.2 Dosing in Neonates and Infants Aged ≤ 12 Weeks (≤ 3 Months)

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. Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin tablets is 30 mg/kg/day divided every 12 hours. There are currently no dosing recommendations for pediatric patients with impaired renal function.

2.3 Dosing for H. pylori Infection

Triple Therapy: The recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days. Dual Therapy: The recommended adult oral dose is 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days. Please refer to clarithromycin and lansoprazole full prescribing information.

2.4 Dosing in Renal Impairment
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 a 875 mg dose. 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 glomerular filtration rate less than 10 mL/min 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.
Amoxicillin

Amoxicillin

2.1 Dosing for Adult and Pediatric Patients > 3 Months of Age

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. In some 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.
Table 1. Dosing Recommendations for Adult and Pediatric Patients > 3 Months of Age Infection Severitya Usual Adult Dose Usual Dose for Children > 3 Monthsb a Dosing for infections caused by bacteria that are intermediate in their susceptibility to amoxicillin should follow the recommendations for severe infections.b 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. Ear/Nose/Throat Skin/Skin Structure Genitourinary Tract Mild/Moderate 500 mg every 12 hours or250 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 or500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours Lower Respiratory Tract Mild/Moderate or Severe 875 mg every 12 hours or500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 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 for oral suspension, 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 children under 2 years of age.
2.2 Dosing in Neonates and Infants Aged 12 Weeks (3 Months)

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. Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin for oral suspension is

30 mg/kg/day divided every 12 hours. There are currently no dosing recommendations for pediatric patients with impaired renal function.

2.3 Dosing for H. pylori Infection

Triple Therapy: The recommended adult oral dose is 1 gram amoxicillin for oral suspension, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days.Dual Therapy: The recommended adult oral dose is 1 gram amoxicillin for oral suspension and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days. Please refer to clarithromycin and lansoprazole full prescribing information.

2.4 Dosing in Renal Impairment
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 a 875 mg dose. 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 glomerular filtration rate less than 10 mL/min 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.
2.5 Directions for Mixing Oral Suspension

Tap bottle until all powder flows freely. Add approximately 1/3 of the total amount of water for reconstitution (see Table 2) and shake vigorously to wet powder. Add remainder of the water and again shake vigorously.
Table 2. Amount of Water for Mixing Oral Suspension Strength Bottle Size Amount of Water Required for Reconstitution Oral Suspension 200 mg/5 mL 50 mL 35 mL 75 mL 52 mL 100 mL 69 mL Oral Suspension 400 mg/5 mL 50 mL 35 mL 75 mL 52 mL 100 mL 69 mL
After reconstitution, the required amount of suspension should be placed directly on the child’s tongue for swallowing. Alternate means of administration are to add the required amount of suspension to formula, milk, fruit juice, water, ginger ale, or cold drinks. These preparations should then be taken immediately. NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING. Keep bottle tightly closed. Any unused portion of the reconstituted suspension must be discarded after 14 days. Refrigeration is preferable, but not required.
Amoxicillin

Amoxicillin

2.1 Dosing for Adult and Pediatric Patients > 3 Months of Age

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
Hydrochlorothiazide

Hydrochlorothiazide

For Control of Hypertension: The adult initial dose of hydrochlorothiazide is one capsule given once daily whether given alone or in combination with other antihypertensives. Total daily doses greater than 50 mg are not recommended.
Bisoprolol Fumarate

Bisoprolol Fumarate

The dose of bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily. In some patients, 2.5 mg may be an appropriate starting dose (see Bronchospastic Disease in WARNINGS). If the antihypertensive effect of 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. Patients with Renal or Hepatic Impairment In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min), the initial daily dose should be 2.5 mg and caution should be used in dose-titration. Since limited data suggest that bisoprolol fumarate is not dialyzable, drug replacement is not necessary in patients undergoing dialysis. Geriatric Patients It is not necessary to adjust the dose in the elderly, unless there is also significant renal or hepatic dysfunction (see above and Geriatric Use in PRECAUTIONS). Pediatric Patients There is no pediatric experience with bisoprolol fumarate.
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) Type of Infection1 Dosed Every 24 hours Duration (days)2 1 Due to the designated pathogens [see Indications and Usage (1)].2 Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.3 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)].4 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)].5 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.6 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.7 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)].8 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 tablets therapy should only be used when the benefit outweighs the risk.9 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 inidicated. Nosocomial Pneumonia 750 mg 7 to 14 Community Acquired Pneumonia3 500 mg 7 to 14 Community Acquired Pneumonia4 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)5 750 mg 5 Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)6 250 mg 10 Uncomplicated Urinary Tract Infection 250 mg 3 Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kg7,8 Pediatric patients < 50 kg and ≥ 6 months of age 7,8 500 mg see Table 2 below (2.2) 608 608 Plague, adult and pediatric patients > 50 kg9 Pediatric patients < 50 kg and ≥ 6 months of age 500 mg see Table 2 below (2.2) 10 to 14 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 1 Due to Bacillus anthracis [see Indications and Usage (1.13)]and Yersinia pestis [see Indications and Usage (1.14)]. 2 Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.3 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)]. 4 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 tablets therapy should only be used when the benefit outweighs the risk. 5 Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Type of Infection1 Dose Freq. Once every Duration2 Inhalational Anthrax (post-exposure)3, 4 Pediatric patients > 50 kg 500 mg 24 hr 60 days4 Pediatric patients < 50 kg and ≥ 6 months of age 8 mg/kg (not to exceed 250 mg per dose) 12 hr 60 days4 Plague5 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 inNormal RenalFunction Every24 hours CreatinineClearance20 to 49 mL/min CreatinineClearance10 to 19 mL/min Hemodialysis orChronic AmbulatoryPeritoneal 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 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 tablets 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)].
Metoprolol Tartrate

Metoprolol Tartrate

Hypertension

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

Angina Pectoris

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

Myocardial Infarction

Early Treatment

During the early phase of definite or suspected acute myocardial infarction, initiate treatment with metoprolol tartrate tablets as soon as possible after the patient's arrival in the hospital. Such treatment should be initiated in a coronary care or similar unit immediately after the patient’s hemodynamic condition has stabilized.Begin treatment in this early phase with the intravenous administration of three bolus injections of 5 mg of metoprolol tartrate each; give the injections at approximately 2-minute intervals. During the intravenous administration of metoprolol, monitor blood pressure, heart rate, and electrocardiogram.In patients who tolerate the full intravenous dose (15 mg), initiate metoprolol tartrate tablets, 50 mg every 6 hours, 15 minutes after the last intravenous dose and continue for 48 hours. Thereafter, the maintenance dosage is 100 mg twice daily (see Late Treatment below).Start patients who appear not to tolerate the full intravenous dose on metoprolol tartrate tablets either 25 mg or 50 mg every 6 hours (depending on the degree of intolerance) 15 minutes after the last intravenous dose or as soon as their clinical condition allows. In patients with severe intolerance, discontinue metoprolol tartrate tablets (see WARNINGS).

Late Treatment

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

Special Populations

Pediatric Patients: No pediatric studies have been performed. The safety and efficacy of metoprolol tartrate tablets in pediatric patients have not been established.Renal Impairment: No dose adjustment of metoprolol tartrate tablets is required in patients with renal impairment.Hepatic Impairment: metoprolol blood levels are likely to increase substantially in patients with hepatic impairment. Therefore, metoprolol tartrate tablets should be initiated at low doses with cautious gradual dose titration according to clinical response.Geriatric Patients (>65 years): In general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.Method of AdministrationFor oral treatment, the tablets should be swallowed un-chewed with a glass of water. Metoprolol tartrate tablets should always be taken in standardized relation with meals. If the physician asks the patient to take metoprolol tartrate tablets either before breakfast or with breakfast, then the patient should continue taking metoprolol with the same schedule during the course of therapy.
Sulfasalazine

Sulfasalazine

The dosage of sulfasalazine delayed release tablets should be adjusted to each individual's response and tolerance.

Patients should be instructed to take sulfasalazine delayed release tablets in evenly divided doses, preferably after meals, and to swallow the tablets whole.

Ulcerative Colitis

Initial Therapy

Adults: 3 to 4 g daily in evenly divided doses with dosage intervals not exceeding eight hours. It may be advisable to initiate therapy with a lower dosage, e.g., 1 to 2 g daily, to reduce possible gastrointestinal intolerance. If daily doses exceeding 4 g are required to achieve the desired therapeutic effect, the increased risk of toxicity should be kept in mind.

Children, six years of age and older: 40 to 60 mg/kg of body weight in each 24-hour period, divided into 3 to 6 doses.

Maintenance Therapy

Adults: 2 g daily.

Children, six years of age and older: 30 mg/kg of body weight in each 24-hour period, divided into 4 doses. The response of acute ulcerative colitis to sulfasalazine delayed release tablets can be evaluated by clinical criteria, including the presence of fever, weight changes, and degree and frequency of diarrhea and bleeding, as well as by sigmoidoscopy and the evaluation of biopsy samples. It is often necessary to continue medication even when clinical symptoms, including diarrhea, have been controlled. When endoscopic examination confirms satisfactory improvement, dosage of sulfasalazine delayed release tablets should be reduced to a maintenance level. If diarrhea recurs, dosage should be increased to previously effective levels.

Sulfasalazine delayed release tablets are particularly indicated in patients who cannot take uncoated sulfasalazine tablets because of gastrointestinal intolerance (e.g., anorexia, nausea). If symptoms of gastric intolerance (anorexia, nausea, vomiting, etc.) occur after the first few doses of sulfasalazine delayed release tablets, they are probably due to increased serum levels of total sulfapyridine, and may be alleviated by halving the daily dose of sulfasalazine delayed release tablets and subsequently increasing it gradually over several days. If gastric intolerance continues, the drug should be stopped for 5 to 7 days, then reintroduced at a lower daily dose.

Adult Rheumatoid Arthritis

2 g daily in two evenly divided doses. It is advisable to initiate therapy with a lower dosage of sulfasalazine delayed release tablets, e.g., 0.5 to 1.0 g daily, to reduce possible gastrointestinal intolerance. A suggested dosing schedule is given below.

In rheumatoid arthritis, the effect of sulfasalazine delayed release tablets can be assessed by the degree of improvement in the number and extent of actively inflamed joints. A therapeutic response has been observed as early as 4 weeks after starting treatment with sulfasalazine delayed release tablets, but treatment for 12 weeks may be required in some patients before clinical benefit is noted. Consideration can be given to increasing the daily dose of sulfasalazine delayed release tablets to 3 g if the clinical response after 12 weeks is inadequate. Careful monitoring is recommended for doses over 2 g per day.

Suggested Dosing Schedule for Adult Rheumatoid Arthritis:
Week of Number of sulfasalazine delayed release tablets Treatment Morning Evening 1 - One 2 One One 3 One Two 4 Two Two
Juvenile Rheumatoid Arthritis - polyarticular course

Children, six years of age and older: 30 to 50 mg/kg of body weight daily in two evenly divided doses. Typically, the maximum dose is 2 g per day. To reduce possible gastrointestinal intolerance, begin with a quarter to a third of the planned maintenance dose and increase weekly until reaching the maintenance dose at one month.

Some patients may be sensitive to treatment with sulfasalazine. Various desensitization-like regimens have been reported to be effective in 34 of 53 patients,8 7 of 8 patients,9 and 19 of 20 patients.10 These regimens suggest starting with a total daily dose of 50 to 250 mg sulfasalazine initially, and doubling it every 4 to 7 days until the desired therapeutic level is achieved. If the symptoms of sensitivity recur, sulfasalazine delayed release tablets should be discontinued. Desensitization should not be attempted in patients who have a history of agranulocytosis, or who have experienced an anaphylactoid reaction while previously receiving sulfasalazine.
Galantamine

Galantamine

The dosage of galantamine tablets shown to be effective in controlled clinical trials is 16 to 32 mg/day given as twice daily dosing. As the dose of 32 mg/day is less well tolerated than lower doses and does not provide increased effectiveness, the recommended dose range is 16 to 24 mg/day given in a BID regimen. The dose of 24 mg/day did not provide a statistically significant greater clinical benefit than 16 mg/day. It is possible, however, that a daily dose of 24 mg of galantamine tablets might provide additional benefit for some patients.The recommended starting dose of galantamine tablets is 4 mg twice a day (8 mg/day). The dose should be increased to the initial maintenance dose of 8 mg twice a day (16 mg/day) after a minimum of 4 weeks. A further increase to 12 mg twice a day (24 mg/day) should be attempted after a minimum of 4 weeks at 8 mg twice a day (16 mg/day). Dose increases should be based upon assessment of clinical benefit and tolerability of the previous dose.Galantamine tablets should be administered twice a day, preferably with morning and evening meals.Patients and caregivers should be advised to ensure adequate fluid intake during treatment. If therapy has been interrupted for several days or longer, the patient should be restarted at the lowest dose and the dose escalated to the current dose.The abrupt withdrawal of galantamine tablets in those patients who had been receiving doses in the effective range was not associated with an increased frequency of adverse events in comparison with those continuing to receive the same doses of that drug. The beneficial effects of galantamine tablets are lost, however, when the drug is discontinued. Doses in Special Populations Galantamine plasma concentrations may be increased in patients with moderate to severe hepatic impairment. In patients with moderately impaired hepatic function (Child-Pugh score of 7 to 9), the total daily dose should generally not exceed 16 mg/day. The use of galantamine tablets in patients with severe hepatic impairment (Child-Pugh score of 10 to 15) is not recommended.For patients with moderate renal impairment the dose should generally not exceed 16 mg/day. In patients with severe renal impairment (creatinine clearance <9 mL/min), the use of galantamine tablets is not recommended.
Famciclovir

Famciclovir

Famciclovir tablets may be taken with or without food.

2.1 Dosing Recommendation in Immunocompetent Adult Patients

Herpes labialis (cold sores): The recommended dosage of famciclovir tablets for the treatment of recurrent herpes labialis is 1500 mg as a single dose. Therapy should be initiated at the first sign or symptom of herpes labialis (e.g., tingling, itching, burning, pain, or lesion).Genital herpes: Recurrent episodes: The recommended dosage of famciclovir tablets for the treatment of recurrent episodes of genital herpes is 1000 mg twice daily for 1 day. Therapy should be initiated at the first sign or symptom of a recurrent episode (e.g., tingling, itching, burning, pain, or lesion). Suppressive therapy: The recommended dosage of famciclovir tablets for chronic suppressive therapy of recurrent episodes of genital herpes is 250 mg twice daily.

2.2 Dosing Recommendation in HIV-Infected Adult Patients

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

2.3 Dosing Recommendation in Patients with Renal Impairment

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

Amlodipine Besylate And Atorvastatin Calcium

Amlodipine besylate and atorvastatin calcium tablets

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

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

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

Amlodipine

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

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

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

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

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

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

Atorvastatin (Hyperlipidemia)

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

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

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

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

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

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

Gabapentin

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

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

2.1 Osteoarthritis

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

2.2 Rheumatoid Arthritis

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

2.3 Juvenile Rheumatoid Arthritis

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

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

2.4 Ankylosing Spondylitis

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

2.5 Management of Acute Pain and Treatment of Primary Dysmenorrhea

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

2.6 Special Populations

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

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

Sulfasalazine

The dosage of sulfasalazine tablets should be adjusted to each individual's response and tolerance.

Initial Therapy

Adults: 3 to 4 g daily in evenly divided doses with dosage intervals not exceeding eight hours. In some cases, it is advisable to initiate therapy with a smaller dosage, e.g., 1 to 2 g daily, to reduce possible gastrointestinal intolerance. If daily doses exceeding 4 g are required to achieve desired effects, the increased risk of toxicity should be kept in mind.

Children, six years of age and older: 40 to 60 mg/kg body weight in each 24-hour period, divided into 3 to 6 doses.

Maintenance Therapy

Adults: 2 g daily.

Children, six years of age and older: 30 mg/kg body weight in each 24-hour period, divided into 4 doses.

The response of acute ulcerative colitis to sulfasalazine tablets can be evaluated by clinical criteria, including the presence of fever, weight changes, and degree and frequency of diarrhea and bleeding, as well as by sigmoidoscopy and the evaluation of biopsy samples. It is often necessary to continue medication even when clinical symptoms, including diarrhea, have been controlled. When endoscopic examination confirms satisfactory improvement, the dosage of sulfasalazine should be reduced to a maintenance level. If diarrhea recurs, the dosage should be increased to previously effective levels. If symptoms of gastric intolerance (anorexia, nausea, vomiting, etc.) occur after the first few doses of sulfasalazine, they are probably due to increased serum levels of total sulfapyridine and may be alleviated by halving the daily dose of sulfasalazine and subsequently increasing it gradually over several days. If gastric intolerance continues, the drug should be stopped for 5 to 7 days, then reintroduced at a lower daily dose.

Some patients may be sensitive to treatment with sulfasalazine. Various desensitization-like regimens have been reported to be effective in 34 of 53 patients,4 7 of 8 patients,5 and 19 of 20 patients.6 These regimens suggest starting with a total daily dose of 50 to 250 mg sulfasalazine initially, and doubling it every 4 to 7 days until the desired therapeutic level is achieved. If the symptoms of sensitivity recur, sulfasalazine should be discontinued. Desensitization should not be attempted in patients who have a history of agranulocytosis, or who have experienced an anaphylactoid reaction while previously receiving sulfasalazine.
Torsemide

Torsemide

General Torsemide 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 Failure The 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 Cirrhosis The usual initial dose is 5 mg or 10 mg of once-daily oral torsemide, 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. Hypertension The 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.
Sumatriptan

Sumatriptan

In controlled clinical trials, single doses of 25, 50, or 100 mg of sumatriptan tablets were effective for the acute treatment of migraine in adults. There is evidence that doses of 50 and 100 mg may provide a greater effect than 25 mg (see CLINICAL TRIALS). There is also evidence that doses of 100 mg do not provide a greater effect than 50 mg. Individuals may vary in response to doses of sumatriptan tablets. The choice of dose should therefore be made on an individual basis, weighing the possible benefit of a higher dose with the potential for a greater risk of adverse events.If the headache returns or the patient has a partial response to the initial dose, the dose may be repeated after 2 hours, not to exceed a total daily dose of 200 mg. If a headache returns following an initial treatment with sumatriptan succinate injection, additional single sumatriptan tablets (up to 100 mg/day) may be given with an interval of at least 2 hours between tablet doses. The safety of treating an average of more than 4 headaches in a 30-day period has not been established.Because of the potential of MAO-A inhibitors to cause unpredictable elevations in the bioavailability of oral sumatriptan, their combined use is contraindicated (see CONTRAINDICATIONS).Hepatic disease/functional impairment may also cause unpredictable elevations in the bioavailability of orally administered sumatriptan. Consequently, if treatment is deemed advisable in the presence of liver disease, the maximum single dose should in general not exceed 50 mg (see CLINICAL PHARMACOLOGY for the basis of this recommendation).
Montelukast Sodium

Montelukast Sodium

2.1 Asthma

Montelukast sodium tablets should be taken once daily in the evening. The following dose is recommended:For adults and adolescents 15 years of age and older: one 10 mg 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-lnduced Bronchoconstriction (EIB) in Patients 15 Years of Age and Older

For prevention of EIB, a single 10 mg dose of montelukast sodium tablets should be taken at least 2 hours before exercise. An additional dose of montelukast sodium tablets should not be taken within 24 hours of a previous dose. Patients already taking montelukast sodium tablets 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 tablets 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 tablets 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 dose for the treatment of symptoms of seasonal allergic rhinitis is recommended:For adults and adolescents 15 years of age and older: one 10 mg tablet.Safety and effectiveness in pediatric patients younger than 2 years of age with seasonal allergic rhinitis have not been established.The following dose for the treatment of symptoms of perennial allergic rhinitis is recommended:For adults and adolescents 15 years of age and older: one 10 mg tablet.Safety and effectiveness in pediatric patients younger than 6 months 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 tablet dose daily in the evening.
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)].
Mirtazapine

Mirtazapine

Initial Treatment The recommended starting dose for mirtazapine tablets is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day. While the relationship between dose and satisfactory response in the treatment of major depressive disorder for mirtazapine has not been adequately explored, patients not responding to the initial 15 mg dose may benefit from dose increases up to a maximum of 45 mg/day. Mirtazapine has an elimination half-life of approximately 20 to 40 hours; therefore, dose changes should not be made at intervals of less than 1 to 2 weeks in order to allow sufficient time for evaluation of the therapeutic response to a given dose. Elderly and Patients with Renal or Hepatic Impairment The clearance of mirtazapine is reduced in elderly patients and in patients with moderate to severe renal or hepatic impairment. Consequently, the prescriber should be aware that plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in younger adults without renal or hepatic impairment (see PRECAUTIONS and CLINICAL PHARMACOLOGY). Maintenance/Extended Treatment It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of mirtazapine tablets has demonstrated that its efficacy in major depressive disorder is maintained for periods of up to 40 weeks following 8 to 12 weeks of initial treatment at a dose of 15 to 45 mg/day (see CLINICAL PHARMACOLOGY). Based on these limited data, it is unknown whether or not the dose of mirtazapine needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with mirtazapine tablets. Conversely, at least 14 days should be allowed after stopping mirtazapine tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS). Use of Mirtazapine Tablets With Other MAOIs, Such as Linezolid or Methylene Blue Do not start mirtazapine tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).In some cases, a patient already receiving therapy with mirtazapine tablets may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, mirtazapine tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with mirtazapine tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with mirtazapine tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).Discontinuation of Mirtazapine Tablets TreatmentSymptoms associated with the discontinuation or dose reduction of mirtazapine tablets have been reported. Patients should be monitored for these and other symptoms when discontinuing treatment or during dosage reduction. A gradual reduction in the dose over several weeks, rather than abrupt cessation, is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient’s clinical response (see PRECAUTIONS and ADVERSE REACTIONS).
Montelukast Sodium

Montelukast Sodium

2.1 Asthma

Montelukast sodium chewable tablets should be taken once daily in the evening. The following doses are recommended:For adults and adolescents 15 years of age and older: 10 mg.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 10 mg dose of montelukast sodium chewable tablets should be taken at least 2 hours before exercise. An additional dose of montelukast sodium chewable tablets should not be taken within 24 hours of a previous dose. Patients already taking montelukast sodium chewable tablets 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 chewable tablets 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 chewable tablets 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: 10 mg.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: 10 mg.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 6 months 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.
Mirtazapine

Mirtazapine

Initial Treatment The recommended starting dose for mirtazapine orally disintegrating tablets is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine tablets in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day. While the relationship between dose and satisfactory response in the treatment of major depressive disorder for mirtazapine has not been adequately explored, patients not responding to the initial 15 mg dose may benefit from dose increases up to a maximum of 45 mg/day. Mirtazapine has an elimination half-life of approximately 20 to 40 hours; therefore, dose changes should not be made at intervals of less than 1 to 2 weeks in order to allow sufficient time for evaluation of the therapeutic response to a given dose.Administration of Mirtazapine Orally Disintegrating Tablets Patients should be instructed to open tablet blister pack with dry hands and place the tablet on the tongue. The tablet should be used immediately after removal from its blister ; once removed, it cannot be stored. Mirtazapine Orally Disintegrating Tablets will disintegrate rapidly on the tongue and can be swallowed with saliva. No water is needed for taking the tablet. Patients should not attempt to split the tablet.Elderly and Patients with Renal or Hepatic Impairment The clearance of mirtazapine is reduced in elderly patients and in patients with moderate to severe renal or hepatic impairment. Consequently, the prescriber should be aware that plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in younger adults without renal or hepatic impairment (see PRECAUTIONS and CLINICAL PHARMACOLOGY). Maintenance/Extended Treatment It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of mirtazapine tablets has demonstrated that its efficacy in major depressive disorder is maintained for periods of up to 40 weeks following 8 to 12 weeks of initial treatment at a dose of 15 to 45 mg/day (see CLINICAL PHARMACOLOGY). Based on these limited data, it is unknown whether or not the dose of mirtazapine needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with mirtazapine orally disintegrating tablets. Conversely, at least 14 days should be allowed after stopping mirtazapine orally disintegrating tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).Use of Mirtazapine Orally Disintegrating Tablets With Other MAOIs, Such as Linezolid or Methylene Blue Do not start mirtazapine orally disintegrating tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).In some cases, a patient already receiving therapy with mirtazapine orally disintegrating tablets may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, mirtazapine orally disintegrating tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with mirtazapine orally disintegrating tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with mirtazapine orally disintegrating tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS). Discontinuation of Mirtazapine Treatment Symptoms associated with the discontinuation or dose reduction of mirtazapine orally disintegrating tablets have been reported. Patients should be monitored for these and other symptoms when discontinuing treatment or during dosage reduction. A gradual reduction in the dose over several weeks, rather than abrupt cessation, is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient’s clinical response (see PRECAUTIONS and ADVERSE REACTIONS).
Paroxetine

Paroxetine

Major Depressive Disorder Usual Initial DosageParoxetine tablets should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dose is 20 mg/day. Patients were dosed in a range of 20 to 50 mg/day in the clinical trials demonstrating the effectiveness of paroxetine tablets in the treatment of major depressive disorder. As with all drugs effective in the treatment of major depressive disorder, the full effect may be delayed. Some patients not responding to a 20 mg dose may benefit from dose increases, in 10 mg/day increments, up to a maximum of 50 mg/day. Dose changes should occur at intervals of at least 1 week.Maintenance TherapyThere is no body of evidence available to answer the question of how long the patient treated with paroxetine tablets should remain on it. 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.Systematic evaluation of the efficacy of paroxetine tablets has shown that efficacy is maintained for periods of up to 1 year with doses that averaged about 30 mg. Obsessive Compulsive Disorder Usual Initial DosageParoxetine tablets should be administered as a single daily dose with or without food, usually in the morning. The recommended dose of paroxetine tablets in the treatment of OCD is 40 mg daily. Patients should be started on 20 mg/day and the dose can be increased in 10 mg/day increments. Dose changes should occur at intervals of at least 1 week. Patients were dosed in a range of 20 to 60 mg/day in the clinical trials demonstrating the effectiveness of paroxetine tablets in the treatment of OCD. The maximum dosage should not exceed 60 mg/day.Maintenance TherapyLong-term maintenance of efficacy was demonstrated in a 6-month relapse prevention trial. In this trial, patients with OCD assigned to paroxetine demonstrated a lower relapse rate compared to patients on placebo (see CLINICAL PHARMACOLOGY: Clinical Trials). OCD is a chronic condition, and it is reasonable to consider continuation for a responding patient. Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment. Panic Disorder Usual Initial DosageParoxetine tablets should be administered as a single daily dose with or without food, usually in the morning. The target dose of paroxetine tablets in the treatment of panic disorder is 40 mg/day. Patients should be started on 10 mg/day. Dose changes should occur in 10 mg/day increments and at intervals of at least 1 week. Patients were dosed in a range of 10 to 60 mg/day in the clinical trials demonstrating the effectiveness of paroxetine tablets. The maximum dosage should not exceed 60 mg/day.Maintenance TherapyLong-term maintenance of efficacy was demonstrated in a 3-month relapse prevention trial. In this trial, patients with panic disorder assigned to paroxetine demonstrated a lower relapse rate compared to patients on placebo (see CLINICAL PHARMACOLOGY: Clinical Trials). Panic disorder is a chronic condition, and it is reasonable to consider continuation for a responding patient. Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment. Generalized Anxiety Disorder Usual Initial DosageParoxetine tablets should be administered as a single daily dose with or without food, usually in the morning. In clinical trials the effectiveness of paroxetine tablets was demonstrated in patients dosed in a range of 20 to 50 mg/day. The recommended starting dosage and the established effective dosage is 20 mg/day. There is not sufficient evidence to suggest a greater benefit to doses higher than 20 mg/day. Dose changes should occur in 10 mg/day increments and at intervals of at least 1 week.Maintenance TherapySystematic evaluation of continuing paroxetine tablets for periods of up to 24 weeks in patients with Generalized Anxiety Disorder who had responded while taking paroxetine tablets during an 8-week acute treatment phase has demonstrated a benefit of such maintenance (see CLINICAL PHARMACOLOGY: Clinical Trials). Nevertheless, patients should be periodically reassessed to determine the need for maintenance treatment. Special Populations Treatment of Pregnant Women During the Third TrimesterNeonates exposed to paroxetine tablets and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see WARNINGS: Usage in Pregnancy). When treating pregnant women with paroxetine during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.Dosage for Elderly or Debilitated Patients, and Patients With Severe Renal or Hepatic ImpairmentThe recommended initial dose is 10 mg/day for elderly patients, debilitated patients, and/or patients with severe renal or hepatic impairment. Increases may be made if indicated. Dosage should not exceed 40 mg/day. 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 paroxetine tablets. Conversely, at least 14 days should be allowed after stopping paroxetine tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS). Use of Paroxetine Tablets With Other MAOIs, Such as Linezolid or Methylene Blue Do not start paroxetine tablets 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 paroxetine tablets may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, paroxetine tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with paroxetine tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with paroxetine tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).

Discontinuation of Treatment With Paroxetine Tablets

Symptoms associated with discontinuation of paroxetine tablets have been reported (see PRECAUTIONS: Discontinuation of Treatment With Paroxetine Tablets). Patients should be monitored for these symptoms when discontinuing treatment, regardless of the indication for which paroxetine tablets is being prescribed. 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.
Glyburide And Metformin...

Glyburide And Metformin Hydrochloride

General Considerations

Dosage of glyburide and metformin hydrochloride tablets must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended daily dose of 20 mg glyburide/2000 mg metformin. Glyburide and metformin hydrochloride tablets

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 glyburide), 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 glyburide and metformin hydrochloride tablets

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 (glycosylated hemoglobin), 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 glyburide and metformin hydrochloride tablets

therapy in patients taking concomitant glyburide (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.

Glyburide and Metformin Hydrochloride Tablets in Patients with Inadequate Glycemic Control on Diet and Exercise

Recommended starting dose: 1.25 mg/250 mg once or twice daily with meals. For patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone, the recommended starting dose of glyburide and metformin hydrochloride tablets is 1.25 mg/250 mg once a day with a meal. As initial therapy in patients with baseline HbA1c >9% or an FPG >200 mg/dL, a starting dose of glyburide and metformin hydrochloride tablet 1.25 mg/250 mg twice daily with the morning and evening meals may be used. Dosage increases should be made in increments of 1.25 mg/250 mg per day every 2 weeks up to the minimum effective dose necessary to achieve adequate control of blood glucose. In clinical trials of glyburide and metformin hydrochloride tablets as initial therapy, there was no experience with total daily doses >10 mg/2000 mg per day. Glyburide and metformin hydrochloride tablet 5 mg/500 mg should not be used as initial therapy due to an increased risk of hypoglycemia.

Glyburide and Metformin Hydrochloride Tablets Use in Patients with Inadequate Glycemic Control on a Sulfonylurea and/or Metformin

Recommended starting dose: 2.5 mg/500 mg or 5 mg/500 mg twice daily with meals. For patients not adequately controlled on either glyburide (or another sulfonylurea) or metformin alone, the recommended starting dose of glyburide and metformin hydrochloride tablet

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 glyburide and metformin hydrochloride tablets should not exceed the daily doses of glyburide 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.For patients previously treated with combination therapy of glyburide (or another sulfonylurea) plus metformin, if switched to glyburide and metformin hydrochloride tablets, the starting dose should not exceed the daily dose of glyburide (or equivalent dose of another sulfonylurea) and metformin already being taken. Patients should be monitored closely for signs and symptoms of hypoglycemia following such a switch and the dose of glyburide and metformin hydrochloride tablets

should be titrated as described above to achieve adequate control of blood glucose.

Addition of Thiazolidinediones to Glyburide and Metformin Hydrochloride Tablets Therapy

For patients not adequately controlled on glyburide and metformin hydrochloride tablets, a thiazolidinedione can be added to glyburide and metformin hydrochloride tablets therapy. When a thiazolidinedione is added to glyburide and metformin hydrochloride tablets therapy, the current dose of glyburide and metformin hydrochloride tablets can be continued and the thiazolidinedione initiated at its recommended starting dose. For patients needing additional glycemic control, the dose of the thiazolidinedione can be increased based on its recommended titration schedule. The increased glycemic control attainable with glyburide and metformin hydrochloride tablets plus a thiazolidinedione may increase the potential for hypoglycemia at any time of day. In patients who develop hypoglycemia when receiving glyburide and metformin hydrochloride tablets and a thiazolidinedione, consideration should be given to reducing the dose of the glyburide component of glyburide and metformin hydrochloride tablets. As clinically warranted, adjustment of the dosages of the other components of the antidiabetic regimen should also be considered.

Specific Patient Populations

Glyburide and metformin hydrochloride tablets are not recommended for use during pregnancy. The initial and maintenance dosing of glyburide and metformin hydrochloride tablets 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 glyburide and metformin hydrochloride tablets 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.)
Penicillin V Potassium

Penicillin V Potassium

The dosage of Penicillin V should be determined according to the sensitivity of the causative microorganism and the severity of infection, and adjusted to the clinical response of the patient.The usual dosage recommendations for adults and children 12 years and over are as follows:Streptococcal Infections - mild to moderately severe - of the upper respiratory tract and including scarlet fever and erysipelas: 125 to 250 mg (200,000 to 400,000 units) every 6 to 8 hours for 10 days.Pneumococcal Infections - mild to moderately severe - of the respiratory tract, including otitis media: 250 to 500 mg (400,000 to 800,000 units) every 6 hours until the patient has been afebrile for at least 2 days.Staphylococcal Infections - mild infections of skin and soft tissue (culture and sensitive tests should be performed): 250 to 500 mg (400,000 to 800,000 units) every 6 to 8 hours.Fusospirochetosis (Vincent’s infection) of the oropharynx. Mild to moderately severe infections: 250 to 500 mg (400,000 to 800,000 units) every 6 to 8 hours.For the prevention of recurrence following rheumatic fever and/or chorea: 125 mg to 250 mg (200,000 to 400,000 units) twice daily on a continuing basis.For prophylaxis against bacterial endocarditis1 in patients with congenital heart disease or rheumatic or other acquired valvular heart disease when undergoing dental procedures or surgical procedures of the upper respiratory tract: 2 gram of penicillin V (1 gram for children under 60 lbs.) 1 hour before the procedure, and then, 1 gram (500 mg for children under 60 lbs.) 6 hours later.
Fosinopril Sodium And H...

Fosinopril Sodium And Hydrochlorothiazide

Fosinopril is an effective treatment of hypertension in once-daily doses of 10 to 80 mg, while hydrochlorothiazide is effective in doses of 12.5 to 50 mg per day. In clinical trials of fosinopril/hydrochlorothiazide combination therapy using fosinopril doses of 2.5 to 40 mg and hydrochlorothiazide doses at 5 to 37.5 mg, the antihypertensive effects increased with increasing dose of either component.The hazards (see WARNINGS) of fosinopril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of fosinopril and hydrochlorothiazide will be associated with both sets of dose-independent hazards. To minimize dose-independent hazards, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Dose Titration by Clinical Effect

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

Use in Renal Impairment

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

Metformin Hydrochloride

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with metformin or any other pharmacologic agent. Dosage of metformin 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 hydrochloride tablets is 2550 mg in adults and 2000 mg in pediatric patients (10 to 16 years of age).Metformin hydrochloride tablets should be given in divided doses with meals and should be started at a low dose, with gradual dose escalation, 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 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, 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 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 hydrochloride tablets 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 hydrochloride tablets 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. Pediatrics – The usual starting dose of metformin hydrochloride tablets 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, 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 and Oral Sulfonylurea Therapy in Adult Patients

If patients have not responded to four weeks of the maximum dose of metformin monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing metformin 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 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 hydrochloride tablets 500 mg and glyburide 20 mg were titrated to 1000/20 mg, 1500/20 mg, 2000/20 mg or 2500/20 mg of metformin hydrochloride tablets 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 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 and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without metformin.

Concomitant Metformin and Insulin Therapy in Adult Patients

The current insulin dose should be continued upon initiation of metformin therapy. Metformin therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of metformin 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 hydrochloride tablets. 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. Further adjustment should be individualized based on glucose-lowering response.

Specific Patient Populations

Metformin is not recommended for use in pregnancy. Metformin hydrochloride tablets are not recommended in patients below the age of 10 years.The initial and maintenance dosing of metformin 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.Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly. (See WARNINGS.)
Valacyclovir Hydrochlor...

Valacyclovir Hydrochloride

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

Cold Sores (Herpes Labialis): The recommended dosage of valacyclovir tablets for treatment of cold sores is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning). Genital Herpes: Initial Episode: The recommended dosage of valacyclovir tablets for treatment of initial genital herpes is 1 gram twice daily for 10 days. Therapy was most effective when administered within 48 hours of the onset of signs and symptoms. Recurrent Episodes: The recommended dosage of valacyclovir tablets for treatment of recurrent genital herpes is 500 mg twice daily for 3 days. Initiate treatment at the first sign or symptom of an episode. Suppressive Therapy: The recommended dosage of valacyclovir tablets for chronic suppressive therapy of recurrent genital herpes is 1 gram once daily in patients with normal immune function. In patients with a history of 9 or fewer recurrences per year, an alternative dose is 500 mg once daily.In HIV-infected patients with a CD4+ cell count
Colgate Great Regular F...

Colgate Great Regular Flavor

Carefully consider the potential benefits and risks of diclofenac sodium/misoprostol tablets and other treatment options before deciding to use diclofenac sodium/misoprostol 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/misoprostol 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/misoprostol tablets are administered as diclofenac sodium/misoprostol 50 (50 mg diclofenac sodium/200 mcg misoprostol) or as diclofenac sodium/misoprostol 75 (75 mg diclofenac sodium/200 mcg misoprostol).

Note: See SPECIAL DOSING CONSIDERATIONS section below.

Osteoarthritis

The recommended dosage for maximal GI mucosal protection is diclofenac sodium/misoprostol 50 tid. For patients who experience intolerance, diclofenac sodium/misoprostol 75 bid or diclofenac sodium/misoprostol 50 bid can be used, but are less effective in preventing ulcers. This fixed combination product, diclofenac sodium/misoprostol 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/misoprostol 50 tidbid 150100 600400 Diclofenac sodium/misoprostol 75 bid 150 400
Rheumatoid Arthritis

The recommended dosage is diclofenac sodium/misoprostol 50 tid or qid. For patients who experience intolerance, diclofenac sodium/misoprostol 75 bid or diclofenac sodium/misoprostol 50 bid can be used, but are less effective in preventing ulcers. This fixed combination product, diclofenac sodium/misoprostol 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/misoprostol 50 qidtidbid 200150100 800600400 Diclofenac sodium/misoprostol 75 bid 150 400
SPECIAL DOSING CONSIDERATIONS

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

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

Alprazolam

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

Anxiety Disorders and Transient Symptoms of Anxiety

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

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

Panic Disorder

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

Dose Titration

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

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

Dose Maintenance

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

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

Dose Reduction

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

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

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

Dosing in Special Populations

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

Alprazolam Xr

Alprazolam XR 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 XR 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 XR 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 XR.

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

Dose Maintenance

In controlled trials conducted to establish the efficacy of Alprazolam XR 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 XR 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 XR (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 XR 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.
Eplerenone

Eplerenone

2.1 Congestive Heart Failure Post-Myocardial Infarction

Treatment should be initiated at 25 mg once daily and titrated to the recommended dose of 50 mg once daily, preferably within 4 weeks as tolerated by the patient. Eplerenone may be administered with or without food.

Once treatment with eplerenone has begun, adjust the dose based on the serum potassium level as shown in Table 1.
Table 1. Dose Adjustment in Congestive Heart Failure Post-MI Serum Potassium(mEq/L) Action Dose Adjustment < 5.0 Increase 25 mg every other day to 25 mg once daily25 mg once daily to 50 mg once daily 5.0–5.4 Maintain No adjustment 5.5–5.9 Decrease 50 mg once daily to 25 mg once daily25 mg once daily to 25 mg every other day25 mg every other day to withhold ≥ 6.0 Withhold Restart at 25 mg every other day when potassium levels fall to <5.5 mEq/L
2.2 Hypertension

The recommended starting dose of eplerenone is 50 mg administered once daily. The full therapeutic effect of eplerenone is apparent within 4 weeks. For patients with an inadequate blood pressure response to 50 mg once daily the dosage of eplerenone should be increased to 50 mg twice daily. Higher dosages of eplerenone are not recommended because they have no greater effect on blood pressure than 100 mg and are associated with an increased risk of hyperkalemia. [See CLINICAL STUDIES (14.2).]

2.3 Recommended Monitoring

Serum potassium should be measured before initiating eplerenone therapy, within the first week, and at one month after the start of treatment or dose adjustment. Serum potassium should be assessed periodically thereafter. Patient characteristics and serum potassium levels may indicate that additional monitoring is appropriate. [See WARNINGS AND PRECAUTIONS (5.1), ADVERSE REACTIONS (6.2).] In the EPHESUS study [See CLINICAL STUDIES (14.1)], the majority of hyperkalemia was observed within the first three months after randomization.

In all patients taking eplerenone who start taking a moderate CYP3A4 inhibitor, check serum potassium and serum creatinine in 3–7 days.

2.4 Dose Modifications for Specific Populations

For hypertensive patients receiving moderate CYP3A4 inhibitors (e.g., erythromycin, saquinavir, verapamil, and fluconazole), the starting dose of eplerenone should be reduced to 25 mg once daily. [See DRUG INTERACTIONS (7.1).]

No adjustment of the starting dose is recommended for the elderly or for patients with mild-to-moderate hepatic impairment. [See CLINICAL PHARMACOLOGY (12.3).]
Spironolactone And Hydr...

Spironolactone And Hydrochlorothiazide

Optimal dosage should be established by individual titration of the components (see boxed Warning).

Edema in adults (congestive heart failure, hepatic cirrhosis, or nephrotic syndrome)

The usual maintenance dose of spironolactone and hydrochlorothiazide tablets is 100 mg each of spironolactone and hydrochlorothiazide daily, administered in a single dose or in divided doses, but may range from 25 mg to 200 mg of each component daily depending on the response to the initial titration. In some instances it may be desirable to administer separate tablets of either spironolactone or hydrochlorothiazide in addition to spironolactone and hydrochlorothiazide tablets in order to provide optimal individual therapy.

The onset of diuresis with spironolactone and hydrochlorothiazide tablets occurs promptly and, due to prolonged effect of the spironolactone component, persists for two to three days after spironolactone and hydrochlorothiazide tablets are discontinued.

Essential hypertension

Although the dosage will vary depending on the results of titration of the individual ingredients, many patients will be found to have an optimal response to 50 mg to 100 mg each of spironolactone and hydrochlorothiazide daily, given in a single dose or in divided doses.

Concurrent potassium supplementation is not recommended when spironolactone and hydrochlorothiazide tablets are used in the long-term management of hypertension or in the treatment of most edematous conditions, since the spironolactone content of spironolactone and hydrochlorothiazide tablets is usually sufficient to minimize loss induced by the hydrochlorothiazide component.
Nadolol

Nadolol

DOSAGE MUST BE INDIVIDUALIZED. NADOLOL TABLET MAY BE ADMINISTERED WITHOUT REGARD TO MEALS.

Angina Pectoris

The usual initial dose is 40 mg nadolol tablet once daily. Dosage may be gradually increased in 40 to 80 mg increments at 3 to 7 day intervals until optimum clinical response is obtained or there is pronounced slowing of the heart rate. The usual maintenance dose is 40 or 80 mg administered once daily. Doses up to 160 or 240 mg administered once daily may be needed.

The usefulness and safety in angina pectoris of dosage exceeding 240 mg per day have not been established. If treatment is to be discontinued, reduce the dosage gradually over a period of one to two weeks (see WARNINGS).

Hypertension

The usual initial dose is 40 mg nadolol tablet once daily, whether it is used alone or in addition to diuretic therapy. Dosage may be gradually increased in 40 to 80 mg increments until optimum blood pressure reduction is achieved. The usual maintenance dose is 40 or 80 mg administered once daily. Doses up to 240 or 320 mg administered once daily may be needed.

Dosage Adjustment in Renal Failure

Absorbed nadolol is excreted principally by the kidneys and, although nonrenal elimination does occur, dosage adjustments are necessary in patients with renal impairment. The following dose intervals are recommended:
Creatinine Clearance(mL/min/1.73m2) Dosage Interval(hours) >50 24 31–50 24–36 10–30 24–48 <10 40–60
Ketorolac Tromethamine

Ketorolac Tromethamine

[see Indications and Usage (1)]

Azithromycin for oral suspension (single dose 1 g packet) can be taken with or without food after constitution. However, increased tolerability has been observed when tablets are taken with food.

Azithromycin for oral suspension (single dose 1 g packet) is not for pediatric use. For pediatric suspension see the prescribing information for azithromycin for oral suspension 100 mg/5 mL and 200 mg/5 mL bottles.

Directions for administration of azithromycin for oral suspension in the single dose packet (1 g): The entire contents of the packet should be mixed thoroughly with two ounces (approximately 60 mL) of water. Drink the entire contents immediately; add an additional two ounces of water, mix, and drink to ensure complete consumption of dosage. The single dose packet should not be used to administer doses other than 1000 mg of azithromycin.

2.1 Sexually Transmitted Diseases

The recommended dose of azithromycin for the treatment of non-gonococcal urethritis and cervicitis due to C. trachomatis is a single 1 gram (1000 mg) dose of azithromycin. This dose can be administered as one single dose packet (1 g).

2.2 Mycobacterial Infections

Prevention of Disseminated MAC Infections

The recommended dose of azithromycin for the prevention of disseminated Mycobacterium avium complex (MAC) disease is: 1200 mg taken once weekly. This dose of azithromycin may be combined with the approved dosage regimen of rifabutin.

Treatment of Disseminated MAC Infections

Azithromycin should be taken at a daily dose of 600 mg, in combination with ethambutol at the recommended daily dose of 15 mg/kg. Other antimycobacterial drugs that have shown in vitro activity against MAC may be added to the regimen of azithromycin plus ethambutol at the discretion of the physician or health care provider.
Clindamycin Phosphate S...

Clindamycin Phosphate Solution Clindamycin Phosphate Lotion Clindamycin Phosphate Gel

Apply a thin film of clindamycin phosphate topical solution, clindamycin phosphate topical lotion, clindamycin phosphate topical gel, or use a clindamycin phosphate topical solution pledget for the application of clindamycin phosphate twice daily to affected area. More than one pledget may be used. Each pledget should be used only once and then be discarded.

Lotion: Shake well immediately before using.

Pledget: Remove pledget from foil just before use. Do not use if the seal is broken. Discard after single use.

Keep all liquid dosage forms in containers tightly closed.
Soriatane

Soriatane

The recommended usual dosage range of trandolapril for hypertension is 1 to 4 mg per day administered in a single dose or two divided doses. The recommended usual dosage range of Isoptin-SR for hypertension is 120 to 480 mg per day administered in a single dose or two divided doses.

The hazards (see WARNINGS) of trandolapril are generally independent of dose; those of verapamil are a mixture of dose-dependent phenomena (primarily dizziness, AV block, constipation) and dose-independent phenomena, the former much more common than the latter. Therapy with any combination of trandolapril and verapamil will thus be associated with both sets of dose-independent hazards. The dose-dependent side effects of verapamil have not been shown to be decreased by the addition of trandolapril nor vice versa.

Rarely, the dose-independent hazards of trandolapril are serious. To minimize dose-independent hazards, it is usually appropriate to begin therapy with trandolapril/verapamil hydrochloride ER tablets only after a patient has either (a) failed to achieve the desired antihypertensive effect with one or the other monotherapy at its respective maximally recommended dose and shortest dosing interval, or (b) the dose of one or the other monotherapy cannot be increased further because of dose-limiting side effects.

Clinical trials with trandolapril/verapamil hydrochloride ER tablets have explored only once-a-day doses. The antihypertensive effect and or adverse effects of adding 4 mg of trandolapril once-a-day to a dose of 240 mg Isoptin-SR administered twice-a-day has not been studied, nor have the effects of adding as little of 180 mg Isoptin-SR to 2 mg trandolapril administered twice-a-day been evaluated. Over the dose range of Isoptin-SR 120 to 240 mg once-a-day and trandolapril 0.5 to 8 mg once-a-day, the effects of the combination increase with increasing doses of either component.

Replacement Therapy

For convenience, patients receiving trandolapril (up to 8 mg) and verapamil (up to 240 mg) in separate tablets, administered once-a-day, may instead wish to receive tablets of trandolapril/verapamil hydrochloride ER tablets containing the same component doses.

Trandolapril/verapamil hydrochloride ER tablets should be administered with food.
Rebif

Rebif

Hypertension

Monotherapy

The recommended initial dosage of quinapril hydrochloride tablets in patients not on diuretics is 10 or 20 mg once daily. Dosage should be adjusted according to blood pressure response measured at peak (2–6 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 40–80 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, a diuretic may be added. In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of quinapril hydrochloride tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued 2 to 3 days prior to beginning therapy with quinapril hydrochloride tablets (see WARNINGS). Then, if blood pressure is not controlled with quinapril hydrochloride tablets 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:
CreatinineClearance Maximum RecommendedInitial 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 tablets in elderly patients is 10 mg given once daily followed by titration (as described above) to the optimal response.

Heart Failure

Quinapril hydrochloride tablets are indicated as adjunctive therapy when added to conventional therapy including diuretics and/or digitalis. The recommended starting dose is 5 mg twice daily. This dose may improve symptoms of heart failure, but increases in exercise duration have generally required higher doses. Therefore, if the initial dosage of quinapril hydrochloride tablets is well tolerated, patients should then be titrated at weekly intervals until an effective dose, usually 20 to 40 mg daily given in two equally divided doses, is reached or undesirable hypotension, orthostatis, or azotemia (see WARNINGS) prohibit reaching this dose.

Following the initial dose of quinapril hydrochloride tablets, 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 tablets is 5 mg in patients with a creatinine clearance above 30 mL/min and 2.5 mg in patients with a creatinine clearance of 10 to 30 mL/min. There is insufficient data for dosage recommendation in patients with a creatinine clearance less than 10 mL/min (see DOSAGE AND ADMINISTRATION, Heart Failure, WARNINGS, and PRECAUTIONS, Drug Interactions).

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

Pravastatin Sodium

The recommended dosage is one drop in the affected eye(s) once daily in the evening. If one dose is missed, treatment should continue with the next dose as normal.

The dosage of latanoprost ophthalmic solution should not exceed once daily; the combined use of two or more prostaglandins, or prostaglandin analogs including latanoprost ophthalmic solution is not recommended. It has been shown that administration of these prostaglandin drug products more than once daily may decrease the intraocular pressure (IOP) lowering effect or cause paradoxical elevations in IOP.

Reduction of the IOP starts approximately 3 to 4 hours after administration and the maximum effect is reached after 8 to 12 hours.

Latanoprost ophthalmic solution may be used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. Contact lenses should be removed prior to the administration of latanoprost ophthalmic solution, and may be reinserted 15 minutes after administration.
Nifedipine

Nifedipine

Dosage must be adjusted according to each patient's needs. Therapy for either hypertension or angina should be initiated with 30 or 60 mg once daily. Nifedipine extended release tablets should be swallowed whole and should not be bitten or divided. In general, titration should proceed over a 7–14 day period so that the physician can fully assess the response to each dose level and monitor blood pressure before proceeding to higher doses. Since steady-state plasma levels are achieved on the second day of dosing, titration may proceed more rapidly, if symptoms so warrant, provided the patient is assessed frequently. Titration to doses above 120 mg are not recommended.

Angina patients controlled on nifedipine immediate-release capsules alone or in combination with other antianginal medications may be safely switched to nifedipine extended release tablets at the nearest equivalent total daily dose (e.g., 30 mg t.i.d. of nifedipine immediate-release capsules may be changed to 90 mg once daily of nifedipine extended release tablets). Subsequent titration to higher or lower doses may be necessary and should be initiated as clinically warranted. Experience with doses greater than 90 mg in patients with angina is limited. Therefore, doses greater than 90 mg should be used with caution and only when clinically warranted.

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

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

Care should be taken when dispensing nifedipine extended release to assure that the extended release dosage form has been prescribed.

Co-Administration with Other Antianginal Drugs

Sublingual nitroglycerin may be taken as required for the control of acute manifestations of angina, particularly during nifedipine titration. See PRECAUTIONS, Drug Interactions, for information on co-administration of nifedipine with beta blockers or long-acting nitrates.
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/hydrochlorothiazide combination therapy using quinapril doses of 2.5 to 40 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects increased with increasing dose of either component.

The side effects (see WARNINGS) of quinapril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of quinapril and hydrochlorothiazide will be associated with both sets of dose-independent side effects, but regimens that combine low doses of hydrochlorothiazide with quinapril produce minimal effects on serum potassium. In clinical trials of quinapril HCl/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/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/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/hydrochlorothiazide tablets 20/25.

Use in Renal Impairment

Regimens of therapy with quinapril HCl/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/hydrochlorothiazide tablets are not recommended for use in these patients.
Zoledronic Acid

Zoledronic Acid

Secondary Amenorrhea

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

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

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

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

When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be re-evaluated periodically as clinically appropriate (for example, 3 to 6 month intervals) to determine if treatment is still necessary (see WARNINGS). For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.

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

Patients should be started at the lowest dose.

The lowest effective dose of MPA has not been determined.
Tolterodine Tartrate

Tolterodine Tartrate

The initial recommended dose of tolterodine tartrate tablets is 2 mg twice daily. The dose may be lowered to 1 mg twice daily based on individual response and tolerability. For patients with significantly reduced hepatic or renal function or who are currently taking drugs that are potent inhibitors of CYP3A4, the recommended dose of tolterodine tartrate is 1 mg twice daily (see PRECAUTIONS, General, PRECAUTIONS, Reduced Hepatic and Renal Function, and PRECAUTIONS, Drug Interactions).
Misoprostol

Misoprostol

The recommended adult oral dose of misoprostol for reducing the risk of NSAID-induced gastric ulcers is 200 mcg four times daily with food. If this dose cannot be tolerated, a dose of 100 mcg can be used (see Clinical Pharmacology: Clinical studies). Misoprostol should be taken for the duration of NSAID therapy as prescribed by the physician. Misoprostol should be taken with a meal, and the last dose of the day should be at bedtime.

Renal impairment

Adjustment of the dosing schedule in renally impaired patients is not routinely needed, but dosage can be reduced if the 200-mcg dose is not tolerated (see Clinical Pharmacology).
Trueplus Diabetics Foot...

Trueplus Diabetics Foot Care

2.1 Prevention of Pregnancy

Both the 1 mL vial and the 1 mL prefilled syringe of Medroxyprogesterone Acetate Injectable Suspension, USP should be vigorously shaken just before use to ensure that the dose being administered represents a uniform suspension.

The recommended dose is 150 mg of Medroxyprogesterone Acetate Injectable Suspension, USP every 3 months (13 weeks) administered by deep IM injection in the gluteal or deltoid muscle. Medroxyprogesterone Acetate Injectable Suspension, USP should not be used as a long-term birth control method (i.e. longer than 2 years) unless other birth control methods are considered inadequate. Dosage does not need to be adjusted for body weight [see Clinical Studies (14.1)].

To ensure the patient is not pregnant at the time of the first injection, the first injection should be given ONLY during the first 5 days of a normal menstrual period; ONLY within the first 5-days postpartum if not breast-feeding; and if exclusively breast-feeding, ONLY at the sixth postpartum week. If the time interval between injections is greater than 13 weeks, the physician should determine that the patient is not pregnant before administering the drug. The efficacy of Medroxyprogesterone Acetate Injectable Suspension, USP depends on adherence to the dosage schedule of administration.

2.2 Switching from other Methods of Contraception

When switching from other contraceptive methods, Medroxyprogesterone Acetate Injectable Suspension, USP should be given in a manner that ensures continuous contraceptive coverage based upon the mechanism of action of both methods, (e.g., patients switching from oral contraceptives should have their first injection of Medroxyprogesterone Acetate Injectable Suspension, USP on the day after the last active tablet or at the latest, on the day following the final inactive tablet).
Colestipol Hydrochlorid...

Colestipol Hydrochloride

For adults, micronized colestipol hydrochloride tablets are recommended in doses of 2 to 16 grams/day given once or in divided doses. The starting dose should be 2 grams once or twice daily. Dosage increases of 2 grams, once or twice daily should occur at 1- or 2-month intervals. Appropriate use of lipid profiles as per NCEP guidelines including LDL-C and triglycerides, is advised so that optimal but not excessive doses are used to obtain the desired therapeutic effect on LDL-C level. If the desired therapeutic effect is not obtained at a dose of 2 to 16 grams/day with good compliance and acceptable side effects, combined therapy or alternate treatment should be considered.

Micronized colestipol hydrochloride tablets must be taken one at a time and be promptly swallowed whole, using plenty of water or other appropriate liquid. Do not cut, crush, or chew the tablets. Patients should take other drugs at least one hour before or four hours after micronized colestipol hydrochloride tablets to minimize possible interference with their absorption. (See DRUG INTERACTIONS.)

Before Administration of Micronized Colestipol Hydrochloride Tablets
Define the type of hyperlipoproteinemia, as described in NCEP guidelines. Institute a trial of diet and weight reduction. Establish baseline serum total and LDL-C and triglyceride levels.
During Administration of Micronized Colestipol Hydrochloride Tablets
The patient should be carefully monitored clinically, including serum cholesterol and triglyceride levels. Periodic determinations of serum cholesterol levels as outlined in the NCEP guidelines should be done to confirm a favorable initial and long-term response. Failure of total or LDL-C to fall within the desired range should lead one to first examine dietary and drug compliance. If these are deemed acceptable, combined therapy or alternate treatment should be considered. Significant rise in triglyceride level should be considered as indication for dose reduction, drug discontinuation, or combined or alternate therapy.
Tolterodine Tartrate Ex...

Tolterodine Tartrate Extended Release

2.1 Dosing Information

The recommended dose of tolterodine tartrate extended-release capsules is 4 mg once daily with water and swallowed whole. The dose may be lowered to 2 mg daily based on individual response and tolerability; however, limited efficacy data are available for tolterodine tartrate extended-release capsules 2 mg [see CLINICAL STUDIES (14)].

2.2 Dosage Adjustment in Specific Populations

For patients with mild to moderate hepatic impairment (Child-Pugh Class A or B) or severe renal impairment (CCr 10–30 mL/min), the recommended dose of tolterodine tartrate extended-release capsules is 2 mg once daily. Tolterodine tartrate extended-release capsules are not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). Patients with CCr<10 mL/min have not been studied and use of tolterodine tartrate extended-release capsules in this population is not recommended [see WARNINGS AND PRECAUTIONS (5.6) and USE IN SPECIFIC POPULATIONS (8.6, 8.7)].

2.3 Dosage Adjustment in Presence of Concomitant Drugs

For patients who are taking drugs that are potent inhibitors of CYP3A4 [e.g., ketoconazole, clarithromycin, ritonavir], the recommended dose of tolterodine tartrate extended-release capsules is 2 mg once daily [see DRUG INTERACTIONS (7.2)].
Venlafaxine Hydrochlori...

Venlafaxine Hydrochloride

Venlafaxine hydrochloride extended-release should be administered in a single dose with food, either in the morning or in the evening at approximately the same time each day [see Clinical Pharmacology (12.3)]. 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 (spheroids).

2.1 Major Depressive Disorder

For most patients, the recommended starting dose for venlafaxine hydrochloride extended-release is 75 mg per day, administered in a single dose. For some patients, it may be desirable to start at 37.5 mg per day for 4 to 7 days to allow new patients to adjust to the medication before increasing to 75 mg per day. Patients not responding to the initial 75 mg per day dose may benefit from dose increases to a maximum of 225 mg per day. Dose increases should be in increments of up to 75 mg per 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 [see Clinical Pharmacology (12.3)]. In the clinical studies establishing efficacy, upward titration was permitted at intervals of 2 weeks or more.

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

2.2 Generalized Anxiety Disorder

For most patients, the recommended starting dose for venlafaxine hydrochloride extended-release is 75 mg per day, administered in a single dose. For some patients, it may be desirable to start at 37.5 mg per day for 4 to 7 days to allow new patients to adjust to the medication before increasing to 75 mg per day. Patients not responding to the initial 75 mg per day dose may benefit from dose increases to a maximum of 225 mg per day. Dose increases should be in increments of up to 75 mg per 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 [see Clinical Pharmacology (12.3)].

2.3 Social Anxiety Disorder (Social Phobia)

The recommended dose is 75 mg per day, administered in a single dose. There was no evidence that higher doses confer any additional benefit.

2.4 Panic Disorder

The recommended starting dose is 37.5 mg per day of venlafaxine hydrochloride extended-release for 7 days. Patients not responding to 75 mg per day may benefit from dose increases to a maximum of approximately 225 mg per day. Dose increases should be in increments of up to 75 mg per day, as needed, and should be made at intervals of not less than 7 days.

2.5 Switching Patients from Venlafaxine hydrochloride Immediate-Release Tablets

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

2.6 Specific Populations

Patients with Hepatic Impairment

The total daily dose should be reduced by 50% in patients with mild (Child-Pugh=5–6) to moderate (Child-Pugh=7–9) hepatic impairment. In patients with severe hepatic impairment (Child-Pugh=10–15) or hepatic cirrhosis, it may be necessary to reduce the dose by 50% or more [See Use in Specific Populations (8.7)].

Patients with Renal Impairment

The total daily dose should be reduced by 25% to 50% in patients with mild (CLcr= 60–89 mL/min) or moderate (CLcr= 30–59 mL/min) renal impairment. In patients undergoing hemodialysis or with severe renal impairment (CLcr < 30 mL/min), the total daily dose should be reduced by 50% or more. Because there was much individual variability in clearance between patients with renal impairment, individualization of dosage may be desirable in some patients [see Use in Specific Populations (8.7)].

2.7 Maintenance Treatment

There is no body of evidence available from controlled studies to indicate how long patients with MDD, GAD, SAD, or PD should be treated with venlafaxine hydrochloride extended-release.

It is generally agreed that acute episodes of MDD require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Venlafaxine hydrochloride extended-release and venlafaxine hydrochloride immediate-release have demonstrated continuation of response in clinical studies up to 52 weeks, at the same dose at which patients responded during the initial treatment [see Clinical Studies (14.1)]. It is not known whether or not the dose of venlafaxine hydrochloride extended-release 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.

In patients with GAD and SAD, venlafaxine hydrochloride extended-release has been shown to be effective in 6-month clinical studies. The need for continuing medication in patients with GAD and SAD who improve with venlafaxine hydrochloride extended-release treatment should be periodically reassessed.

In a clinical study for PD, patients continuing venlafaxine hydrochloride extended-release at the same dose at which they responded during the initial 12 weeks of treatment experienced a statistically significantly longer time to relapse than patients randomized to placebo [see Clinical Studies (14.4)]. The need for continuing medication in patients with PD who improve with venlafaxine hydrochloride extended-release treatment should be periodically reassessed.

2.8 Discontinuing Venlafaxine hydrochloride Extended-Release

A gradual reduction in the dose, rather than abrupt cessation, is recommended whenever possible. In clinical studies with venlafaxine hydrochloride extended-release, tapering was achieved by reducing the daily dose by 75 mg at one-week intervals. Individualization of tapering may be necessary [see Warnings and Precautions (5.7)].

2.9 Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI (intended to treat psychiatric disorders) and initiation of therapy with venlafaxine hydrochloride extended-release. In addition, at least 7 days should be allowed after stopping venlafaxine hydrochloride extended-release before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.2), Warnings and Precautions (5.2), and Drug Interactions (7.2)].

Use of Venlafaxine hydrochloride Extended-Release with other MAOIs such as Linezolid or Intravenous Methylene Blue

Do not start venlafaxine hydrochloride extended-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 (4.2)].

In some cases, a patient already receiving venlafaxine hydrochloride extended-release therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue 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 hydrochloride extended-release should be stopped promptly, and linezolid or intravenous methylene blue can be administered. Monitor the patient 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 hydrochloride extended-release can be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg concomitantly with venlafaxine hydrochloride extended-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 (5.2)].
Acnefree Severe Termina...

Acnefree Severe Terminator Maximum Strength

Ethosuximide is administered by the oral route. The initial dose for patients 3 to 6 years of age is one teaspoonful (250 mg) per day; for patients 6 years of age and older, 2 teaspoonfuls (500 mg) per day. The dose thereafter must be individualized according to the patient's response. Dosage should be increased by small increments. One useful method is to increase the daily dose by 250 mg every four to seven days until control is achieved with minimal side effects. Dosages exceeding 1.5 g daily, in divided doses, should be administered only under the strictest supervision of the physician. The optimal dose for most pediatric patients is 20 mg/kg/day. This dose has given average plasma levels within the accepted therapeutic range of 40 to 100 mcg/mL. Subsequent dose schedules can be based on effectiveness and plasma level determinations.

Ethosuximide may be administered in combination with other anticonvulsants when other forms of epilepsy coexist with absence (petit mal). The optimal dose for most pediatric patients is 20 mg/kg/day.
Citrucel

Citrucel

Sirolimus is to be administered orally once daily, consistently with or without food [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)].

Tablets should not be crushed, chewed or split. Patients unable to take the tablets should be prescribed the solution and instructed in its use.

2.1 General Dosing Guidance for Renal Transplant Patients

The initial dose of sirolimus should be administered as soon as possible after transplantation. It is recommended that sirolimus be taken 4 hours after administration of cyclosporine oral solution (MODIFIED) and or/cyclosporine capsules (MODIFIED) [see Drug Interactions (7.2)].

Frequent sirolimus dose adjustments based on non-steady-state sirolimus concentrations can lead to overdosing or underdosing because sirolimus has a long half-life. Once sirolimus maintenance dose is adjusted, patients should continue on the new maintenance dose for at least 7 to 14 days before further dosage adjustment with concentration monitoring. In most patients, dose adjustments can be based on simple proportion: new sirolimus dose = current dose × (target concentration/current concentration). A loading dose should be considered in addition to a new maintenance dose when it is necessary to increase sirolimus trough concentrations: sirolimus loading dose = 3 × (new maintenance dose - current maintenance dose). The maximum sirolimus dose administered on any day should not exceed 40 mg. If an estimated daily dose exceeds 40 mg due to the addition of a loading dose, the loading dose should be administered over 2 days. Sirolimus trough concentrations should be monitored at least 3 to 4 days after a loading dose(s).

Two milligrams (2 mg) of sirolimus oral solution have been demonstrated to be clinically equivalent to 2 mg sirolimus tablets; hence, are interchangeable on a mg-to-mg basis. However, it is not known if higher doses of sirolimus oral solution are clinically equivalent to higher doses of sirolimus tablets on a mg-to-mg basis [see Clinical Pharmacology (12.3)].

2.2 Renal Transplant Patients at Low- to Moderate-Immunologic Risk

Sirolimus and Cyclosporine Combination Therapy

For de novo renal transplant patients, it is recommended that sirolimus tablets be used initially in a regimen with cyclosporine and corticosteroids. A loading dose of sirolimus equivalent to 3 times the maintenance dose should be given, i.e. a daily maintenance dose of 2 mg should be preceded with a loading dose of 6 mg. Therapeutic drug monitoring should be used to maintain sirolimus drug concentrations within the target-range [see Dosage and Administration (2.5)].

Sirolimus Following Cyclosporine Withdrawal

At 2 to 4 months following transplantation, cyclosporine should be progressively discontinued over 4 to 8 weeks, and the sirolimus dose should be adjusted to obtain sirolimus whole blood trough concentrations within the target-range [see Dosage and Administration (2.5)]. Because cyclosporine inhibits the metabolism and transport of sirolimus, sirolimus concentrations may decrease when cyclosporine is discontinued, unless the sirolimus dose is increased [see Clinical Pharmacology (12.3)].

2.3 Renal Transplant Patients at High-Immunologic Risk

In patients with high-immunologic risk, it is recommended that sirolimus be used in combination with cyclosporine and corticosteroids for the first 12 months following transplantation [see Clinical Studies (14.3)]. The safety and efficacy of this combination in high-immunologic risk patients has not been studied beyond the first 12 months. Therefore, after the first 12 months following transplantation, any adjustments to the immunosuppressive regimen should be considered on the basis of the clinical status of the patient.

For patients receiving sirolimus with cyclosporine, sirolimus therapy should be initiated with a loading dose of up to 15 mg on day 1 post-transplantation. Beginning on day 2, an initial maintenance dose of 5 mg/day should be given. A trough level should be obtained between days 5 and 7, and the daily dose of sirolimus should thereafter be adjusted [see Dosage and Administration (2.5)].

The starting dose of cyclosporine should be up to 7 mg/kg/day in divided doses and the dose should subsequently be adjusted to achieve target whole blood trough concentrations [see Dosage and Administration (2.5)]. Prednisone should be administered at a minimum of 5 mg/day.

Antibody induction therapy may be used.

2.4 Dosing in Patients with Lymphangioleiomyomatosis

For patients with lymphangioleiomyomatosis, the initial Sirolimus dose should be 2 mg/day. Sirolimus whole blood trough concentrations should be measured in 10–20 days, with dosage adjustment to maintain concentrations between 5–15 ng/mL [see Dosage and Administration (2.5)].

In most patients, dose adjustments can be based on simple proportion: new Sirolimus dose = current dose × (target concentration/current concentration). Frequent Sirolimus dose adjustments based on non-steady-state sirolimus concentrations can lead to overdosing or under dosing because sirolimus has a long half-life. Once Sirolimus maintenance dose is adjusted, patients should continue on the new maintenance dose for at least 7 to 14 days before further dosage adjustment with concentration monitoring. Once a stable dose is achieved, therapeutic drug monitoring should be performed at least every three months.

2.5 Therapeutic Drug Monitoring

Monitoring of sirolimus trough concentrations is recommended for all patients, especially in those patients likely to have altered drug metabolism, in patients ≥13 years who weigh less than 40 kg, in patients with hepatic impairment, when a change in the sirolimus dosage form is made, and during concurrent administration of strong CYP3A4 inducers and inhibitors [see Drug Interactions (7)].

Therapeutic drug monitoring should not be the sole basis for adjusting sirolimus therapy. Careful attention should be made to clinical signs/symptoms, tissue biopsy findings, and laboratory parameters.

When used in combination with cyclosporine, sirolimus trough concentrations should be maintained within the target-range [see Clinical Studies (14), Clinical Pharmacology (12.3)]. Following cyclosporine withdrawal in transplant patients at low- to moderate-immunologic risk, the target sirolimus trough concentrations should be 16 to 24 ng/mL for the first year following transplantation. Thereafter, the target sirolimus concentrations should be 12 to 20 ng/mL.

The above recommended 24-hour trough concentration ranges for sirolimus are based on chromatographic methods. Currently in clinical practice, sirolimus whole blood concentrations are being measured by both chromatographic and immunoassay methodologies. Because the measured sirolimus whole blood concentrations depend on the type of assay used, the concentrations obtained by these different methodologies are not interchangeable [see Warnings and Precautions (5.15), Clinical Pharmacology (12.3)]. Adjustments to the targeted range should be made according to the assay utilized to determine sirolimus trough concentrations. Since results are assay and laboratory dependent, and the results may change over time, adjustments to the targeted therapeutic range must be made with a detailed knowledge of the site-specific assay used. Therefore, communication should be maintained with the laboratory performing the assay. A discussion of different assay methods is contained in Clinical Therapeutics, Volume 22, Supplement B, April 2000 [see References (15)].

2.6 Patients with Low Body Weight

The initial dosage in patients ≥13 years who weigh less than 40 kg should be adjusted, based on body surface area, to 1 mg/m2/day. The loading dose should be 3 mg/m2.

2.7 Patients with Hepatic Impairment

It is recommended that the maintenance dose of sirolimus be reduced by approximately one third in patients with mild or moderate hepatic impairment and by approximately one half in patients with severe hepatic impairment. It is not necessary to modify the sirolimus loading dose [see Clinical Pharmacology (12.3)].

2.8 Patients with Renal Impairment

Dosage adjustment is not needed in patients with impaired renal function [see Use in Specific Populations (8.7)].
Cabergoline

Cabergoline

The recommended dosage of cabergoline tablets for initiation of therapy is 0.25 mg twice a week. Dosage may be increased by 0.25 mg twice weekly up to a dosage of 1 mg twice a week according to the patient's serum prolactin level. Before initiating treatment, cardiovascular evaluation should be performed and echocardiography should be considered to assess for valvular disease.

Dosage increases should not occur more rapidly than every 4 weeks, so that the physician can assess the patient's response to each dosage level. If the patient does not respond adequately, and no additional benefit is observed with higher doses, the lowest dose that achieved maximal response should be used and other therapeutic approaches considered. Patients receiving long term treatment with cabergoline should undergo periodic assessment of their cardiac status and echocardiography should be considered.

After a normal serum prolactin level has been maintained for 6 months, cabergoline may be discontinued, with periodic monitoring of the serum prolactin level to determine whether or when treatment with cabergoline should be reinstituted. The durability of efficacy beyond 24 months of therapy with cabergoline has not been established.
Divalproex Sodium

Divalproex Sodium

2.1 Adult Patients

[See Indications and Usage (1.1) and Clinical Pharmacology (12.3)]
Infection* Recommended Dose/Duration of Therapy * DUE TO THE INDICATED ORGANISMS [see Indications and Usage (1.1)] Community-acquired pneumonia Pharyngitis/tonsillitis (second-line therapy) Skin/skin structure (uncomplicated) 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 Acute bacterial exacerbations of chronic obstructive pulmonary disease 500 mg once daily for 3 daysOR500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 Acute bacterial sinusitis 500 mg once daily for 3 days Genital ulcer disease (chancroid) One single 1 gram dose Non-gonococcal urethritis and cervicitis One single 1 gram dose Gonococcal urethritis and cervicitis One single 2 gram dose
AZITHROMYCIN tablets can be taken with or without food.

2.2 Pediatric Patients1
Infection* Recommended Dose/Duration of Therapy 1 see dosing tables below for maximum doses evaluated by indication * DUE TO THE INDICATED ORGANISMS [see Indications and Usage (1.2)] Acute otitis media 30 mg/kg as a single dose or 10 mg/kg once daily for 3 days or 10 mg/kg as a single dose on Day 1 followed by 5 mg/kg/day on Days 2 through 5. Acute bacterial sinusitis 10 mg/kg once daily for 3 days. Community-acquired pneumonia 10 mg/kg as a single dose on Day 1 followed by 5 mg/kg once daily on Days 2 through 5. Pharyngitis/tonsillitis 12 mg/kg once daily for 5 days.
AZITHROMYCIN for oral suspension can be taken with or without food.
PEDIATRIC DOSAGE GUIDELINES FOR OTITIS MEDIA, ACUTE BACTERIAL SINUSITIS, AND COMMUNITY-ACQUIRED PNEUMONIA (Age 6 months and above, [see Use in Specific Populations (8.4)]) Based on Body Weight OTITIS MEDIA AND COMMUNITY-ACQUIRED PNEUMONIA: (5-Day Regimen)* Dosing Calculated on 10 mg/kg/day Day 1 and 5 mg/kg/day Days 2 to 5. Weight 100 mg/5 mL 200 mg/5 mL Total mL per Treatment Course Total mg per Treatment Course Kg Lbs. Day 1 Days 2–5 Day 1 Days 2–5 * Effectiveness of the 3-day or 1-day regimen in pediatric patients with community-acquired pneumonia has not been established. 5 11 2.5 mL; (½ tsp) 1.25 mL;(¼ tsp) 7.5 mL 150 mg 10 22 5 mL; (1tsp) 2.5 mL; (½ tsp) 15 mL 300 mg 20 44 5 mL; (1 tsp) 2.5 mL; (½ tsp) 15 mL 600 mg 30 66 7.5 mL; (1½ tsp) 3.75 mL; (¾ tsp) 22.5 mL 900 mg 40 88 10 mL; (2 tsp) 5 mL; (1 tsp) 30 mL 1200 mg 50 and above 110 and above 12.5 mL; (2½ tsp) 6.25 mL; (1¼ tsp) 37.5 mL 1500 mg OTITIS MEDIA AND ACUTE BACTERIAL SINUSITIS: (3-Day Regimen)* Dosing Calculated on 10 mg/kg/day. Weight 100 mg/5 mL 200 mg/5 mL Total mL per Treatment Course Total mg per Treatment Course Kg Lbs. Days 1–3 Days 1–3 * Effectiveness of the 5-day or 1-day regimen in pediatric patients with acute bacterial sinusitis has not been established. 5 11 2.5 mL; (1/2 tsp) 7.5 mL 150 mg 10 22 5 mL; (1 tsp) 15 mL 300 mg 20 44 5 mL (1 tsp) 15 mL 600 mg 30 66 7.5 mL (1½ tsp) 22.5 mL 900 mg 40 88 10 mL (2 tsp) 30 mL 1200 mg 50 and above 110 and above 12.5 mL (2 ½ tsp) 37.5 mL 1500 mg OTITIS MEDIA: (1-Day Regimen) Dosing Calculated on 30 mg/kg as a single dose. Weight 200 mg/5 mL Total mL per Treatment Course Total mg per Treatment Course Kg Lbs. 1-Day Regimen 5 11 3.75 mL;(3/4 tsp) 3.75 mL 150 mg 10 22 7.5 mL;(1½ tsp) 7.5 mL 300 mg 20 44 15 mL;(3 tsp) 15 mL 600 mg 30 66 22.5 mL;(4½ tsp) 22.5 mL 900 mg 40 88 30 mL;(6 tsp) 30 mL 1200 mg 50 and above 110 and above 37.5 mL;(7½ tsp) 37.5 mL 1500 mg
The safety of re-dosing azithromycin in pediatric patients who vomit after receiving 30 mg/kg as a single dose has not been established. In clinical studies involving 487 patients with acute otitis media given a single 30 mg/kg dose of azithromycin, eight patients who vomited within 30 minutes of dosing were re-dosed at the same total dose.

Pharyngitis/Tonsillitis: The recommended dose of AZITHROMYCIN for children with pharyngitis/tonsillitis is 12 mg/kg once daily for 5 days. (See chart below.)
PEDIATRIC DOSAGE GUIDELINES FOR PHARYNGITIS/TONSILLITIS (Age 2 years and above, [see Use in Specific Populations (8.4)]) Based on Body Weight PHARYNGITIS/TONSILLITIS: (5-Day Regimen) Dosing Calculated on 12 mg/kg/day for 5 days. Weight 200 mg/5 mL Total mL per Treatment Course Total mg per Treatment Course Kg Lbs. Day 1–5 8 18 2.5 mL; (½ tsp) 12.5 mL 500 mg 17 37 5 mL; (1 tsp) 25 mL 1000 mg 25 55 7.5 mL; (1½ tsp) 37.5 mL 1500 mg 33 73 10 mL; (2 tsp) 50 mL 2000 mg 40 88 12.5 mL; (2½ tsp) 62.5 mL 2500 mg
Constituting instructions for AZITHROMYCIN Oral Suspension 300, 600, 900, 1200 mg bottles. The table below indicates the volume of water to be used for constitution:
Amount of water to be added Total volume after constitution (azithromycin content) Azithromycin concentration after constitution Shake well before each use. Oversized bottle provides shake space. Keep tightly closed. 9 mL (300 mg) 15 mL (300 mg) 100 mg/5 mL 9 mL (600 mg) 15 mL (600 mg) 200 mg/5 mL 12 mL (900 mg) 22.5 mL (900 mg) 200 mg/5 mL 15 mL (1200 mg) 30 mL (1200 mg) 200 mg/5 mL
After mixing, store suspension at 5° to 30°C (41° to 86°F) and use within 10 days. Discard after full dosing is completed.
Doxazosin Mesylate

Doxazosin Mesylate

DOSAGE MUST BE INDIVIDUALIZED. The initial dosage of doxazosin mesylate tablet 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 mesylate tablet. 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 mesylate tablet administration is discontinued for several days, therapy should be restarted using the initial dosing regimen.

Concomitant administration of doxazosin mesylate tablet 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 mesylate tablet.

A. BENIGN PROSTATIC HYPERPLASIA 1–8 mg once daily

The initial dosage of doxazosin mesylate tablet 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 1–2 weeks. Blood pressure should be evaluated routinely in these patients.

B. HYPERTENSION 1–16 mg once daily

The initial dosage of doxazosin mesylate tablet is 1 mg given once daily. Depending on the individual patient's standing blood pressure response (based on measurements taken at 2–6 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.
Triazolam

Triazolam

It is important to individualize the dosage of triazolam tablets for maximum beneficial effect and to help avoid significant adverse effects.

The recommended dose for most adults is 0.25 mg before retiring. A dose of 0.125 mg may be found to be sufficient for some patients (e.g., low body weight). A dose of 0.5 mg should be used only for exceptional patients who do not respond adequately to a trial of a lower dose since the risk of several adverse reactions increases with the size of the dose administered. A dose of 0.5 mg should not be exceeded.

In geriatric and/or debilitated patients the recommended dosage range is 0.125 mg to 0.25 mg. Therapy should be initiated at 0.125 mg in these groups and the 0.25 mg dose should be used only for exceptional patients who do not respond to a trial of the lower dose. A dose of 0.25 mg should not be exceeded in these patients.

As with all medications, the lowest effective dose should be used.
Fluconazole

Fluconazole

Dosage and Administration in Adults

Single Dose

Vaginal candidiasis

The recommended dosage of fluconazole for vaginal candidiasis is 150 mg as a single oral dose.

Multiple Dose

SINCE ORAL ABSORPTION IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE IS THE SAME FOR ORAL (TABLETS AND SUSPENSION) AND INTRAVENOUS ADMINISTRATION. In general, a loading dose of twice the daily dose is recommended on the first day of therapy to result in plasma concentrations close to steady-state by the second day of therapy.

The daily dose of fluconazole for the treatment of infections other than vaginal candidiasis should be based on the infecting organism and the patient's response to therapy. Treatment should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse.

Oropharyngeal candidiasis

The recommended dosage of fluconazole for oropharyngeal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Clinical evidence of oropharyngeal candidiasis generally resolves within several days, but treatment should be continued for at least 2 weeks to decrease the likelihood of relapse.

Esophageal candidiasis

The recommended dosage of fluconazole for esophageal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Doses up to 400 mg/day may be used, based on medical judgment of the patient's response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least two weeks following resolution of symptoms.

Systemic Candida infections

For systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia, optimal therapeutic dosage and duration of therapy have not been established. In open, noncomparative studies of small numbers of patients, doses of up to 400 mg daily have been used.

Urinary tract infections and peritonitis

For the treatment of Candida urinary tract infections and peritonitis, daily doses of 50–200 mg have been used in open, noncomparative studies of small numbers of patients.

Cryptococcal meningitis

The recommended dosage for treatment of acute cryptococcal meningitis is 400 mg on the first day, followed by 200 mg once daily. A dosage of 400 mg once daily may be used, based on medical judgment of the patient's response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10–12 weeks after the cerebrospinal fluid becomes culture negative. The recommended dosage of fluconazole for suppression of relapse of cryptococcal meningitis in patients with AIDS is 200 mg once daily.

Prophylaxis in patients undergoing bone marrow transplantation

The recommended fluconazole daily dosage for the prevention of candidiasis in patients undergoing bone marrow transplantation is 400 mg, once daily. Patients who are anticipated to have severe granulocytopenia (less than 500 neutrophils per cu mm) should start fluconazole prophylaxis several days before the anticipated onset of neutropenia, and continue for 7 days after the neutrophil count rises above 1000 cells per cu mm.

Dosage and Administration in Children

The following dose equivalency scheme should generally provide equivalent exposure in pediatric and adult patients:
Pediatric Patients Adults * Some older children may have clearances similar to that of adults. Absolute doses exceeding 600 mg/day are not recommended. 3 mg/kg 100 mg 6 mg/kg 200 mg 12* mg/kg 400 mg
Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. (See CLINICAL PHARMACOLOGY.) Based on the prolonged half-life seen in premature newborns (gestational age 26 to 29 weeks), these children, in the first two weeks of life, should receive the same dosage (mg/kg) as in older children, but administered every 72 hours. After the first two weeks, these children should be dosed once daily. No information regarding fluconazole pharmacokinetics in full-term newborns is available.

Oropharyngeal candidiasis

The recommended dosage of fluconazole for oropharyngeal candidiasis in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Treatment should be administered for at least 2 weeks to decrease the likelihood of relapse.

Esophageal candidiasis

For the treatment of esophageal candidiasis, the recommended dosage of fluconazole in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Doses up to 12 mg/kg/day may be used, based on medical judgment of the patient's response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least 2 weeks following the resolution of symptoms.

Systemic Candida infections

For the treatment of candidemia and disseminated Candida infections, daily doses of 6–12 mg/kg/day have been used in an open, noncomparative study of a small number of children.

Cryptococcal meningitis

For the treatment of acute cryptococcal meningitis, the recommended dosage is 12 mg/kg on the first day, followed by 6 mg/kg once daily. A dosage of 12 mg/kg once daily may be used, based on medical judgment of the patient's response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10–12 weeks after the cerebrospinal fluid becomes culture negative. For suppression of relapse of cryptococcal meningitis in children with AIDS, the recommended dose of fluconazole is 6 mg/kg once daily.

Dosage In Patients With Impaired Renal Function

Fluconazole is cleared primarily by renal excretion as unchanged drug. There is no need to adjust single dose therapy for vaginal candidiasis because of impaired renal function. In patients with impaired renal function who will receive multiple doses of fluconazole, an initial loading dose of 50 to 400 mg should be given. After the loading dose, the daily dose (according to indication) should be based on the following table:
Creatinine Clearance (mL/min) Percent of Recommended Dose >50 100% ≤50 (no dialysis) 50% Regular dialysis 100% after each dialysis
Patients on regular dialysis should receive 100% of the recommended dose after each dialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.

These are suggested dose adjustments based on pharmacokinetics following administration of multiple doses. Further adjustment may be needed depending upon clinical condition.

When serum creatinine is the only measure of renal function available, the following formula (based on sex, weight, and age of the patient) should be used to estimate the creatinine clearance in adults:

Males:                Weight (kg) × (140 – age)                         72 × serum creatinine (mg/100 mL)

Females:    0.85 × above value

Although the pharmacokinetics of fluconazole has not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults. The following formula may be used to estimate creatinine clearance in children:

K ×            linear length or height (cm)                 serum creatinine (mg/100 mL)

(Where K=0.55 for children older than 1 year and 0.45 for infants.)

Administration

Fluconazole is administered orally. Fluconazole can be taken with or without food.

Directions for Mixing the Oral Suspension

Prepare a suspension at time of dispensing as follows: tap bottle until all the powder flows freely. To reconstitute, add 24 mL of distilled water or Purified Water (USP) to fluconazole bottle and shake vigorously to suspend powder. Each bottle will deliver 35 mL of suspension. The concentrations of the reconstituted suspensions are as follows:
Fluconazole Content per Bottle Concentration of Reconstituted Suspension 350 mg 10 mg/mL 1400 mg 40 mg/mL
Note: Shake oral suspension well before using. Store reconstituted suspension between 86°F (30°C) and 41°F (5°C) and discard unused portion after 2 weeks. Protect from freezing.
Aldara

Aldara

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

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

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

If symptoms so warrant, titration may proceed more rapidly provided that the patient is assessed frequently. Based on the patient's physical activity level, attack frequency, and sublingual nitroglycerin consumption, the dose of Nifedipine capsules may be increased from 10 mg t.i.d. to 20 mg t.i.d. and then to 30 mg t.i.d. over a three-day period.

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

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

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

Co-Administration with Other Antianginal Drugs

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

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