Cadila Pharmaceuticals Limited

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Acute Treatment of Herpes Zoster: 800 mg every 4 hours orally, 5 times daily for 7 to 10 days.Genital Herpes: Treatment of Initial Genital Herpes: 200 mg every 4 hours, 5 times daily for 10 days.Chronic Suppressive Therapy for Recurrent Disease: 400 mg 2 times daily for up to 12 months, followed by re-evaluation. Alternative regimens have included doses ranging from 200 mg 3 times daily to 200 mg 5 times daily.The frequency and severity of episodes of untreated genital herpes may change over time. After 1 year of therapy, the frequency and severity of the patient’s genital herpes infection should be re-evaluated to assess the need for continuation of therapy with acyclovir.Intermittent Therapy: 200 mg every 4 hours, 5 times daily for 5 days. Therapy should be initiated at the earliest sign or symptom (prodrome) of recurrence.Treatment of Chickenpox: Children (2 years of age and older): 20 mg/kg per dose orally 4 times daily (80 mg/kg/day) for 5 days. Children over 40 kg should receive the adult dose for chickenpox.Adults and Children over 40 kg: 800 mg 4 times daily for 5 days.Intravenous acyclovir is indicated for the treatment of varicella-zoster infections in immunocompromised patients.When therapy is indicated, it should be initiated at the earliest sign or symptom of chickenpox. There is no information about the efficacy of therapy initiated more than 24 hours after onset of signs and symptoms.Patients With Acute or Chronic Renal Impairment:In patients with renal impairment, the dose of Acyclovir Tablets should be modified as shown in Table 3.

Table 3. Dosage Modification for Renal Impairment Normal Dosage Regimen Creatinine Clearance (mL/min/1.73 m2) Adjusted Dosage Regimen Dose (mg) Dosing Interval 200 mg every 4 hours >100-10 200200 every 4 hours, 5x dailyevery 12 hours 400 mg every 12 hours >100-10 400200 every 12 hoursevery 12 hours 800 mg every 4 hours >2510-250-10 800800800 every 4 hours, 5x dailyevery 8 hoursevery 12 hours

Hemodialysis:  For patients who require hemodialysis, the mean plasma half-life of acyclovir during hemodialysis is approximately 5 hours. This results in a 60% decrease in plasma concentrations following a 6-hour dialysis period. Therefore, the patient’s dosing schedule should be adjusted so that an additional dose is administered after each dialysis.Peritoneal Dialysis:No supplemental dose appears to be necessary after adjustment of the dosing interval.Bioequivalence of Dosage Forms:  One Acyclovir 800-mg tablet was shown to be bioequivalent to four Acyclovir 200-mg capsules (n = 24).

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Oral administration is preferred. Although most patients with malabsorption cannot absorb food folates, they are able to absorb folic acid, USP given orally. Parenteral administration is not advocated but may be necessary in some individuals (e.g., patients receiving parenteral or enteral alimentation). Doses greater than 0.1 mg should not be used unless ane mia due to vitamin B12 deficiency has been ruled out or is being adequately treated with a cobalamin. Daily doses greater than 1 mg do not enhance the hematologic effect, and most of the excess is excreted unchanged in the urine.The usual therapeutic dosage in adults and children (regard less of age) is up to 1 mg daily. Resistant cases may require larger doses. When clinical symptoms have subsided and the blood picture has become normal, a daily maintenance level should be used, i.e., 0.1 mg for infants and up to 0.3 mg for children under 4 years of age, 0.4 mg for adults and children 4 or more years of age, and 0.8 mg for pregnant and lactating women, but never less than 0.1 mg/day. Patients should be kept under close supervision and adjustment of the maintenance level made if relapse appears imminent.In the presence of alcoholism, hemolytic anemia, anti-convulsant therapy, or chronic infection, the maintenance level may need to be increased.

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Acute Treatment of Herpes Zoster: 800 mg every 4 hours orally, 5 times daily for 7 to 10 days. Genital Herpes:  Treatment of Initial Genital Herpes: 200 mg every 4 hours, 5 times daily for 10 days. Chronic Suppressive Therapy for Recurrent Disease: 400 mg 2 times daily for up to 12 months, followed by re-evaluation. Alternative regimens have included doses ranging from 200 mg 3 times daily to 200 mg 5 times daily.The frequency and severity of episodes of untreated genital herpes may change over time. After 1 year of therapy, the frequency and severity of the patient’s genital herpes infection should be re-evaluated to assess the need for continuation of therapy with acyclovir.Intermittent Therapy: 200 mg every 4 hours, 5 times daily for 5 days. Therapy should be initiated at the earliest sign or symptom (prodrome) of recurrence.Treatment of Chickenpox: Children (2 years of age and older): 20 mg/kg per dose orally 4 times daily (80 mg/kg/day) for 5 days. Children over 40 kg should receive the adult dose for chickenpox.Adults and Children over 40 kg: 800 mg 4 times daily for 5 days.Intravenous acyclovir is indicated for the treatment of varicella-zoster infections in immunocompromised patients.When therapy is indicated, it should be initiated at the earliest sign or symptom of chickenpox. There is no information about the efficacy of therapy initiated more than 24 hours after onset of signs and symptoms.Patients With Acute or Chronic Renal Impairment: In patients with renal impairment, the dose of Acyclovir Capsules should be modified as shown in Table 3.Table 3. Dosage Modification for Renal Impairment

Normal DosageRegimen Creatinine Clearance(mL/min/1.73 m2) Adjusted Dosage Regimen Dose (mg) Dosing Interval 200 mg every 4 hours >100-10 200200 every 4 hours, 5x dailyevery 12 hours 400 mg every 12 hours >100-10 400200 every 12 hoursevery 12 hours 800 mg every 4 hours >2510-250-10 800800800 every 4 hours, 5x dailyevery 8 hoursevery 12 hours

Hemodialysis: For patients who require hemodialysis, the mean plasma half-life of acyclovir during hemodialysis is approximately 5 hours. This results in a 60% decrease in plasma concentrations following a 6-hour dialysis period. Therefore, the patient’s dosing schedule should be adjusted so that an additional dose is administered after each dialysis. Peritoneal Dialysis: No supplemental dose appears to be necessary after adjustment of the dosing interval. Bioequivalence of Dosage Forms: Acyclovir Suspension was shown to be bioequivalent to Acyclovir Capsules (n = 20) and 1 Acyclovir 800-mg tablet was shown to be bioequivalent to 4 Acyclovir 200-mg capsules (n = 24).

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The usual dose of ofloxacin tablets is 200 mg to 400 mg orally every 12 h as described in the following dosing chart. These recommendations apply to patients With normal renal function (i.e., creatinine clearance > 50 mL/min). For patients with altered renal function (i.e., creatinine clearance ≤ 50 mL/min), see the Patients With Impaired Renal Function subsection. 

Infection* UnitDose Frequency Duration DailyDose Acute Bacterial Exacerbation of Chronic Bronchitis 400 mg q12h 10 days 800 mg Comm. Acquired Pneumonia 400 mg q12h 10 days 800 mg Uncomplicated Skin and Skin Structure Infections 400 mg q12h 10 days 800 mg Acute, Uncomplicated Urethral and Cervical Gonorrhea 400 mg single dose 1 day 400 mg Nongonococcal Cervicitis/Urethritis due to C. trachomatis 300 mg q12h 7 days 600 mg Mixed Infection of the Urethra and Cervix due to C. trachomatis and N. gonorrhoeae  300 mg q12h 7 days 600 mg Acute Pelvic Inflammatory Disease 400 mg q12h 10 to 14 days 800 mg Uncomplicated Cystitis due to E. coli or K. pneumoniae 200 mg q12h 3 days 400 mg Uncomplicated Cystitis due to Other Approved Pathogens 200 mg q12h 7 days 400 mg Complicated UTI’s 200 mg q12h 10 days 400 mg Prostatitis due to E. coli 300 mg q12h 6 weeks 600 mg

* DUE TO THE DESIGNATED PATHOGENS (see INDICATIONS AND USAGE). Antacids containing calcium, magnesium, or aluminum; sucralfate; divalent or trivalent cations such as iron; or multivitamins containing zinc; or didanosine, chewable/buffered tablets or the pediatric powder for oral solution should not be taken within the two-hour period before or within the two-hour period after taking ofloxacin (see PRECAUTIONS).Patients With Impaired Renal Function Dosage should be adjusted for patients with a creatinine clearance ≤ 50 mL/min. After a normal initial dose, dosage should be adjusted as follows: 

Creatinine Clearance Maintenance Dose Frequency 20 - 50 mL/min the usual recommended unit dose q24h < 20 mL/min ½ the usual recommended unit dose q24h

When only the serum creatinine is known, the following formula may be used to estimate creatinine clearance.

Women: 0.85 × the value calculated for men.The serum creatinine should represent a steady-state of renal function.Patients With Cirrhosis The excretion of ofloxacin may be reduced in patients with severe liver function disorders (e.g., cirrhosis with or without ascites). A maximum dose of 400 mg of ofloxacin per day should therefore not be exceeded.

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Initiate therapy in gradually increasing dosages; adjust according to individual response. Start with 10 mg four times daily for the first 2 to 4 days, increase to 25 mg four times daily for the balance of the first week. For the second and subsequent weeks, increase dosage to 50 mg four times daily. For maintenance, adjust dosage to the lowest effective levels.

The incidence of toxic reactions, particularly the L.E. cell syndrome, is high in the group of patients receiving large doses of hydrALAZINE hydrochloride tablets.

In a few resistant patients, up to 300 mg of hydrALAZINE hydrochloride tablets daily may be required for a significant antihypertensive effect. In such cases, a lower dosage of hydrALAZINE combined with a thiazide and/or reserpine or a beta blocker may be considered. However, when combining therapy, individual titration is essential to ensure the lowest possible therapeutic dose of each drug.