ACYCLOVIR- acyclovir_capsule

VIROLOGY
Mechanism of Antiviral Action: in vitro in vivo In vitro, Antiviral Activities: in vitro 50 50 50 50 Drug Resistance:.
CLINICAL PHARMACOLOGY
Pharmacokinetics: Table 1 Table 1. Acyclovir Pharmacokinetic Characteristics (Range) * Bioavailability decreases with increasing dose. Parameter Range Plasma protein binding 9% to 33% Plasma elimination half-life 2. 3 h Average oral bioavailability 10% to 20%* In one multiple-dose, crossover study in healthy subjects (n = 23), it was shown that increases in plasma acyclovir concentrations were less than dose proportional with increasing dose, as shown in Table 2 Table 2: Acyclovir Peak and Trough Concentrations at Steady State Parameter 200 mg 400 mg 800 mg C SS max 0. 83 mcg/mL 1. 21 mcg/mL 1. 61 mcg/mL C SS trough 0. 46 mcg/mL 0. 63 mcg/mL 0. 83 mcg/mL There was no effect of food on the absorption of acyclovir (n = 6); therefore, acyclovir capsules may be administered with or without food. The only known urinary metabolite is 9-[(carboxymethoxy) methyl ] guanine. Special Populations: Adults with Impaired Renal Function: The half-life and total body clearance of acyclovir are dependent on renal function. A dosage adjustment is recommended for patients with reduced renal function (see DOSAGE AND ADMINISTRATION Geriatrics: Error! Hyperlink reference not valid. Pediatrics: 2 2 Drug Interactions: Initial Genital Herpes: Recurrent Genital Herpes: In a study of patients who received acyclovir 400 mg twice daily for 3 years, 45%, 52%, and 63% of patients remained free of recurrences in the first, second, and third years, respectively. Serial analyses of the 3-month recurrence rates for the patients showed that 71% to 87% were recurrence free in each quarter. Herpes Zoster Infections: In a similar double-blind, placebo-controlled study, acyclovir (800 mg 5 times daily for 7 days) shortened the times to complete lesion scabbing, healing, and cessation of pain; reduced the duration of new lesion formation; and reduced the prevalence of localized zoster-associated neurologic symptoms (paresthesia, dysesthesia, or hyperesthesia). Treatment was begun within 72 hours of rash onset and was most effective if started within the first 48 hours. Adults greater than 50 years of age showed greater benefit. Chickenpox:.

Herpes Zoster Infections: Genital Herpes: Chickenpox:.

Acute Treatment of Herpes Zoster: Genital Herpes: Treatment of Initial Genital Herpes: Chronic Suppressive Therapy for Recurrent Disease: 400 mg 2 times daily for up to 12 months, followed by reevaluation. Alternative regimens have included doses ranging from 200 mg 3 times daily to 200 mg 5 times daily. The frequency and severity of episodes of untreated genital herpes may change over time. After 1 year of therapy, the frequency and severity of the patient's genital herpes infection should be re-evaluated to assess the need for continuation of therapy with acyclovir. Intermittent Therapy: Treatment of Chickenpox: Children (2 years of age and older): Adults and Children over 40 kg: 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: Table 3 Table 3. Dosage Modification for Renal Impairment Normal Dosage Creatinine Clearance Adjusted Dosage Regimen Regimen mL/min/1. 73 m 2 Dose (mg) Dosing Interval 200 mg every >10 200 every 4 hours, 4 hours 5x daily 0-10 200 every 12 hours 400 mg every >10 400 every 12 hours 12 hours 0-10 200 every 12 hours 800 mg every >25 800 every 4 hours, 4 hours 5x daily 10-25 800 every 8 hours 0-10 800 every 12 hours Hemodialysis: Peritoneal Dialysis: Bioequivalence of Dosage Forms:.

Herpes Simplex: Short-Term Administration: Long-Term Administration: Herpes Zoster: Chickenpox: Observed During Clinical Practice: General: Nervous: PRECAUTIONS Digestive: Hematologic and Lymphatic: Hepatobiliary Tract and Pancreas: Musculoskeletal: Skin: Special Senses: Urogenital: WARNINGS.

Acyclovir is contraindicated for patients who develop hypersensitivity to acyclovir or valacyclovir.

Clinical Trials:
Initial Genital Herpes: Recurrent Genital Herpes: In a study of patients who received acyclovir 400 mg twice daily for 3 years, 45%, 52%, and 63% of patients remained free of recurrences in the first, second, and third years, respectively. Serial analyses of the 3-month recurrence rates for the patients showed that 71% to 87% were recurrence free in each quarter. Herpes Zoster Infections: In a similar double-blind, placebo-controlled study, acyclovir (800 mg 5 times daily for 7 days) shortened the times to complete lesion scabbing, healing, and cessation of pain; reduced the duration of new lesion formation; and reduced the prevalence of localized zoster-associated neurologic symptoms (paresthesia, dysesthesia, or hyperesthesia). Treatment was begun within 72 hours of rash onset and was most effective if started within the first 48 hours. Adults greater than 50 years of age showed greater benefit. Chickenpox:.
WARNINGS
Acyclovir capsules are intended for oral ingestion only. Renal failure, in some cases resulting in death, has been observed with acyclovir therapy (see Error! Hyperlink reference not valid. OVERDOSAGE
OVERDOSAGE
Overdoses involving ingestion of up to 100 capsules (20 g) have been reported. Adverse events that have been reported in association with overdosage include agitation, coma, seizures, and lethargy. Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. Overdosage has been reported following bolus injections or inappropriately high doses and in patients whose fluid and electrolyte balance were not properly monitored. This has resulted in elevated BUN and serum creatinine and subsequent renal failure. In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored (see DOSAGE AND ADMINISTRATION

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