ACYCLOVIR

Acyclovir, USP is a synthetic nucleoside analogue active against herpesviruses. Acyclovir Suspension, USP is formulated for oral administration. Each teaspoonful (5 mL) of Acyclovir Oral Suspension, USP contains 200 mg of acyclovir and the following inactive ingredients: banana flavor, carboxymethylcellulose sodium, glycerin, methylparaben, microcrystalline cellulose, propylparaben, purified water and sorbitol. Acyclovir is a white, crystalline powder with the molecular formula C 8 H 11 N 5 O 3 and a molecular weight of 225.20. The maximum solubility in water at 37°C is 2.5 mg/mL. The pka's of acyclovir are 2.27 and 9.25. The chemical name of Acyclovir is 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one; it has the following structural formula: "Image Description"

Herpes Zoster Infections: Acyclovir is indicated for the acute treatment of herpes zoster (shingles). Genital Herpes: Acyclovir is indicated for the treatment of initial episodes and the management of recurrent episodes of genital herpes. Chickenpox: Acyclovir is indicated for the treatment of chickenpox (varicella).

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 oral suspension should be modified as shown in Table 3. Table 3. Dosage Modification for Renal Impairment Normal Dosage Regimen Creatinine Clearance (mL/min/1.73 m 2 ) Adjusted Dosage Regimen Dose (mg) Dosing Interval 200 mg every 4 hours >10 0-10 200 200 every 4 hours, 5x daily every 12 hours 400 mg every 12 hours >10 0-10 400 200 every 12 hours every 12 hours 800 mg every 4 hours >25 10-25 0-10 800 800 800 every 4 hours, 5x daily every 8 hours every 12 hours Hemodialysis: For patients who require hemodialysis, the mean plasma half-life of acyclovir during hemodialysis is approximately 5 hours. This results in a 60% decrease in plasma concentrations following a 6-hour dialysis period. Therefore, the patient's dosing schedule should be adjusted so that an additional dose is administered after each dialysis. Peritoneal Dialysis: No supplemental dose appears to be necessary after adjustment of the dosing interval. Bioequivalence of Dosage Forms: Acyclovir oral 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).

Acyclovir oral suspension is contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction [e.g., anaphylaxis, severe cutaneous adverse reactions (SCARS)] to acyclovir, valacyclovir or any component of the formulation (see WARNINGS and ADVERSE REACTIONS ).

Herpes Simplex: Short-Term Administration: The most frequent adverse events reported during clinical trials of treatment of genital herpes with acyclovir 200 mg administered orally 5 times daily every 4 hours for 10 days were nausea and/or vomiting in 8 of 298 patient treatments (2.7%). Nausea and/or vomiting occurred in 2 of 287 (0.7%) patients who received placebo. Long-Term Administration: The most frequent adverse events reported in a clinical trial for the prevention of recurrences with continuous administration of 400 mg (two 200-mg capsules) 2 times daily for 1 year in 586 patients treated with acyclovir were nausea (4.8%) and diarrhea (2.4%). The 589 control patients receiving intermittent treatment of recurrences with acyclovir for 1 year reported diarrhea (2.7%), nausea (2.4%), and headache (2.2%). Herpes Zoster: The most frequent adverse event reported during 3 clinical trials of treatment of herpes zoster (shingles) with 800 mg of oral acyclovir 5 times daily for 7 to 10 days in 323 patients was malaise (11.5%). The 323 placebo recipients reported malaise (11.1%). Chickenpox: The most frequent adverse event reported during 3 clinical trials of treatment of chickenpox with oral acyclovir at doses of 10 to 20 mg/kg 4 times daily for 5 to 7 days or 800 mg 4 times daily for 5 days in 495 patients was diarrhea (3.2%). The 498 patients receiving placebo reported diarrhea (2.2%). Observed During Clinical Practice: In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of acyclovir. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, potential causal connection to acyclovir, or a combination of these factors. General: Anaphylaxis, angioedema, fever, headache, pain, peripheral edema. Nervous: Aggressive behavior, agitation, ataxia, coma, confusion, decreased consciousness, delirium, dizziness, dysarthria, encephalopathy, hallucinations, paresthesia, psychosis, seizure, somnolence, tremors. These symptoms may be marked, particularly in older adults or in patients with renal impairment (see PRECAUTIONS ). Digestive: Diarrhea, gastrointestinal distress, nausea. Hematologic and Lymphatic: Anemia, leukocytoclastic vasculitis, leukopenia, lymphadenopathy, thrombocytopenia. Hepatobiliary Tract and Pancreas: Elevated liver function tests, hepatitis, hyperbilirubinemia, jaundice. Musculoskeletal: Myalgia. Skin and Subcutaneous Tissue Disorders: Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme (EM), rashes including photosensitivity, alopecia, pruritus, urticaria (see CONTRAINDICATIONS and WARNINGS ). Special Senses: Visual abnormalities. Urogenital: Renal failure, renal pain (may be associated with renal failure), elevated blood urea nitrogen, elevated creatinine, hematuria (see WARNINGS ). Call your doctor for medical advice about side effects. To report SUSPECTED ADVERSE REACTIONS, contact Chartwell RX, LLC. at 1-845-232-1683 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .