Zovirax - Drug Monograph

Introduction

Zovirax (acyclovir) is an antiviral medication belonging to the class of synthetic nucleoside analogues. It was the first commercially available antiviral agent specifically developed for herpesvirus infections and remains a cornerstone therapy for various herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Available in oral, topical, and intravenous formulations, Zovirax has revolutionized the management of herpesvirus infections since its introduction in the 1980s.

Mechanism of Action

Acyclovir is selectively activated by viral thymidine kinase phosphorylation to acyclovir monophosphate, which is then converted to acyclovir triphosphate by cellular enzymes. Acyclovir triphosphate competitively inhibits viral DNA polymerase and incorporates into the growing viral DNA chain, causing premature chain termination. This selective activation in infected cells results in minimal effects on uninfected host cells, providing a favorable therapeutic index.

Indications

• Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) infections in immunocompromised patients
• Management of initial genital herpes in immunocompetent patients
• Chronic suppressive therapy for recurrent genital herpes
• Treatment of herpes zoster (shingles)
• Treatment of chickenpox (varicella) in immunocompetent patients
• Herpes simplex encephalitis
• Neonatal herpes simplex virus infections

• Prophylaxis against HSV reactivation in immunocompromised patients
• Herpetic whitlow
• Eczema herpeticum
• Herpes simplex keratitis (ophthalmic formulation)

Dosage and Administration

• Genital herpes (initial): 200 mg every 4 hours (5x daily) for 10 days
• Chronic suppression: 400 mg twice daily or 200 mg 3-5 times daily
• Herpes zoster: 800 mg every 4 hours (5x daily) for 7-10 days
• Chickenpox: 20 mg/kg/dose (max 800 mg) QID for 5 days

• HSV in immunocompromised: 5 mg/kg every 8 hours
• Herpes encephalitis: 10 mg/kg every 8 hours for 14-21 days
• Neonatal HSV: 10 mg/kg every 8 hours for 14 days (skin/eye/mouth) or 21 days (CNS/disseminated)

• Renal impairment: CrCl 10-25 mL/min: extend dosing interval to q12h; CrCl <10 mL/min: extend to q24h
• Hemodialysis: Administer dose after dialysis
• Elderly: Consider renal function adjustments
• Pediatric: Dose based on body surface area or weight

Pharmacokinetics

Contraindications

• Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation
• Patients with a history of serious adverse reactions to acyclovir

Warnings and Precautions

• Intravenous administration may cause renal failure, which may be prevented by adequate hydration and dose adjustment for renal function

• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) reported in immunocompromised patients
• Neurologic symptoms including agitation, hallucinations, confusion, coma, and seizures
• Use with caution in patients with pre-existing renal impairment or dehydration
• Monitor for signs of thrombocytopenia in immunocompromised patients
• Topical application may cause local irritation, burning, or rash
• Consider potential for emergence of resistant viral strains in immunocompromised patients

Drug Interactions

• Probenecid: Increases acyclovir AUC by approximately 40% and half-life by 40%
• Nephrotoxic drugs (aminoglycosides, amphotericin B, cisplatin, cyclosporine, IV pentamidine, vancomycin): Increased risk of nephrotoxicity
• Zidovudine: May cause increased drowsiness and lethargy
• Mycophenolate mofetil: Potential for increased concentrations of both drugs

Adverse Effects

• Nausea/vomiting (oral: 2-5%; IV: 5-9%)
• Diarrhea (2-3%)
• Headache (2%)
• Rash (1-2%)
• Injection site inflammation (IV: 9%)

• Acute renal failure (IV formulation)
• Neurotoxicity (agitation, confusion, hallucinations, seizures, coma)
• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
• Hepatotoxicity
• Anaphylaxis
• Bone marrow suppression (leukopenia, thrombocytopenia)

Monitoring Parameters

• Renal function (BUN, serum creatinine, CrCl)
• CBC with differential
• LFTs
• Hydration status

• Renal function (at least 2x weekly with IV therapy)
• Neurologic status (especially with IV therapy)
• CBC weekly in immunocompromised patients
• Signs/symptoms of adequate hydration
• Therapeutic response and adverse effects

Patient Education

• Complete the full course of therapy as prescribed
• Maintain adequate hydration, especially with oral therapy
• Topical cream: Apply with finger cot or glove to prevent autoinoculation or transmission
• Oral therapy: May be taken with or without food
• Notify healthcare provider if experiencing decreased urine output, unusual bleeding/bruising, neurologic symptoms, or severe gastrointestinal symptoms
• Does not prevent transmission of herpes to others; continue safe sex practices
• For genital herpes: Continue therapy even during asymptomatic periods if prescribed suppressive therapy
• Store at room temperature; protect from moisture

References

1. American Academy of Pediatrics. Red Book: 2021-2024 Report of the Committee on Infectious Diseases. 32nd ed. 2021. 2. Kimberlin DW, et al. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013;131(2):e635-e646. 3. Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002;347(5):340-346. 4. Tyring SK, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. Ann Intern Med. 1995;123(2):89-96. 5. Package Insert. Zovirax (acyclovir). GlaxoSmithKline; 2021. 6. Lexicomp Online. Acyclovir monograph. Wolters Kluwer Clinical Drug Information. Accessed January 2023. 7. Micromedex Solutions. Acyclovir drug monograph. IBM Watson Health. Accessed January 2023. 8. CDC. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187.