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Aciclovir

Aciclovir (commonly spelled Acyclovir in the US)

Zovirax Sitavig Acivir Herpex Aciclovir

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Updated: December 06, 2025

Overview

Aciclovir is a synthetic nucleoside analogue antiviral drug primarily used to treat infections caused by herpes simplex virus (HSV) and varicella-zoster virus (VZV). It was one of the first antiviral agents developed and remains a cornerstone of herpesvirus treatment. As a selective inhibitor of viral DNA synthesis, aciclovir demonstrates high therapeutic efficacy with relatively low toxicity to host cells. It is particularly effective in immunocompromised patients and for severe herpes infections, though it does not eliminate latent virus.

Drug Class

Antiviral agent Synthetic purine nucleoside analogue DNA polymerase inhibitor

Mechanism of Action

Aciclovir is converted to aciclovir monophosphate by viral thymidine kinase, then to active triphosphate form by host cell kinases: • Acyclovir triphosphate inhibits viral DNA polymerase • Competes with deoxyguanosine triphosphate • Incorporates into viral DNA causing chain termination • 30-50 times more affinity for viral than cellular DNA polymerase

Pharmacokinetics

Absorption: 15-30% oral bioavailability (dose-dependent) Distribution: Widely distributed (Vd 0.7 L/kg) • CSF concentrations ~50% plasma • Crosses placenta and blood-brain barrier Metabolism: Minimal hepatic metabolism (~10-15%) Excretion: Renal elimination (62-91% unchanged) • Tubular secretion and glomerular filtration Half-life: 2-3 hours (adults with normal renal function) • Up to 20 hours in ESRD

Pharmacodynamics

• Reduces viral shedding and lesion formation • Decreases healing time by 1-2 days in recurrent HSV • Suppresses clinical manifestations but doesn't eradicate latent virus • Post-exposure prophylaxis reduces outbreak severity

Indications

• Treatment of herpes simplex virus (HSV) infections (genital herpes, labialis, keratitis) • Management of varicella-zoster virus infections (chickenpox, shingles) • Herpes encephalitis (IV formulation) • Prophylaxis in immunocompromised patients • Neonatal herpes simplex infections

Contraindications

Absolute: • Hypersensitivity to aciclovir or valaciclovir Relative: • Renal impairment (CrCl <25 mL/min) • Severe dehydration • Neurological disorders

Dosage & Administration

Herpes simplex (initial episode): 200mg 5 times daily for 10 days Herpes zoster: 800mg every 4 hours (5x daily) for 7-10 days Chronic suppression: 400mg twice daily IV dosing: 5-10mg/kg every 8 hours Topical: Apply to lesions 5 times daily

Special Populations

Pediatric: 20mg/kg/dose 4 times daily (max 80mg/kg/day) Geriatric: Reduce dose based on renal function Renal impairment: • CrCl 10-25: Extend dosing interval to q12h • CrCl <10: Extend to q24h Hepatic impairment: No adjustment needed

Adverse Effects

Common (>10%): • Nausea/vomiting (12-38%) • Headache (12-26%) • Diarrhea (5-18%) Serious (<1%): • Acute renal failure (crystal nephropathy) • Neurotoxicity (confusion, hallucinations) • Thrombotic thrombocytopenic purpura

Drug Interactions

• Probenecid: Increases aciclovir AUC by 40% • Nephrotoxic drugs (aminoglycosides, vancomycin): Increased renal toxicity risk • Zidovudine: May cause increased drowsiness • Mycophenolate: Potentiates antiviral effects

Warnings & Precautions

• Maintain adequate hydration to prevent crystal nephropathy • Monitor neurological status in high-dose therapy • Risk of thrombotic microangiopathy with prolonged use • IV administration requires slow infusion (≥1 hour)

Pregnancy & Lactation

Pregnancy: Category B • No evidence of fetal harm in human studies • Benefits may outweigh risks in severe infections Lactation: Excreted in breast milk (milk:plasma ratio 0.6-4.1) • Consider risks/benefits before breastfeeding

Monitoring Parameters

• Renal function (BUN, creatinine) • Neurological status (confusion, seizures) • Hydration status • CBC in prolonged therapy • Liver function tests (rare hepatotoxicity)

Patient Counseling

• Complete full course even if symptoms improve • Maintain adequate hydration • Topical: Use glove for application to prevent autoinoculation • Recognize signs of neurotoxicity (confusion, tremors) • Does not prevent sexual transmission of HSV

Storage & Stability

• Tablets: 15-25°C in tight containers • IV solution: 15-25°C (use within 24 hours) • Topical: Below 25°C • Protect from moisture

Clinical Pearls

• Start within 72 hours of symptom onset for maximum benefit • IV therapy required for CNS infections • Consider resistance in immunocompromised patients (1-7% prevalence) • Dose adjustment critical in renal impairment • Topical formulation less effective than systemic

References

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13th Ed • Lexicomp Drug Information • Micromedex Solutions • Kimberlin DW, et al. Pediatrics 2013;131:e635-46 (neonatal herpes) • Clinical Pharmacology [Internet database]