Acyclovir

Acyclovir is a synthetic purine nucleoside analog that is selectively active against herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). It requires three-step intracellular activation: (1) uptake into infected cells via viral thymidine kinase (TK); (2) monophosphorylation by viral TK to acyclovir monophosphate (100x more efficient in infected cells); (3) further phosphorylation by cellular kinases to acyclovir triphosphate. Acyclovir triphosphate competitively inhibits viral DNA polymerase, incorporating into the growing DNA chain and causing chain termination. The drug has approximately 100-fold greater affinity for viral DNA polymerase than for cellular DNA polymerase, providing selective antiviral activity with minimal host cell toxicity.

Adult

Genital HSV (initial): 400 mg PO TID x 7-10 days OR 200 mg PO 5x/day x 10 days. Genital HSV (recurrent): 400 mg PO TID x 5 days OR 800 mg PO BID x 5 days. Suppression: 400 mg PO BID. Shingles: 800 mg PO 5x/day x 7-10 days. HSV encephalitis: 10 mg/kg IV q8h x 14-21 days. Chickenpox: 800 mg PO QID x 5 days.

Pediatric

HSV (≥2 years): 40-80 mg/kg/day PO divided QID. Chickenpox (≥2 years): 20 mg/kg PO QID (max 800 mg/dose) x 5 days. Neonatal HSV: 20 mg/kg IV q8h x 14-21 days.

Renal adjustment

CrCl 25-50: extend interval to q12h. CrCl 10-25: extend to q24h. CrCl <10: extend to q24h and reduce dose by 50%. HD: dose after dialysis. Ensure adequate hydration to prevent crystalluria.

Hepatic adjustment

No adjustment required (minimal hepatic metabolism).

Geriatric

Reduce dose and/or extend interval based on renal function. Monitor for neurotoxicity (confusion, agitation, tremor) — more common in elderly with renal impairment.

Max dose

800 mg PO 5x/day (4 g/day); 10 mg/kg IV q8h (30 mg/kg/day)

• Hypersensitivity to acyclovir, valacyclovir, or any component
• Relative: severe renal impairment (dose reduction mandatory to prevent crystalluria and neurotoxicity)