acyclovir
Brand: Zovirax
Prototype Drug
Drug Class: antiviral
Drug Family: antiviral
Subclass: acyclic nucleoside analogue / herpesvirus antiviral
Organ Systems: infectious-disease
Mechanism of Action
Prodrug selectively phosphorylated by herpesvirus-encoded thymidine kinase (TK) to acyclovir monophosphate; cellular kinases convert to acyclovir triphosphate, which competitively inhibits viral DNA polymerase and acts as an obligate chain terminator; selectivity is due to viral TK specificity.
herpesvirus thymidine kinaseviral DNA polymerase
Indications
- herpes simplex virus (HSV) infections: genital herpes (treatment/suppression), herpes labialis, mucocutaneous HSV
- herpes zoster (shingles)
- varicella (chickenpox)
- HSV encephalitis (IV — first-line)
- neonatal HSV (IV)
Contraindications
- severe acyclovir hypersensitivity
Adverse Effects
Common
- nausea
- headache
- diarrhea (oral)
- injection site phlebitis (IV)
Serious
- nephrotoxicity (IV — crystalline nephropathy from acyclovir crystal precipitation; prevent with adequate hydration)
- neurotoxicity (IV, especially in renal failure: tremor, confusion, agitation, hallucinations)
- thrombotic thrombocytopenic purpura (rare, immunocompromised patients)
Pharmacokinetics (ADME)
| Absorption | Oral bioavailability 10–30% (poor; valacyclovir provides higher levels) |
| Distribution | Protein binding 9–33%; Vd ~0.8 L/kg; good CNS penetration |
| Metabolism | Minimal; 9-carboxymethoxymethylguanine is the primary metabolite |
| Excretion | Renal via glomerular filtration and tubular secretion; dose adjustment required for CrCl <50 mL/min |
| Half-life | 2.5–3.5 hours (normal renal function); prolonged in CKD |
| Onset | 1–2 hours |
| Peak | 1.5–2 hours (oral) |
| Duration | 5–8 hours (q8h dosing for IV HSV encephalitis; oral q12–24h for suppression) |
| Protein Binding | 9–33% |
| Vd | ~0.8 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| nephrotoxic drugs (NSAIDs, aminoglycosides, cyclosporine) | additive nephrotoxicity; crystal deposition risk | major |
| probenecid | reduces renal tubular secretion of acyclovir; higher levels | moderate |
| zidovudine | additive neurotoxicity (somnolence, lethargy) | moderate |
Nursing Considerations
- IV acyclovir: infuse over 1 hour minimum; ensure adequate pre-hydration (IV fluids) and maintain adequate urine output (>0.5 mL/kg/h) to prevent acyclovir crystal precipitation in renal tubules
- Dose MUST be adjusted for renal function — check CrCl before and during IV therapy; acyclovir neurotoxicity (tremor, confusion, encephalopathy) is a sign of accumulation in renal failure
- Oral acyclovir has very low bioavailability; for recurrent herpes, valacyclovir (prodrug with 55% bioavailability) or famciclovir are preferred because of better and more consistent drug levels
- HSV encephalitis requires IV acyclovir 10 mg/kg q8h for 14–21 days — subtherapeutic dosing is associated with relapse; empiric treatment should not be delayed pending PCR results
Clinical Pearls
- Acyclovir's selectivity is its most elegant pharmacological property — it requires viral thymidine kinase for initial phosphorylation; cells not infected with herpesvirus cannot activate it, minimizing host cell toxicity
- IV acyclovir nephrotoxicity is due to crystal precipitation in tubular lumens at physiologic urinary pH — this is entirely preventable with adequate hydration (not merely a toxicity to avoid post-hoc)
Safety Profile
Pregnancy generally-safe
Lactation safe
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
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