ACYCLOVIR
Clinical safety rating: safe
Human studies have proved safety
Acyclovir is a synthetic nucleoside analog that inhibits viral DNA replication. It is phosphorylated to acyclovir monophosphate by viral thymidine kinase, then converted to acyclovir triphosphate by cellular kinases. Acyclovir triphosphate competes with deoxyguanosine triphosphate for viral DNA polymerase, incorporating into viral DNA and causing chain termination.
| Metabolism | Acyclovir is partially metabolized by alcohol and aldehyde dehydrogenase. The major metabolite is 9-carboxymethoxymethylguanine (CMMG), which is inactive. Hepatic metabolism is minimal, and the drug is predominantly excreted unchanged in urine via glomerular filtration and tubular secretion. |
| Excretion | Renal excretion of unchanged drug via glomerular filtration and tubular secretion accounts for 62-90% of elimination. Fecal elimination is <2%. |
| Half-life | Terminal elimination half-life is 2.5–3.3 hours in adults with normal renal function; increases to 19.5 hours in anuria. |
| Protein binding | 9–33% bound to plasma proteins (albumin). |
| Volume of Distribution | Vd: 0.5–1.5 L/kg. Distributes widely; crosses blood-brain barrier achieving 50% of plasma CSF concentration. |
| Bioavailability | Oral: 15–30% (dose-dependent). Topical: Minimal systemic absorption (<5%). |
| Onset of Action | IV: Immediate (within minutes). Oral: 1–2 hours. Topical: Hours to days for lesion resolution. |
| Duration of Action | Plasma levels decline rapidly; antiviral effect persists ~4–6 hours. Dosing: 3–5 times daily orally; IV every 8 hours. |
| Molecular Weight | 225.2 |
400 mg orally twice daily for herpes zoster; 200 mg orally 5 times daily for genital herpes; 5-10 mg/kg intravenously every 8 hours for severe infections.
| Dosage form | TABLET |
| Renal impairment | CrCl >25 mL/min: no adjustment; CrCl 10-25 mL/min: standard dose every 12 hours; CrCl <10 mL/min: standard dose every 24 hours. |
| Liver impairment | No dose adjustment required for hepatic impairment; no Child-Pugh based modifications established. |
| Pediatric use | Neonates: 10-20 mg/kg intravenously every 8 hours; Children: 250-600 mg/m² orally 3-5 times daily or 5-10 mg/kg intravenously every 8 hours. |
| Geriatric use | Adjust based on renal function; start at low end of dosing range; monitor for neurotoxicity. |
| 1st trimester | Use only if potential benefit justifies potential risk to fetus. No adequate well-controlled studies in pregnant women; however, fetal anomalies not observed in animal studies. |
| 2nd trimester | Use only if clearly needed. Acyclovir is generally considered low risk; no evidence of increased malformations. |
| 3rd trimester | Use only if clearly needed. Acyclovir crosses the placenta; levels may approach maternal concentrations. |
Clinical note
Probenecid may decrease acyclovir clearance increasing its levels Maintain adequate hydration to prevent nephrotoxicity especially in elderly or dehydrated patients.
| Placental transfer | Acyclovir crosses the placenta with cord blood concentrations approximately 1-2 times maternal plasma concentrations. |
| Breastfeeding | Acyclovir is excreted into breast milk in small amounts. The American Academy of Pediatrics considers acyclovir compatible with breastfeeding. Infant dose is approximately 1% of maternal dose; no adverse effects reported. |
■ FDA Black Box Warning
None. Acyclovir does not have a black box warning.
| Common Effects | Vomiting Nausea Photosensitivity Rash Anaphylactic reaction Headache Fast heart rate Hypotension low blood pressure |
| Serious Effects |
Hypersensitivity to acyclovir or valacyclovir
| Precautions | Renal impairment: Dose adjustment required for CrCl < 50 mL/min; risk of acute renal failure due to crystallization in renal tubules, especially with rapid IV infusion or dehydration, Neurologic toxicity: Elderly patients or those with renal impairment may develop CNS effects (agitation, hallucinations, seizures); use with caution, Hematologic: Rare reports of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) in immunocompromised patients, IV administration: Avoid rapid infusion, ensure adequate hydration to prevent renal damage |
| Food/Dietary |
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| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Acyclovir is generally considered low risk during pregnancy. Data from the Acyclovir Pregnancy Registry and postmarketing studies do not show an increased risk of major birth defects compared to the general population. However, high-dose IV acyclovir in first trimester for severe infections carries theoretical risk; use only if clearly needed. No known specific fetal risks by trimester beyond those of the underlying infection. |
| Fetal Monitoring | No specific fetal monitoring required. For maternal therapy, monitor renal function (serum creatinine, BUN) and hydration status, especially with high-dose IV acyclovir. In pregnant women with genital HSV, clinical monitoring for recurrence is standard. Consider serial fetal ultrasound if maternal infection causes complications (e.g., preterm labor). |
| Fertility Effects | No known adverse effects on fertility in animal studies or human data. Acyclovir does not impair spermatogenesis or oogenesis at therapeutic doses. Reversible chromosomal damage at high concentrations in vitro, but no clinical relevance. |
| No significant food interactions. High-fat meals may reduce absorption but not clinically significant. Avoid excessive alcohol as it may worsen side effects (e.g., dizziness). |
| Clinical Pearls | Acyclovir requires adequate hydration to prevent crystalluria and nephrotoxicity; ensure urine output >500 mL/q8h. For IV acyclovir, infuse over at least 1 hour to avoid renal damage. Dose adjustment required in renal impairment (CrCl <50 mL/min). Early initiation (within 72 hours of rash) improves outcomes in herpes zoster. Oral acyclovir has low bioavailability (15-30%); valacyclovir is a prodrug with better absorption. |
| Patient Advice | Take acyclovir exactly as prescribed, even if symptoms improve. · Drink plenty of water during treatment to prevent kidney problems. · Start medication at the first sign of outbreak for best results. · Do not share your medication with others. · Avoid sexual contact when lesions are present to prevent transmission. · Inform your doctor if you are pregnant, breastfeeding, or have kidney disease. |