ZOVIRAX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOVIRAX (ZOVIRAX).
After intracellular phosphorylation to acyclovir triphosphate, selectively inhibits viral DNA polymerase and incorporates into viral DNA, causing chain termination.
| Metabolism | Not significantly metabolized; undergoes phosphorylation by viral thymidine kinase and cellular kinases; eliminated primarily unchanged in urine via glomerular filtration and tubular secretion. |
| Excretion | Renal excretion of unchanged drug via glomerular filtration and tubular secretion accounts for 76-82% of elimination; fecal excretion is less than 2%. |
| Half-life | Terminal elimination half-life is 2.5-3.3 hours in adults with normal renal function; prolonged to 19.5 hours in anuria (creatinine clearance <10 mL/min). |
| Protein binding | 9-33% (primarily albumin); concentration-dependent binding. |
| Volume of Distribution | 0.6-1.2 L/kg; indicates distribution into total body water, with extensive distribution into tissues (e.g., brain, kidney, liver). |
| Bioavailability | Oral: 10-20% (dose-dependent, saturable absorption); topical: minimal systemic absorption (<0.1%). |
| Onset of Action | Oral: 1.5-2 hours to peak antiviral effect; IV: immediate upon infusion; topical: within 1 hour for lesion healing. |
| Duration of Action | Oral/IV: 4-6 hours (dosing interval determined by half-life); topical: limited local activity for 4-6 hours. |
| Action Class | Antiviral (Non-HIV) drugs |
Herpes simplex: 200 mg orally 5 times daily for 10 days; or 400 mg orally 3 times daily for 5-10 days. Herpes zoster: 800 mg orally 5 times daily for 7-10 days. IV: 5-10 mg/kg every 8 hours for immunocompromised patients with HSV/VZV.
| Dosage form | CREAM |
| Renal impairment | CrCl >50 mL/min: standard dose every 8 hours. CrCl 25-50 mL/min: standard dose every 12 hours. CrCl 10-25 mL/min: standard dose every 24 hours. CrCl 0-10 mL/min: 50% of standard dose every 24 hours. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Severe hepatic impairment (Child-Pugh C): consider dose reduction due to potential accumulation, but specific guidelines not established; use with caution. |
| Pediatric use | Neonates (0-3 months): IV 10 mg/kg/dose every 8 hours for HSV. Children (3 months-12 years): IV 250-500 mg/m² every 8 hours; oral for HSV: 20 mg/kg/dose (max 400 mg) 4-5 times daily for 5-10 days. VZV: oral 20 mg/kg/dose (max 800 mg) 4 times daily for 5 days. |
| Geriatric use | Start at lower end of dosing range due to age-related renal decline. Adjust dose based on creatinine clearance. Monitor for neurotoxicity (e.g., confusion, hallucinations), especially with high doses. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZOVIRAX (ZOVIRAX).
| Breastfeeding | Excreted into breast milk; M/P ratio 0.6-0.9; infant dose approximately 1-2% of maternal weight-adjusted dose; considered compatible with breastfeeding by American Academy of Pediatrics; monitor for rash, diarrhea, or irritability in infant. |
| Teratogenic Risk | First trimester: No evidence of increased risk of major birth defects based on >2000 first-trimester exposures; limited data on second and third trimesters; animal studies show no teratogenicity at systemic exposures up to 60 times human dose. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to acyclovir or valacyclovir"]
| Precautions | ["Renal impairment may require dose adjustment; maintain adequate hydration to prevent crystalluria","Neurologic toxicity (e.g., agitation, hallucinations, confusion) more common in elderly or renally impaired","Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) reported in immunocompromised patients","Use caution in pregnancy (FDA category B) and lactation"] |
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| No specific fetal monitoring required; monitor maternal renal function (creatinine clearance) if prolonged therapy or high doses; in neonatal herpes, monitor for CNS involvement. |
| Fertility Effects | No evidence of impaired fertility in humans; animal studies showed no effect on fertility at oral doses up to 450 mg/kg/day; high-dose intravenous may cause reversible testicular effects in animal models. |