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. |
| Molecular Weight | 225.21 |
| 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 | No increased risk of major birth defects based on large pregnancy registries; use if benefits outweigh risks. |
| 2nd trimester | No evidence of fetal harm; oral acyclovir is preferred for suppression near term to prevent neonatal HSV. |
| 3rd trimester | Safe for maternal treatment of HSV/VZV; close to term, consider IV acyclovir for severe VZV. |
Clinical note
Comprehensive clinical and safety monograph for ZOVIRAX (ZOVIRAX).
| Placental transfer | Crosses placenta; fetal serum levels reach approximately 60-80% of maternal levels after oral dosing and 100% after IV dosing. |
| Breastfeeding | Acyclovir is excreted into breast milk in low concentrations (approximately 0.6-4.1% of maternal dose). No adverse effects reported in breastfed infants. Considered compatible with breastfeeding; however, monitor for rash, diarrhea, or candidiasis. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to acyclovir or valacyclovirHypersensitivity to any component of the formulation
| 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 |
| Food/Dietary | No significant food interactions. However, acyclovir absorption from tablets or capsules is not affected by food. Maintain adequate hydration (at least 8 glasses of water daily) to reduce risk of renal crystal formation. |
Loading safety data…
| Lactation Rating | L1 (Safe) |
| 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 | 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. |
| Clinical Pearls | Zovirax (acyclovir) is a nucleoside analog antiviral active against HSV-1, HSV-2, and VZV. For herpes encephalitis, maintain high-dose IV acyclovir (10 mg/kg q8h) with adequate hydration to prevent crystalluria. Renal function monitoring is essential, especially in elderly or dehydrated patients. Topical formulations are less effective than oral for genital herpes. Early initiation (within 72 hours) of oral acyclovir for shingles reduces pain and lesion duration. Intravenous acyclovir can cause nephrotoxicity and neurotoxicity (e.g., confusion, seizures), particularly in renal impairment. |
| Patient Advice | Take Zovirax exactly as prescribed; do not skip doses to reduce viral resistance. · Increase fluid intake during treatment to prevent kidney damage. · Start medication at first sign of herpes outbreak for best results. · May cause dizziness; avoid driving if affected. · Do not share Zovirax with others; it is not a cure for herpes. · Topical cream should be applied with a finger cot to avoid spreading infection. · Report any signs of kidney problems (decreased urination, swelling) or neurological symptoms (confusion, hallucinations) immediately. |