ACYCLOVIR SODIUM
Clinical safety rating: safe
Acyclovir sodium is an intravenous antiviral agent indicated for the treatment of severe herpes simplex virus (HSV) infections, including encephalitis and neonatal disease, and varicella-zoster virus (VZV) infections in immunocompromised patients. It is a nucleoside analogue with selective activity against herpesviruses and remains a first-line therapy for these life-threatening conditions.
Acyclovir is a synthetic nucleoside analogue with activity against herpes simplex virus (HSV) types 1 and 2, and varicella-zoster virus (VZV). It is converted to acyclovir monophosphate by viral thymidine kinase, then further phosphorylated to acyclovir triphosphate, which competitively inhibits viral DNA polymerase and incorporates into viral DNA, causing chain termination.
| Metabolism | Acyclovir is primarily excreted unchanged in the urine via glomerular filtration and tubular secretion. Hepatic metabolism is minimal, with less than 15% metabolized to 9-carboxymethoxymethylguanine via alcohol dehydrogenase and aldehyde dehydrogenase. |
| Excretion | Primarily renal excretion via glomerular filtration and tubular secretion: 62-91% of dose excreted unchanged in urine within 24 hours; minor biliary/fecal elimination (<2%). |
| Half-life | Terminal elimination half-life: 2.5-3.3 hours in adults with normal renal function; up to 20 hours in anuria/end-stage renal disease. |
| Protein binding | 9-33% bound primarily to albumin. |
| Volume of Distribution | 0.6-1.0 L/kg; approximates total body water, indicating wide distribution including into vesicles and CSF (CSF concentrations ~50% of plasma). |
| Bioavailability | Oral: 10-20% (dose-dependent, saturable absorption); topical: negligible systemic absorption. |
| Onset of Action | IV: immediate onset; oral: peak antiviral effect correlates with time to peak concentration (1.5-2 hours); topical: local effect within minutes. |
| Duration of Action | Dosing interval typically 8 hours due to short half-life; antiviral effect persists as long as drug levels exceed IC50 (usually 4-6 hours post-dose). |
Dosing is indication-specific. For herpes simplex encephalitis: 10 mg/kg IV every 8 hours for 10–14 days (adults and children ≥12 years) or 20 mg/kg IV every 8 hours (3 months–12 years). For severe genital herpes: 5 mg/kg IV every 8 hours for 5 days. For mucocutaneous HSV in immunocompromised: 5 mg/kg IV every 8 hours for 7–14 days. For varicella zoster in immunocompromised: 10 mg/kg IV every 8 hours for 7 days. For neonatal HSV: 20 mg/kg IV every 8 hours for 14–21 days (disseminated/CNS) or 14 days (skin/eyes/mouth).
| Dosage form | INJECTABLE |
| Renal impairment | Adjust dosing interval based on creatinine clearance (CrCl): 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: reduce dose by 50% and administer every 24 hours. Hemodialysis: administer after dialysis; typically 50% of standard dose every 24 hours, with a supplemental dose post-dialysis. |
| Liver impairment | No dosage adjustment required in isolated hepatic impairment; caution if concomitant renal dysfunction. |
| Pediatric use | Indicated in neonates and children. Neonates: 20 mg/kg/dose IV every 8 hours. Infants >3 months: 10–20 mg/kg/dose every 8 hours based on indication. For HSV encephalitis: children 3 months–12 years: 20 mg/kg/dose every 8 hours; ≥12 years: 10 mg/kg/dose every 8 hours. Doses are based on ideal body weight in obese patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Acyclovir is considered compatible with pregnancy when clinically indicated for life-threatening maternal HSV or VZV infections. A registry of exposed pregnancies has not demonstrated an increased risk of major birth defects; however, human data are limited. Benefit outweighs risk in severe disease.
| FDA category | Human |
| Placental transfer | Acyclovir crosses the placenta, achieving fetal cord blood concentrations similar to maternal serum levels. |
| Breastfeeding |
■ FDA Black Box Warning
None.
| Common Effects | Nausea, Vomiting, Diarrhea, Headache, Elevated liver enzymes, Phlebitis at injection site, Rash, Malaise |
| Serious Effects | Acute renal failure, neurotoxicity (encephalopathy, seizures, coma), thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) in immunocompromised patients, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, hepatitis. |
["Hypersensitivity to acyclovir or valacyclovir"]
| Precautions | ["Renal impairment: Dose adjustment required in patients with decreased renal function.","Neurotoxicity: May cause tremors, seizures, hallucinations, or confusion, particularly in elderly patients or those with renal impairment.","Hydration: Ensure adequate hydration during administration to prevent renal tubule crystallization.","Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) reported in immunocompromised patients.","Do not administer by intramuscular or subcutaneous injection due to tissue irritation."] |
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| Geriatric use | No age-specific dose adjustment; dose adjustments are based on renal function, which is often reduced in the elderly. Monitor renal function closely and consider risk of neurotoxic side effects. |
| Acyclovir is excreted in breast milk; M/P ratio 0.6-4.1. Typically compatible with breastfeeding; monitor infant for rash or gastrointestinal disturbances. |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in humans; fetal risks not established in first trimester. Use during pregnancy only if clearly needed. |
| Fetal Monitoring | Monitor renal function (serum creatinine, BUN) and hydration status. Assess for CNS effects. In neonates, monitor for acyclovir-induced nephrotoxicity. |
| Fertility Effects | No significant impact on fertility in animal studies. Limited human data; no reported adverse effects on fertility. |
| Food/Dietary | No significant food interactions. Maintain adequate fluid intake to prevent renal precipitation. |
| Clinical Pearls | Monitor renal function closely; adjust dose in renal impairment. Ensure adequate hydration to prevent crystalluria. Infuse over at least 1 hour to avoid phlebitis. Use with caution in elderly and those with pre-existing renal disease. Neurotoxicity may occur at high doses or in renal failure. Not effective for EBV or CMV treatment. |
| Patient Advice | Drink plenty of water during treatment to prevent kidney problems. · Report any signs of kidney issues like decreased urine output or swelling. · Notify healthcare provider if you experience confusion, hallucinations, or seizures. · This medication is for intravenous use only and will be given in a medical setting. · Inform your doctor about all medications you are taking, especially other nephrotoxic drugs. |