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# Drug Information Request: Acyclovir
## Overview
Acyclovir is a synthetic purine nucleoside analogue that inhibits herpes simplex virus (HSV) and varicella-zoster virus (VZV) DNA polymerase, requiring viral thymidine kinase for initial phosphorylation to its active form (acyclovir triphosphate).
## Primary Indications
* Herpes simplex virus (HSV-1 and HSV-2) infections (mucocutaneous, genital, encephalitis).
* Varicella-zoster virus (VZV) infections (varicella/chickenpox, herpes zoster/shingles).
## Adult Dosing
* **HSV (Genital, initial):** 400 mg PO TID for 7–10 days.
* **HSV (Genital, severe/hospitalized):** 5-10 mg/kg IV q8h for 2–7 days.
* **Herpes Zoster (Shingles):** 800 mg PO 5 times daily for 7 days.
* **HSV Encephalitis:** 10 mg/kg IV q8h for 14–21 days.
## Pediatric Dosing
* **Neonatal HSV:** 20 mg/kg IV q8h for 14–21 days.
* **Varicella (>2 years):** 20 mg/kg/dose PO QID (max 800 mg/dose) for 5 days.
* **Severe HSV/VZV:** 10 mg/kg/dose IV q8h.
## Dose Adjustments
Renal impairment requires significant dose reduction and increased intervals based on creatinine clearance (CrCl). Utilize institutional protocols or updated references (e.g., Lexicomp/UpToDate) for specific CrCl thresholds, as IV dosing is highly dependent on renal function.
## Contraindications
* Hypersensitivity to acyclovir or valacyclovir.
## Adverse Effects
* **Renal:** Crystalline nephropathy (risk increases with rapid IV infusion and dehydration).
* **Neurological:** Neurotoxicity (agitation, tremors, seizures, lethargy), particularly in patients with renal impairment.
* **GI:** Nausea, vomiting, diarrhea.
* **Local:** Phlebitis at the injection site.
## Key Drug Interactions
* **Nephrotoxic agents:** Concurrent use with aminoglycosides, NSAIDs, or amphotericin B increases risk of renal injury.
* **Probenecid:** Decreases renal clearance of acyclovir, increasing serum concentrations.
* **Zidovudine:** May increase risk of neurotoxicity (lethargy).
## Monitoring
* **Renal Function:** Monitor serum creatinine and BUN regularly, especially during IV therapy.
* **Hydration:** Maintain adequate urine output to prevent crystalluria.
* **CNS Status:** Monitor for signs of neurotoxicity, especially in elderly or renally impaired patients.
## Clinical Pearls
* **IV Administration:** IV acyclovir must be infused slowly over at least 1 hour to prevent crystallization in renal tubules.
* **Hydration:** Aggressive hydration before and during IV administration is mandatory.
* **Bioavailability:** PO bioavailability is low (15–30%); valacyclovir (the L-valyl ester) is preferred for oral therapy due to superior absorption.
* **Timing:** Efficacy is highest when initiated within 48–72 hours of symptom onset.
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**Educational Disclaimer:** This information is for educational purposes only. Clinical dosing is subject to institutional policy, patient weight, renal function, and specific severity of illness. Always verify current prescribing information in an official reference (e.g., Lexicomp, UpToDate) before administering medication.
