Generic Name

Selective activation

Mechanism

• Selective activation by viral thymidine kinase to acyclovir monophosphate (viral specific).
• Host cellular kinases convert it to the triphosphate form.
• The triphosphate competitively inhibits viral DNA polymerase and incorporates into nascent DNA strands, causing chain termination.
• High selectivity for infected cells reduces host toxicity.

Pharmacokinetics

Indications

• Herpes simplex (HSV‑1/2) ulcers, genital herpes, and encephalitis.
• Varicella‑zoster disease (chronic, post‑herpetic neuralgia).
• Immunocompromised patients with disseminated HSV or VZV.
• Prophylaxis for transplant recipients or severe immunosuppression.

Contraindications

• Severe renal impairment (CrCl < 30 mL/min) – requires dose adjustment.
• Known hypersensitivity to acyclovir or guanosine analogues.
• Pregnancy Category B – use only if clearly indicated.
• Potential for crystalluria in high doses or rapid IV infusion → hydrate and slow infusion rate.

Dosing

• Adult (PO):
• HSV/Genital: 400 mg TID for 7–10 days.
• VZV: 200 mg QID for 7–12 days.
• Prophylaxis (immunocompromised): 400 mg BID to 1 g BID.
• IV (Adults):
• HSV encephalitis: 5 mg/kg IV q8h for 5–14 days.
• VZV dissemination: 10 mg/kg IV q8h.
• Children: Adjust by weight (5 mg/kg PO q8h or IV q8h).
• Hydrate > 1 L/d for IV to prevent crystalluria.

Adverse Effects

• Common:
• GI upset, rash, headache.
• Cramps, mild renal impairment.
• Serious:
• Renal tubular dysfunction → acute kidney injury or Fanconi syndrome.
• Neurotoxicity (confusion, seizures) at high IV doses or in renal failure.
• Clostridium difficile colitis.

Monitoring

• Renal function: CrCl before starting, then every 3 days during IV courses > 7 days.
• Urinalysis: for crystals or hematuria during IV therapy.
• Neurologic assessment: monitor for confusion or seizures.
• Blood counts: if used long‑term in immunocompromised pts.

Clinical Pearls

• “Crystallinity can kill”: Aggressive hydration (≥1 L/d) and slow IV infusion (≥20 min) mitigate renal crystal formation.
• Dosing in CrCl ≤ 30 mL/min: Divide daily dose into 2–3 smaller doses to maintain trough concentrations.
• Commercial formulations: Foscarnet is an alternative for acyclovir‑resistant strains; choose when nephrotoxicity is anticipated.
• Bioavailability boost: 200 mg PO q6h achieves similar plasma levels to 400 mg PO t.i.d, useful in pediatric settings.
• Activate quickly: In HSV encephalitis, start IV acyclovir within 12 h of symptom onset; delay > 48 h worsens outcomes.

Key Takeaway: Acyclovir’s viral‑specific activation, low systemic toxicity, and clear PK profile make it the frontline agent for HSV/VZV infections, but vigilant renal monitoring and hydration are essential to prevent crystal‑induced nephropathy.

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• References

1. DiLabio MA, Marra G. A