Acyclovir is a synthetic purine nucleoside analogue with potent inhibitory activity against human herpesviruses, particularly herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and varicella-zoster virus (VZV). It is a prodrug that requires viral thymidine kinase for activation, making it selectively toxic to virus-infected cells. The 400mg tablet is a standard strength used primarily for the suppression of recurrent genital herpes and the treatment of herpes zoster (shingles).
Adult: **Genital Herpes Suppression:** 400mg orally twice daily. **Herpes Zoster:** 800mg orally 5 times daily for 7-10 days (Note: 400mg tablet is not the standard for this; two 400mg tablets may be used per dose).
Note: Administer with or without food. Take with a full glass of water. Maintain adequate hydration during therapy to prevent crystalluria and renal toxicity. For suppression therapy, doses should be spaced approximately 12 hours apart. Do not crush or chew unless advised for specific patient needs (e.g., feeding tube).
Acyclovir is a prodrug. It enters virus-infected cells where it is selectively monophosphorylated by virus-encoded thymidine kinase. Cellular enzymes then convert it to the active diphosphate and triphosphate forms. Acyclovir triphosphate competitively inhibits viral DNA polymerase and, to a much lesser extent, cellular DNA polymerase. It is also incorporated into the elongating viral DNA chain, acting as a chain terminator due to its lack of a 3'-hydroxyl group, thereby halting viral DNA synthesis.
Pregnancy: Pregnancy Category B (US FDA). Animal studies show no risk, but adequate and well-controlled studies in pregnant women are lacking. Use only if clearly needed, weighing benefits against risks. Registry data have not shown an increased risk of major birth defects.
Driving: May cause dizziness, somnolence, or confusion. Patients should be cautioned about operating machinery or driving until they know how the drug affects them.
| Probenecid | Increases mean half-life and AUC of acyclovir by reducing renal tubular secretion. May increase risk of neurotoxicity. | Moderate |
| Zidovudine | May potentiate neurotoxicity (lethargy, fatigue) when used concomitantly. | Moderate |
| Nephrotoxic drugs (Aminoglycosides, Amphotericin B, Ciclosporin, Tacrolimus, IV Pentamidine, Foscarnet) | Increased risk of renal impairment. Concurrent use requires intensive renal function monitoring. | Major |
| Mycophenolate Mofetil | Potential pharmacokinetic interaction; significance in oral acyclovir use is unclear but monitor for increased side effects. | Minor |