1. Clinical Overview
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).
| Onset | Duration | Bioavailability |
|---|---|---|
| Plasma concentrations peak within 1.5 to 2.5 hours after oral administration. | Dosing interval is typically 4 to 8 hours, depending on the indication and renal function. The antiviral effect persists for the duration of cellular exposure to the active triphosphate form. | Approximately 10-30% (dose-dependent, lower with higher doses). Bioavailability decreases with increasing dose. |
2. Mechanism of Action
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.
3. Indications & Uses
- Suppression (prevention) of recurrent genital herpes infections in immunocompetent patients
- Treatment of herpes zoster (shingles) in immunocompetent patients
4. Dosage & Administration
Adult Dosage: **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).
Administration: 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).
5. Side Effects
Common side effects may include:
- Nausea
- Vomiting
- Diarrhea
- Headache
- Malaise
- Skin rash (non-serious)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| 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 |
7. Patient Counselling
- DO take the medication exactly as prescribed, at evenly spaced intervals.
- DO maintain adequate fluid intake (drink plenty of water) while on this medicine.
- DO start therapy at the earliest sign of recurrence if on episodic treatment.
- DO use barrier protection (condoms) during suppressive therapy, as viral shedding may still occur.
- DONT share your medication with others, even if they have similar symptoms.
- DONT stop the medication abruptly if on suppressive therapy without consulting your doctor.
- DONT use it for cold sores or other infections unless specifically directed by your doctor for that purpose.
8. Toxicology & Storage
Overdose: Symptoms may include agitation, coma, lethargy, seizures, obtundation. Precipitation of acyclovir in renal tubules can lead to renal failure (elevated BUN/creatinine, crystalluria).
Storage: Store at room temperature (15-25°C), protected from light and moisture. Keep in the original blister pack or container. Keep out of reach of children. Do not use after the expiry date printed on the pack.