Acyclovir

Acyclovir: An In-Depth Review

Acyclovir is a synthetic purine nucleoside analogue, derived from guanine, primarily used as an antiviral agent against the Herpesviridae family, notably herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), and varicella-zoster virus (VZV). It operates by selectively inhibiting viral DNA synthesis, thus interrupting replication within infected host cells. Introduced in the late 1970s, Acyclovir revolutionised herpesvirus management and remains a cornerstone of antiviral pharmacotherapy due to its high specificity and low host cell toxicity.

Uses

Acyclovir has a wide range of clinical applications in the treatment of HSV and VZV infections. It is indicated for managing primary and recurrent genital herpes, herpes labialis (cold sores), neonatal herpes, herpetic keratitis, and herpes simplex encephalitis. It is also employed in the treatment and prevention of varicella (chickenpox) and herpes zoster (shingles). In immunocompromised patients—such as those undergoing chemotherapy or organ transplantation—Acyclovir is indispensable for prophylaxis and treatment, significantly decreasing morbidity by curbing viral replication.

Dosage and Administration

Acyclovir is administered orally, intravenously, or topically, depending on the clinical scenario. Oral doses typically range from 200 mg to 800 mg, administered five times a day for 5–10 days for acute episodes. Suppressive therapy involves lower, long-term dosing schedules. In severe cases, IV Acyclovir is administered at 5–10 mg/kg every eight hours, based on actual body weight. The topical 5% cream is applied directly to lesions five times a day.

Dose Adjustment in Specific Conditions

Since Acyclovir is renally eliminated, dose adjustment is critical in patients with renal impairment to prevent toxicity. Dosage intervals should be adjusted in line with creatinine clearance. Hepatic dysfunction does not significantly alter its pharmacokinetics, but clinical monitoring is still advised. Acyclovir is classified as FDA Pregnancy Category B, indicating no harm in animal studies; nonetheless, therapeutic decisions during pregnancy must weigh benefits against potential risks, particularly to prevent neonatal herpes.

Effects and Side Effects

Acyclovir is generally well tolerated. Common side effects include nausea, vomiting, diarrhoea, headache, and fatigue. IV administration may lead to phlebitis, nephrotoxicity (especially via crystalluria), and neurotoxicity, particularly in renally impaired patients. Ensuring adequate hydration and administering the drug slowly help mitigate these risks. Topical use may cause mild local irritation.

Mechanism of Action

Acyclovir's pharmacodynamics involve activation by viral thymidine kinase, converting it into Acyclovir monophosphate. Subsequent phosphorylation by host cell enzymes produces Acyclovir triphosphate, which inhibits viral DNA polymerase and terminates DNA synthesis. Its selective activation in infected cells underpins its efficacy and safety.

Drug Combinations and Infusion Considerations

Acyclovir may be used with corticosteroids in severe herpes zoster or with foscarnet for resistant strains. Combination therapy in immunocompromised patients broadens antiviral coverage. During IV infusion, it is essential to administer Acyclovir over at least one hour and maintain hydration to prevent nephrotoxicity. Renal function must be monitored regularly.

Available Formulations and Dosage

Form	Strength	Route	Frequency
Tablets	200 mg, 400 mg, 800 mg	Oral	Five times daily
Cream/Ointment	5%	Topical	Five times daily for 4–5 days
Injection (vial)	250 mg, 500 mg, 1000 mg	Intravenous	Every 8 hours (weight-based)

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Pharmacokinetics, Pharmacodynamics, and Microbial Coverage

Oral bioavailability of Acyclovir is modest (15–30%) but sufficient for therapeutic efficacy. Peak plasma concentrations occur within 1.5–2 hours. It penetrates well into tissues, including cerebrospinal fluid, making it effective for central nervous system infections. It is excreted largely unchanged by the kidneys. Acyclovir targets HSV-1, HSV-2, and VZV specifically, with no antibacterial activity.

Drug Interactions

Several drugs interact with Acyclovir. Probenecid and cimetidine reduce renal clearance, increasing Acyclovir levels. Co-use with nephrotoxic drugs (e.g., aminoglycosides, cyclosporine) raises the risk of renal damage. Zidovudine may intensify neurotoxicity when combined. Monitoring renal function and adjusting doses is crucial when using interacting drugs.

Comparative Overview

Drug	Bioavailability	Dosing Frequency	Nephrotoxicity Risk	Use in Pregnancy	Clinical Notes
Acyclovir	15–30%	Five times/day	Moderate	Category B	Requires frequent dosing
Valacyclovir	54%	2–3 times/day	Low	Category B	Prodrug with better oral bioavailability
Famciclovir	77%	Twice daily	Low	Category B	Longer half-life enhances compliance

Special Considerations and Precautions

Patients with renal impairment, the elderly, and those receiving IV therapy require close monitoring. Hydration before and after IV infusion reduces renal risks. Neurological side effects should be observed in susceptible patients. Topical forms should not be applied to mucosal surfaces, and patient compliance is critical to treatment success.

Toxicity and Overdose Management

Overdosing can result in acute kidney injury and neurological symptoms such as seizures. Toxicity is often due to intratubular crystallisation. No antidote exists; haemodialysis effectively removes the drug. Management involves supportive care, including fluids and electrolyte correction.

2025 Guidelines and Updates

Recent 2025 guidelines reaffirm Acyclovir’s role in managing HSV encephalitis and disseminated VZV, particularly in immunosuppressed patients. It is now incorporated into prophylactic regimens for stem cell recipients. Newer formulations with improved absorption and less frequent dosing are under investigation.

Key Fact

Initiating Acyclovir within 72 hours of herpes zoster onset reduces pain, accelerates healing, and prevents complications such as post-herpetic neuralgia.

Did You Know?

The development of Acyclovir helped Gertrude B. Elion win the Nobel Prize in Physiology or Medicine. It was one of the first antivirals to specifically target herpesviruses.

References

1. British National Formulary (BNF), 2025 Edition

2. NHS Clinical Guidelines, 2025

3. World Health Organization (WHO) Drug Info Sheet

4. PubMed Central – Pharmacokinetics of Acyclovir

5. Journal of Antiviral Research, Volume 132, 2025

6. European Medicines Agency – Acyclovir Review Update, 2025

7. British Infection Association – Guidelines for Viral Encephalitis, 2025