Formulary
Acyclovir: Uses, Dosing, Side Effects and Indian Brand Names
Acyclovir is a guanosine analogue selectively activated by viral thymidine kinase, the gold standard for HSV encephalitis and herpes zoster, with valacyclovir preferred for oral therapy due to superior bioavailability.
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Acyclovir: Uses, Dosing, Side Effects and Indian Brand Names
Acyclovir is a guanosine analogue selectively activated by viral thymidine kinase, the gold standard for HSV encephalitis and herpes zoster, with valacyclovir preferred for oral therapy due to superior bioavailability.
NEET PG High-Yield: Selective activation by VIRAL thymidine kinase (TK) -- infected cells only. Chain terminator (no 3'-OH). Poor oral bioavailability (10-20%) -- valacyclovir is the prodrug for oral use. Covers HSV-1, HSV-2, VZV. Does NOT cover CMV (use ganciclovir). Resistance = TK-negative mutants (treat with foscarnet). Nephrotoxicity from crystalluria (hydrate well). Gertrude Elion -- Nobel Prize 1988. HSV encephalitis: temporal lobe, do not delay treatment.
Clinical overview
Acyclovir, developed by Gertrude Elion (Nobel Prize 1988), revolutionised the treatment of herpesvirus infections through its elegant mechanism of selective activation by viral thymidine kinase, making it one of the most selectively toxic antiviral drugs available. It is most active against herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and varicella-zoster virus (VZV), with much lower activity against Epstein-Barr virus (EBV) and negligible activity against cytomegalovirus (CMV -- which lacks a classical thymidine kinase; ganciclovir is needed for CMV). For HSV encephalitis, IV acyclovir (10 mg/kg every 8 hours for 14-21 days) is the standard of care and has reduced mortality from >70% to approximately 20%. Oral bioavailability is poor (10-20%), which is why the prodrug valacyclovir (L-valyl ester of acyclovir, oral bioavailability 55%) is preferred for oral therapy. Acyclovir is primarily renally excreted and crystallises in renal tubules if hydration is inadequate, causing obstructive nephropathy -- patients must receive adequate IV fluids and slow infusion. Resistance develops through mutations in the viral thymidine kinase gene (TK-negative mutants cannot activate acyclovir); foscarnet (which does not require activation) is the treatment for acyclovir-resistant HSV. In India, acyclovir is widely available and affordable, with both generic and branded formulations for oral, IV, and topical use.
Pharmacological class
Acyclovir belongs to the Antiviral Agents (Nucleoside Analogue / Guanosine Analogue) class. Prodrug that requires three sequential phosphorylation steps for activation. The FIRST phosphorylation is performed by viral thymidine kinase (TK), which is present only in virus-infected cells -- this provides extraordinary selectivity. Cellular kinases then complete the di- and tri-phosphorylation. Acyclovir triphosphate competitively inhibits viral DNA polymerase and, being incorporated into the growing DNA chain, causes chain termination (it lacks the 3'-hydroxyl group needed for the next phosphodiester bond).
Indian brand names and formulations
Available as: Zovirax (GSK), Acivir (Cipla), Herpex (Torrent), Cyclovir (FDC).
Tablets: 200 mg, 400 mg, 800 mg. Suspension: 200 mg/5 mL. IV infusion: 250 mg, 500 mg vials (reconstitute and dilute in normal saline, infuse over 1 hour). Cream: 5% (topical). Ophthalmic ointment: 3%.
Regulatory status
Acyclovir is classified under Schedule H in India under the Drugs and Cosmetics Act, 1940. Prescription-only for oral and IV formulations. Topical cream (5%) may be available without prescription in some pharmacies.
Indications
- HSV encephalitis (IV -- medical emergency, drug of choice)
- Genital herpes (first episode and recurrences; suppressive therapy)
- Herpes zoster (shingles) -- preferably valacyclovir for oral therapy
- Varicella (chickenpox) in adults, immunocompromised, or severe cases
- Herpes labialis (cold sores)
- HSV keratitis (topical ophthalmic)
- Neonatal herpes (IV)
- Prophylaxis in immunosuppressed patients (transplant, chemotherapy)
Dosing
HSV encephalitis: IV 10 mg/kg every 8 hours for 14-21 days. Herpes zoster: Oral 800 mg 5 times daily for 7 days (started within 72 hours of rash onset). Genital herpes (first episode): 400 mg three times daily for 7-10 days. Suppressive therapy: 400 mg twice daily. Varicella: 20 mg/kg (max 800 mg) 4 times daily for 5 days. Renal impairment: reduce dose and/or extend interval (primarily renal excretion).
Contraindications
- Known hypersensitivity to acyclovir or valacyclovir
- Dehydration (high risk of crystalluria and renal toxicity -- ensure adequate hydration before IV administration)
Adverse effects
- Nephrotoxicity (crystalluria and obstructive nephropathy -- prevent with adequate hydration and slow IV infusion over 1 hour)
- Nausea, vomiting, and diarrhoea
- Headache
- Neurotoxicity (tremor, confusion, hallucinations, seizures -- more common in renal impairment with drug accumulation)
- Phlebitis at IV infusion site
- Thrombotic thrombocytopaenic purpura/haemolytic uraemic syndrome (rare, usually with immunosuppressed patients on high doses)
Drug interactions
- Probenecid: reduces renal tubular secretion of acyclovir, increasing levels
- Nephrotoxic drugs (aminoglycosides, cyclosporine, amphotericin B): additive nephrotoxicity
- Mycophenolate mofetil: acyclovir and MMF compete for renal tubular secretion; both levels may increase
- Zidovudine: additive fatigue and lethargy
Pregnancy and lactation
Category B. Extensive clinical experience supports safety, particularly for genital herpes suppression in late pregnancy (reduces neonatal transmission risk). Acyclovir is the preferred antiviral for herpes in pregnancy. Registry data (Acyclovir in Pregnancy Registry) shows no increase in birth defects.
Exam-style clinical scenario
A 30-year-old presents with acute fever, confusion, temporal lobe seizure, and CSF showing lymphocytic pleocytosis with raised protein and normal glucose. MRI shows temporal lobe hyperintensity. What is the immediate treatment while awaiting HSV PCR results? IV acyclovir 10 mg/kg every 8 hours -- do NOT wait for PCR confirmation. HSV encephalitis is rapidly fatal without treatment.
Cost in India
Rs 30-70 for a strip of 10 tablets (400 mg). IV: Rs 80-150 per 250 mg vial. Cream (5%): Rs 30-60 per 5 g tube.
Clinical governance
Author: MedNext Editorial Team. Clinical reviewer: Awaiting clinical review. Jurisdiction: India (Drugs and Cosmetics Act, 1940). Sources: CIMS India, Indian Pharmacopoeia. Publication state: Awaiting clinical review. Correction: Report errors at support@mednext.academy.
Frequently Asked Questions
Why does acyclovir not affect uninfected cells?
Acyclovir requires phosphorylation by viral thymidine kinase (TK) for its first activation step. Uninfected cells lack viral TK and cannot perform this phosphorylation, so acyclovir remains inactive. This gives acyclovir a therapeutic index approximately 3000 times more favourable than early antivirals. This selective activation mechanism earned Gertrude Elion the Nobel Prize.
Why is valacyclovir preferred over oral acyclovir?
Valacyclovir is the L-valyl ester prodrug of acyclovir. After oral absorption, it is rapidly converted to acyclovir by intestinal and hepatic esterases. The key advantage: oral bioavailability of valacyclovir is approximately 55% compared to 10-20% for acyclovir. This means less frequent dosing and more reliable serum levels, improving patient compliance and efficacy for herpes zoster and genital herpes.
How does acyclovir resistance develop and what is the treatment?
Resistance most commonly develops through mutations in the viral thymidine kinase (TK) gene, producing TK-negative or TK-altered mutants that cannot phosphorylate acyclovir. This occurs almost exclusively in immunocompromised patients (HIV, transplant) with prolonged or repeated acyclovir exposure. Treatment of acyclovir-resistant HSV is foscarnet (a pyrophosphate analogue that directly inhibits viral DNA polymerase without requiring TK activation).
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