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[Pharmacology](https://durgical.com/en/pharmacology/) · [Anti-herpesvirus agents](https://durgical.com/en/pharmacology/classes/anti-herpesvirus-agents/)

# Aciclovir

The classic antiviral for herpes simplex and varicella-zoster. Given early, it shortens outbreaks; IV it treats herpes encephalitis.

Updated 2026-11-01

- Class: [Anti-herpesvirus agents](https://durgical.com/en/pharmacology/classes/anti-herpesvirus-agents/)
- Enzyme: Viral DNA polymerase (herpes simplex and varicella-zoster)
- ATC code: J05AB01
- WHO Model List of Essential Medicines

Also called: acyclovir

✂**Viral DNA polymerase (herpes simplex and varicella-zoster)**Aciclovir

ⓘ The figure shows aciclovir triphosphate, the active form, in the herpes simplex virus 1 DNA polymerase bound to DNA (cryo-EM).

**Target in 3D:** Viral DNA polymerase (herpes simplex and varicella-zoster). PDB structure 8V1T (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/8V1T) · Drag to rotate · pinch to zoom

## Mechanism of action

Aciclovir is a guanosine analogue. In infected cells the viral thymidine kinase adds the first phosphate, and cellular enzymes then make aciclovir triphosphate. The triphosphate inhibits the viral DNA polymerase and, once built into the new DNA, stops the chain because it lacks the 3'-hydroxyl group needed to add the next nucleotide. Uninfected cells barely activate it, which explains its selectivity.

- Viral thymidine kinase phosphorylates aciclovir in infected cells
- Cellular kinases make aciclovir triphosphate
- The triphosphate inhibits the viral DNA polymerase
- Built into viral DNA, it ends the chain

## Pharmacokinetics

**Absorption**
Poorly absorbed by mouth; intravenous for severe infections

**Distribution**
Low protein binding; cerebrospinal fluid levels about half those in plasma

**Elimination**
Mostly unchanged in the urine, by filtration and tubular secretion

**Half-life**
About 2.5 to 3 hours with normal kidney function, much longer in kidney failure

## Indications

- Genital herpes (first episode and recurrences) and mucocutaneous herpes simplex in immunocompromised people [Genital herpes (herpes simplex infection) →](https://durgical.com/en/conditions/genital-herpes/)
- Herpes simplex encephalitis (intravenous) [Viral encephalitis (herpes simplex encephalitis) →](https://durgical.com/en/conditions/viral-encephalitis/)
- Herpes zoster (shingles) [Herpes zoster (shingles) →](https://durgical.com/en/conditions/herpes-zoster/)
- Varicella (chickenpox) [Varicella (chickenpox) →](https://durgical.com/en/conditions/varicella/)
- Neonatal herpes simplex infection (intravenous)

## Adverse effects

### Common

- Nausea, vomiting and diarrhoea
- Phlebitis at the infusion site
- Transient rise in creatinine, more with rapid infusion
- Rash and itching

### Serious (rare, important)

- Crystal nephropathy and acute kidney injury
- Neurotoxicity (confusion, tremor, hallucinations, seizures, coma), more often with kidney failure
- Thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome in immunocompromised patients
- Tissue necrosis after extravasation

## Contraindications

- Hypersensitivity to aciclovir or valaciclovir

## Key interactions

**Probenecid**
Lowers the renal clearance of aciclovir and raises its levels

**Nephrotoxic drugs (e.g. ciclosporin)**
Higher risk of kidney injury, as with dehydration or prior kidney disease

## What is monitored

- Serum creatinine and urine output during intravenous treatment
- Mental status (confusion, agitation) in older people and in kidney failure
- Hydration status

## Administration and safety

- Intravenous form by slow infusion only: never as a bolus, intramuscular or subcutaneous injection
- Good hydration during infusion to prevent crystals in the renal tubules
- Check the line: extravasation can cause severe local inflammation and necrosis
- Once diluted, the solution is used within 24 hours

## Nursing care

- Start as early as possible in an outbreak; in suspected encephalitis it is not delayed for test results
- Record fluid intake and urine output; encourage fluids
- Watch for confusion, tremor or seizures, especially with kidney failure
- Inspect the infusion site for redness or swelling
- Teach that it controls but does not cure herpes, and that genital herpes can spread without visible lesions

## Pregnancy and breastfeeding

Registry data have not shown a higher rate of birth defects, although the numbers are limited; untreated herpes in pregnancy carries its own risks to the baby.

## Memory aid

Aciclovir needs the virus's own «key» (thymidine kinase): no kinase, no effect. And «Hydrate, then infuse slowly» to protect the kidney.

## Test yourself

Think of the answer, then tap the question to see it.

## Why does aciclovir act mainly in infected cells?

Its first phosphorylation is done by the viral thymidine kinase, which uninfected cells do not have.

## How is crystal nephropathy prevented with intravenous aciclovir?

With good hydration and slow infusion, never as a bolus.

## What is the treatment of choice for suspected herpes simplex encephalitis?

Intravenous aciclovir, started as soon as the diagnosis is suspected.

## Which drug is used for aciclovir-resistant herpes simplex in an immunocompromised patient?

Foscarnet, which does not need the viral thymidine kinase.

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## Related drugs

- [Valaciclovir](https://durgical.com/en/pharmacology/valaciclovir/)
- [Famciclovir](https://durgical.com/en/pharmacology/famciclovir/)
- [Ganciclovir](https://durgical.com/en/pharmacology/ganciclovir/)
- [Foscarnet](https://durgical.com/en/pharmacology/foscarnet/)

## Related conditions

- [Genital herpes (herpes simplex infection)](https://durgical.com/en/conditions/genital-herpes/)
- [Viral encephalitis (herpes simplex encephalitis)](https://durgical.com/en/conditions/viral-encephalitis/)
- [Herpes zoster (shingles)](https://durgical.com/en/conditions/herpes-zoster/)
- [Varicella (chickenpox)](https://durgical.com/en/conditions/varicella/)

[← Back to the class: Anti-herpesvirus agents](https://durgical.com/en/pharmacology/classes/anti-herpesvirus-agents/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - ACYCLOVIR injection, solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cb64dfab-52ee-4312-bc9c-c3d04efe9109) (DailyMed (U.S. National Library of Medicine), 2026); [Acyclovir: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a681045.html) (MedlinePlus (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 62 (McGraw Hill, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=J05AB01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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