Acyclovir

Antiviral Nucleoside analogue (guanine analogue)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 10-20 mg/kg q8h Duration: 5-7 days
Notes: Limited evidence; use with caution. For herpesvirus infections.
Cat PO 50-100 mg/kg q8h Duration: 7-10 days
Notes: High doses required due to poor bioavailability. Monitor for renal toxicity and GI upset. Often used off-label.
Cat Ophthalmic (topical) 0.5% ointment or 1% solution 5-6 times daily Duration: Until resolution
Notes: For FHV-1 keratitis.
Horse PO 20-30 mg/kg q8h Duration: 5-7 days
Notes: Limited efficacy; may be used for EHV-1. Monitor for GI effects.
Horse IV 5-10 mg/kg q8h Duration: 5-7 days
Notes: Slow infusion over 1 hour.

Clinical Indications & Species Uses

General Indications
  • Treatment of herpesvirus infections in susceptible species
Dog (Canine)
  • Treatment of herpesvirus infections (e.g., canine herpesvirus) - limited efficacy
  • Treatment of ocular herpesvirus infections (topical ophthalmic)
  • Off-label for viral dermatitis
Cat (Feline)
  • Treatment of feline herpesvirus type 1 (FHV-1) infections - limited efficacy due to poor oral bioavailability
  • Topical ophthalmic for FHV-1 keratitis
  • Oral high-dose therapy (off-label) for systemic FHV-1
Horse (Equine)
  • Treatment of equine herpesvirus (EHV-1) infections - limited efficacy
  • Treatment of equine herpesvirus keratitis (topical)

Pharmacology & Mechanism of Action

Drug Class: Antiviral | Pharmacological Group: Nucleoside analogue (guanine analogue)

Mechanism of Action: Acyclovir is a synthetic purine nucleoside analogue that inhibits viral DNA replication. It is selectively phosphorylated by viral thymidine kinase to acyclovir monophosphate, which is then converted to the active triphosphate form by host cellular kinases. Acyclovir triphosphate competitively inhibits viral DNA polymerase and acts as a chain terminator, incorporating into the growing viral DNA chain and preventing further elongation. This results in inhibition of viral replication. The selectivity is due to the higher affinity of viral thymidine kinase for acyclovir compared to host enzymes, and the higher affinity of viral DNA polymerase for acyclovir triphosphate.

Pharmacodynamics: Acyclovir is active against herpesviruses, including herpes simplex virus types 1 and 2, varicella-zoster virus, and to a lesser extent, feline herpesvirus type 1 (FHV-1) and equine herpesvirus. It has low toxicity to host cells because it requires viral thymidine kinase for initial phosphorylation. The antiviral effect is dose-dependent and time-dependent. In vitro, acyclovir inhibits FHV-1 replication at concentrations of 0.5-10 μg/mL. However, clinical efficacy in cats is limited due to poor oral bioavailability and the need for high doses to achieve therapeutic concentrations.

⚡ Pharmacokinetics Summary

Absorption: In humans, oral bioavailability is 15-30% and decreases with increasing dose. In dogs, oral bioavailability is approximately 80% (higher than humans), but in cats it is poor, around 5-10%. Absorption is variable and influenced by food. Topical and ophthalmic formulations provide local absorption.
Distribution: Acyclovir distributes widely into body tissues and fluids, including cerebrospinal fluid (approximately 50% of plasma concentration). It crosses the placenta and is excreted in breast milk. Volume of distribution is approximately 0.7 L/kg in humans. In animals, distribution is similar.
Metabolism: Acyclovir is minimally metabolized in the liver. The primary metabolite is 9-carboxymethoxymethylguanine, which is formed by alcohol and aldehyde dehydrogenase. Metabolism is not significant in most species.
Excretion: Acyclovir is primarily excreted unchanged in the urine via glomerular filtration and active tubular secretion. Renal clearance is higher than creatinine clearance, indicating active secretion. In animals with renal impairment, dosage adjustment is necessary.
Half-Life: In dogs: 2-3 hours; in cats: 2-3 hours (but with poor bioavailability); in horses: 1-2 hours; in humans: 2.5-3.5 hours.
Bioavailability: Oral: dogs ~80%, cats ~5-10%, horses ~3-5% (variable). Intravenous: 100%.
Protein Binding: Acyclovir is only 15-30% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet 200 mg, 400 mg, 800 mg (PO)
Oral Capsule 200 mg (PO)
Oral Suspension 200 mg/5 mL (PO)
Injectable Solution 50 mg/mL (as sodium salt) (IV)
Ophthalmic Ointment 3% (human product; often used in animals) (Ophthalmic)
Ophthalmic Solution 1% (compounded) (Ophthalmic)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to acyclovir or valacyclovir
  • Severe renal impairment (unless dose adjusted)
  • Dehydrated animals (risk of crystalluria)
  • Pregnancy (use only if benefits outweigh risks; limited safety data)
Warnings & Clinical Precautions:
  • Use with caution in animals with renal disease; adjust dose and monitor renal function.
  • Ensure adequate hydration to prevent crystalluria.
  • Oral administration in cats may cause severe GI upset; consider antiemetics.
  • High doses in cats may cause neurotoxicity (e.g., tremors, ataxia).
  • Not effective against all herpesvirus strains; sensitivity testing may be needed.
  • Use in food animals is prohibited or requires extended withdrawal times; not approved.

Adverse Effects & Reactions

Common:

  • Gastrointestinal upset (vomiting, diarrhea, anorexia)
  • Injection site reactions (with IV)
  • Local irritation with ophthalmic use

Serious / Severe:

  • Renal toxicity (crystalluria, acute kidney injury)
  • Neurotoxicity (tremors, seizures, ataxia) especially in cats
  • Bone marrow suppression (rare)
  • Hepatotoxicity (rare)

Rare:

  • Allergic reactions (angioedema, anaphylaxis)
  • Hemolytic anemia
  • Stevens-Johnson syndrome

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Probenecid Decreases renal excretion of acyclovir, increasing plasma levels and risk of toxicity. Moderate
Nephrotoxic drugs (e.g., aminoglycosides, NSAIDs, amphotericin B) Additive nephrotoxicity. High
Mycophenolate mofetil May increase acyclovir levels and risk of toxicity. Moderate
Zidovudine May cause additive neurotoxicity. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Seizures
  • Lethargy
  • Tremors
  • Renal failure (oliguria, anuria)
  • Coma

Emergency Treatment Protocol: Immediate discontinuation of drug. Supportive care: IV fluids to enhance renal excretion, hemodialysis in severe cases (especially in humans; in animals, peritoneal dialysis may be considered). Monitor renal function and neurological status. Symptomatic treatment for seizures (e.g., diazepam).

Food Animal Withdrawal Times

Not approved for food animals. Use in food animals is prohibited or requires extended withdrawal times; consult regulatory authorities. No established withdrawal times.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C) in a dry place.

Handling & Special Conditions: Protect from moisture. Ophthalmic ointment: store at 15-30°C. Injectable: store at controlled room temperature; protect from freezing.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use.

Extra-Label (Off-Label) Use: In the US, acyclovir is not FDA-approved for veterinary use. Use in animals is extra-label and must comply with AMDUCA regulations. For food animals, extra-label use is prohibited if the drug is not approved for that species and if there is no established withdrawal time.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Acyclovir is an antiviral agent used primarily for herpesvirus infections. In veterinary medicine, its use is limited by poor oral bioavailability in cats and variable efficacy against feline herpesvirus. High doses are required in cats, which increases the risk of adverse effects. Topical ophthalmic formulations are more effective for ocular herpesvirus infections. In dogs, oral bioavailability is better, but clinical efficacy for canine herpesvirus is not well-established. In horses, acyclovir is used for EHV-1, but efficacy is questionable. Always ensure adequate hydration and monitor renal function during therapy. Consider alternative antivirals such as famciclovir (which has better oral bioavailability in cats) for systemic FHV-1 infections. Acyclovir should be used with caution in pregnant animals due to limited safety data.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)