Valacyclovir Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	10-15 mg/kg	q8h	Duration: 5-7 days or as clinically indicated Notes: Dose based on acyclovir equivalent; adjust for renal impairment.
Cat	PO	Not recommended; if used, extremely low dose (e.g., 10-20 mg/kg q12h) with close monitoring	q12h	Duration: Short-term (max 7 days) Notes: High risk of fatal hepatotoxicity and nephrotoxicity in cats; famciclovir is preferred.
Horse	PO	20-30 mg/kg	q8h	Duration: 5-7 days or as clinically indicated Notes: Oral bioavailability is low; higher doses may be needed. IV acyclovir may be more effective.

Clinical Indications & Species Uses

General Indications

Herpesvirus infections in susceptible species

Dog (Canine)

Treatment of canine herpesvirus infections (e.g., neonatal herpesvirus, herpesvirus dermatitis)
Treatment of herpesvirus-associated keratitis (topical or systemic adjunct)
Off-label use for other herpesvirus infections

Cat (Feline)

Treatment of feline herpesvirus type 1 (FHV-1) infections (upper respiratory, ocular, dermatologic)
Note: Use is controversial due to potential severe toxicity; alternative antivirals (e.g., famciclovir) are preferred

Horse (Equine)

Treatment of equine herpesvirus type 1 (EHV-1) infections (respiratory, neurologic, abortion)
Prophylaxis in outbreaks (off-label)

Pharmacology & Mechanism of Action

Drug Class: Antiviral | Pharmacological Group: Nucleoside analogue (prodrug of acyclovir)

Mechanism of Action: Valacyclovir is the L-valyl ester prodrug of acyclovir. After oral administration, it is rapidly and almost completely converted to acyclovir by first-pass intestinal and hepatic metabolism via the enzyme valacyclovir hydrolase. Acyclovir is a synthetic purine nucleoside analogue that inhibits herpesvirus DNA polymerase. Inside virus-infected cells, acyclovir is phosphorylated to acyclovir monophosphate by virus-encoded thymidine kinase (TK), then further phosphorylated by host cellular kinases to the active triphosphate form. Acyclovir triphosphate competitively inhibits viral DNA polymerase and, being a chain terminator, is incorporated into the growing viral DNA chain, causing premature chain termination and preventing viral replication. The selectivity is due to the requirement for viral TK for initial phosphorylation, and the higher affinity of acyclovir triphosphate for viral DNA polymerase compared to host DNA polymerase.

Pharmacodynamics: Valacyclovir itself has minimal antiviral activity; its activity is attributed to acyclovir. Acyclovir is active against herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), and to a lesser extent, feline herpesvirus type 1 (FHV-1) and equine herpesvirus type 1 (EHV-1). In cats, valacyclovir has been shown to reduce clinical signs of FHV-1 infection but with significant toxicity. In horses, valacyclovir is used to treat EHV-1 infections, but its efficacy is variable. The antiviral effect is time-dependent, and the drug is most effective when initiated early in the course of infection. Resistance can develop through mutations in viral TK or DNA polymerase genes.

⚡ Pharmacokinetics Summary

Absorption: In humans, valacyclovir is rapidly absorbed after oral administration, with bioavailability of about 54% (compared to acyclovir's 10-20%). In dogs, oral bioavailability is approximately 80% after conversion to acyclovir. In cats, absorption is rapid but conversion to acyclovir is less efficient, leading to lower acyclovir concentrations. In horses, oral bioavailability is low (approximately 3-4%) due to poor absorption and extensive first-pass metabolism.

Distribution: Acyclovir distributes widely into body tissues and fluids, including cerebrospinal fluid (CSF), where concentrations are about 50% of plasma levels. It crosses the placenta and is excreted in breast milk. Protein binding is low (9-33%). Volume of distribution in humans is about 0.7 L/kg.

Metabolism: Valacyclovir is rapidly converted to acyclovir by first-pass metabolism in the liver and intestine. Acyclovir is minimally metabolized in the liver; the major metabolite is 9-carboxymethoxymethylguanine (CMMG), formed by alcohol and aldehyde dehydrogenase. In cats, conversion of valacyclovir to acyclovir is less efficient, and cats may accumulate valacyclovir, leading to toxicity.

Excretion: Acyclovir and its metabolites are primarily excreted by the kidneys via glomerular filtration and tubular secretion. In humans, about 70-80% of an oral dose is recovered in urine as acyclovir and metabolites. In dogs, renal excretion is also the primary route. In horses, due to poor absorption, most of the drug is excreted in feces.

Half-Life: Dog: 2-3 hours (acyclovir); Cat: 3-4 hours (acyclovir); Horse: 1-2 hours (acyclovir); Human: 2.5-3.5 hours.

Bioavailability: Dog: ~80% (as acyclovir); Cat: ~50% (as acyclovir); Horse: ~3-4% (as acyclovir); Human: ~54%.

Protein Binding: Acyclovir: 9-33% (low).

Available Formulations & Strengths

Oral Tablet 500 mg, 1000 mg (PO)

Oral Tablet (film-coated) 500 mg, 1000 mg (PO)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to valacyclovir, acyclovir, or any component of the formulation
Cats: Severe hepatic or renal impairment (relative contraindication due to high toxicity risk)
Use in animals with known deficiency of thymidine kinase (viral resistance)

Warnings & Clinical Precautions:

Cats: Extremely toxic; can cause fatal hepatic necrosis, renal failure, and bone marrow suppression. Use only if no alternative and with intensive monitoring.
Horses: Oral absorption is poor; consider alternative routes or drugs (e.g., acyclovir IV) for severe infections.
Renal impairment: Dose adjustment may be necessary; monitor renal function.
Pregnancy: Use with caution; safety not established in all species.
Lactation: Excreted in milk; use with caution.
May cause gastrointestinal upset; administer with food to reduce nausea.
In immunocompromised animals, resistance may develop.

Adverse Effects & Reactions

Common:

Gastrointestinal signs (vomiting, diarrhea, nausea)
Lethargy
Anorexia

Serious / Severe:

Acute renal failure (especially with dehydration or concurrent nephrotoxic drugs)
Hepatotoxicity (especially in cats)
Bone marrow suppression (neutropenia, thrombocytopenia, anemia)
Neurological signs (ataxia, tremors, seizures) in overdose or renal impairment

Rare:

Allergic reactions (urticaria, angioedema)
Crystalluria
Hemolytic uremic syndrome (in humans; rare in animals)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Probenecid	Reduces renal tubular secretion of acyclovir, increasing plasma concentrations and risk of toxicity.	Moderate
Nephrotoxic drugs (e.g., aminoglycosides, NSAIDs, amphotericin B)	Additive nephrotoxicity; increased risk of renal impairment.	High
Cimetidine	May increase acyclovir concentrations by reducing renal clearance.	Mild
Mycophenolate mofetil	Possible increased risk of both drug toxicities; monitor.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Acute renal failure (oliguria, azotemia)
Neurological signs (agitation, tremors, seizures, coma)
Gastrointestinal signs (vomiting, diarrhea)
Hepatotoxicity (elevated liver enzymes, jaundice)

Emergency Treatment Protocol: Treatment is primarily supportive. Induce emesis if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide aggressive intravenous fluid therapy to maintain hydration and enhance renal excretion. Monitor renal function, electrolytes, and neurological status. In severe cases, hemodialysis may be considered. There is no specific antidote.

Food Animal Withdrawal Times

Not approved for food animals; withdrawal times not established. Do not use in food-producing animals.

Storage, Handling & Regulatory Information

Storage Temperature: Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F).

Handling & Special Conditions: Protect from moisture. Keep in tightly closed container.

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, valacyclovir is not FDA-approved for veterinary use; use in animals is extra-label. Under AMDUCA, extra-label use is permitted in non-food animals by or on the order of a veterinarian within a valid VCPR. Use in food animals is prohibited due to lack of withdrawal times.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Valacyclovir is a prodrug of acyclovir with improved oral bioavailability in humans and dogs. In veterinary medicine, its use is primarily in dogs and horses for herpesvirus infections. In cats, it is generally avoided due to severe toxicity (hepatic and renal failure) and poor conversion to acyclovir; famciclovir is the preferred antiviral for FHV-1. In horses, oral valacyclovir has low bioavailability, so high doses are required; intravenous acyclovir may be more effective for severe EHV-1 infections. Always monitor renal function and adjust doses in patients with renal impairment. Early initiation of therapy is critical for efficacy. Due to lack of veterinary-specific formulations, human tablets are often used; ensure accurate dosing and consider compounding if needed.

References & Literature

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