Zidovudine — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Cat	PO	5-10 mg/kg	q12h	Duration: Variable; often 3-6 months or long-term Notes: Monitor for anemia and neutropenia. Adjust dose in renal impairment.
Cat	IV	2.5-5 mg/kg	q12h	Duration: Short-term for acute management Notes: Administer slowly over 30 minutes. Use with caution.
Dog	PO	5-10 mg/kg	q12h	Duration: Variable Notes: Limited evidence; use with caution and monitor blood counts.

Clinical Indications & Species Uses

General Indications

Antiviral therapy for retroviral infections in companion animals

Dog (Canine)

Treatment of canine retrovirus infections (rarely used; limited evidence)
Off-label for FeLV or FIV in dogs (not common)

Cat (Feline)

Treatment of feline immunodeficiency virus (FIV) infection
Treatment of feline leukemia virus (FeLV) infection (adjunctive therapy)

Pharmacology & Mechanism of Action

Drug Class: Nucleoside Reverse Transcriptase Inhibitor (NRTI) | Pharmacological Group: Antiviral Agent

Mechanism of Action: Zidovudine is a thymidine analog that inhibits viral reverse transcriptase. It is phosphorylated intracellularly to zidovudine triphosphate, which competes with thymidine triphosphate for incorporation into viral DNA. Once incorporated, it causes chain termination, preventing viral DNA synthesis and replication. It is active against retroviruses, including feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV).

Pharmacodynamics: Zidovudine inhibits viral replication by targeting reverse transcriptase, an enzyme essential for retroviral replication. It has a higher affinity for viral reverse transcriptase than for human DNA polymerases, resulting in selective antiviral activity. In cats, it reduces viral load and improves clinical signs in FIV-infected individuals, but does not eliminate the virus. It may also have some activity against FeLV, though efficacy is variable.

⚡ Pharmacokinetics Summary

Absorption: Zidovudine is well absorbed after oral administration in most species. In cats, oral bioavailability is approximately 70-80%. Absorption is rapid, with peak plasma concentrations occurring within 1-2 hours.

Distribution: Zidovudine distributes widely throughout the body, including into the central nervous system (CSF concentrations are about 50-60% of plasma levels). It crosses the placenta and is distributed into milk. Volume of distribution is approximately 1.6 L/kg in humans, but species-specific data are limited.

Metabolism: Zidovudine is primarily metabolized in the liver via glucuronidation to an inactive metabolite (GAZT). In cats, glucuronidation capacity is limited, leading to slower metabolism and potential accumulation. This is an important species difference.

Excretion: Zidovudine and its metabolites are excreted primarily by the kidneys via glomerular filtration and active tubular secretion. In cats, renal excretion is the major route, with approximately 70-80% of the dose recovered in urine.

Half-Life: Cats: approximately 1-2 hours (may be prolonged with renal impairment). Dogs: approximately 1 hour. Humans: 1-3 hours.

Bioavailability: Oral bioavailability: Cats ~70-80%, Dogs ~60-70%, Humans ~60-70%.

Protein Binding: Zidovudine is approximately 25-38% bound to plasma proteins.

Available Formulations & Strengths

Oral Capsule 100 mg, 250 mg (PO)

Oral Solution 10 mg/mL (PO)

Injectable Solution 10 mg/mL (IV)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to zidovudine or any component
Severe bone marrow suppression (neutropenia, anemia)
Concurrent use with other myelosuppressive drugs (e.g., ganciclovir, doxorubicin)
Pregnancy (unless benefits outweigh risks; potential teratogenicity)
Lactation (excreted in milk; use with caution)

Warnings & Clinical Precautions:

Monitor complete blood count (CBC) regularly, especially during the first 3 months of therapy.
Use with caution in patients with renal or hepatic impairment; dose adjustment may be necessary.
In cats, glucuronidation is deficient, leading to slower metabolism; monitor for toxicity.
May cause anemia, neutropenia, and leukopenia; discontinue if severe.
Use with caution in animals with pre-existing bone marrow suppression.
Not recommended for use in food-producing animals due to lack of withdrawal data.
Handle with care; zidovudine is potentially carcinogenic and mutagenic in humans.

Adverse Effects & Reactions

Common:

Anemia
Neutropenia
Leukopenia
Gastrointestinal upset (vomiting, diarrhea)
Lethargy

Serious / Severe:

Severe bone marrow suppression
Hepatotoxicity
Lactic acidosis (rare)
Myopathy

Rare:

Seizures
Pancreatitis
Skin rash
Nephrotoxicity

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Ganciclovir	Additive myelosuppression; increased risk of neutropenia and anemia.	High
Doxorubicin	Additive bone marrow suppression.	High
Probenecid	Decreases renal excretion of zidovudine, increasing plasma levels and toxicity risk.	Moderate
Clarithromycin	May reduce zidovudine absorption; separate administration by at least 2 hours.	Moderate
Ribavirin	Antagonizes zidovudine antiviral activity; avoid concurrent use.	High
Phenytoin	May alter phenytoin levels; monitor.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Severe bone marrow suppression (anemia, neutropenia, thrombocytopenia)
Gastrointestinal signs (vomiting, diarrhea)
Neurological signs (seizures, ataxia)
Hepatotoxicity

Emergency Treatment Protocol: There is no specific antidote. Treatment is supportive and symptomatic. Discontinue the drug, provide fluid therapy, and consider blood transfusions for severe anemia. Monitor CBC and serum chemistry. In acute overdose, consider gastric lavage if recent ingestion. Hematopoietic growth factors (e.g., erythropoietin, G-CSF) may be considered in severe cases.

Food Animal Withdrawal Times

Not approved for use in food-producing animals. Withdrawal times are not established. Do not use in animals intended for human consumption.

Storage, Handling & Regulatory Information

Storage Temperature: 15-25°C (59-77°F)

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Store in a tightly closed container. Keep out of reach of children and animals.

Dispensing Status: Prescription Required (Rx Only)

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

Extra-Label (Off-Label) Use: In the US, zidovudine is not FDA-approved for veterinary use, but it may be used extra-label under the Animal Medicinal Drug Use Clarification Act (AMDUCA) for non-food animals. Extra-label use in food animals is prohibited.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Zidovudine is primarily used in cats for FIV and FeLV infections. It can reduce viral load and improve clinical signs, but it is not curative. Treatment should be individualized, and regular monitoring of CBC and serum chemistry is essential. Anemia is the most common dose-limiting adverse effect; if hematocrit drops below 20%, consider dose reduction or temporary discontinuation. In cats, due to deficient glucuronidation, lower doses may be needed. Zidovudine should be used as part of a comprehensive management plan including good nutrition, parasite control, and treatment of secondary infections. It is not recommended for use in food animals. Always follow safe handling precautions due to potential human carcinogenicity.

References & Literature

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