Hydroxyurea — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	50-80 mg/kg	q48h (every 48 hours) or 3 times per week	Duration: Variable; often used for 2-4 weeks then reassessed, or long-term for myeloproliferative disorders Notes: Dose may be adjusted based on hematologic monitoring. For mast cell tumors, some protocols use 10-20 mg/kg daily for 3 days per week. Use with caution in patients with renal or hepatic impairment.
Cat	PO	25-50 mg/kg	q48h or 3 times per week	Duration: Variable; often used for 2-4 weeks then reassessed, or long-term for myeloproliferative disorders Notes: Cats may be more sensitive to myelosuppression; start at lower end of dose range. Monitor CBC closely.
Horse	PO	10-20 mg/kg	q24h or q48h	Duration: Variable; often used for 2-4 weeks then reassessed Notes: Limited data; use with caution. Monitor hematologic parameters.
Cattle	Not applicable	Not established	Not applicable	Duration: Not applicable Notes: Not commonly used in cattle; no approved indications.
Small Ruminants	Not applicable	Not established	Not applicable	Duration: Not applicable Notes: Not commonly used in small ruminants; no approved indications.
Rabbit	Not applicable	Not established	Not applicable	Duration: Not applicable Notes: Not commonly used in rabbits; no established dosage.
Bird/Poultry	Not applicable	Not established	Not applicable	Duration: Not applicable Notes: Not commonly used in birds; no established dosage.
Exotic/Other	Not applicable	Not established	Not applicable	Duration: Not applicable Notes: Not commonly used in exotic species; no established dosage.

Clinical Indications & Species Uses

General Indications

Myeloproliferative disorders (polycythemia vera, essential thrombocythemia, chronic myeloid leukemia)
Certain solid tumors (as a palliative or adjunctive therapy)

Dog (Canine)

Treatment of mast cell tumors (as an adjunct to surgery or when surgery is not feasible)
Treatment of chronic myeloid leukemia
Treatment of polycythemia vera
Treatment of essential thrombocythemia
Treatment of various solid tumors (e.g., squamous cell carcinoma, melanoma) when other therapies are not available

Cat (Feline)

Treatment of mast cell tumors (especially non-resectable or metastatic)
Treatment of polycythemia vera
Treatment of eosinophilic granuloma complex (off-label)
Treatment of chronic myeloid leukemia

Horse (Equine)

Treatment of sarcoids (topical or systemic, though systemic use is limited)
Treatment of chronic myelogenous leukemia (rare)

Pharmacology & Mechanism of Action

Drug Class: Antineoplastic agent | Pharmacological Group: Antimetabolite (ribonucleotide reductase inhibitor)

Mechanism of Action: Hydroxyurea inhibits the enzyme ribonucleotide reductase, which catalyzes the conversion of ribonucleotides to deoxyribonucleotides, a rate-limiting step in DNA synthesis. By depleting deoxyribonucleotide pools, hydroxyurea arrests cells in the S phase of the cell cycle, leading to inhibition of DNA synthesis and repair. It also induces differentiation of certain malignant cells and has immunosuppressive effects.

Pharmacodynamics: Hydroxyurea is cell-cycle specific, acting primarily on cells in the S phase. It reduces the production of deoxyribonucleotides, thereby inhibiting DNA synthesis. In addition to its antineoplastic activity, it increases fetal hemoglobin production in erythroid precursors, which is beneficial in myeloproliferative disorders and sickle cell disease. Its effects are reversible upon drug removal.

⚡ Pharmacokinetics Summary

Absorption: Hydroxyurea is well absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours in most species. Bioavailability is approximately 80-100% in humans and is expected to be similar in animals.

Distribution: Hydroxyurea distributes widely throughout the body, including into cerebrospinal fluid and effusions. It crosses the blood-brain barrier and placenta. Volume of distribution is approximately equal to total body water.

Metabolism: Hydroxyurea is partially metabolized in the liver, but a significant portion is excreted unchanged. It is also degraded by urease in the gastrointestinal tract.

Excretion: Renal excretion is the primary route of elimination, with about 50-80% of the drug excreted unchanged in urine. Biliary excretion is minor. Clearance is reduced in patients with renal impairment.

Half-Life: Dogs: approximately 4-6 hours; Cats: approximately 3-5 hours; Horses: approximately 2-4 hours; Humans: 3-4 hours.

Bioavailability: Oral bioavailability is high, approximately 80-100% in most species.

Protein Binding: Minimal protein binding (<10%).

Available Formulations & Strengths

Oral Capsule 200 mg, 300 mg, 400 mg, 500 mg (PO)

Oral Tablet 500 mg (PO)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to hydroxyurea or any component of the formulation
Severe bone marrow suppression (e.g., leukopenia, thrombocytopenia, anemia) unless due to the disease being treated
Pregnancy (teratogenic in animals; avoid unless benefits outweigh risks)
Lactation (excreted in milk; use with caution)

Warnings & Clinical Precautions:

Hydroxyurea is a cytotoxic drug; handle with care. Wear gloves when administering or handling capsules.
Monitor complete blood count (CBC) regularly, especially during the first few weeks of therapy. Dose adjustments may be necessary based on neutrophil and platelet counts.
Use with caution in patients with renal or hepatic impairment; dose reduction may be required.
May cause immunosuppression; avoid live vaccines during therapy.
Carcinogenic potential in animals; long-term use may increase risk of secondary malignancies.
Use with caution in patients with a history of gout or renal stones; hydroxyurea may increase uric acid levels.
In horses, use with caution due to limited safety data.

Adverse Effects & Reactions

Common:

Myelosuppression (leukopenia, thrombocytopenia, anemia)
Gastrointestinal signs (vomiting, diarrhea, anorexia)
Lethargy
Alopecia (especially in dogs)
Skin reactions (rash, hyperpigmentation)

Serious / Severe:

Severe bone marrow suppression leading to infection or bleeding
Pulmonary toxicity (interstitial lung disease, pulmonary fibrosis)
Hepatotoxicity
Neurotoxicity (drowsiness, dizziness, hallucinations)
Secondary leukemia or skin cancer with long-term use

Rare:

Oral ulceration
Gastrointestinal ulceration
Renal impairment
Fever
Peripheral neuropathy

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Other myelosuppressive agents (e.g., cyclophosphamide, doxorubicin)	Additive bone marrow suppression; increased risk of leukopenia and thrombocytopenia.	High
Antiviral agents (e.g., didanosine, stavudine)	Increased risk of pancreatitis and hepatotoxicity.	High
Live vaccines	Immunosuppression may reduce vaccine efficacy and increase risk of infection.	Moderate
Allopurinol	May increase risk of skin toxicity.	Moderate
Warfarin	May alter anticoagulant effect; monitor coagulation parameters.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe myelosuppression (pancytopenia)
Gastrointestinal ulceration
Mucositis
Neurological signs (confusion, seizures)
Hepatotoxicity
Renal failure

Emergency Treatment Protocol: There is no specific antidote. Treatment is supportive and symptomatic. Induce vomiting if recent ingestion and the animal is stable. Administer activated charcoal to reduce absorption. Monitor CBC, liver and renal function. Provide supportive care including fluids, blood transfusions if needed, and antiemetics. In severe cases, consider hospitalization and intensive care.

Food Animal Withdrawal Times

Hydroxyurea is not approved for use in food animals. If used off-label in food animals, a prolonged withdrawal period is recommended (e.g., at least 30 days for meat and 7 days for milk) due to potential toxicity and lack of residue data. Consult regulatory authorities.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25°C, 68-77°F).

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

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Hydroxyurea is FDA-approved for human use (e.g., for sickle cell anemia, certain cancers). It is not FDA-approved for veterinary use, but it is used off-label in veterinary medicine.

Extra-Label (Off-Label) Use: In the US, extra-label use of hydroxyurea in animals is permitted under AMDUCA (Animal Medicinal Drug Use Clarification Act) provided there is a valid veterinarian-client-patient relationship, and no approved animal drug is available. However, it is not approved for veterinary use, so use is extra-label. Withdrawal times must be established by the veterinarian.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Hydroxyurea is an oral antineoplastic agent used in veterinary medicine primarily for the treatment of mast cell tumors in dogs and cats, and for myeloproliferative disorders such as polycythemia vera and chronic myeloid leukemia. It is a cell-cycle-specific agent that inhibits DNA synthesis. Dosing is typically intermittent (e.g., every 48 hours or three times weekly) to minimize myelosuppression. Close monitoring of complete blood counts is essential, especially during the first month of therapy. Gastrointestinal side effects are common and may be managed with antiemetics and dose adjustments. Hydroxyurea is teratogenic and should not be used in pregnant animals. Due to its potential for severe bone marrow suppression, it should be used with caution in patients with pre-existing hematologic abnormalities. In food animals, its use is not recommended due to lack of residue data and potential toxicity. Always handle the drug with care to avoid exposure to humans.

References & Literature

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