Cytarabine — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	SC	100-200 mg/m²	q24h for 4 days, repeated every 3 weeks (as rescue for lymphoma)	Duration: Variable; depends on protocol and response Notes: Commonly used in rescue protocols for lymphoma (e.g., L-asparaginase, cytarabine, and prednisone).
Dog	IV	100-200 mg/m²	q24h for 4 days, repeated every 3 weeks	Duration: Variable Notes: For leukemia or as part of combination protocols.
Dog	SC	5-10 mg/m²	q12h	Duration: For immune-mediated diseases (e.g., steroid-responsive meningitis-arteritis), often used long-term with tapering. Notes: Low-dose continuous immunosuppression.
Cat	SC	100 mg/m²	q24h for 2 days, repeated every 3 weeks	Duration: Variable Notes: For lymphoma, especially CNS involvement.
Cat	IV	100 mg/m²	q24h for 2 days, repeated every 3 weeks	Duration: Variable Notes: For leukemia.
Horse	IV	100-200 mg/m²	q24h for 4 days, repeated every 3 weeks	Duration: Variable Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications

Antineoplastic agent for lymphoproliferative and myeloproliferative disorders
Immunosuppressive agent for certain immune-mediated diseases

Dog (Canine)

Treatment of lymphoma (as part of combination protocols, e.g., rescue therapy)
Treatment of leukemia (acute lymphoblastic leukemia, chronic lymphocytic leukemia)
Treatment of meningioma (as an adjunct to surgery/radiation)
Treatment of immune-mediated diseases (e.g., steroid-responsive meningitis-arteritis, immune-mediated hemolytic anemia, immune-mediated thrombocytopenia) as an immunosuppressive agent

Cat (Feline)

Treatment of lymphoma (especially CNS lymphoma)
Treatment of leukemia
Treatment of immune-mediated diseases (less common)

Horse (Equine)

Treatment of lymphoma (rarely used)
Treatment of immune-mediated diseases (e.g., immune-mediated keratitis, uveitis) - limited evidence

Pharmacology & Mechanism of Action

Drug Class: Antineoplastic agent | Pharmacological Group: Pyrimidine nucleoside analog

Mechanism of Action: Cytarabine (cytosine arabinoside, ara-C) is a deoxycytidine analog that undergoes intracellular phosphorylation to the active metabolite cytarabine triphosphate (ara-CTP). Ara-CTP competitively inhibits DNA polymerase, leading to inhibition of DNA synthesis and chain termination. It also incorporates into DNA and RNA, causing DNA fragmentation and apoptosis. Its cytotoxicity is cell-cycle specific, primarily affecting cells in the S-phase (DNA synthesis).

Pharmacodynamics: Cytarabine is a potent myelosuppressive agent with immunosuppressive properties. It inhibits both cellular and humoral immunity. In veterinary medicine, it is used primarily for its antineoplastic effects, particularly in lymphomas and leukemias, and for its immunosuppressive effects in certain immune-mediated diseases. The drug's efficacy is schedule-dependent, with more frequent dosing or continuous infusion being more effective than single large doses.

⚡ Pharmacokinetics Summary

Absorption: Cytarabine is poorly absorbed orally due to first-pass metabolism by cytidine deaminase in the gastrointestinal tract and liver. Therefore, it is administered parenterally (IV, SC, or intrathecal). After subcutaneous administration, absorption is slow and prolonged, resulting in lower peak concentrations but sustained levels.

Distribution: Cytarabine is widely distributed into tissues and body fluids, including cerebrospinal fluid (CSF). However, CSF concentrations are only about 20-40% of plasma concentrations after systemic administration. It crosses the blood-brain barrier to a limited extent, but intrathecal administration is used to achieve therapeutic CSF levels. It is distributed into the central nervous system, and its volume of distribution is approximately 0.6 L/kg in dogs.

Metabolism: Cytarabine is rapidly metabolized in the liver and other tissues by cytidine deaminase to the inactive metabolite uracil arabinoside (ara-U). This metabolism is rapid, with a short plasma half-life. The rate of metabolism varies among species.

Excretion: The inactive metabolite ara-U is primarily excreted renally. In dogs, approximately 70-80% of the dose is excreted in urine as ara-U within 24 hours. Only a small fraction is excreted unchanged.

Half-Life: Dog: 0.8-1.5 hours (initial phase); Cat: 1-2 hours; Horse: 1-2 hours; Cattle: 1-2 hours (estimated).

Bioavailability: Oral bioavailability is low (<20%) due to first-pass metabolism; subcutaneous bioavailability is approximately 100% but with slower absorption.

Protein Binding: Cytarabine has low protein binding, approximately 13% in humans; similar in animals.

Available Formulations & Strengths

Injectable Solution 100 mg/mL, 20 mg/mL (as cytarabine hydrochloride) (IV, SC, intrathecal)

Lyophilized Powder for Injection 100 mg, 500 mg, 1 g, 2 g per vial (IV, SC, intrathecal)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to cytarabine or any component of the formulation
Severe myelosuppression (unless intended as part of treatment)
Active severe infections (due to immunosuppressive effects)
Pregnancy (teratogenic potential)
Lactation (excreted in milk; risk to offspring)

Warnings & Clinical Precautions:

Cytarabine is a hazardous drug; handle with appropriate protective equipment (gloves, gown, eye protection) and follow safe handling guidelines.
Myelosuppression is dose-limiting; monitor complete blood counts (CBC) regularly.
May cause immunosuppression; monitor for signs of infection.
Use with caution in patients with hepatic or renal impairment (dose adjustment may be necessary).
Extravasation may cause tissue necrosis; administer IV carefully.
Intrathecal administration should only be performed by experienced personnel; use preservative-free formulations.
In cats, monitor for signs of neurotoxicity (rare).
In horses, use with caution due to limited safety data.

Adverse Effects & Reactions

Common:

Myelosuppression (leukopenia, thrombocytopenia, anemia)
Gastrointestinal effects (vomiting, diarrhea, anorexia)
Lethargy
Injection site reactions (pain, swelling)

Serious / Severe:

Severe neutropenia with increased risk of infection
Thrombocytopenia with bleeding risk
Hepatotoxicity (elevated liver enzymes)
Neurotoxicity (especially with high doses or intrathecal administration)
Pancreatitis (rare)
Pulmonary toxicity (rare)

Rare:

Anaphylaxis
Alopecia
Oral ulceration
Renal toxicity
Cardiotoxicity (with high doses)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Other myelosuppressive agents (e.g., doxorubicin, cyclophosphamide)	Additive myelosuppression; increased risk of bone marrow suppression.	High
Digoxin	Cytarabine may reduce the absorption of oral digoxin, decreasing its efficacy.	Moderate
Gentamicin	Potential for increased risk of renal toxicity when used concurrently.	Moderate
Live vaccines	Immunosuppression may increase the risk of infection from live vaccines; avoid concurrent administration.	High

Overdose & Toxicity Management

Signs of Toxicity:

Severe myelosuppression (pancytopenia)
Gastrointestinal toxicity (severe vomiting, diarrhea, mucositis)
Hepatotoxicity
Neurotoxicity (seizures, ataxia, coma)
Potential for secondary infections

Emergency Treatment Protocol: There is no specific antidote for cytarabine overdose. Treatment is primarily supportive and symptomatic. Monitor CBC and vital signs closely. Provide supportive care including intravenous fluids, antiemetics, and antimicrobial therapy if infection develops. In severe cases, consider granulocyte colony-stimulating factor (G-CSF) to hasten neutrophil recovery. For intrathecal overdose, immediate cerebrospinal fluid exchange may be considered (in humans).

Food Animal Withdrawal Times

Cytarabine is not approved for use in food animals. Withdrawal times are not established. Use in food animals is prohibited or requires extreme caution and extended withdrawal periods; consult regulatory authorities.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F); protect from light.

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

Handling & Special Conditions: Reconstituted solutions are stable for 48 hours at room temperature and 7 days under refrigeration (2-8°C). Protect from light. Do not freeze.

Dispensing Status: Prescription Required (Rx Only)

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

Extra-Label (Off-Label) Use: Cytarabine is not FDA-approved for veterinary use; its use in animals is extra-label. In the US, extra-label use is permitted under AMDUCA (Animal Medicinal Drug Use Clarification Act) for non-food animals. For food animals, extra-label use is prohibited if an approved drug is available and effective, and withdrawal times must be established by a veterinarian.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Cytarabine is a valuable chemotherapeutic agent in veterinary oncology, particularly for the treatment of lymphoma and leukemia in dogs and cats. It is also used as an immunosuppressant for certain immune-mediated diseases. Due to its short half-life, it is often administered as a continuous infusion or in multiple daily doses to maximize efficacy. Myelosuppression is the primary dose-limiting toxicity, so careful monitoring of blood counts is essential. The drug is generally well tolerated, but gastrointestinal side effects are common. In dogs, subcutaneous administration is convenient and effective, with similar bioavailability to IV. For CNS lymphoma, cytarabine may be used systemically or intrathecally, but intrathecal administration requires expertise. Always use appropriate safety precautions when handling and administering this hazardous drug. Prognosis and treatment protocols should be tailored to the individual patient and disease stage.

References & Literature

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