Cytarabine

Overview

Cytarabine (Cytosine Arabinoside; Cytosar-U®) is an antineoplastic and immunosuppressive drug used in dogs and cats for the treatment of certain cancers and inflammatory neurologic diseases. In veterinary medicine it is commonly used for lymphoreticular neoplasms, leukemias, and immune-mediated inflammatory brain diseases such as meningoencephalomyelitis of unknown origin (MUO).

The drug is frequently administered as part of combination chemotherapy protocols for lymphoproliferative or myeloproliferative diseases. In dogs with lymphoma involving the bone marrow, addition of cytarabine to combination chemotherapy protocols may improve survival time. It is also widely used together with corticosteroids, particularly prednisolone, in the management of immune-mediated encephalitides.

Mechanism of Action (MOA): Cytarabine is a cytotoxic antimetabolite that interferes with DNA synthesis in rapidly dividing cells. After entering cells, the drug inhibits DNA replication and cell division, leading to suppression of malignant or rapidly proliferating cells.

Indications

Cytarabine is used in dogs and cats as an antineoplastic and immunosuppressive medication. In veterinary medicine it is commonly included in chemotherapy protocols for hematologic cancers and is also widely used for certain immune-mediated neurologic diseases.

• Lymphoproliferative and myeloproliferative disorders: Cytarabine may be used in the management of cancers affecting lymphoid or bone marrow–derived cells, including lymphoma and leukemia.
• Combination chemotherapy protocols (dogs): In dogs with lymphoma involving the bone marrow, cytarabine may be included in a VCAA-based chemotherapy protocol to improve survival time.
• Meningoencephalomyelitis of unknown origin (MUO): Cytarabine is widely used in dogs with MUO (previously termed granulomatous meningoencephalitis, GME) and other suspected immune-mediated encephalitides.
• Adjunct immunosuppressive therapy (dogs): The drug is often administered together with corticosteroids such as prednisolone when treating inflammatory or immune-mediated neurologic conditions.

Dosage (Reference)

Dog

In dogs, cytarabine is administered by injection. It may be given intravenously (IV), subcutaneously (SC), as a continuous IV infusion (CRI), or intrathecally depending on the disease being treated and the chemotherapy protocol used.

Cat

In cats, cytarabine is primarily used in chemotherapy protocols for lymphoproliferative neoplastic disease. The dosing approach is generally similar to that used in dogs.

Warnings & Precautions

Cytarabine is a potent antineoplastic and immunosuppressive drug that can cause significant toxicity depending on the dose and method of administration. Because of the potential for serious adverse effects, treatment should only be performed in patients that can be carefully monitored during therapy.

• Hypersensitivity: Cytarabine is contraindicated in animals with a known hypersensitivity to this medication.
• Bone marrow suppression: Use cautiously in patients with pre-existing bone marrow depression because the drug can further suppress blood cell production.
• Hepatic or renal dysfunction: Animals with liver or kidney disease may have an increased risk of toxicity and should be monitored closely during treatment.
• Concurrent infection: Because cytarabine suppresses the immune system, use cautiously in animals with active infections.
• Severe toxicity risk: Toxicity can vary depending on the dose and rate of administration; careful dosing and monitoring are essential.
• Hazardous drug handling: Cytarabine is classified by the National Institute for Occupational Safety and Health (NIOSH) as a hazardous drug. Appropriate protective equipment should be used when handling the medication.

Drug Interactions

Cytarabine may interact with certain medications that affect bone marrow function, immune response, or vaccine effectiveness. When these drugs are used together, careful monitoring and risk assessment are recommended.

• Flucytosine (5-FC): Cytarabine may reduce the antifungal effectiveness of flucytosine.
• Myelosuppressive drugs (e.g., antineoplastic agents, immunosuppressants, iron chelators): Concurrent use may increase the risk of bone marrow suppression such as neutropenia or thrombocytopenia.
• Vaccines (live or inactivated): Cytarabine may reduce vaccine effectiveness and may increase adverse effects associated with live vaccines due to immunosuppression.

Side Effects & Overdose

Side Effects

The adverse effects of cytarabine in dogs and cats are mainly related to gastrointestinal irritation and bone marrow suppression. The likelihood and severity of these effects may depend on the dose, treatment duration, and route of administration.

• Gastrointestinal effects: Loss of appetite, nausea, vomiting, diarrhea, and oral ulceration may occur.
• Myelosuppression: Bone marrow suppression may result in anemia, neutropenia, or thrombocytopenia. Hematologic toxicity may be more pronounced with intravenous administration compared with subcutaneous dosing.
• Elevated liver enzymes: Increased ALT activity has been reported in some dogs during treatment.
• Lethargy and fever: Some animals may develop decreased activity levels or fever during therapy.
• Hair coat changes: Alopecia and delayed regrowth of clipped hair have been reported in dogs, particularly in breeds with continuously growing hair coats.
• Injection site reactions: Rarely, calcinosis cutis has been reported at subcutaneous injection sites in dogs receiving cytarabine together with corticosteroids.
• Other rare toxicities: Neurotoxicity, hepatotoxicity, and pulmonary complications have been reported in some cases.

Overdose

Cytarabine toxicity is dose-dependent and related to the rate of administration. There is no specific antidote for overdose.

• Clinical signs: Severe gastrointestinal signs, marked bone marrow suppression, and systemic weakness may occur.
• Supportive treatment: Management focuses on supportive care and monitoring of blood cell counts and organ function.
• Dialysis: Cytarabine is dialyzable, and dialysis may be considered in severe cases.

Key Notes

Practical clinical points that may help optimize the use of cytarabine in dogs and cats:

• Poor oral absorption: Cytarabine has very low systemic availability when given orally, therefore it is administered parenterally (e.g., IV, SC, intrathecal).
• Blood–brain barrier penetration: Cytarabine can reach therapeutic concentrations in the central nervous system, which explains its frequent use in neurologic diseases such as immune-mediated encephalitis.
• Short elimination half-life: The drug is eliminated relatively quickly from the body, which is why repeated injections or continuous infusions are often used in treatment protocols.
• Rapid metabolism: Cytarabine is rapidly metabolized in the liver to an inactive metabolite (ara-U), and most of the drug and its metabolites are excreted in the urine.
• Placental transfer: The drug can cross the placenta, indicating potential fetal exposure during pregnancy.