Vincristine

Overview

Vincristine (Oncovin®, Vincristine®) is a vinca alkaloid antineoplastic agent widely used in dogs and cats as part of multidrug chemotherapy protocols. It is particularly valuable in the treatment of lymphoproliferative disorders and other neoplastic diseases, where it is commonly combined with additional anticancer medications.

Beyond its antineoplastic activity, vincristine is also used to increase circulating platelet numbers in selected patients with immune-mediated thrombocytopenia and is an established treatment for transmissible venereal tumor (TVT). The drug is administered intravenously and must be given through a properly placed catheter because accidental perivascular administration can result in severe local tissue irritation.

Vincristine is a substrate for P-glycoprotein and may produce increased toxicity in susceptible patients. Careful monitoring is therefore important during treatment, particularly when used as part of combination chemotherapy protocols.

Mechanism of Action (MOA): Vincristine interferes with microtubule assembly within dividing cells, disrupting mitotic spindle formation and causing metaphase arrest. This inhibition of cell division ultimately leads to cell death, particularly in rapidly proliferating cells.

Indications

Vincristine is used in dogs and cats for selected neoplastic and hematologic conditions.

• Lymphoproliferative disorders: Used as part of combination chemotherapy protocols for canine and feline lymphoid malignancies.
• Transmissible venereal tumor (TVT): Commonly used for the treatment of canine transmissible venereal tumors.
• Immune-mediated thrombocytopenia (IMT): Used to stimulate the release of platelets and increase circulating platelet numbers.

Dosage (Reference)

Dog

Vincristine dosing varies according to the condition being treated. For antineoplastic use, doses are typically calculated using body surface area (BSA) rather than body weight.

Cat

In cats, vincristine is used in chemotherapy protocols and occasionally to increase circulating platelet numbers. Antineoplastic doses are generally calculated using body surface area.

Warnings & Precautions

Vincristine is a cytotoxic chemotherapeutic agent that requires careful administration and patient monitoring due to its potential hematologic, neurologic, and tissue toxicity.

• Hepatic disease: Use cautiously in patients with impaired liver function, as reduced drug metabolism may increase toxicity. Dose reduction may be required. consider 50% reduction or avoid altogether if serum bilirubin >2 mg/dL).
• Leukopenia: Contraindicated in patients with pre-existing leukopenia or granulocytopenia, UNLESS the cytopenia is a direct result of the disease being treated. Pre-existing low neutrophil counts must be confirmed before each dose.
• Concurrent infection: Contraindicated. Treat the infection first; do not administer vincristine until the infection is controlled.
• Neuromuscular disorders: Use with caution in patients with pre-existing neuromuscular disease due to the risk of neurologic adverse effects.
• MDR1 mutation: Herding breeds such as Collies and related breeds may be more susceptible to toxicity because vincristine is a P-glycoprotein substrate.
• Extravasation risk: Vincristine is a potent tissue irritant and must be administered through a properly placed intravenous catheter to avoid severe local tissue injury.
• Cytotoxic drug handling: Vincristine is classified by NIOSH as a hazardous drug; appropriate PPE (gloves, gowns, eye protection) should be used during preparation and administration.
• Refrigerated storage: The product should be stored under refrigeration according to manufacturer recommendations.
• Pregnancy & lactation: Vincristine is teratogenic and embryotoxic in laboratory animals (including malformations, embryo resorption, and embryonic death). It may also cause aspermia in males. Excretion in milk is unknown; if a nursing dam requires vincristine, use milk replacer for the offspring.
• Tall-man lettering: Write ‘vinCRIStine’ on prescriptions and orders to reduce confusion with vinBLAStine. The two are easily confused and have different dose schedules and adverse-effect profiles.

Drug Interactions

The most clinically important interactions with vincristine involve drugs that inhibit its metabolism, resulting in increased drug exposure and a higher risk of toxicity.

• CYP3A inhibitors: Drugs that inhibit CYP3A enzymes may decrease vincristine metabolism and increase the risk of adverse effects and toxicity.
• L-asparaginase: When used in combination, vincristine should be administered 12–24 hours before L-asparaginase. Giving L-asparaginase first or concurrently may reduce vincristine clearance and increase toxicity.
• Calcium channel blockers: May inhibit vincristine metabolism and increase the likelihood of toxic effects.
• Cimetidine: May reduce vincristine metabolism, potentially increasing toxicity.
• Cyclosporine: May increase vincristine toxicity through inhibition of drug metabolism.
• Macrolide antibiotics: Macrolide antibiotics (erythromycin, clarithromycin — but NOT azithromycin): may inhibit vincristine metabolism through P-glycoprotein inhibition. Azithromycin is specifically excluded from this concern.
• Azole Antifungals: (itraconazole, ketoconazole, fluconazole): may significantly increase vincristine exposure and toxicity through P-glycoprotein inhibition.
• Cholestyramine: Blocks enterohepatic recirculation of vincristine and may reduce drug exposure. This mechanism is also exploited in overdose management.
• Immunosuppressive drugs: Additive immunosuppression with increased infection risk; monitor closely.
• Mitomycin: Severe bronchospasm has been reported in humans receiving mitomycin-C concurrent with vinca alkaloids; consider this risk in animal patients.
• Other myelosuppressive agents: Additive bone-marrow suppression; avoid combination when possible.
• Live and inactivated vaccines: Vincristine may diminish vaccine efficacy and enhance adverse effects. Do not administer live or modified-live vaccines during chemotherapy.
• Additional P-glycoprotein inhibitors: Amiodarone, Carvedilol, Quinidine, Spironolactone, Tamoxifen, Verapamil. Use caution and monitor for additive toxicity, particularly in MDR1-mutation breeds.

Side Effects & Overdose

Side Effects

Adverse effects of vincristine are primarily neurologic and gastrointestinal in nature, although hematologic toxicity may also occur. The severity of adverse effects can vary depending on dose, treatment protocol, and individual patient susceptibility.

• Peripheral neuropathy: One of the most important toxicities. Clinical signs may include proprioceptive deficits, spinal hyporeflexia, paresthesias, and paralytic ileus with resulting constipation. Caution is advised in patients with predisposing neuropathic disorders (e.g., degenerative myelopathy).
• Gastrointestinal toxicity: Vomiting, diarrhea, and anorexia have been reported. GI effects are considered frequent but generally mild compared with other chemotherapeutics.
• Constipation and ileus: Reduced gastrointestinal motility may occur and can progress to clinically significant ileus.
• Myelosuppression: Bone marrow suppression may develop, although it is generally less pronounced than with some other vinca alkaloids.
• Severe local tissue irritation: Accidental perivascular administration may cause marked local tissue damage and inflammation.
• Cats: Particularly susceptible to GI hypomotility, constipation, and paralytic ileus from vincristine neurotoxicity, which can aggravate anorexia. Reversible axon swelling and paranodal demyelination have been reported. A case report of vincristine-attributed pulmonary edema in a cat has been published; vinblastine is commonly substituted in cats due to the higher feline GI adverse-effect profile of vincristine.
• SIADH: Vincristine may cause inappropriate ADH secretion; consider in patients with unexplained hyponatremia or fluid retention.
• Jaw pain, alopecia, stomatitis: Reported with vincristine. Significant alopecia is more likely in breeds with continuously growing hair coats (Poodles, Terriers, Afghan Hounds, Old English Sheepdogs).
• Erythrocyte dysplasia (dogs): Reported but deemed clinically insignificant.

Overdose

Overdose is expected to result in exaggerated manifestations of the drug’s known toxicities, particularly neurologic, gastrointestinal, and hematologic adverse effects.

• Severe neurotoxicity: Marked peripheral neuropathy, weakness, and worsening neurologic dysfunction may occur.
• Severe gastrointestinal hypomotility: Constipation, ileus, and gastrointestinal dysfunction may become pronounced.
• Enhanced myelosuppression: Significant bone marrow suppression may increase the risk of infection and other hematologic complications.
• Severe extravasation injury: Accidental tissue exposure can result in extensive local irritation and tissue damage.
• Management: Treatment is supportive. If overdose is acute (<6 hours), consider plasmapheresis, activated charcoal, and cholestyramine . For ileus, start a metoclopramide CRI ± other prokinetics (cisapride, erythromycin). For severe myelosuppression, consider filgrastim (G-CSF) plus broad-spectrum antibiotics. Consult a 24-hour veterinary poison control center.
• Dog maximum tolerated dose: 0.06 mg/kg every 7 days for 6 weeks. Signs at this dose include mild anemia, leukopenia, increased liver enzyme activity, and neuronal shrinkage in peripheral nerves and CNS. Megaesophagus and hemorrhagic diarrhea have been reported in 1 dog after accidental overdose.
• Cat lethal dose: Reportedly 0.1 mg/kg. Cats receiving toxic doses showed weight loss, seizures, leukopenia, and general debilitation. A cat receiving vincristine 5 mg/m² (10× the recommended dose) died 72 hours after overdose despite intensive treatment with calcium folinate.
• 24-hour poison consultation: For suspected or confirmed overdose, consult a 24-hour veterinary poison consultation center for case-specific guidance.

Key Notes

Practical clinical points that help optimize the use of vincristine in dogs and cats undergoing chemotherapy:

• Widely used in oncology protocols: Vincristine is a core component of many multidrug chemotherapy protocols used in veterinary oncology.
• Dual clinical applications: In addition to its antineoplastic activity, vincristine is sometimes used to increase circulating platelet numbers in selected patients with immune-mediated thrombocytopenia.
• Body surface area dosing: Most oncology protocols use body surface area (mg/m²) rather than body weight when calculating doses.
• Particularly effective for TVT: Vincristine remains one of the most commonly used and effective treatments for canine transmissible venereal tumors.
• Less myelosuppressive than vinblastine: Although bone marrow suppression can occur, vincristine generally produces less myelosuppression than vinblastine.
• Protocol-dependent scheduling: Treatment intervals vary widely depending on tumor type and the chemotherapy protocol being used.
• Oncology-guided therapy: Treatment plans should be individualized based on tumor type, treatment response, and current oncology recommendations.
• IV use only — vesicant: Vincristine must NEVER be given subcutaneously, intramuscularly, or by any other non-IV route. These routes are not just ineffective but potentially fatal due to severe tissue injury.
• MDR1 testing: Consider MDR1 (ABCB1) genotype testing in at-risk breeds before starting vincristine. Reduce dose by 25–30% in mutant/normal or mutant/mutant patients (WSU VCPL).
• Tall-man lettering: Write ‘vinCRIStine’ on prescriptions to distinguish from vinBLAStine. The two are easily confused and have different dose schedules and adverse-effect profiles.
• Cat vinblastine substitution: Because of higher GI adverse effects with vincristine in cats, vinblastine is commonly substituted in feline COP-based lymphoma protocols.
• NIOSH hazardous drug handling: Use appropriate PPE (gloves, gowns, eye protection) during preparation and administration. Advise clients to wear disposable gloves when handling animal waste for at least 3 days after each treatment.