DRUG STUDY AND INFORMATION FORMGeneric Name: Vincristine

Trade Name: Vincasar PFS

Drug Class: Vinca Alkaloids (Microtubule-damaging Agents)

Structure/Chemistry: Asymmetrical dimeric compounds formed by condesation of the vindoline and catharanthine subunits.

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Mechanism of Action: Cell cycle-specific, blocks cells in mitosis. Binds β tubulin to block its polymerization with α tubulin.

Pharmacologic Effects: Mitotic failure creating an inability for cells to divide.

Drug Resistance or Tolerance: Mediated by mdr (multi-drug resistance) gene, increase in P-glycoprotein (membrane efflux transporter; reversed by Ca2+ channel blockers such as verapamil), mutations in β tubulin or in the relative expression of isoforms of β tubulin

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Absorption:

Distribution:

Elimination: Excreted in the bile; t1/2 of 20 hours

Metabolism: Extensively metabolized by liver cytochromes

Adverse Side Effects/Toxicity: Mostly neurological (microtubules are found in high concentration in the brain and contribute to cellular functions such as movement, phagocytosis, and axonal transport), very little myelosuppression, severe constipation (sometimes resulting in colicky abdominal pain), alopecia (20% patients), modest leukopenia, thrombocytopenia, anemia, GI cholic and obstipation

Drug Interactions:

Therapeutic uses: Use together with glucocorticoids as treatment of choice for childhood leukemia; use in combination with alkylating agents and anthracycline for pediatric sarcomas. Use for pediatric leukemias, lyphomas, solid tumors, and large-cell non-Hodgkin’s lymphomas

Miscellaneous: From the Madagascar periwinkle plant. Tolerated better by children than adults. Avoid extravasation during administration. Reduce by 50% to 75% for patients with plasma bilirubin >1.5 mg/dL or >3 mg/dL, respectively.