Pharmacokinetic drug interactions of vinca alkaloids: summary of case reports.
Involvement of the cytochrome P450 (CYP) 3A subfamily in the metabolism of vincristine is well established. However, information is limited regarding vincristine's drug interaction profile. All the substrates and inhibitors of CYP3A4 such as the azole antifungals (itraconazole, ketoconazole), cyclosporine, isoniazid, and nifedipine have very high propensity to interfere with vincristine metabolism. The proposed mechanism is most likely attributed to either inhibition of 3A4 enzymes or blockade of P-glycoprotein pumps. These interactions are clinically significant and can lead to severe vincristine toxicity if not detected. Although case reports discussed here exclusively involve vincristine, it is important to assume that all vinca alkaloids interact in the same manner until proved otherwise, because they share similar metabolism pathways.
Chan
J D
JD
School of Pharmacy, University of Washington, Seattle 98195, USA.
D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D014748:Vinca Alkaloids / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014750:Vincristine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D014748:Vinca Alkaloids; D014750:Vincristine