Vincristine with itraconazole

Gillies J, Hung KA, Fitzsimons E, et al. Severe vincristine toxicity in combination with itraconazole. Clin Lab Haematol 1998 20 123-124. 

Two adults with acute lymphoblastic leukemia developed unusually severe neurotoxicity caused by vincristine, which was probably the result of an interaction with itraconazole suspension (127). 

Four out of 14 patients with ALL given induetion chemotherapy with weekly injections of vincristine (with prednisone, daunorubicin and asparaginase) and antifungal prophylaxis with itraconazole 400 mg daily, developed severe and early vincristine-induced neurotoxicity (paraesthe-sia and muscle weakness of the hands and feet, paralytic ileus, mild laryngeal nerve paralysis). The degree and early onset of these neurotoxic reactions were unusual, and were all reversible except for mild paraesthe-sia in one patient. The complications were more serious than in a previous... 

Vincristine levels may be increased when given with drugs that inhibit cytochrome P450 3A enzyme (itraconazole). 

Jeng MR, Feusner J. Itraconazole-enhanced vincristine neurotoxicity in a child with acute lymphoblastic leukemia. Pediatr Hematol Oncol 2001 18(2) 137-42. 

Kamaluddin M, McNally P, Breatnach F, O Marcaigh A, Webb D, O Dell E, Scanlon P, Butler K, O Meara A. Potentiation of vincristine toxicity by itraconazole in children with lymphoid malignancies. Acta Paediatr 2001 90(10) 1204-7. 

The concomitant use of itraconazole with vincristine increased the incidence of neurotoxicity in children and adults with ALL (95,96). 

Clinically important, potentially hazardous interactions with alprazolam, astemizole, carbamazepine, cisapride, clarithromycin, dexamethasone, diltiazem, docetaxel, ifosfamide, imatinib, irinotecan, itraconazole, ketoconazole, methylprednisolone, midazolam, nefazodone, oral contraceptives, paroxetine, phenytoin, pimozide, rifampin, ritonavir, terfenadine, tolbutamide, trabectedin, troleandomycin, vinblastine, vincristine, warfarin... 

Clinically important, potentially hazardous interactions with abacavir, atorvastatin, bepridil, bupropion, carbamazepine, clarithromycin, cyclosporine, dexamethasone, digoxin, felodipine, fluticasone propionate, fosamprenavir, itraconazole, ketoconazole, lovastatin, methadone, midazolam, nicardipine, nifedipine, phenobarbital, phenytoin, rifabutin, simvastatin, sirolimus, St John s wort, systemic lidocaine, tacrolimus, tenofovir, trazodone, vinblastine, vincristine, voriconazole, warfarin, zidovudine... 

Ariffin H, Omar KZ, Ang EL, Shekhar K. Severe vincristine neurotoxicity with concomitant use of itraconazole. J Paediatr Child Health (2003) 39, 638-9. 

Muenchow N, Janka G, ErttmannR, Looft G, Bielack S, Winkler K. Increased vincristine neurotoxicity during treatment wifii itraconazole in 3 pediatric patients with acute myelogenous leukaemia. Blood(1999) 94 (Suppl 1, part 2) 234b. 

Information seems to be limited to this report. On the basis of their findings the authors suggest that erythromycin should be avoided at the time of vinblastine infusion. Use with clarithromycin may be safe. The UK manufacturers of vincristine and vindesine have warned that caution should be exercised in patients taking any drugs known to inhibit the CYP3A subfamily because of the risk of an earlier onset and/or increased severity of adverse effects. One manufacturer of vinblastine states that erythromycin may increase vinblastine toxicity. Note that itraconazole, another CYP3A4 inhibitor, is known to increase the toxicity of vincristine, see Vinca alkaloids -i- Azoles , p.668. 

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