Vincristine Itraconazole

Sathiapalan RK, Al-Nasser A, El-Sohl H, Al-Mohsen I, Al-Jumaah S. Vincristine-itraconazole interaction cause for increasing concern. JPediatr Hematol Oncol (2002) 24, 591. 

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

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Bohme A, Ganser A, Hoelzer D. Aggravation of vincristine-induced neurotoxicity by itraconazole in the treatment of adult ALL. Ann Hematol 1995 71 311-312. 

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

Acyclovir Erythromycin Ivermectin Itraconazole Rifampin Actinomycin D Daunorubicin Doxorubicin Docetaxel Epirubicin Etoposide Imatinib Irinotecan Paclitaxel Vinblastine Vincristine Amprenavir Indinavir Nelfinavir Ritonavir Saquinavir Cyclosporine A Tacrolimus Digoxin Quinidine Verapamil Diltiazem Aldosterone Cortisol Corticosterone Dexamethasone Hydrocortisone Cyclosporine Metkephamid Enkephalin... 

FLUCONAZOLE, ITRACONAZOLE, KETOCONAZOLE, VORICONAZOLE (POSSIBLY POSACONAZOLE) VINCA ALKALOIDS -VINBLASTINE, VINCRISTINE, VINORELBINE t adverse effects of vinblastine and vincristine Inhibition of CYP3A4-mediated metabolism. Also inhibition of P-gp efflux of vinblastine Monitor FBCs and watch for early features of toxicity (pain, numbness, tingling in the fingers and toes, jaw pain, abdominal pain, constipation, ileus). Consider selecting an alternative drug... 

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). 

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). 

A 19-year-old woman developed severe abdominal pain and constipation 28 days after starting to take itraconazole as antifungal prophylaxis when receiving vincristine... 

Concomitant use of itraconazole 2.5 mg/kg/day and vincristine in five children receiving vincristine resulted in hypertension, paralytic ileus, and SIADH (95). 

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... 

Itraconazole can increase the toxicity of vincristine and vinblastine posaconazoie and voriconazoie may interact similarly. There is a theoreticai possibility that itraconazole and ketoconazole may increase the toxicity of vinoreibine. 

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... 

The reasons for this interaction are not understood, but among the suggestions are that the itraconazole inhibits the metabolism of vincristine by the cytochrome P450 enzyme system, so that it is cleared from the body less quickly. Another possible explanation is that itraconazole inhibits P-glycoprotein, and increased vincristine neurotoxicity may be the result of the inhibition of this pump in endothelial cells of the blood-brain barri-... 

The authors of one report suggest that itraconazole should be avoided in patients taking vincristine, and the manufacturers of vincristine also issue a warning about the increased risks of concurrent use. ... 

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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