Vinorelbine 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,... 

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... 

Bosque E. Possible drug interaction between itraconazole and vinorelbine tartrate leading to death after one dose of chemotherapy. Ann Intern Med 2001 134(5) 427. 

A 72-year-old patient developed painful oral mucositis and constipation 3 days after being given vinorelbine and itraconazole (97). Further complications included neutropenia and hjrpoxia and he died. 

Some UK and US" manufacturers advise caution if vinorelbine, which is metabolised by CYP3A4, is given with inhibitors of this isoenzyme such as itraconazole and ketoconazole because of the theoretical risk of increased neurotoxicity. The manufacturers of vindesine note that concurrent administration with CYP3A inhibitors may result in early onset or increased severity of vindesine side-effects. ... 

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