Paclitaxel Ketoconazole

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,... 

Jamis-Dow CA, Pearl ML, Watkins PB, et al. Predicting drug interactions in vivo from experiments in vitro human studies with paclitaxel and ketoconazole. Am J Clin Oncol 1997 20 592-599. 

In patients with ovarian cancer, ketoconazole, 100-1600 mg as a single oral dose 3 hours after paclitaxel 175 mg/m as a 3-hour continuous intravenous infusion, did not alter plasma concentrations of paclitaxel or its principal metabolite, 6-alpha-hydroxypaclitaxel (57). 

Other possible chemotherapeutic regimens suggested by the NCCN guidelines and clinical trials include ketoconazole plus doxorubicin, estramustine plus etoposide, or estramustine plus paclitaxel. ... 

CYP2C8 <5 1-2 Disopyramide Amiodarone Clozapine Diclofenac Fluvastatin Nicardipine Paclitaxel Retinoic acid Rosiglitazone Torsemide Repaglinide Amiodarone Celecoxib Felodipine Nicardipine Fluoxetine Ketoconazole Ritonavir Indinavir Troglitazone Zafirlukast Retinoic acid Clotrimazole Phenobarbital Dexamethasone Gemfibrozil Rifampin Phenytoin Ritonavir... 

Ketoconazole does not appear to affect the pharmacokinetics of paclitaxel. 

Especially the inhibition or induction of cytochrome P450 subtype 3A4 (CYP 3A4) is clinically relevant, because a variety of active substances and food substances (e.g. grapefruit juice) are able to affect this enzyme. Substances inhibiting CYP 3A4 include ciclosporin, dihydropyridines, verapamil, midazolam, paclitaxel, simvastatin, lovastatin, atorvastatin, cimetidine, erythromycin, troleandomycin, ketoconazole (and other azoles). Substances inducing CYP 3A4 include steroids, rifampicin, phenobarbital and St John s wort. 

Fig. 5.1 MBP classification system (MCS). Circle stands for Easy drug and triangle stemds for Mfficult drug. DIP dipyridamole, DNZ danazol, FFB fenofibrate, GRI grisoeMvin, IDM indomethacin, 177 itraconazole, AIPX naproxen, AW nifedipine, Al/Lnilvadipine, ATP nitrendipine, PHE phenytoin, PMZ pimozide, PTX paclitaxel, KTZ ketoconazole. A-L, Roche in-house drugs. MBP preparation condition polymer HPMCAS pH 2 drug/polymer ratio = 3/7...

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