Protease inhibitors Docetaxel

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

DOCETAXEL ANTIVIRALS-PROTEASE INHIBITORS t risk of adverse effects of docetaxel Inhibition of CYP3A4-mediated metabolism. Also inhibition of P-gp efflux of vinblastine Use with caution. Additional monitoring required. Monitor FBC weekly... 

Life-threatening haematological toxicities have been reported in a few patients taking protease inhibitors when given paclitaxel or docetaxel. Nelfinavir and ritonavir appear to inhibit the clearance of paclitaxel and are predicted to inhibit the metabolism of docetaxel by CYP3A4. 

Paclitaxel is metabolised by the cytochrome P450 enzymes CYP2C8 and CYP3A4. Docetaxel is metabolised by CYP3A4. Protease inhibitors such as ritonavir and indinavir are known to inhibit CYP3A4, which might result in increased taxane levels and toxicity. 

Evidence is limited, nevertheless the UK manufacturers advise that paclitaxel should be given to patients also receiving protease inhibitors with caution. The manufacturers of docetaxel also advise that it should be used with caution with drugs that inhibit CYP3A4, see Taxanes Docetaxel + Miscellaneous , below, which would include the protease inhibitors. 

Ikezoe T, Hisatake Y, Takeuchi T, Ohtsuki Y, Yang Y, Said JW, Taguchi H, Koeffler HP. HIV-1 protease inhibitor, ritonavir a potent inhibitor of CYP3A4, enhanced the anticancer effects of docetaxel in androgen-independent prostate cancer cells in vitro and in vivo. Cancer Res 2004 64(20) 7426-31. 

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