Docetax Drug Interactions

Drugs that induce, inhibit or are metabolized by CYP450 3A4: In vitro studies have shown that docetaxel metabolism may be modified by concomitant administration of compounds that induce, inhibit or are metabolized by CYP450 3A such as cyclosporine, terfenadine, ketoconazole, erythromycin and troleandomycin. Caution should be exercised when treating patients with these drugs as concomitant therapy since there is a potential for a significant interaction.
Concomitant use of potent CYP3A4 inhibitors (e.g., clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) with docetaxel should be avoided. If such concomitant use cannot be avoided, a dose-adjustment of docetaxel may be suitable, with careful monitoring for toxicity, should be considered.
Ketoconazole: The mean dose-normalized AUC of docetaxel was increased 2.2-fold and its clearance was reduced by 49% when docetaxel was co-administered with ketoconazole.
In vitro plasma protein binding of docetaxel was not affected by dexamethasone, erythromycin, salicylate, sulfamethoxazole, diphenhydramine, propranolol, propafenone, phenytoin, and sodium valproate. The binding of digoxin was not affected by docetaxel. Dexamethasone did not affect protein binding of docetaxel.
Pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their concomitant use.
Carboplatin: There is limited data on the interaction between docetaxel and carboplatin. When combined with docetaxel, the clearance of carboplatin was about 50% higher than the values previously reported for carboplatin monotherapy.
Prednisone: There is no statistically significant effect of prednisone on the pharmacokinetics of docetaxel.