Clipax Drug Interactions

Paclitaxel clearance is not affected by Cimetidine premedication.
Cisplatin: Paclitaxel is recommended to be administered before Cisplatin. When given before Cisplatin, the safety profile of Paclitaxel is consistent with that reported for single agent use. Administration of Paclitaxel after Cisplatin treatment leads to greater myelosuppression and about a 20% decrease in Paclitaxel clearance. Patients treated with Paclitaxel and Cisplatin may have an increased risk of renal failure as compared to Cisplatin alone in gynecological cancers.
Doxorubicin: Since the elimination of Doxorubicin and its active metabolites can be reduced when Paclitaxel and Doxorubicin are given closer in time, Paclitaxel for initial treatment of metastatic breast cancer should be administered 24 hours after Doxorubicin.
Active substances metabolized in the liver: Caution should be exercised during concurrent administration of active substances which are metabolized in the liver as such active substances may inhibit the metabolism of Paclitaxel. The metabolism of Paclitaxel is catalyzed, in part, by cytochrome P450 (CYP450) isoenzymes CYP2C8 and 3A4.
Clinical studies have demonstrated that CYP2C8-mediated metabolism of Paclitaxel (to 6α-hydroxypaclitaxel) is the major metabolic pathway in humans. Based on current knowledge, clinically relevant interactions between Paclitaxel and other CYP2C8 substrates are not anticipated. Concurrent administration of Ketoconazole (a known potent inhibitor of CYP3A4) does not inhibit the elimination of Paclitaxel in patients; thus, both medicinal products may be administered together without dosage adjustment. Further data on the potential of interactions between Paclitaxel and other CYP3A4 substrates/inhibitors are limited. Therefore, caution should be exercised when administering Paclitaxel concomitantly with medicines known to inhibit (e.g. Erythromycin, Fluoxetine, Gemfibrozil) or induce (e.g. Rifampicin, Carbamazepine, Phenytoin, Phenobarbital, Efavirenz, Nevirapine) either CYP2C8 or 3A4.
Studies in KS patients, who were taking multiple concomitant medications, suggest that the systemic clearance of Paclitaxel was significantly lower in the presence of Nelfinavir and Ritonavir, but not with Indinavir. Insufficient information is available on interactions with other protease inhibitors. Consequently, Paclitaxel should be administered with caution in patients receiving protease inhibitors as concomitant therapy.