In a Phase 1 trial using escalating doses of TAXOL (110–200 mg/m2) and cisplatin (50 or 75 mg/m2) given as sequential infusions, myelosuppression was more profound when TAXOL was given after cisplatin than with the alternate sequence (ie, TAXOL before cisplatin). Pharmacokinetic data from these patients demonstrated a decrease in paclitaxel clearance of approximately 33% when TAXOL was administered following cisplatin.
The metabolism of TAXOL is catalyzed by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Caution should be exercised when administering TAXOL concomitantly with known substrates, inducers (eg, rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine), or inhibitors (eg, erythromycin, fluoxetine, gemfibrozil) of the cytochrome P450 isoenzymes CYP2C8 and CYP3A4. (See CLINICAL PHARMACOLOGY.)
Potential interactions between TAXOL, a substrate of CYP3A4, and protease inhibitors (ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical trials.
Reports in the literature suggest that plasma levels of doxorubicin (and its active metabolite doxorubicinol) may be increased when paclitaxel and doxorubicin are used in combination.
There is no known antidote for TAXOL (paclitaxel) overdosage. The primary anticipated complications of overdosage would consist of bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity (see PRECAUTIONS: Pediatric Use).
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Bristol-Myers Squibb Company
Princeton, NJ 08543 USA
Rev July 2007