Using escalating doses of PAXOLL (110-200 mg/m2) and cisplatin (50 or 75 mg/m2) given as sequential infusions, myelosuppression is more profound when PAXOLL is given after cisplatin than with the alternate sequence (i.e., PAXOLL before cisplatin). The metabolism of PAXOLL is catalyzed by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. In the absence of formal clinical drug interaction studies, caution should be exercised when administering PAXOLL concomitantly with known substrates, inducers or inhibitors of the cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Plasma levels of doxorubicin (and its active metabolite doxorubicinol) may be increased when paclitaxel and doxorubicin are used in combination, which result in neutropenic and stomatitis episodes.
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