Drug interactions with the taxanes: clinical implications

Background: The taxanes paclitaxel and docetaxel are among the most active antitumor agents. Clinically important pharmacodynamic interactions have be en reported to occur with these agents that are sequence or schedule depend ent. Because the taxanes undergo hepatic oxidation via the cytochrome P450 system, pharmacokinetic interactions due to enzyme induction or inhibition can also occur. Methods: A comprehensive literature search was conducted using Medline to i dentify clinically important drug-interactions with the taxanes. Results: Clinically significant taxane interactions were identified for car boplatin, cisplatin, doxorubicin, docetaxel, epirubicin and anticonvulsants . Doxorubicin and epirubicin should be administered 24 h before paclitaxel, and the cumulative anthracycline dose limited to 360 mg/m(2). This will pr event the enhanced toxicities due to sequence and schedule dependent intera ctions between anthracyclines and paclitaxel. Conversely, paclitaxel should be administered at least 24 h before cisplatin to avoid a decrease in clea rance and increase in myelosuppression. With concurrent anticonvulsant ther apy, cytochrome p450 enzyme induction results in decreased paclitaxel plasm a steady state concentrations, possibly requiring an increased dose of pacl itaxel. A number of other drug interactions have been reported in prelimina ry studies for which clinical significance has yet to be established. Conclusion: Clinically significant drug interactions have been reported to occur when paclitaxel is administered with doxorubicin, cisplatin, or antic onvulsants (phenytoin, carbamazepine, and phenobarbital). (C) 2001 Harcourt Publishers Ltd.