Treatment with cimetidine has no influence on paclitaxel clearance.
In the first-line therapy of ovarian cancer, the recommended treatment regimen is to give paclitaxel before cisplatin. If paclitaxel is administered prior to cisplatin, the safety profile is similar to the use of paclitaxel as a single agent. Administration of paclitaxel after cisplatin has led to an increase in myelotoxicity and 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.
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.
The metabolisation of paclitaxel is catalysed by the cytochrome P450 isoenzymes CYP2C8 and CYP3A4 (see Pharmacology: Pharmacokinetics under Actions). Clinical trials have shown that CYP2C8-mediated metabolisation to 6α-hydroxy paclitaxel is the main step in the human metabolism. Concomitant use of ketokonazole, which is known as a strong inhibitor of CYP3A4, does not inhibit the elimination of paclitaxel in patient. Therefore no further dose adjustment is necessary in the combination therapy of paclitaxel and ketoknoazole. Since additional data on paclitaxel and other CYP3A4 substrates/inhibitors are limited, special care must be exercised when using paclitaxel in combination with known substrates or inhibitors of CYP3A4.