Cisplatin: The recommended regimen of paclitaxel administration for the first line chemotherapy of ovarian carcinoma is for paclitaxel to be given before cisplatin. When paclitaxel is given before cisplatin, the safety profile of paclitaxel is consistent with that reported for single agent use. Administration of cisplatin prior to paclitaxel treatment leads to greater myelosuppression than that seen when paclitaxel is given prior to cisplatin. In patients receiving cisplatin prior to paclitaxel, there is about a 33% 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: Sequence effects characterised by more profound neutropenic and stomatitis episodes have been observed with combination use of paclitaxel and doxorubicin when paclitaxel was administered before doxorubicin and using longer than recommended infusion times (paclitaxel administered over 24 hours; doxorubicin over 48 hours). Plasma levels of doxorubicin (and its active metabolite doxorubicinol) may be increased when paclitaxel and doxorubicin are used in combination and are given closer in time. Paclitaxel for initial treatment of metastatic breast cancer should be administered 24 hours after doxorubicin (see Dosage & Administration). However, data from a trial using bolus doxorubicin and 3 hour paclitaxel infusion found no sequence effects on the pattern of toxicity.
Cimetidine: Paclitaxel clearance is not affected by cimetidine premedication.
Drugs metabolised in the liver: The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and 3A4. Clinical studies have demonstrated that CYP2C8 mediated metabolism of paclitaxel, to 6α-hydroxypaclitaxel, is the major metabolic pathway in humans. 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 drug interactions between paclitaxel and CYP2C8 and 3A4 substrates/inhibitors are limited. Therefore, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit (e.g., erythromycin, fluoxetine, gemfibrozil, deferasirox, trimethoprim) or induce (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital, efavirenz, nevirapine, St John's wort) either CYP2C8 or 3A4.
When paclitaxel was used in combination with trastuzumab (Herceptin), mean serum trough concentrations of trastuzumab were consistently elevated 1.5 fold as compared with serum concentrations of trastuzumab in combination with anthracycline plus cyclophosphamide (AC).
Arthralgia or myalgia adverse events of paclitaxel appear to be of a higher incidence in patients being treated concurrently with filgrastim (granulocyte colony stimulating factor; G-CSF).