Cisplatin: 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.
Ketoconazole: As ketoconazole may inhibit the metabolism of paclitaxel, patients receiving paclitaxel and ketoconazole should be closely monitored or the combination of these drugs should be avoided.
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. However, data from a trial using bolus doxorubicin and 3 hour paclitaxel infusion found no sequence effects on the pattern of toxicity.
Drugs metabolised in the liver: Caution should be exercised during concurrent administration of drugs which are metabolised in the liver (e.g. erythromycin) as such drugs may inhibit the metabolism of paclitaxel.
The metabolism of paclitaxel is catalysed by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. In the absence of formal clinical drug interaction studies caution should be exercised when administering Anzatax Injection Concentrate concomitantly with known substrates or inhibitors of these isoenzymes.
In the clinical trial of paclitaxel 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).