Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the blood concentrations of the taxanes, docetaxel and paclitaxel, which have been shown to be substrates of the efflux transporter. The clinical significance has not been fully elucidated. However, use of dual CYP450 3A4 and P-gp inhibitors such as ketoconazole, amiodarone, and dronedarone have been shown to increase the systemic exposure of docetaxel and paclitaxel. In a case report involving a 77-year-old woman with HER2-positive invasive ductal breast cancer on long-term amiodarone therapy, 4 cycles of paclitaxel (80 mg/m2 weekly) and trastuzumab led to development of increasing abdominal discomfort and skin lesions. However, switching to reduced dose docetaxel (100 mg or 75 mg/m2 weekly) led to the development of severe skin and mucosal toxicity, requiring hospitalization 8 days after the first docetaxel dose was administered. Analysis of two blood samples taken 9 and 10 days after docetaxel administration showed an approximately fivefold increase in its AUC as well as the presence of paclitaxel in unquantifiable levels, 20 and 21 days after it was last administered. The authors of this case study propose that, in addition to CYP450 3A4 inhibition, P-gp inhibition due to amiodarone may have contributed to the interaction.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of paclitaxel or docetaxel therapy should be considered during coadministration with P-gp inhibitors, including adverse effects such as myelosuppression, stomatitis, neurotoxicity (e.g., paraesthesia, dysesthesia, pain), myalgia, asthenia, fluid retention, nausea, vomiting, and diarrhea. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a P-gp inhibitor is added to or withdrawn from therapy.

You should preferably avoid the regular consumption of grapefruits and grapefruit juice while taking DOCEtaxel. Grapefruit and grapefruit juice can significantly increase the blood levels of DOCEtaxel. This may increase the risk of side effects such as nausea, vomiting, diarrhea, mouth sores, fluid retention, nerve pain, numbness, tingling, muscle pain or weakness, and impaired bone marrow function resulting in low numbers of different types of blood cells. You may also be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. You should contact your doctor if you develop paleness, fatigue, dizziness, fainting, unusual bruising or bleeding, fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.