Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4), and is transported by organic anion transporting peptides (OATPs) and ABCB1, and its blood concentration is known to affect the risk of some docetaxel-related adverse drug reactions (ADRs). Thus, the concomitant use of docetaxel with drugs that inhibit or induce these transporters or CYP3A4 requires careful attention. A 58-year-old woman was receiving clarithromycin (400 mg twice daily), rifampicin (450 mg once daily) and ethambutol (500 mg once daily) for nontuberculous mycobacteriosis. The patient was diagnosed as having stage IV HER2-positive breast cancer, which was treated with a regimen of trastuzumab (8 mg/kg), pertuzumab (first dose: 840 mg; second dose onward: 420 mg) and docetaxel (75 mg/m2) every 3 weeks. To predict the risk of serious drug interactions with rifampicin and clarithromycin, the blood concentration of docetaxel was analyzed after administration of the first course. The docetaxel levels at 22 and 159 h after administration were 36.1 and 6.5 ng/ml, respectively, which were higher than previously reported data. In addition, the calculated elimination half-life of 55.7 h was ~3 times longer than previously reported data. Although the docetaxel level was high, the same dosage was used in subsequent courses because no serious ADRs were observed during the first course of therapy. After 4 months of chemotherapy, the patient received complete remission. In conclusion, concomitant use of rifampicin and clarithromycin may increase the blood concentration of docetaxel.
Keywords: clarithromycin; docetaxel; drug interaction; nontuberculous mycobacteriosis; rifampicin; therapeutic drug monitoring.
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