Influence of Concomitant Polypharmacy on Docetaxel-induced Febrile Neutropenia

Docetaxel (DTX) is metabolized by liver cytochromes P450 (CYP) 3A4 (CYP3A4) and 3A5 (CYP3A5) CYP3A4 activity is considered the main factor affecting the effectiveness in DTX clearance. We, therefore, explored the association between DTX-induced febrile neutropenia (FN) and concomitant polypharmacy involving CYP3A4 inhibitors in cancer patients.

Among patients who received docetaxel, we compared the number of concomitant medications between patients with and without FN, and risk factors associated with FN were identified.

The total number of concomitant CYP3A4 inhibitors and substrates used was significantly higher in patients with FN [mean: 2.1 (95% confidence interval (CI)=1.5-2.9)] than in those without FN [mean: 1.4 (95% CI=1.0-1.8)] (p=0.01). The only risk factor for FN was the use of ≥2 concomitant CYP3A4 inhibitors and substrates in total (OR=4.82, 95% CI=1.77-14.1; p=0.002).

Polypharmacy involving CYP3A4 inhibitors and substrates increases the risk of DTX-induced FN.