<p>In vitro studies indicate that neither alectinib nor its major active metabolite (M4) inhibits CYP1A2, CYP2B6, CYP2C9, CYP2C19, or CYP2D6 at clinically relevant concentrations. Alectinib and M4 show weak time-dependent inhibition of CYP3A4. In vitro, alectinib exhibits a weak induction potential of CYP3A4 and CYP2B6 at clinical concentrations. Results from a clinical drug-drug interaction study in ALK-positive NSCLC patients demonstrated that multiple doses of alectinib had no influence on the exposure of midazolam, a sensitive CYP3A substrate. Therefore, no dose adjustment is required for co-administered CYP3A substrates. Although in vitro studies indicate that alectinib is an inhibitor of CYP2C8, physiologically based pharmacokinetic (PBPK) modeling supports that at clinically relevant concentrations alectinib does not have the potential to increase plasma concentrations of co-administered substrates of CYP2C8.</p>