Drug Interaction Report

MONITOR: Coadministration with dacomitinib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is reduced clearance due to inhibition of CYP450 2D6 by dacomitinib. When dextromethorphan, a probe substrate for CYP450 2D6, was coadministered with a single 45 mg dose of dacomitinib, dextromethorphan peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 9.7- and 9.6-fold, respectively. The interaction may be particularly important for sensitive CYP450 2D6 substrates or those that demonstrate a narrow therapeutic index.

MANAGEMENT: Caution is advised if dacomitinib is used in combination with CYP450 2D6 substrates. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever dacomitinib is added to or withdrawn from therapy. Avoid concomitant use with dacomitinib where minimal increases in concentration of the CYP450 2D6 substrate may lead to serious or life-threatening toxicities.

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.