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Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever dacomitinib is added to or withdrawn from therapy.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: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.