Drug Interaction Report

MONITOR: Coadministration with tucatinib may increase the plasma concentrations of CYP450 3A4 substrates. The mechanism involves tucatinib-mediated inhibition of CYP450 3A isoenzymes. When a single 2 mg dose of midazolam, a CYP450 3A substrate, was administered with tucatinib (300 mg twice daily), midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3-fold and 5.7-fold, respectively. Increased exposure to the CYP450 3A substrate may increase the risk of toxicity.

MANAGEMENT: Caution is advised when tucatinib is used concomitantly with drugs that undergo metabolism by CYP450 3A4. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever tucatinib is added to or withdrawn from therapy.

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.