Drug Interaction Report

MONITOR: Coadministration with rolapitant may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. Rolapitant is a moderate CYP450 2D6 inhibitor, with inhibitory effect lasting at least 7 days after a single dose. When a 30 mg dose of dextromethorphan, a CYP450 2D6 probe substrate, was administered with a 180 mg dose of rolapitant on day 1 of a pharmacokinetic study, dextromethorphan peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 120% and 160%, respectively. When dextromethorphan was administered on day 8 without rolapitant, Cmax and AUC increased by 180% and 230%, respectively. The duration of CYP450 2D6 inhibition was not studied beyond 7 days and may last longer.

MANAGEMENT: Caution is advised when rolapitant is prescribed with drugs that are significantly metabolized by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever rolapitant is added to or withdrawn from therapy. Due to the prolonged duration of CYP450 2D6 inhibition by rolapitant, prolonged monitoring for adverse effects of drugs that are substrates of CYP450 2D6 may be required for at least 28 days after administration of rolapitant.

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.

The recommended maximum number of medicines in the 'antiemetics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antiemetics' category:

• Pro-Med (promethazine)
• rolapitant

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.