Drug Interaction Report

GENERALLY AVOID: Coadministration with potent CYP450 3A4 inducers may significantly decrease the plasma concentrations and pharmacologic effects of ritlecitinib. The proposed mechanism is increased clearance of ritlecitinib due to induction of the CYP450 3A4 isoenzyme, one of the pathways of elimination of ritlecitinib. When a single 50 mg dose of ritlecitinib was administered in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 8 days), the mean peak plasma concentration (Cmax) and systemic exposure (AUC) of ritlecitinib decreased by approximately 25% and 44%, respectively, compared to ritlecitinib administered alone.

MANAGEMENT: Given the risk of reduced or loss of clinical response, the manufacturer advises that the concomitant use of ritlecitinib with potent CYP450 3A4 inducers should generally be avoided. Alternative therapeutic agents with less enzyme induction potential should be considered.

ADJUST DOSING INTERVAL: Fat-rich food enhances the absorption of mitotane. One study evaluated blood levels of mitotane (o,p'-DDD) after subjects ingested a single dose of 2 g administered using various delivery vehicles (e.g., tablets, granules, milk, chocolate or oil emulsion). Mitotane plasma levels were significantly higher for milk, chocolate, and oil emulsion when compared to those who received tablets or granules alone. In the same study, mitotane levels were evaluated in subjects following long-term treatment (total dose of 200 g over 30 to 60 days) in tablet, oil emulsion, or milk formulations. Significantly higher mean plasma levels were recorded in subjects who received mitotane as an oil emulsion or mixed in milk, when compared to tablets alone. Additionally, the recovery of o,p'-DDD from the feces was about 5 times higher in subjects who received tablets alone, suggesting absorption was reduced when compared to subjects who received mitotane mixed with a fat-rich vehicle (e.g., oil emulsion or milk).

GENERALLY AVOID: Concomitant use of mitotane with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: According to product labeling, mitotane tablets should be taken during meals containing fat-rich food (e.g., milk, chocolate, or oil) and with a full glass of water. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.