Drug Interaction Report

MONITOR: Coadministration with CYP450 3A4 inducers may decrease the plasma concentration 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. Data are not available of other, less potent inducers.

MANAGEMENT: Caution is advised when ritlecitinib is used with CYP450 3A4 inducers. The possibility of diminished therapeutic effects should be considered.

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.