Drug Interaction Report

MONITOR: Coadministration with pitolisant may reduce plasma concentrations of substrates of CYP450 2C, P-glycoprotein (P-gp), and uridine diphosphate glucuronosyltransferases (UGTs). Based on in vitro data, pitolisant and its main metabolites may induce CYP450 2C, P-gp, and UGTs. Clinical data are not available.

MANAGEMENT: Caution is recommended if pitolisant is used in combination with substrates of CYP450 2C, P-gp, and/or UGTs. Clinical and laboratory monitoring may be appropriate for some drugs whenever pitolisant is added to or withdrawn from therapy.

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.