Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with fenfluramine may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of the CYP450 2B6 and/or CPY3A4 isoenzymes. The proposed mechanism, based on in vitro data, might be increased clearance due to induction of CYP450 2B6 and intestinal CYP450 3A4.

MANAGEMENT: Caution and monitoring are recommended if fenfluramine is used concomitantly with drugs that are substrates of CYP450 2B6 and/or CYP450 3A4, particularly sensitive substrates or those with a narrow therapeutic range. Monitoring for potential loss of therapeutic efficacy is recommended. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of a CYP450 2B6 and/or CYP450 3A4 inducer.

Using fenfluramine with alcohol can increase the risk of cardiovascular side effects such as increased heart rate, chest pain, or blood pressure changes. In addition, you may also be more likely to experience nervous system side effects such as dizziness, drowsiness, depression, and difficulty concentrating. You should avoid or limit the use of alcohol while being treated with fenfluramine. Do not use more than the recommended dose of fenfluramine, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medication without first talking to your doctor.

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of macitentan, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. The interaction has not been studied with grapefruit juice but has been reported for ketoconazole, a potent CYP450 3A4 inhibitor. In ten healthy subjects, coadministration of a single 10 mg oral dose of macitentan on day 5 of treatment with ketoconazole (400 mg daily for 24 days) resulted in an approximately 2-fold increase in macitentan systemic exposure compared to administration alone. However, the clinical significance of the interaction is unclear. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Until further information is available, patients receiving macitentan therapy should avoid the consumption of grapefruit or grapefruit juice.