Drug Interaction Report

The following interaction applies only if you are receiving the oral formulation of lefamulin (Xenleta), but not the intravenous formulation:

Lefamulin taken orally may increase the blood levels and effects of macitentan. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications 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.

The following interaction applies only if you are taking lefamulin (Xenleta) orally:

Food may interfere with the absorption of lefamulin, which may lead to lower blood levels of the medication and possibly reduced effectiveness. You should take lefamulin at least 1 hour before or 2 hours after a meal. It is best to avoid or limit the consumption of grapefruit and grapefruit juice during treatment with lefamulin, as it may increase blood levels of the medication and increase side effects. Talk to your doctor or pharmacist if you have any questions or concerns.