Drug Interaction Report

Leflunomide may cause liver problems, and using it with other medications that can also affect the liver such as macitentan may increase that risk. Because leflunomide can stay in your blood for a prolonged period after the last dose, interactions with other drugs may occur for some time even after you have stopped taking it. You should avoid or limit the use of alcohol while being treated with these medications. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark colored urine, light colored stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. Talk to your doctor or pharmacist if you have any questions or concerns. 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.

Leflunomide can be taken with or without food. It is important to take leflunomide regularly to get the most benefit. Discuss with your doctor the use of alcohol while taking leflunomide. Alcohol and leflunomide can both be damaging to the liver.

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.