Drug Interaction Report

Talk to your doctor before using macitentan together with fexinidazole. Fexinidazole may increase the blood levels of macitentan. In some cases, this may increase the risk and/or severity of side effects such as headache, anemia and liver problems, especially during prolonged treatment. Your doctor may be able to prescribe alternatives that do not interact. 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. 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.

Food can enhance the levels of fexinidazole in your body. To ensure maximal oral absorption, fexinidazole should be administered with or immediately after the main meal of the day. This will make it easier for your body to absorb the medication. Use of herbal medicines and supplements during treatment with fexinidazole should be avoided. Grapefruit or grapefruit juice should not be consumed during treatment with fexinidazole. Grapefruit juice can significantly increase the blood levels and effects of fexinidazole, which can increase the risk of an irregular heart rhythm that may be serious and potentially life-threatening, although it is a rare side effect. You may be more susceptible if you have a heart condition called congenital long QT syndrome, other cardiac diseases, conduction abnormalities, or electrolyte disturbances (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting). You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment with these medications, whether together or alone. Consumption of alcoholic beverages or products containing alcohol or propylene glycol during treatment with fexinidazole may occasionally trigger a reaction in some patients similar to the disulfiram reaction, which includes unpleasant effects such as flushing, throbbing in head and neck, throbbing headache, difficulty breathing, nausea, vomiting, sweating, thirst, chest pain, rapid heartbeat, palpitation, low blood pressure, dizziness, lightheadedness, blurred vision, and confusion. Rarely, more severe reactions may include abnormal heart rhythm, heart attack, heart failure, unconsciousness, convulsions, and even death. Patients treated with fexinidazole should avoid using any products containing alcohol or propylene glycol during and for at least 48 hours after completion of therapy. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. 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.