Drug Interaction Report

Using macitentan together with sparsentan is not recommended. Combining these medications can increase the risk of serious side effects such as kidney problems, low blood pressure, and high potassium levels in the blood. High levels of potassium can develop into a condition known as hyperkalemia, which in severe cases can lead to kidney failure, muscle paralysis, irregular heart rhythm, and cardiac arrest. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact. 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.

If you are taking sparsentan you should avoid potassium-containing salt substitutes or over-the-counter potassium supplements without first talking to your doctor. This can cause high levels of potassium in your blood. High levels of potassium can cause weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs. Call your doctor at once if you have any of these symptoms.

Consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit should be avoided during treatment with sparsentan as they may increase the blood levels of sparsentan. This may increase the risk of side effects such as hepatotoxicity, acute kidney injury, hyperkalemia, edema, and hypotension.

Swallow sparsentan whole with water before your morning or evening meal. Take your dose with the same meal each day. Talk to your doctor 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.

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.