Drug Interactions between eplerenone and macitentan / tadalafil

Consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit should be avoided during treatment with eplerenone as they may increase the blood levels and effects of eplerenone. High blood levels of eplerenone can increase the risk of side effects including hyperkalemia (high blood potassium), which in severe cases can lead to kidney failure, muscle paralysis, irregular heart rhythm, and cardiac arrest. You may be more likely to develop hyperkalemia during treatment with eplerenone if you are elderly, dehydrated, or have kidney disease, diabetes, or advanced heart failure. You should seek medical attention if you experience nausea, vomiting, weakness, confusion, tingling of the hands and feet, feelings of heaviness in the legs, a weak pulse, or a slow or irregular heartbeat, as these may be symptoms of hyperkalemia. 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.

Tadalafil can lower blood pressure, and combining it with alcohol may further increase this effect. You may be more likely to experience symptoms such as dizziness, lightheadedness, fainting, flushing, headache, and heart palpitations. You should avoid or limit the use of alcohol to not more than 4 alcohol-containing drinks during a small period of time while being treated with tadalafil, and use caution when getting up from a sitting or lying position. You may also want to avoid drinking large amounts of grapefruit juice, since it may increase the blood levels and effects of tadalafil. 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.