Drug Interactions between Isoptin and macitentan

You may take verapamil with or without food, but take it the same way every time. You should avoid consuming grapefruit or grapefruit juice as much as possible during treatment with verapamil. If you have been regularly consuming grapefruit or grapefruit juice with verapamil, do not increase or decrease the amounts of these products in your diet without first talking to your doctor. Grapefruit juice can increase the blood levels and effects of verapamil. Contact your doctor if you experience sudden, unexplained weight gain; swelling of the hands, ankles, or feet; chest pain; or difficulty breathing. Avoid driving or operating hazardous machinery until you know how the medication affects you, and use caution when getting up from a sitting or lying position. 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.

Ask your doctor before using verapamil together with ethanol (alcohol). Verapamil may increase the blood levels and intoxicating effects of ethanol (alcohol). This can cause symptoms of extreme drowsiness, confusion, and nausea. If you experience any of these side effect you should avoid activities requiring mental alertness. 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.

Using verapamil together with multivitamin with minerals can decrease the effects of verapamil. Talk with your doctor before using verapamil and multivitamin with minerals together. You may need a dose adjustment or need your blood pressure checked more often if you take both medications. 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.