Drug Interactions between hyoscyamine / phenobarbital and macitentan

Ask your doctor before using PHENobarbital together with ethanol (alcohol), this can add to dizziness, drowsiness and other side effects of PHENobarbital. Be careful if you drive or do activities that require you to be awake and alert. Talk with your doctor before using any medications together, or drinking alcohol with PHENobarbital. 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 hyoscyamine together with ethanol (alcohol). Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while you are taking hyoscyamine. You should be warned not to exceed recommended dosages and to avoid activities requiring mental alertness. If your doctor prescribes these medications together, you may need a dose adjustment to safely take this combination. 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.