Drug Interactions between macitentan / tadalafil and st. john's wort

While you are taking St. John's wort, you must not eat or drink certain foods and beverages that are high in tyramine. Eating these foods while you are taking St. John's wort can raise your blood pressure to dangerous levels. This may cause life threatening symptoms such as sudden and severe headache, confusion, blurred vision, problems with speech or balance, nausea, vomiting, chest pain, seizure (convulsions), and sudden numbness or weakness (especially on one side of the body). Call your doctor at once if you have any of these symptoms. Foods that are high in tyramine include: air dried meats, aged or fermented meats, sausage or salami, pickled herring, and any spoiled or improperly stored beef, poultry, fish, or liver, red wine, beer from a tap, beer that has not been pasteurize, aged cheeses, including blue, brick, brie, cheddar, parmesan, romano, and swiss, sauerkraut, over the counter supplements or cough and cold medicines that contain tyramine, soy beans, soy sauce, tofu, miso soup, bean curd, fava beans, or yeast extracts (such as Marmite). Caffeine intake should be limited as well. You should avoid or limit the use of alcohol while being treated with St. John's wort. Alcohol can increase the nervous system side effects of St. John's wort such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. Talk to your doctor or pharmacist if you have any questions or concerns.

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.