Drug Interactions between isoniazid and macitentan / tadalafil

Food can decrease the levels of isoniazid in your body. Taking isoniazid on an empty stomach (at least 30 minutes before or 2 hours after a meal) will make it easier for your body to absorb the medication. Avoid drinking alcohol while taking isoniazid because alcohol use may increase the risk of damage to your liver and your risk of experiencing a condition known as peripheral neuropathy (i.E., weakness, numbness, and pain typically in the hands and feet). Your doctor may advise you to take a vitamin B6 (pyridoxine) supplement during your treatment to help prevent peripheral neuropathy. Isoniazid may interact with foods containing histamine or tyramine (e.G., aged cheese, cured meats such as sausages and salami, fava beans, sauerkraut, soy sauce, beer, red wine, skipjack, tuna, mackerel, salmon), which can cause symptoms like headache, sweating, flushing, palpitations, dizziness, lightheadedness, or feeling faint. These foods should generally be avoided. It is important to seek immediate medical care if you experience any severe side effects or symptoms of liver damage such as fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, and/or yellowing of the skin or eyes. 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.