Drug Interactions between ivacaftor / tezacaftor and ozanimod

Ivacaftor should be taken with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products to help with its absorption. Do not consume grapefruit juice or any food that contains grapefruit or Seville oranges during treatment with ivacaftor unless directed otherwise by your doctor. Grapefruit juice can significantly increase the blood levels of ivacaftor. This may increase the risk and/or severity of serious side effects such as liver damage. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark urine, pale stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. 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: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. 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. The risk and/or severity of serious side effects such as liver damage may be increased.

ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.

Ozanimod may be taken with or without food. While there is no need to strictly avoid most foods and beverages that contain tyramine (usually aged, fermented, cured, smoked, or pickled foods such as air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, and sauerkraut) during treatment with ozanimod, certain foods such as some of the aged cheeses (for example, Boursault, Liederkrantz, Mycella, and Stilton) and pickled herring may contain very high amounts of tyramine and should generally be avoided if possible. Consumption of very high levels of tyramine (greater than 150 mg) while on ozanimod treatment may lead to dangerous increases in your blood pressure, a condition known as hypertensive crisis. Talk to your doctor or pharmacist if you are uncertain about what foods, if any, to avoid. You should seek immediate medical attention if you experience sudden and severe headache, blurred vision, confusion, seizures, chest pain, nausea or vomiting, sudden numbness or weakness (especially on one side of the body), speech difficulties, fever, sweating, lightheadedness, and/or fainting during treatment with ozanimod, as these may be signs and symptoms of a hypertensive crisis. 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.