Drug Interactions between ivacaftor / tezacaftor and levoketoconazole

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.

You should avoid the use of alcohol while being treated with levoketoconazole. Levoketoconazole may cause liver damage and using it with alcohol or products containing alcohol may increase that risk. In addition, consumption of alcoholic beverages or products containing alcohol during treatment with levoketoconazole may trigger a disulfiram-like reaction in some patients, with unpleasant symptoms such as flushing, palpitations, and nausea. Levoketoconazole may be taken with or without food. You should avoid consumption of grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with levoketoconazole unless directed otherwise by your doctor. Grapefruit juice may increase the blood levels of levoketoconazole. This may increase the risk and/or severity of side effects and liver problems. You should seek immediate medical attention if you develop signs and symptoms of liver damage during treatment with levoketoconazole, such as joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, light colored stools, and yellowing of the skin or eyes. Talk to your doctor if you have any questions or concerns. 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.