Drug Interactions between ivacaftor / tezacaftor and paclitaxel

Grapefruits and grapefruit juice may increase the blood levels and effects of PACLitaxel. This can increase the risk of side effects such as nausea, diarrhea, hair loss, muscle pain or weakness, nerve damage, and impaired bone marrow function resulting in low numbers of different types of blood cells. You may also be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. Contact your doctor if you experience paleness, fatigue, dizziness, fainting, unusual bruising or bleeding, fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, pain or burning during urination, vision problems, and/or numbness, burning or tingling in your hands and feet. You may need a dose adjustment and/or more frequent monitoring by your doctor to safely use both medications. 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.

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.