Drug Interaction Report

Treatment with cholecalciferol may require you to adjust your dietary intake of foods which contain natural or added calcium, phosphate (organic and inorganic), and vitamin D. Ingesting too much vitamin D or having elevated calcium and/or phosphorus levels in the blood and urine can lead to toxic effects, such as having an irregular heart rhythm, seizures, kidney stones, and eventual calcification of your blood vessels, cornea and/or the soft tissues in your body. Your doctor will monitor the levels of calcium and phosphorus in your blood during treatment with cholecalciferol. Please speak with your healthcare team to determine if you require a specialized diet, particularly if you have reduced kidney function, and to discuss any other questions or concerns you have. You may require additional monitoring or a dose adjustment of cholecalciferol if your diet changes. Fortified foods will state on their labeling how much calcium, phosphate, and/or vitamin D has been added. The National Institutes of Health, Office of Dietary Supplements also provides information on which foods contain calcium, phosphorus, and vitamin D. You should avoid abrupt changes in your dietary calcium intake and seek medical attention if you experience early symptoms of vitamin D intoxication such as weakness, fatigue, headache, drowsiness, vertigo, ringing in the ears, loss of appetite, nausea, vomiting, constipation, dry mouth, metallic taste, muscle pain, bone pain, muscle incoordination, and low muscle tone. Late symptoms may include frequent urination, excessive thirst, weight loss, conjunctivitis ("pink eye"), light sensitivity, runny nose, itching, increased body temperature, and irregular heart rhythm. 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.