Drug Interaction Report

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vanzacaftor, tezacaftor, and deutivacaftor, drugs primarily metabolized by the isoenzyme. Physiologically based pharmacokinetic (PBPK) simulations suggest that coadministration with the potent CYP450 3A4 inducer rifampin may decrease vanzacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) by 78% and 82%, respectively, and may decrease deutivacaftor Cmax and AUC by 80% and 90%, respectively. Similarly, the moderate CYP450 3A4 inducer efavirenz is predicted to decrease vanzacaftor Cmax and AUC by 65% and 69%, respectively; and may decrease deutivacaftor Cmax and AUC by 56% and 73%, respectively. No pharmacokinetic data are available for tezacaftor, but decreased exposures are expected according to prescribing information.

MANAGEMENT: Concomitant use of vanzacaftor, tezacaftor, and deutivacaftor containing medications with potent CYP450 3A4 inducers is not recommended.

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vanzacaftor, tezacaftor, and deutivacaftor, drugs primarily metabolized by the isoenzyme. Physiologically based pharmacokinetic (PBPK) simulations suggest that coadministration with the potent CYP450 3A4 inducer rifampin may decrease vanzacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) by 78% and 82%, respectively, and may decrease deutivacaftor Cmax and AUC by 80% and 90%, respectively. Similarly, the moderate CYP450 3A4 inducer efavirenz is predicted to decrease vanzacaftor Cmax and AUC by 65% and 69%, respectively; and may decrease deutivacaftor Cmax and AUC by 56% and 73%, respectively. No pharmacokinetic data are available for tezacaftor, but decreased exposures are expected according to prescribing information.

MANAGEMENT: Concomitant use of vanzacaftor, tezacaftor, and deutivacaftor containing medications with potent CYP450 3A4 inducers is not recommended.

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vanzacaftor, tezacaftor, and deutivacaftor, drugs primarily metabolized by the isoenzyme. Physiologically based pharmacokinetic (PBPK) simulations suggest that coadministration with the potent CYP450 3A4 inducer rifampin may decrease vanzacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) by 78% and 82%, respectively, and may decrease deutivacaftor Cmax and AUC by 80% and 90%, respectively. Similarly, the moderate CYP450 3A4 inducer efavirenz is predicted to decrease vanzacaftor Cmax and AUC by 65% and 69%, respectively; and may decrease deutivacaftor Cmax and AUC by 56% and 73%, respectively. No pharmacokinetic data are available for tezacaftor, but decreased exposures are expected according to prescribing information.

MANAGEMENT: Concomitant use of vanzacaftor, tezacaftor, and deutivacaftor containing medications with potent CYP450 3A4 inducers is not recommended.

While you are taking St. John's wort, you must not eat or drink certain foods and beverages that are high in tyramine. Eating these foods while you are taking St. John's wort can raise your blood pressure to dangerous levels. This may cause life threatening symptoms such as sudden and severe headache, confusion, blurred vision, problems with speech or balance, nausea, vomiting, chest pain, seizure (convulsions), and sudden numbness or weakness (especially on one side of the body). Call your doctor at once if you have any of these symptoms. Foods that are high in tyramine include: air dried meats, aged or fermented meats, sausage or salami, pickled herring, and any spoiled or improperly stored beef, poultry, fish, or liver, red wine, beer from a tap, beer that has not been pasteurize, aged cheeses, including blue, brick, brie, cheddar, parmesan, romano, and swiss, sauerkraut, over the counter supplements or cough and cold medicines that contain tyramine, soy beans, soy sauce, tofu, miso soup, bean curd, fava beans, or yeast extracts (such as Marmite). Caffeine intake should be limited as well. You should avoid or limit the use of alcohol while being treated with St. John's wort. Alcohol can increase the nervous system side effects of St. John's wort such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. Talk to your doctor or pharmacist if you have any questions or concerns.

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.

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.

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.