Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Concomitant use of hormonal contraceptives and ivacaftor/tezacaftor/elexacaftor (IVA/TEZ/ELX) or vanzacaftor, tezacaftor, and deutivacaftor may increase the risk for rash events. In one clinical study, the overall incidence of rash events was 10.9% in IVA/TEZ/ELX-treated and 6.5% in placebo-treated patients. The incidence of rash events was 16.3% in females and 5.8% in males for IVA/TEZ/ELX-treated patients and 8.3% in females and 4.8% in males for placebo-treated patients. For IVA/TEZ/ELX-treated patients, the incidence of rash events was 20.5% in females taking a hormonal contraceptive and 13.6% in females not taking a hormonal contraceptive. In other studies, the incidence of rash was 11% in vanzacaftor, tezacaftor, and deutivacaftor treated patients and 7.7% in IVA/TEZ/ELX-treated patients. The incidence of rash was 9.4% in males and 13% in females with vanzacaftor, tezacaftor, and deutivacaftor treatment and 7.6% in males and 7.9% in females with IVA/TEZ/ELX treatment. Rash events were generally mild to moderate in severity with either treatment. The mechanism of this interaction is unknown.

MANAGEMENT: Monitor for rash in patients taking hormonal contraceptives and IVA/TEZ/ELX or vanzacaftor, tezacaftor, and deutivacaftor. Consider interrupting IVA/TEZ/ELX or vanzacaftor, tezacaftor, and deutivacaftor and hormonal contraceptives in patients who develop rash. Once the rash clears, IVA/TEZ/ELX or vanzacaftor, tezacaftor, and deutivacaftor may be restarted without the hormonal contraceptives. If rash does not recur, resumption of hormonal contraceptives can be considered.

Consumer information for this interaction is not currently available.

MONITOR: Concomitant use of hormonal contraceptives and ivacaftor/tezacaftor/elexacaftor (IVA/TEZ/ELX) or vanzacaftor, tezacaftor, and deutivacaftor may increase the risk for rash events. In one clinical study, the overall incidence of rash events was 10.9% in IVA/TEZ/ELX-treated and 6.5% in placebo-treated patients. The incidence of rash events was 16.3% in females and 5.8% in males for IVA/TEZ/ELX-treated patients and 8.3% in females and 4.8% in males for placebo-treated patients. For IVA/TEZ/ELX-treated patients, the incidence of rash events was 20.5% in females taking a hormonal contraceptive and 13.6% in females not taking a hormonal contraceptive. In other studies, the incidence of rash was 11% in vanzacaftor, tezacaftor, and deutivacaftor treated patients and 7.7% in IVA/TEZ/ELX-treated patients. The incidence of rash was 9.4% in males and 13% in females with vanzacaftor, tezacaftor, and deutivacaftor treatment and 7.6% in males and 7.9% in females with IVA/TEZ/ELX treatment. Rash events were generally mild to moderate in severity with either treatment. The mechanism of this interaction is unknown.

MANAGEMENT: Monitor for rash in patients taking hormonal contraceptives and IVA/TEZ/ELX or vanzacaftor, tezacaftor, and deutivacaftor. Consider interrupting IVA/TEZ/ELX or vanzacaftor, tezacaftor, and deutivacaftor and hormonal contraceptives in patients who develop rash. Once the rash clears, IVA/TEZ/ELX or vanzacaftor, tezacaftor, and deutivacaftor may be restarted without the hormonal contraceptives. If rash does not recur, resumption of hormonal contraceptives can be considered.

Consumer information for this interaction is not currently available.

MONITOR: Concomitant use of hormonal contraceptives and ivacaftor/tezacaftor/elexacaftor (IVA/TEZ/ELX) or vanzacaftor, tezacaftor, and deutivacaftor may increase the risk for rash events. In one clinical study, the overall incidence of rash events was 10.9% in IVA/TEZ/ELX-treated and 6.5% in placebo-treated patients. The incidence of rash events was 16.3% in females and 5.8% in males for IVA/TEZ/ELX-treated patients and 8.3% in females and 4.8% in males for placebo-treated patients. For IVA/TEZ/ELX-treated patients, the incidence of rash events was 20.5% in females taking a hormonal contraceptive and 13.6% in females not taking a hormonal contraceptive. In other studies, the incidence of rash was 11% in vanzacaftor, tezacaftor, and deutivacaftor treated patients and 7.7% in IVA/TEZ/ELX-treated patients. The incidence of rash was 9.4% in males and 13% in females with vanzacaftor, tezacaftor, and deutivacaftor treatment and 7.6% in males and 7.9% in females with IVA/TEZ/ELX treatment. Rash events were generally mild to moderate in severity with either treatment. The mechanism of this interaction is unknown.

MANAGEMENT: Monitor for rash in patients taking hormonal contraceptives and IVA/TEZ/ELX or vanzacaftor, tezacaftor, and deutivacaftor. Consider interrupting IVA/TEZ/ELX or vanzacaftor, tezacaftor, and deutivacaftor and hormonal contraceptives in patients who develop rash. Once the rash clears, IVA/TEZ/ELX or vanzacaftor, tezacaftor, and deutivacaftor may be restarted without the hormonal contraceptives. If rash does not recur, resumption of hormonal contraceptives can be considered.

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.