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Drug Interactions between Alyftrek and voriconazole

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

voriconazole tezacaftor

Applies to: voriconazole and Alyftrek (deutivacaftor / tezacaftor / vanzacaftor)

ADJUST DOSE: Coadministration with potent or moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of vanzacaftor, tezacaftor and deutivacaftor, which are primarily metabolized by the isoenzyme. In clinical studies, itraconazole, a potent CYP450 3A4 inhibitor increased vanzacaftor systemic exposure (AUC) by 6.4-fold, tezacaftor AUC by 4 to 4.5-fold and deutivacaftor AUC by 11.1-fold. Erythromycin, a moderate CYP450 3A4 inhibitor, is predicted to increase vanzacaftor peak plasma concentration (Cmax) and AUC by 3.2- and 3.3-fold, respectively, and deutivacaftor Cmax and AUC by 2.9- and 4.1-fold, respectively. Likewise, fluconazole, another moderate CYP450 3A4 inhibitor, is predicted to increase vanzacaftor and deutivacaftor Cmax and AUC by 2.6- and 2.5-fold; and 3.1- and 2.3-fold, respectively. The risk and/or severity of serious side effects such as liver damage may be increased.

MANAGEMENT: Please consult manufacturer's product labeling for complete dosing information.
For vanzacaftor/tezacaftor/deutivacaftor:
- For patients 6 to less than 12 years old, weighing less than 40 kg:
Potent CYP450 3A4 inhibitors: The dose should be reduced to two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg once a week (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100mg).
Moderate CYP450 3A4 inhibitors: The dose should be reduced to two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg every other day (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100 mg).

- For patients 6 years old to less than 12 years old, weighing 40 kg or more:
Potent CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once a week.
Moderate CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg every other day.

-For patients 12 years old and older:
Potent CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once a week
Moderate CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg every other day.

For tezacaftor/ivacaftor:
- The morning dose of tezacaftor/ivacaftor should be reduced to one tablet twice a week, approximately 3 to 4 days apart, and the evening ivacaftor dose should not be taken during treatment with potent CYP450 3A4 inhibitors. The frequency of dosing should be reduced to a single morning dose of one tezacaftor/ivacaftor tablet alternating with one ivacaftor tablet every other morning during treatment with moderate CYP450 3A4 inhibitors. The evening dose of ivacaftor should not be taken.

For elexacaftor/tezacaftor/ivacaftor:
- The morning dose of 2 elexacaftor/tezacaftor/ivacaftor tablets once a day should be reduced to 2 tablets twice a week, approximately 3 to 4 days apart, and the evening ivacaftor dose should not be taken during treatment with potent CYP450 3A4 inhibitors. The frequency of dosing should be reduced to a single morning dose of two elexacaftor /tezacaftor /ivacaftor tablets alternating with one ivacaftor tablet every other day during treatment with moderate CYP450 3A4 inhibitors. The evening dose of ivacaftor should not be taken.

References (6)
  1. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  2. (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
  3. (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  4. (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
  5. (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
  6. (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
Major

voriconazole vanzacaftor

Applies to: voriconazole and Alyftrek (deutivacaftor / tezacaftor / vanzacaftor)

ADJUST DOSE: Coadministration with potent or moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of vanzacaftor, tezacaftor and deutivacaftor, which are primarily metabolized by the isoenzyme. In clinical studies, itraconazole, a potent CYP450 3A4 inhibitor increased vanzacaftor systemic exposure (AUC) by 6.4-fold, tezacaftor AUC by 4 to 4.5-fold and deutivacaftor AUC by 11.1-fold. Erythromycin, a moderate CYP450 3A4 inhibitor, is predicted to increase vanzacaftor peak plasma concentration (Cmax) and AUC by 3.2- and 3.3-fold, respectively, and deutivacaftor Cmax and AUC by 2.9- and 4.1-fold, respectively. Likewise, fluconazole, another moderate CYP450 3A4 inhibitor, is predicted to increase vanzacaftor and deutivacaftor Cmax and AUC by 2.6- and 2.5-fold; and 3.1- and 2.3-fold, respectively. The risk and/or severity of serious side effects such as liver damage may be increased.

MANAGEMENT: Please consult manufacturer's product labeling for complete dosing information.
For vanzacaftor/tezacaftor/deutivacaftor:
- For patients 6 to less than 12 years old, weighing less than 40 kg:
Potent CYP450 3A4 inhibitors: The dose should be reduced to two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg once a week (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100mg).
Moderate CYP450 3A4 inhibitors: The dose should be reduced to two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg every other day (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100 mg).

- For patients 6 years old to less than 12 years old, weighing 40 kg or more:
Potent CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once a week.
Moderate CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg every other day.

-For patients 12 years old and older:
Potent CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once a week
Moderate CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg every other day.

For tezacaftor/ivacaftor:
- The morning dose of tezacaftor/ivacaftor should be reduced to one tablet twice a week, approximately 3 to 4 days apart, and the evening ivacaftor dose should not be taken during treatment with potent CYP450 3A4 inhibitors. The frequency of dosing should be reduced to a single morning dose of one tezacaftor/ivacaftor tablet alternating with one ivacaftor tablet every other morning during treatment with moderate CYP450 3A4 inhibitors. The evening dose of ivacaftor should not be taken.

For elexacaftor/tezacaftor/ivacaftor:
- The morning dose of 2 elexacaftor/tezacaftor/ivacaftor tablets once a day should be reduced to 2 tablets twice a week, approximately 3 to 4 days apart, and the evening ivacaftor dose should not be taken during treatment with potent CYP450 3A4 inhibitors. The frequency of dosing should be reduced to a single morning dose of two elexacaftor /tezacaftor /ivacaftor tablets alternating with one ivacaftor tablet every other day during treatment with moderate CYP450 3A4 inhibitors. The evening dose of ivacaftor should not be taken.

References (6)
  1. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  2. (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
  3. (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  4. (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
  5. (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
  6. (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
Major

voriconazole deutivacaftor

Applies to: voriconazole and Alyftrek (deutivacaftor / tezacaftor / vanzacaftor)

ADJUST DOSE: Coadministration with potent or moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of vanzacaftor, tezacaftor and deutivacaftor, which are primarily metabolized by the isoenzyme. In clinical studies, itraconazole, a potent CYP450 3A4 inhibitor increased vanzacaftor systemic exposure (AUC) by 6.4-fold, tezacaftor AUC by 4 to 4.5-fold and deutivacaftor AUC by 11.1-fold. Erythromycin, a moderate CYP450 3A4 inhibitor, is predicted to increase vanzacaftor peak plasma concentration (Cmax) and AUC by 3.2- and 3.3-fold, respectively, and deutivacaftor Cmax and AUC by 2.9- and 4.1-fold, respectively. Likewise, fluconazole, another moderate CYP450 3A4 inhibitor, is predicted to increase vanzacaftor and deutivacaftor Cmax and AUC by 2.6- and 2.5-fold; and 3.1- and 2.3-fold, respectively. The risk and/or severity of serious side effects such as liver damage may be increased.

MANAGEMENT: Please consult manufacturer's product labeling for complete dosing information.
For vanzacaftor/tezacaftor/deutivacaftor:
- For patients 6 to less than 12 years old, weighing less than 40 kg:
Potent CYP450 3A4 inhibitors: The dose should be reduced to two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg once a week (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100mg).
Moderate CYP450 3A4 inhibitors: The dose should be reduced to two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg every other day (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100 mg).

- For patients 6 years old to less than 12 years old, weighing 40 kg or more:
Potent CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once a week.
Moderate CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg every other day.

-For patients 12 years old and older:
Potent CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once a week
Moderate CYP450 3A4 inhibitors: The dose should be reduced to one tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg every other day.

For tezacaftor/ivacaftor:
- The morning dose of tezacaftor/ivacaftor should be reduced to one tablet twice a week, approximately 3 to 4 days apart, and the evening ivacaftor dose should not be taken during treatment with potent CYP450 3A4 inhibitors. The frequency of dosing should be reduced to a single morning dose of one tezacaftor/ivacaftor tablet alternating with one ivacaftor tablet every other morning during treatment with moderate CYP450 3A4 inhibitors. The evening dose of ivacaftor should not be taken.

For elexacaftor/tezacaftor/ivacaftor:
- The morning dose of 2 elexacaftor/tezacaftor/ivacaftor tablets once a day should be reduced to 2 tablets twice a week, approximately 3 to 4 days apart, and the evening ivacaftor dose should not be taken during treatment with potent CYP450 3A4 inhibitors. The frequency of dosing should be reduced to a single morning dose of two elexacaftor /tezacaftor /ivacaftor tablets alternating with one ivacaftor tablet every other day during treatment with moderate CYP450 3A4 inhibitors. The evening dose of ivacaftor should not be taken.

References (6)
  1. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  2. (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
  3. (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  4. (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
  5. (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
  6. (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals

Drug and food interactions

Moderate

voriconazole food

Applies to: voriconazole

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

References (2)
  1. (2002) "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67
Moderate

tezacaftor food

Applies to: Alyftrek (deutivacaftor / tezacaftor / vanzacaftor)

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.

References (6)
  1. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  2. (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
  3. (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  4. (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
  5. (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
  6. (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
Moderate

vanzacaftor food

Applies to: Alyftrek (deutivacaftor / tezacaftor / vanzacaftor)

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.

References (6)
  1. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  2. (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
  3. (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  4. (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
  5. (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
  6. (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
Moderate

deutivacaftor food

Applies to: Alyftrek (deutivacaftor / tezacaftor / vanzacaftor)

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.

References (6)
  1. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  2. (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
  3. (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  4. (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
  5. (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
  6. (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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