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Drug Interaction Report

7 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Moderate

sofosbuvir tezacaftor

Applies to: sofosbuvir / velpatasvir / voxilaprevir, deutivacaftor / tezacaftor / vanzacaftor

MONITOR: Coadministration with tezacaftor and/or deutivacaftor may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. The mechanism is decreased clearance via inhibition of the transporter by tezacaftor and/or deutivacaftor. In study subjects, digoxin (single 0.5 mg dose) systemic exposure (AUC) increased by 1.3-fold when it was administered with tezacaftor 25 mg and ivacaftor 50 mg daily. No pharmacokinetic data are available for deutivacaftor, but increased exposures of certain P-gp substrates are expected according to prescribing information.

MANAGEMENT: Caution is advised when tezacaftor and/or deutivacaftor are used with drugs that are P-gp substrates, particularly those where minimal concentration changes may lead to serious adverse reactions.

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

sofosbuvir deutivacaftor

Applies to: sofosbuvir / velpatasvir / voxilaprevir, deutivacaftor / tezacaftor / vanzacaftor

MONITOR: Coadministration with tezacaftor and/or deutivacaftor may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. The mechanism is decreased clearance via inhibition of the transporter by tezacaftor and/or deutivacaftor. In study subjects, digoxin (single 0.5 mg dose) systemic exposure (AUC) increased by 1.3-fold when it was administered with tezacaftor 25 mg and ivacaftor 50 mg daily. No pharmacokinetic data are available for deutivacaftor, but increased exposures of certain P-gp substrates are expected according to prescribing information.

MANAGEMENT: Caution is advised when tezacaftor and/or deutivacaftor are used with drugs that are P-gp substrates, particularly those where minimal concentration changes may lead to serious adverse reactions.

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

velpatasvir voxilaprevir

Applies to: sofosbuvir / velpatasvir / voxilaprevir, sofosbuvir / velpatasvir / voxilaprevir

MONITOR: Coadministration with inhibitors of organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations of voxilaprevir, which is a substrate of the hepatic uptake transporters. When a single 100 mg dose of voxilaprevir was administered with a single 600 mg dose of the potent OATP 1B1/1B3 inhibitor cyclosporine (n=24), mean voxilaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 19.0- and 9.4-fold, respectively. Inhibition of P-glycoprotein (P-gp)- and breast cancer resistance protein (BCRP)-mediated intestinal transport and CYP450 3A4-mediated metabolism of voxilaprevir may also contribute to the overall interaction with cyclosporine. The safety of such high levels of voxilaprevir has not been established.

MANAGEMENT: Caution and monitoring are advised when voxilaprevir is used with OATP 1B1 or 1B3 inhibitors.

References (1)
  1. (2017) "Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir)." Gilead Sciences

Drug and food interactions

Moderate

voxilaprevir food

Applies to: sofosbuvir / velpatasvir / voxilaprevir

ADJUST DOSING INTERVAL: Administration with food enhances the oral bioavailability of sofosbuvir, velpatasvir, and voxilaprevir. Relative to fasting conditions, mean sofosbuvir systemic exposure (AUC) increased by 64% to 144%, mean velpatasvir AUC increased by 40% to 166%, and mean voxilaprevir AUC increased by 112% to 435% when the combined sofosbuvir/velpatasvir/voxilaprevir formulation is administered with food.

MANAGEMENT: Sofosbuvir/velpatasvir/voxilaprevir should be administered with food.

References (1)
  1. (2017) "Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir)." Gilead Sciences
Moderate

tezacaftor food

Applies to: 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: 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: 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 duplication 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.

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Further information

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