Drug Interaction Report
6 potential interactions and/or warnings found for the following 2 drugs:
- deutivacaftor / tezacaftor / vanzacaftor
- ezetimibe / rosuvastatin
Interactions between your drugs
ezetimibe rosuvastatin
Applies to: ezetimibe / rosuvastatin, ezetimibe / rosuvastatin
MONITOR: Coadministration with ezetimibe may rarely increase the risk of myopathy and serum transaminase elevations associated with HMG-CoA reductase inhibitors (i.e., statins). The mechanism of interaction is unknown. A case report describes two patients whose serum creatine kinase increased after ezetimibe was added to their statin therapy (atorvastatin and fluvastatin, respectively). One of the patients also developed myalgia and tendinopathy, which resolved promptly after withdrawal of both drugs. Statin therapy was subsequently reintroduced at the previous dosage without incident. In the other patient, serum creatine kinase returned to normal within 4 weeks after discontinuation of ezetimibe while the statin was continued. On the contrary, no cases of myopathy or tendinopathy occurred in a study of 33 hypercholesterolemic patients treated with ezetimibe and atorvastatin or simvastatin. There were also no reports of myopathy or significant increases in serum creatine kinase in a study of 32 subjects treated with ezetimibe and fluvastatin. In controlled clinical studies, the incidence of consecutive elevations (greater than 3 times the upper limit of normal) in serum transaminases was 1.3% for patients treated with ezetimibe in combination with a statin versus 0.4% for patients treated with a statin alone. These elevations were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment.
MANAGEMENT: Until further information is available, use of a statin in combination with ezetimibe should be approached with caution. Some authorities consider concomitant use to be contraindicated in patients with active liver disease or unexplained persistent elevations in serum transaminases. Patients should be advised to promptly report to their physician any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. The drugs should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. In addition, liver function tests should be performed at initiation of therapy and according to the recommendations of the HMG-CoA reductase inhibitor.
References (6)
- Gagne C, Gaudet D, Bruckert E (2002) "Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia." Circulation, 105, p. 2469-75
- Fux R, Morike K, Gundel UF, Hartmann R, Gleiter CH (2004) "Ezetimibe and statin-associated myopathy." Ann Intern Med, 140, p. 671-2
- (2024) "Product Information. Ezetimibe (ezetimibe)." Camber Pharmaceuticals, Inc
- (2023) "Product Information. Ag-Ezetimibe (ezetimibe)." Angita Pharma Inc.
- (2024) "Product Information. Ezetimibe (Apo) (ezetimibe)." Apotex Pty Ltd
- (2024) "Product Information. Ezetimibe (ezetimibe)." Sandoz Ltd
rosuvastatin vanzacaftor
Applies to: ezetimibe / rosuvastatin, deutivacaftor / tezacaftor / vanzacaftor
MONITOR: Coadministration with vanzacaftor and/or deutivacaftor, both in vitro inhibitors of the breast cancer resistance protein (BCRP), may increase the plasma concentrations and pharmacologic effects of sensitive BCRP substrates. The proposed mechanism involves decreased clearance due to inhibition of BCRP by vanzacaftor and/or deutivacaftor. However, this interaction has not been studied clinically.
MANAGEMENT: Caution is advised when vanzacaftor and/or deutivacaftor are used concomitantly with drugs that are sensitive substrates of the BCRP transporter. Monitoring for signs and symptoms of increased exposure to the BCRP substrate should be considered whenever vanzacaftor and/or deutivacaftor are added to or withdrawn from therapy. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of the BCRP inhibitor.
References (1)
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
rosuvastatin deutivacaftor
Applies to: ezetimibe / rosuvastatin, deutivacaftor / tezacaftor / vanzacaftor
MONITOR: Coadministration with vanzacaftor and/or deutivacaftor, both in vitro inhibitors of the breast cancer resistance protein (BCRP), may increase the plasma concentrations and pharmacologic effects of sensitive BCRP substrates. The proposed mechanism involves decreased clearance due to inhibition of BCRP by vanzacaftor and/or deutivacaftor. However, this interaction has not been studied clinically.
MANAGEMENT: Caution is advised when vanzacaftor and/or deutivacaftor are used concomitantly with drugs that are sensitive substrates of the BCRP transporter. Monitoring for signs and symptoms of increased exposure to the BCRP substrate should be considered whenever vanzacaftor and/or deutivacaftor are added to or withdrawn from therapy. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of the BCRP inhibitor.
References (1)
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
Drug and food interactions
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)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
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)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
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)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (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.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
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