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Drug Interaction Report

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

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Interactions between your drugs

Major

rosuvastatin vadadustat

Applies to: ezetimibe / rosuvastatin, vadadustat

ADJUST DOSE: Coadministration with vadadustat, an inhibitor of breast cancer resistance protein (BCRP), may increase the plasma concentrations and pharmacologic effects of drugs that are substrates of BCRP such as atorvastatin, rosuvastatin, and simvastatin. The proposed mechanism involves decreased clearance due to inhibition of BCRP by vadadustat. According to product labeling, when vadadustat was coadministered with the BCRP substrates simvastatin and rosuvastatin, systemic exposure (AUC) of the substrates increased 2-fold, and 2 to 3-fold, respectively. High levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity, such as myopathy and rarely, rhabdomyolysis.

MANAGEMENT: When concomitant use of vadadustat is required, product labeling recommends limiting the starting dose of simvastatin to 5 mg and the daily dose to 20 mg, and the daily dose of rosuvastatin to 5 mg. The prescribing information for other BCRP substrates should be consulted for any dosage adjustments that may be required during coadministration and/or following the discontinuation of a BCRP inhibitor. Patients should be advised to monitor for signs and symptoms of adverse effects and promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.

References (4)
  1. (2023) "Product Information. Vafseo (vadadustat)." Adjutor Healthcare Pty Ltd
  2. Groenendaal-van de Meent D, den Adel M, Kerbusch V, van Dijk J, shibata t, Kato K (2023) Effect of roxadustat on the pharmacokinetics of simvastatin, rosuvastatin, and atorvastatin in healthy subjects: results from 3 phase 1, open label, 1 sequence, crossover studies. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306950/
  3. (2024) "Product Information. Vafseo (vadadustat)." Akebia Therapeutics
  4. (2024) "Product Information. Vafseo (vadadustat)." Medice UK Ltd
Moderate

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)
  1. 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
  2. Fux R, Morike K, Gundel UF, Hartmann R, Gleiter CH (2004) "Ezetimibe and statin-associated myopathy." Ann Intern Med, 140, p. 671-2
  3. (2024) "Product Information. Ezetimibe (ezetimibe)." Camber Pharmaceuticals, Inc
  4. (2023) "Product Information. Ag-Ezetimibe (ezetimibe)." Angita Pharma Inc.
  5. (2024) "Product Information. Ezetimibe (Apo) (ezetimibe)." Apotex Pty Ltd
  6. (2024) "Product Information. Ezetimibe (ezetimibe)." Sandoz Ltd

Drug and food interactions

Moderate

vadadustat food

Applies to: vadadustat

MONITOR: Smoking and alcohol consumption during therapy with vadadustat may increase the risk of gastrointestinal erosions. Serious erosions, including gastrointestinal bleeding and the need for red blood cell transfusions, have been reported during vadadustat clinical trials. Patients with a history of gastrointestinal erosion, peptic ulcer disease, and current tobacco smokers and alcohol drinkers may be at higher risk of gastrointestinal injury.

MANAGEMENT: Caution is advised if vadadustat is prescribed to current tobacco smokers or alcohol drinkers. Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, hematemesis, trouble swallowing, chest or throat pain, and/or black, tarry stools.

References (3)
  1. (2023) "Product Information. Vafseo (vadadustat)." Adjutor Healthcare Pty Ltd
  2. (2024) "Product Information. Vafseo (vadadustat)." Akebia Therapeutics
  3. (2024) "Product Information. Vafseo (vadadustat)." Medice UK Ltd

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