Ezetimibe with Cyclosporine Interaction Details

Brand Names Associated with Ezetimibe

Brand Names Associated with Cyclosporine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 28, 2024

Interaction Effect

Increased ezetimibe and cycloSPORINE exposure

Interaction Summary

Concomitant use of ezetimibe with cycloSPORINE may increase the exposure of both drugs[1]. Separate studies have demonstrated a greater than 3-fold increase of ezetimibe exposure in post-renal transplant patients with normal to mildly impaired renal function when coadministered with cycloSPORINE, and an average of 15% increase in the cycloSPORINE AUC in a group of twelve healthy subjects with the coadministration of the two drugs [2]. Monitor cycloSPORINE levels in patients also receiving ezetimibe. In patients treated with cyclosporine, the potential effects of the increased exposure to ezetimibe from concomitant use should be carefully weighed against the benefits of alterations in lipid levels provided. The degree of increase in ezetimibe exposure may be greater in patients with severe renal insufficiency [1][2].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of ezetimibe with cycloSPORINE may increase the exposure of either drug. Monitor cycloSPORINE levels in patients also receiving ezetimibe. In patients treated with cyclosporine, the potential effects of the increased exposure to ezetimibe from concomitant use should be carefully weighed against the benefits of alterations in lipid levels provided. The degree of increase in ezetimibe exposure may be greater in patients with severe renal insufficiency[1][2].

Mechanism Of Interaction

Unknown

Literature Reports

A) Ezetimibe reduced LDL-C to an unexpected level when administered concomitantly with cycloSPORINE in a 64-year-old male orthotopic heart transplant patient. The patient was receiving cycloSPORINE 100 mg twice daily and mycophenolate mofetil 1500 mg twice day and could not tolerate high-dose atorvastatin treatment to control his hypercholesterolemia. His LDL-C level was 126 mg/dL when ezetimibe 10 mg daily was initiated. After 2 months, the LDL-C level dropped an expected 60% to 51 mg/dL. The ezetimibe dose was decreased to 5 mg daily and 2 months later, the LDL-C level was 57 mg/dL [3].

B) In a pharmacokinetic study involving 8 post-renal transplant patient with normal to mildly impaired renal function (creatinine clearance >50 ml/min) concomitant exposure to ezetimibe and cycloSPORINE increased ezetimibe plasma concentrations over 3-fold. Patients received stable doses of cycloSPORINE 75 to 150 mg twice daily and experienced increases in the mean area under the concentration-time curve (AUC) and maximum concentration (Cmax) of ezetimibe of 3.4-fold (range 2.3 to 7.9-fold) and 3.9-fold (range 3.0 to 4.4-fold), respectively, compared to a historical healthy population (n=17). In a separate case study, a patient with severe renal impairment (creatinine clearance of 13.2 mL/min/1.73 (m)2) receiving multiple therapies including cycloSPORINE, had 12 times the exposure to ezetimibe compared to healthy subjects [2].

C) In a two-period crossover study, the mean AUC of cycloSPORINE increased 15% with concomitant exposure to ezetimibe as compared to cycloSPORINE alone. Twelve healthy subjects received ezetimibe 20 mg daily for 8 days with a single dose of cycloSPORINE 100 mg on day 7. The cycloSPORINE AUC increased an average of 15% (range 10% decrease to 51% increase) compared to a single dose of cycloSPORINE 100 mg alone [2].

References

1 ) Product Information: Ezetimibe oral tablets, ezetimibe oral tablets. Aurobindo Pharma USA Inc (per DailyMed), East Windsor, NJ, 2020.

2 ) Product Information: ZETIA(R) oral tablets, ezetimibe oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2023.

3 ) Koshman SL, Lalonde LD, Burton I, et al: Supratherapeutic response to ezetimibe administered with cyclosporine. Ann Pharmacother 2005; 39:1561-1565.

Ezetimibe Overview

• Ezetimibe is used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount of cholesterol (a fat-like substance) and other fatty substances in the blood. It may be used alone or in combination with an HMG-CoA reductase inhibitor (statin). Ezetimibe is in a class of medications called cholesterol-lowering medications. It works by preventing the absorption of cholesterol in the intestine.

• Buildup of cholesterol and fats along the walls of the blood vessels (a process known as atherosclerosis) decreases blood flow, which decreases the oxygen supply to the heart, brain, and other parts of the body. Lowering blood levels of cholesterol and fats may help reduce this buildup and may decrease your chances of developing heart conditions such as angina (chest pain), strokes, and heart attacks. Results of a clinical study that compared people who took ezetimibe and simvastatin with people who took simvastatin alone found that although the group of people taking ezetimibe and simvastatin had lower amounts of cholesterol in the blood, there was no difference between the two groups in the amount of cholesterol and fat buildup on the insides of the blood vessels in the neck. It is not currently understood why the additional lowering of cholesterol levels in the blood did not lead to a greater decrease in cholesterol and fat buildup along the walls of the blood vessels in people taking ezetimibe and simvastatin. Further studies are underway to compare treatment with ezetimibe and simvastatin to treatment with simvastatin alone to see if there is a difference in the risk of developing heart disease. Talk to your doctor if you have questions about the risks and benefits of treating increased amounts of cholesterol in your blood with ezetimibe and other medications.

• In addition to taking a cholesterol-lowering medication, making certain changes in your daily habits can also lower your blood cholesterol levels. You should eat a diet that is low in saturated fat and cholesterol (see SPECIAL DIETARY); exercise 30 minutes on most, if not all, days; and lose weight if you are overweight.

Cyclosporine Overview

• Cyclosporine and cyclosporine (modified) are used with other medications to prevent transplant rejection (attack of the transplanted organ by the immune system of the person who received the organ) in people who have received kidney, liver, and heart transplants. Cyclosporine (modified) is also used alone or with methotrexate (Rheumatrex) to treat the symptoms of rheumatoid arthritis (arthritis caused by swelling of the lining of the joints) in patients whose symptoms were not relieved by methotrexate alone. Cyclosporine (modified) is also used to treat psoriasis (a skin disease in which red, scaly patches form on some areas of the body) in certain patients who have not been helped by other treatments. Cyclosporine and cyclosporine (modified) are in a class of medications called immunosuppressants. They work by decreasing the activity of the immune system.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.