Clopidogrel with Simvastatin Interaction Details

Brand Names Associated with Clopidogrel

Brand Names Associated with Simvastatin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

Decreased formation of clopidogrel active metabolite resulting in high on-treatment platelet reactivity

Interaction Summary

Patients treated with clopidogrel, which is partially metabolized to its active metabolite by CYP3A4 and P-glycoprotein efflux transport, may develop high on-treatment platelet reactivity with concomitant use of a CYP3A4-metabolized statin (ie, atorvastatin, lovastatin, or simvastatin). In a clinical study, patients undergoing percutaneous coronary intervention with high on-treatment platelet reactivity during concurrent use of clopidogrel and atorvastatin demonstrated a significant reduction in platelet reactivity and enhanced clinical response to clopidogrel after switching to pravastatin or rosuvastatin (both non-CYP3A4-metabolized statins). If a patient develops high on-treatment platelet reactivity during concomitant treatment with clopidogrel and a CYP3A4-metabolized statin (ie, atorvastatin, lovastatin, or simvastatin), consider discontinuation of that statin, and substitution with a statin that is not metabolized by CYP3A4 (ie, pravastatin or rosuvastatin).

Severity

Moderate

Onset

Unspecified

Evidence

Established

How To Manage Interaction

If a patient develops high on-treatment platelet reactivity during treatment with clopidogrel and a statin metabolized by CYP3A4 (ie, atorvastatin, lovastatin, or simvastatin), discontinue the statin and substitute a statin that is not metabolized by CYP3A4 (ie, pravastatin or rosuvastatin).

Mechanism Of Interaction

Competition with CYP3A4-mediated metabolism and inhibition of P-glycoprotein efflux transport of clopidogrel by CYP3A4-metabolized statins

Literature Reports

A) Patients undergoing percutaneous coronary intervention (PCI) with high on-treatment platelet reactivity (HPR; defined as 20 micromoles adenosine diphosphate (ADP)-induced maximal platelet aggregation (MPA) greater than 50%) received chronic atorvastatin 10 mg daily and clopidogrel 75 mg daily and then were randomly assigned to receive 15 days of either rosuvastatin 10 mg (n=25) or pravastatin 20 mg (n=25) daily instead of atorvastatin. After switching statins, MPA levels after stimuli with 20 and 5 micromolar ADP decreased by 6.6% (95% CI, 3.2%% to 10.1%; p less than 0.001) in the rosuvastatin group and by 6.3% (95% CI, 2.5 to 10.2%; p=0.002) in the pravastatin group and the prevalence of HPR decreased by 24% (p less than 0.001) .

Clopidogrel Overview

• Clopidogrel is used alone or with aspirin to prevent serious or life-threatening problems with the heart and blood vessels in people who have had a stroke, heart attack, or severe chest pain. This includes people who have percutaneous coronary intervention (PCI; angioplasty; a type of heart surgery) that may involve inserting coronary stents (metal tubes surgically placed in clogged blood vessels to improve blood flow) or who have coronary artery bypass grafting (CABG; a type of heart surgery). Clopidogrel is also used to prevent serious or life-threatening problems with the heart and blood vessels in people who have peripheral arterial disease (poor circulation in the blood vessels that supply blood to the legs). Clopidogrel is in a class of medications called antiplatelet medications. It works by preventing platelets (a type of blood cell) from collecting and forming clots that may cause a heart attack or stroke.

Simvastatin Overview

• Simvastatin is used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Simvastatin is also used to decrease the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol (''bad cholesterol'') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol (''good cholesterol'') in the blood. Simvastatin may also be used to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 10 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Simvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

• Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with simvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

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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.