Clopidogrel with Felodipine Interaction Details
Brand Names Associated with Clopidogrel
- Clopidogrel
- Plavix®
Brand Names Associated with Felodipine
- Felodipine
- Lexxel® (as a combination product containing Enalapril, Felodipine)
- Plendil®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 11, 2023
Interaction Effect
Decreased antiplatelet effect and increased risk of thrombotic events
Interaction Summary
Although the effects from coadministration of clopidogrel and felodipine (a calcium channel blocker (CCB)) have not been studied in a large number of patients, in 2 prospective studies, other CCBs significantly decreased the effect of clopidogrel on platelet activity by CYP3A inhibition of the activation of clopidogrel to its active metabolite, and increased subsequent thrombotic events. The addition of cilostazol may reduce these potentially harmful interactions . Caution is advised if clopidogrel and CCBs, such as felodipine are used concurrently. Monitor patient for loss of clopidogrel efficacy.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Coadministration of clopidogrel and felodipine, a calcium channel blocker, may decrease the effect of clopidogrel on platelet inhibition, and increase the risk of atherothrombotic events. The addition of cilostazol may reduce these potentially harmful interactions . Use caution if clopidogrel and felodipine are used concurrently and monitor patients for loss of clopidogrel efficacy.
Mechanism Of Interaction
Inhibition of CYP3A-mediated clopidogrel activation by felodipine
Literature Reports
A) In a prospective, observational study of 200 patients with coronary artery disease undergoing percutaneous coronary intervention, coadministration of clopidogrel and calcium channel blocking agents (n=45; amlodipine, n=35; nifedipine, nitrendipine, and diltiazem, n=3; nisoldipine, n=1) significantly decreased clopidogrel inhibitory effects as assessed by vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay. Platelet reactivity index (PRI) was significantly higher in patients receiving clopidogrel and a calcium channel blocker (61%) compared to patients receiving clopidogrel alone (48%). Similarly, decreased platelet inhibition by clopidogrel (PRI greater than 69%) was found in 40% of patients given both drugs compared with 20% of those treated with clopidogrel alone (p=0.008). No significant effect on platelet aggregation was seen in vitro when clopidogrel was combined with a calcium channel blocker, suggesting the interaction is mediated by the CYP3A4 enzyme. Patients were followed for 6 months, and those (25%) treated with clopidogrel and a calcium channel blocker experienced death from cardiovascular causes, non fatal myocardial infarction, stent thrombosis, revascularization, or coronary artery bypass graft compared with 8% of patients treated with clopidogrel alone .
B) In a post-hoc analysis of the prospective, randomized study of 900 Korean patients with coronary heart disease undergoing percutaneous coronary intervention (PCI) with drug-eluting stents, concomitant use of clopidogrel with aspirin and calcium channel blockers (CCB, n=239; amlodipine, 55%, n=132; diltiazem, 34.7%, n=83) significantly decreased the antiplatelet effect of clopidogrel as assessed by the VerifyNow P2Y12 assay and significantly increased the rate of a composite of cardiac death, non-fatal myocardial infarction, and ischemic stroke. In patients who received clopidogrel 75 mg/day and aspirin 100 mg/day, the on-treatment platelet reactivity (OPR) at discharge significantly increased with concomitant CCB use as compared with CCB non-use (mean OPR +/- standard error of the mean (SEM) 251.2+/-7.6 vs 225.6+/-5.1, respectively; p=0.008). However, this difference was moderated in those patients who received cilostazol 200 mg/day in addition to the clopidogrel plus aspirin therapy (mean OPR +/- SEM at discharge, 214.5+/-9.1 vs 203.4+/-5.6 for CCB users vs non-users; p=0.297). At the 6-month follow-up, these effects were maintained. A composite of cardiac death, non-fatal myocardial infarction, and ischemic stroke was also assessed at 6 months after PCI. This composite increased in patients who received clopidogrel and aspirin with CCB use as compared with CCB non-use (4.9% vs 0.9%, respectively; p=0.016), but not in patients who also received cilostazol (0% vs 1.8% for CCB users vs non-users; p=0.346) .
Clopidogrel Overview
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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.
Felodipine Overview
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Felodipine is used to treat high blood pressure. Felodipine is in a class of medications called calcium channel blockers. It works by relaxing the blood vessels so your heart does not have to pump as hard.
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High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.
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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:
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.