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Clopidogrel (plavix®) presentation
- 1. Clopidogrel (Plavix®) Carmen G. Rolf Lamar University Fall 2015
- 2. Clopidogrel Antiplatelet Inhibits ADP Prevents Aggregation Activation Metabolized in liver Quick acting No antidote Risk: bleeding
- 3. Acute Coronary Syndromes First line of defense after previous MI Treats stable and unstable angina Helps prevent new MI Can be combined with aspirin Use with stents http://humanbodydisease.com/ischemi c-heart-disease-intro-795.html
- 4. Intended Drug Response Irreversibly binds to P2Y12 receptors on platelet surfaces Prevents ADP from binding to receptors Platelet inactive for life- span (7-10 days) Prevents clot formation Thienopyridines block ADP receptors. Source:Harvey, R; Champe, P “Lippincott illustrated reviews: Pharmacology”, 4th edition. LWW: 2009.
- 5. Potential Interactions Hundreds of drugs Proton Pump Inhibitors Prilosec®, Nexium®, pantoprazole (Protonix®) Warfarin (Coumadin®) NSAIDs SSRIs Prozac® SNRIs
- 6. Adverse Reactions Bleeding is greatest risk Increased risk when combined with aspirin
- 7. Side Effects/Patient reports Headache GI upset Myalgias Skin problems Confusion
- 8. Pharmacokinetics Easily absorbed from intestine 50% available 6 hr half-life Metabolized in liver 2 step process 85% inactive Uses P450 enzymes CYP2C19 Results in 2 hours Steady state within 1 week 40 – 60 % platelet inhibition in normal metabolizers Ultra rapid to poor metabolizers Stop at least 5 days before invasive procedures
- 9. Drug Binding Issues Any drugs that use the CYP2C19 enzyme for metabolism Most important: Proton pump inhibitors Increased risk of clots Omeprazole and esomeprazole worst Pantoprazole better
- 10. Improving Communication All insurance companies involved in oversight with pharmacists Educate insurance companies on the benefit to risk ratio of clopidogrel versus warfarin Encourage all providers to communicate with each other Refine electronic medical records to either alert or allow all providers access to medication changes Encourage patients to report all medications and side effects to all providers
- 11. Home Health Care Report new medications found in home to all providers Educate patient Need for med Possible side effects Update/report med list Educate insurance companies
Editor's Notes
- Clopidogrel is in a class of drugs called antiplatelets. These drugs prevent platelet aggregation and stop clots from forming. Another drug from this class is aspirin; however, aspirin works on the COX receptors, and clopidogrel works by inhibiting adenosine phosphate (ADP). This prevents platelet aggregation and activation. Clopidogrel is metabolized in the liver and requires two steps to become an active drug. It is fast acting, but there is no antidote like there is for warfarin or heparin. The greatest risk if bleeding.
- Clopidogrel is the first line of defense after an MI. It is used to treat the pathophysiology of atherosclerotic disease and prevent clot formation (thrombus) at the site of a plaque rupture. Most patients that have an MI have further cardiovascular disease that increases the risk for a new MI. This is the development and growth of atherosclerotic plaques. These plaques can grow and sometimes rupture. Clopidogrel prevents platelet aggregation at the site of the rupture to prevent a new occlusion from forming and blocking the coronary artery, thus preventing new ischemia.
- After being metabolized in the liver, the active drug binds irreversibly to the P2Y12 receptors on platelet surfaces. These are the same receptors that ADP uses to bind to and active a platelet. By preventing the ADP from binding, clopidogrel prevents the platelet from activating or attracting more platelets for aggregation (platelet plug formation). The affected platelets are inactive for their life-span (7-10 days). By reducing the amount of platelets available for clotting, clopidogrel helps reduce clot formation and prevents further ischemia.
- There are hundreds of drugs that can interact with clopidogrel. The most important drugs are warfarin, NSAIDs, SSRIs, and SNRIs which all increase the risk of bleeding. Proton pump inhibitors can interfere with clopidogrel’s mode of action because they uses the same metabolic pathway in the liver. They can prevent clopidogrel from inhibiting platelet aggregation. This may lead to an increased chance of an MI.
- Bleeding is the most significant adverse reaction. This is increased when clopidogrel is combined with aspirin.
- There are very few other side effects noted, and those that are reported do not appear to be common. The side effects listed here are from patient reports and have not been verified as caused by clopidogrel.
- The FDA labeling states that clopidogrel is easily absorbed from the intestinal tract with or without food (The Rx List, 2015). It is metabolized in the liver in a two step process that produces only a small percentage of active drug. Some patients have defective CYP2C19 enzymes and are either ultra rapid or poor metabolizers. There are also normal and intermediate metabolizers. Poor metabolizers do not see the same aggregate benefits from clopidogrel and may be more at risk for an ischemic event. The drug begins working quickly, and it is readily available. It takes up to a week to reach a steady state, and produces 40 -60 % inhibition of platelet aggregation. Clopidogrel should be stopped at least 5 days before any procedures where bleeding is a risk. Seven to ten days is better.
- Omeprazole and esomeprazole are strong inhibitors of the CYP2C19 enzyme and exert a greater inhibition on clopidogrel metabolism. Pantoprazole does not inhibit the enzyme as drastically.
- Insurance companies do a type of audit with the pharmacist every quarter. This helps to keep the pharmacist and the insurance company on the same page in relation to the patient’s current medications. However, not all companies participate. Educating the companies on the benefits of clopidogrel versus the lesser cost of warfarin may make providers more likely to prescribe this drug. All doctors and providers should communicate with each other. They should especially let the primary care provider know of any medication changes. Electronic medical records are supposed to help with continuity of care. Currently, there is no way for all medication information to be available to all healthcare providers. In the meantime, encouraging patients to report all medications, side effects, and changes will help to improve safety and outcomes.