Plavix and Omeprazole are two very commonly used medications. Often these drugs are taken together since omeprazole is combined to avoid the gastrointestinal side effects associated with aspirin or clopidogrel. However, the FDA recommends avoiding these two drugs in combination because omeprazole may reduce the efficacy of Clopidogrel. What options do you have then? Which antacid or proton pump inhibitor should you use with Clopidogrel (Plavix)?
What is Plavix (Clopidogrel)?
Clopidogrel (Plavix) is an antiplatelet drug like aspirin, prasugrel, and ticagrelor. It is used in the treatment of patients with ST-elevation and non-ST-elevation myocardial infarction, ischemic stroke, and other atherosclerotic diseases.
It inhibits platelet clumping by binding to the ADP receptors present on the platelet surface thereby preventing the activation of the GPIIb/IIIa receptor complex. The effect of clopidogrel is irreversible and lasts until the lifespan of the platelets. Thus, the antiplatelet effect of clopidogrel may last for up to five days after the discontinuation of the drug.
Clopidogrel is a prodrug and it is first activated to its active metabolite by the cytochrome P-450 system. The primary enzyme responsible for its activation is CYP2C19. Some individuals may lack the enzyme genetically and therefore clopidogrel may not exert its antiplatelet activity in these patients. These patients are termed as “CYP2C19 poor metabolizers”. Patients should be ideally tested for CYP2C19 activity before starting clopidogrel therapy. Individuals who lack the enzyme should be given alternate antiplatelet medications (P2Y12 inhibitors).
What is Omeprazole?
Omeprazole is a proton-pump inhibitor. It is used to treat patients who have heartburn, GERD (gastroesophageal reflux disease), peptic ulcer disease, erosive gastritis, Zollinger Ellison syndrome, and Helicobacter Pylori (H. PYlori) eradication in combination with other medications.
It inhibits the secretion of acid produced by the parietal cells of the stomach. It irreversibly inhibits the Hydrogen-Potassium ATP pump resulting in a powerful inhibition of acid secretion. It suppresses the basal acid secretion as in the fasting or resting state as well as the acid secretion by a stimulus such as food.
It suppresses gastric acid within one hour of its administration with a peak effect within 2 hours. The usual duration of action is three days, however, half of its maximum effect is seen within 24 hours. When administered on a daily basis, the maximum antisecretory effect may be observed after four days.
Omeprazole is primarily metabolized in the liver via the enzyme CYP2C19. This is the same enzyme that is required for the activation of Clopidogrel into its active metabolite.
Why the FDA does not recommend the combined use of Plavix and Omeprazole?
The FDA has advised avoiding the concomitant use of Plavix and Omeprazole [Ref]. The concomitant use of these two medications should be avoided because of their interactions with each other. It was found in clinical research that when the two drugs are combined, the antiplatelet activity of Plavix is reduced.
A higher dose of Plavix may restore some of the antiplatelet activity of the drug, however, since alternate antacids and proton-pump inhibitors are available, it is best to avoid taking these two drugs combined. Because omeprazole has a long half-life, taking it even 12 hours apart is also not recommended.
The primary mechanism of its reduced antiplatelet activity is the enzyme CYP2C19. Plavix requires the enzyme CYP2C19 for its activation before exerting antiplatelet activity. Omeprazole, on the other hand, is metabolized by the enzyme CYP2C19 to its inactive metabolites. Since the enzyme is busy metabolizing Omeprazole, it is not available in sufficient amounts to activate clopidogrel. Thus, the efficacy of Plavix (Clopidogrel) is compromised in patients using omeprazole.
Which proton pump inhibitor can you use while taking Plavix (Clopidogrel)?
Most patients who require Plavix (Clopidogrel) for the primary or secondary prevention or treatment of acute coronary syndrome, stroke, or another atherosclerotic disease, also require some form of an antacid or PPI for the prevention of gastric ulcers.
Proton-pump inhibitors that are commonly used are Omeprazole, esomeprazole, lansoprazole, Dexlansoprazole, Rabeprazole, and Pantoprazole.
Both Omeprazole and Esomeprazole are primarily metabolized by the enzyme CYP2C19. Therefore, these two PPIs should be avoided when combined with clopidogrel (Plavix).
All the other four PPIs (Lansoprazole, Dexlansoprazole, Rabeprazole, and Pantoprazole) have a lesser effect on the antiplatelet activity of Clopidogrel. Any of the above-mentioned PPIs can be used, however, the concomitant monitoring of antiplatelet activity is still recommended. Preferably, Rabeprazole or Pantoprazole should be used.
Here is a list of drugs that affect the levels of the enzyme CYP2C19 [Ref]:
Examples of CYP2C19 Inducers
|Strong enzyme Inducers||
|Moderate enzyme Inducers||
|Weak Enzyme Inducers||
Examples of CYP2C19 Inhibitors
|Strong enzyme inhibitors||
|Moderate enzyme inhibitors||
|Weak enzyme inhibitors||
It is best to avoid using Plavix and omeprazole together. Alternative medicines such as pantoprazole may be used.