Plavix + Prilosec = Problem?

Acid Stopping Drugs May Inhibit Clopidogrel (Plavix)

Mar 12, 2009 James Cooper

Prilosec and other proton pump inhibitors (PPIs) may block activation of clopidogrel in the liver, reducing clopidogrel's benefit. UPDATED NOV 19/2009

Some people are advised to take aspirin as well as clopidogrel (Plavix) for their heart condition. Many are also advised to take a proton pump inhibitor (PPI) such as omeprazole (Prilosec) to reduce the chance of aspirin causing stomach inflammation. These well-intentioned recommendations may conflict, reducing the benefit from clopidogrel, according to the US Food and Drug Administration (FDA).

Update: November 19,2009

The FDA has alerted the public about this problem. They also point out that taking the drugs at separate times does not eliminate the negative interaction.

Platelet Active Drugs

Both clopidogrel and aspirin affect platelets. One cause of heart attacks is that abnormal platelet-rich clumps inside blood vessels break off and clog narrowed heart blood vessels downstream, choking off the oxygen supply. These drugs reduce platelet stickiness, reducing the chances for platelet-rich clumps to form.

Some experts believe there is benefit to using both drugs at the same time.

Stomach Inflammation

Aspirin may cause stomach inflammation in some people. To prevent it, many health care providers recommend taking an acid-reducing drug. PPIs block the stomach’s acid production, so they do an excellent job of preventing inflammation. So, many people taking Plavix are also taking aspirin, and many of those people also take a PPI. Prilosec (omeprazole) is probably the most popular PPI in the US.

How PPIs Interact With Clopidogrel

Clopidogrel is a pro-drug. Enzymes in the liver, particularly P450 2C19, convert it to its active form. But some PPIs block that enzyme. Without the enzyme working, clopidogrel is mostly impotent. Prilosec blocks the enzyme. Pantoprazole (Protonix) apparently does not. Neither do acid-reducing drugs called H2 blockers, such as Zantac and Pepcid.

The Incriminating Study

Over 13,000 patients taking clopidogrel after a heart attack were studied. Over 700 had a repeat heart attack. Patients also taking omeprazole were over 25% more likely to be repeat heart attack victims.

Why are Pro-drugs Used?

Pro-drugs offer several possible advantages. They may:

• Be more stable, with longer shelf-life, reducing distribution costs
• Provide smoother concentration curves—less jolt of high concentration when swallowed, as the liver slowly converts the pro-drug into active form
• Sometimes be less expensive to manufacture

Advice From the FDA

While the study should be considered preliminary, the FDA does give this advice:

1. “Healthcare providers should continue to prescribe and patients should continue to take clopidogrel as directed, because clopidogrel has demonstrated benefits in preventing blood clots that could lead to a heart attack or stroke.
2. Healthcare providers should re-evaluate the need for starting or continuing treatment with a PPI, including Prilosec ..., in patients taking clopidogrel.
3. Patients taking clopidogrel should consult with their healthcare provider if they are currently taking or considering taking a PPI, including Prilosec ...”

Sources

A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009; DOI: 10.1503/cmaj.082001.

US FDA Advice

The copyright of the article Plavix + Prilosec = Problem? in General Medicine is owned by James Cooper. Permission to republish Plavix + Prilosec = Problem? in print or online must be granted by the author in writing.

Plavix & Prilosec--Problem?

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