Prilosec Plavix Interaction Together May Kill You Says FDA.

Taking Plavix and Prilosec together may kill you.  Or so I read today on the LA Times Health Blog about this damning evidence.  Folks, this is bad news.  Really bad news.  A safety review is on regarding a potentially deadly interaction of Plavix (generic name clopidogrel) with proton pump inhibitors (PPIs) prilosec (omeprazole) and others.  PPIs are acid suppression medications such as Prilosec, Nexium, Protonix among others.  Plavix is a permanent platelet aggregation inhibitor.  That is, it prevents platelets from clumping together, which is one of the requirements of clot formation.  It is indicated for the prevention of arterial type thrombosis events.  Most notably, it is used extensively to try and prevent thrombosis of arterial stents.

 Proton pump inhibitors  are used universally for heart burn suppression and the treatment of ulcers, gastritis, esophagitis and GERD.  You name it.  Any irritation in the esophageal-gastric tract gets a PPI.  We use it extensively in the ICU for gastric suppression.  It's also used fairly often in other hospitalized patients as well for protection of gastric mucosa from acute hospitalized illness (but shouldn't be).

I suspect it won't be anymore.  This news is not looking good.  The study out of  Circulation says that those taking Plavix and a PPI  such as (Prilosec) had a higher incidence of adverse outcomes after one year.  Here's what the FDA says to do (link no longer available):

Until further information is available FDA recommends the following:
  • 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.
  • Healthcare providers should re-evaluate the need for starting or continuing treatment with a PPI, including Prilosec OTC, in patients taking clopidogrel. 
  • Patients taking clopidogrel should consult with their health care provider if they are currently taking or considering taking a PPI, including Prilosec OTC.
This is not good. Many patients have symptomatic relief of severe heart burn with the use of these PPIs.  These folks are often smokers and often obese, two of the main risk factors for GERD related symptoms.  It just so happens that these are the same people who develop CAD and require cardiac stents, which then require Plavix to keep from clotting off.  How do you treat a patient with a bleeding ulcer who requires a PPI who also happens to be on Plavix for their cardiac stents (or renal stents or peripheral arterial stents)?.  How do you treat severe GERD  in a patient with stents?

Which would you rather have, painful GERD symptoms all the time or an MI that could potentially kill you or leave you with significant cardiac morbidity?  It's one more reason to get out and exercise, stop smoking and eat healthy.  Drugs won't fix you.    In fact, a false sense of comfort in their efficacy can be destroyed instantly when you read about stuff like this.
UPDATE TO STORY November 2009:

Earlier this year retrospective analysis suggested that people talking Prilosec and Plavix had a statistically significant increase in major cardiovascular events.

This week the FDA confirmed those warnings. 
Omeprazole inhibits the drug metabolizing enzyme (CYP2C19) which is responsible for the conversion of clopidogrel into its active form (active metabolite). The new studies compared the amount of clopidogrel's active metabolite in the blood and its effect on platelets (anti-clotting effect) in people who took clopidogrel plus omeprazole versus those who took clopidogrel alone. A reduction in active metabolite levels of about 45% was found in people who received clopidogrel with omeprazole compared to those taking clopidogrel alone. The effect of clopidogrel on platelets was reduced by as much as 47% in people receiving clopidogrel and omeprazole together. These reductions were seen whether the drugs were given at the same time or 12 hours apart.

In the same report the FDA indicates concerns regarding other Drug-Plavix interactions because of their inhibitor effects on CYP2C19. 
These include: cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, and ticlopidine. Since the level of inhibition among other PPIs varies, it is unknown to what amount other PPIs may interfere with clopidogrel. However, esomeprazole, a PPI that is a component of omeprazole, inhibits CYP2C19 and should also be avoided in combination with clopidogrel
What do we do now?  Here are some key clinical points to consider:

Is taking Prilosec in the morning and Plavix at night OK?  The answer is no.  The two should be avoided if you don't want to increase your risk of a major cardiovascular event.

Should all proton pump inhibitors (PPIs) be avoided in patients taking Plavix?  The FDA does not have data yet to support that statement.  However, if other PPIs work through the same cytochrome system, I think the answer would be obviously yes.  If I was a patient on Plavix I wouldn't take any PPI until I had more data showing safety.

Should other acid suppression medications such as H2 blockers or antacids  be avoided in patients taking Plavix?  Other than Cimetidine (Tagamet), the answer is no.  These drugs are not known to affect the efficacy of Plavix.

As medicine becomes more complicated, relying on your friendly neighborhood pharmacist to flag potentially deadily drug interactions will be key.  Implementing office and hospital based red-flag pharmacy systems also becomes important for the safety of patient care.  There are simply too many interactions to be memorized and remembered on a daily basis.

The other alternative places you, the patient, in control of your own safety.   As I often say on The Happy Hospitalist, the best solution to avoiding deadly drug interactions is not to put yourself at increased risk of developing life limiting and disabling disease that require medications in the first place.    That means lifestyle modification  will always be the key to your health care salvation.

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11 Outbursts:

  1. i guess there are alternative choices, from dispectic events rathen than using PPI we could use H2 blockers thats my guess, there are several alternatives, we all know that, PPI is a strong medication against ulcers, gastritis, esophagitis and GERD, but H2 blockers doenst seem so bad, in our service we use them cause we dont have PPI. how can you substitue plavix?

  2. PPI's can cause B12 deficiency anyway. Lots of medications can cause GERD and Plavix itself can upset the stomache, so give it with meals. Yes, H2 blockers, tums, bromelain (that pineapple enzyme can get in health stores). Maloxx. Peptobismol. No substitute for plavix, but can do aspirin with Dipyridamole. Apparently Bromelain has some other good benefits according to wikipedia:
    Medical uses
    Bromelain can be used in a vast array of medical conditions. It was first introduced in this area in 1957, and works by blocking some proinflammatory metabolites that accelerate and worsen the inflammatory process. It is an anti-inflammatory agent, and so can be used for sports injury, trauma, arthritis, and other kinds of swelling. Its main uses are treatment of athletic injuries, digestive problems, phlebitis, sinusitis, and aiding healing after surgery. Doses of 200 mg have proven to be an efficacious alternative to NSAIDS.[2]

    It has also been proposed for the treatment of arthritis,[3] chronic venous insufficiency, easy bruising, gout, hemorrhoids, menstrual pain, autoimmune disorders, and ulcerative colitis.

    Studies have shown that bromelain can also be useful in the reduction of platelet clumping and blood clots in the bloodstream, especially in the arteries.

    It may have treatment potential for HIV.[4]

    Proprietary bromelain mixtures are being used for third degree burn treatment, and more are being approved.

    Bromelain supplementation up to 460 mg has been shown to have no effect on human heart rate or blood pressure; however, increasing doses up to 1840 mg have been shown to increase the heart rate proportionately[citation needed].

  3. I tend to usually write for pepcid anyway. The H2 blockers are fairly effective, although not for everyone. Looks like patients taking clopidogrel just have one less option. This is very helpful data though.

  4. Jeez, do like I do and take a tums and an aspirin...

  5. Very nice post anonymous. But there is an alternative for Plavix. Ticlid (ticopidine) was originally used for post stent patients until Plavix came on the market. Nobody uses Ticlid unless they have a Plavix allergy because it can cause agranulocytosis, TTP, etc - and its BID dosing which reduces compliance. Patients also need CBCs every couple of months or so which increases the hassel factor for both patients and physicians. Plavix is just so much easier. Interesting though regarding the PPI. I wonder if this will increase the drive to perform platelet aggregation studies on all post stent patients on plavix - "individualized medicine."

  6. oops, ticlopidine

  7. Thanks for mentioning the ticlopidine. Will check it out. Here's the rest of the concern regarding Plavix right now, so yes, perhaps some individualized medicine is in order:

    "....Two studies published last month and reported by heartwire at that time showed strong associations between a CYP2C19 variant and recurrent thrombotic coronary events in clopidogrel-treated patients. The genetic variant is extremely common, occurring in 30% of individuals of European ancestry, 40% of individuals of African ancestry, and more than 50% of individuals of Asian ancestry, suggesting that a large number of patients are at a considerably higher risk of stent thrombosis despite treatment with clopidogrel.

    The FDA early communication also states that published reports suggest that PPIs might interfere with the effectiveness of clopidogrel by inhibiting the enzyme that converts clopidogrel into its biologically active form. Not all studies have suggested this effect, the agency notes, but the drugs are commonly prescribed to patients treated with clopidogrel, as the antiplatelet can cause irritation of the stomach...."

  8. Now we have Prasugrel (Effient). It is effective immediately and does not have to be metaolized by the liver enzyme before it starts to work...

  9. I had surgey in 92 to remove scar tissue caused by acid influx, I had trouble swallowing waterand food. The Dr prescribed Prilosec. In 94 I had a small stroke cleared by a Dr over several weeks. He prescribed Plavix. I have been on this combinationfor fifteen years and never had a problem.Now I will, What to look forward to , Stroke or acid influx. Thanks FDA.

  10. I had stents as result of a heart attack in 2004...that same year I also had an aortic dissection with major surgery....after that surgery I started taking Plavix...starting back in the late 1990's I had acid reflux with major problems swallowing...I would have spasums from esophagitis to the point that I would have to go to the hospital to resume swallowing...on one occasion I went 10 hours without being able to swallow...I first went on Nexium which helped my esophagi to heal...since then I have used Prilosec....No when I went to my gastro doctor he told me about this report....I stopped taking Prilosec and within two weeks I had another episod of not being able to swallow....Any suggestions..

  11. I am sure that quitting the cigs will indeed knock out the need for Prilosec and the like... It has worked for me.


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