Category Archives: ezetimibe

Is there a Yelp for Medications and should you be using it?

The skeptical cardiologist recently prescribed ezetimibe to a patient who was leery of taking statin drugs for her elevated cholesterol. In the past she had taken red yeast rice in the belief that this was a safe and natural way to lower her cholesterol. I told her that I had looked into and researched red yeast rice (and wrote about it here), and that it was neither safe nor effective.

When I saw her back at our next office visit, she informed me that she had done her own research. She had gone on the internet and Googled ezetimibe and based on its “reviews” she felt it was an unsafe and dangerous drug.

It occurred to me at that point that patients like Ms X may actually believe that they can get reliable information on drug side effects and efficacy by going to a website where patients leave reviews on drugs they have taken.

Yelp For Medications

Such sites would be the equivalent of Yelp, which the wife of the skeptical cardiologist utilizes extensively to determine which restaurants we should patronize.

Lo and behold, if one Googles “reviews Zetia” a whole host of websites pop up offering you the opinions of random individuals on the drug.

On Everday Health Zetia gets 2 stars from 34 reviews with the most recent review being quite negative;

I hadRated Zetia for Rheumatoid Arthritis Report BEWARE. My husband took Zetia along with stantin, Crestor. Within a week, his leg muscles inflamed and shut down his kidneys and liver. He has been in the hospital for over a month and his condition has not improved. He’s on dialysis and can not walk. He is an alcoholic and his liver failed with Zetia.

The 234 reviews of Zetia on WebMD (another site I don’t recommend) are also pretty negative. Here’s a typical one;

Low dose of Zetia ….After just first days had severe diarrhea, halfed the dose. After a month I started seeing flashes in my right eye. Lots of eye fatigue, now a lot of ‘floaters’ in my right eye. Got checked by eye doctor to make sure it wasn’t optical nerve damage. Scarey. Coincidence? Don’t think so. 

Limitations of The Yelp Concept In Assessing Medications

I empathize with and totally respect my patient’s desire to do her own independent research on the potential side effects of a drug that she will be putting in her body.

However, the Yelp approach just does not work well for medications.

There are three problems with relying on these kinds of patient-reported medication side effects.

The first is that the patients who leave comments on these sites are not representative of the overall pool of patients receiving the drug. Patients who feel they have been harmed in some significant way are much more likely to be motivated to spend the time recording what happened to them than are the individuals who felt fine after taking the drug.

There were 4 million prescriptions for ezetimibe written in 2015 and the number of patients leaving comments on these patient-review websites at most number in the hundreds. Thus, 99.9% of those taking ezetimibe are being silent, most likely because they are doing fine with the drug.

Secondly, most of the side effects reported by patients after taking ezetimibe occur at about the same frequency in those who take a placebo.

Although the package insert for ezetimibe lists various “common” side effects of the drug (such as diarrhea and upper respiratory infection), this table from the same package insert shows that such ailments are about as common in the group taking placebo.

The manufacturer, following FDA guidelines, reports out adverse reactions that are more common than 2% and numerically greater than placebo, but these are not necessarily significant differences.

Thus, we see that 4.1% of patients taking Zetia had diarrhea, but also that 3.7% of patients taking placebo had diarrhea.

If you take any group of several thousand individuals and follow them for a couple of months, probably 4% will get diarrhea whether or not they are taking ezetimibe.

The Nocebo Effect

Finally, we have to take into account the nocebo effect. The opposite of the placebo effect, in which inert substances make patients feel better, the nocebo effect makes patients who believe a drug will have side effects much more likely to experience those side effects.

The nocebo effect is quite common in patients who have read very negative comments on the internet about statin side effects. It is clear to me that this statin-related nocebo effect has also influenced patients taking non-statin cholesterol lowering medications like ezetimibe.

This is such an important factor in how patient’s tolerate ezetimibe that I spend considerable time during office visits emphasizing that ezetimibe works in a totally different way than statins, and is not associated with muscle aches/myalgias.

Alas, my patient has chosen to rely on the Yelp approach to deciding which medications to take. I’ve given her the best information I could on the safety and efficacy of ezetimibe based on my years of prescribing it and studying it. At this point it is her decision to make, and I accept it and we move forward managing her cardiovascular disease with the other tools in my toolkit.

Unlike an inaccurate restaurant review, however, a single individual describing inaccurately horrific side effects of a medication has the potential to steer thousands of patients away from potentially life-saving therapy.

Skeptically Yours,

-ACP