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Hypertension drug linked to severe gastrointestinal issues
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Mayo Clinic researchers have reported an association between olmesartan and severe gastrointestinal issues such as nausea, vomiting, diarrhea, weight loss and electrolyte abnormalities.
According to a report published in Mayo Clinic Proceedings, Mayo Clinic physicians treated 22 patients (13 women; mean age, 69.5 years) with symptoms similar to celiac disease, including intestinal inflammation and abnormalities, from 2008 to 2011.
All presented with chronic diarrhea and weight loss; median weight loss was 39 lb and one patient lost 125 lb. Fourteen (64%) of the 22 patients were hospitalized due to the severity of their symptoms. After a blood test, however, the patients did not have results typical of celiac disease. They also did not respond to treatments such as a gluten-free diet, according to information from a press release.
“We thought these cases were celiac diseases initially because their biopsies showed features very like celiac disease, such as inflammation,” Murray stated in the press release. “What made them different was they did not have the antibodies in their blood that are typical for celiac disease.”
After examining the patients’ medications, Mayo Clinic gastroenterologist, Joseph A. Murray, MD, pulled several patients off olmesartan (Benicar, Daiichi Sankyo) and their symptoms dramatically improved. Eventually, all of the 22 patients were taken off olmesartan, and all showed improvement. Histologic recovery of improvement of the duodenum after discontinuation of olmesartan was confirmed in 18 of the 22 patients, according to the abstract.
Most patients were taking 40 mg of olmesartan daily.
The researchers acknowledged that this case series reflects an association, rather than proving causality.
“We report a unique case series to support a novel association between severe spruelike enteropathy and olmesartan. Physicians who encounter patients with diarrheal syndromes should consider medications as a cause, although the potential role for olmesartan had not been considered in these patients by any of the physicians prescribing the medications or treating the diarrheal illness,” Murray and colleagues wrote in the study.
For more information:
Rubio-Tapia A. Mayo Clin Proc. 2012;doi:10.1016/j.mayocp.2012.06.003.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Franz H. Messerli, MD
The report from the Mayo Clinic suggesting that olmesartan is associated with severe gastrointestinal adverse effects is of concern. Olmesartan sales have exceeded $500 million a year in the United States alone and the drug, as are all angiotensin receptor blockers, is perceived as being unique because of its paucity of adverse effects. Several issues should be scrutinized in this context:
- Were any of the patients re-exposed to olmesartan and did the symptoms recur? Mere cessation of a drug and vanishing of a symptom is not an acceptable criterion for confirming a cause-and-effect relationship. Only systematic (and not anecdotal) re-exposure can confirm that the gastrointestinal side effects were indeed due to olmesartan.
- Has there been any other angiotensin receptor blocker indicted for the same issue or are the findings unique to olmesartan? Is this a class effect or is it specific to olmesartan?
- Was this syndrome ever seen in the extensive database with olmesartan or with any other angiotensin receptor blocker? There are numerous clinical trials with olmesartan and gastrointestinal adverse effects are exceedingly uncommon. What are the thoughts of the FDA when they were informed by MedWatch?
- And, most importantly, what is the putative pathophysiologic mechanism? In this context, the possibility of intestinal angioedema comes to mind, which has been observed occasionally with ACE inhibitors, but, to my knowledge, not with angiotensin receptor blockers. If it were olmesartans’s inhibitory effects on transforming growth factor B action as the authors suggest, then this phenomenon should have been observed with other angiotensin receptor blockers such as losartan (Cozaar, Merck) and valsartan (Diovan, Novartis, which are more commonly prescribed than olmesartan, as well.
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