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LAS VEGAS – A patient's insightful question led to the identification of almost two dozen cases of severe enteropathy associated with use of a blood pressure medication, investigators reported here.

All of the cases involved use of the angiotensin receptor blocker olmesartan (Benicar), which has since been linked to more than 60 probable cases of severe sprue-like enteropathy, since an initial report of 22 cases, Margot Herman, MD, said at the American College of Gastroenterology meeting.

The patient in question, a 59-year-old woman with hypertension, had severe treatment-resistant diarrhea for a year, resulting in substantial weight loss. During a visit with clinicians, the patient asked whether the illness could be caused by her blood pressure medication -- olmesartan.

"It seemed unlikely because she had been on olmesartan for more than a year before the onset of symptoms," said Herman, of the Mayo Clinic in Rochester, Minn. "However, that week another patient asked a similar question."

Considering the second patient's question more than a coincidence, investigators reviewed records for an ongoing cohort study of patients with collagenous sprue. They found that 30% of the patients were taking olmesartan.

As Herman and colleagues , they initially identified 22 patients with severe sprue-like enteropathy associated with use of olmesartan. They had been evaluated at the Mayo Clinic between August 2008 and 2011.

All of the patients had chronic unexplained diarrhea and a median weight loss of 40 pounds, requiring hospitalization in 14 cases and total parenteral nutrition in four. None of the patients responded to a gluten-free diet, and celiac disease was ruled out in all cases.

The patients had a median age of 69.5, and all but one were white. All of the patients received olmesartan for treatment of hypertension, and dosage ranged from 10 to 40 mg/d. All of the patients had used the drug for at least a year before developing symptoms, and some had taken olmesartan for more than 3 years.

Duration of diarrheal illness averaged 19 months, ranging to 53 months. The diarrhea frequently was accompanied by nausea and vomiting, abdominal pain, and bloating.

Intestinal biopsies revealed villous atrophy and evidence of mucosal inflammation in most of the patients. Seven patients had substantial subepithelial collagen deposits.

After discontinuing olmesartan, the 22 patients gained an average of 27 pounds. Follow-up biopsies in 18 patients showed histologic recovery or improvement of the duodenum.

Olmesartan is one of seven FDA-approved ARBs, but the only one linked to sprue-like enteropathy. Herman cited a characteristic of olmesartan that distinguishes it from the other ARBs and possibly provides a clue to the drug's association with the severe diarrhea and weight loss: prodrug activation in the small intestine.

Since identifying the initial 22 patients with olmesartan-associated sprue-like enteropathy, investigators at Mayo have found at least 22 more cases among patient records. Reports from other centers and from individual patients have raised the total case count to more than 60.

Wondering aloud whether the findings represent "the tip of the iceberg," a member of the audience asked Herman whether she and her colleagues had examined FDA data on adverse events associated with olmesartan.

"We believe it is the tip of the iceberg, or it appears that it is," said Herman. "We have looked at FDA data. Unfortunately, because of the significant delay in the onset of this reaction, we haven't been able to find much evidence."

In response to a request from 名媛直播, a spokesperson for drug manufacturer Daiichi-Sankyo said by email, "We are aware of the publication which reports on a total of 22 patients taking olmesartan who experienced unexplained sprue-like enteropathy. Improvement of gastrointestinal symptoms was observed once olmesartan was stopped. It's important to note that the authors acknowledge that 'this case series lacks all the information necessary to prove causality but rather reflects an association'."

"Patient safety is important to us. Our olmesartan medoxomil family of products has a well-established safety profile with tens of millions of patient-years of use worldwide since 2002. In pivotal phase III studies, olmesartan medoxomil as monotherapy, and in combination with hydrochlorothiazide or amlodipine, has been shown to be safe, effective and well-tolerated, with an incidence of adverse events similar to placebo."

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