WASHINGTON -- The FDA ordered the maker of the blood pressure drug olmesartan (Benicar) to add a warning about the risk of an intestinal condition known as sprue-like enteropathy to the drug's label.
The connection between sprue-like enteropathy and olmesartan was first reported in June 2012 by Mayo Clinic researchers who, from 2008-2010, had seen 22 patients with symptoms suggestive of celiac disease but antibody blood tests that did not support the diagnosis.
Later in October 2012, researchers at the American College of Gastroenterology meeting noted that olmesartan, an angiotensin II receptor blocker, or ARB, had been linked to another 40 such cases of sprue-like enteropathy.
"We believe it is the tip of the iceberg," said Margot Herman, MD, at the GI meeting.
Symptoms of sprue-like enteropathy include severe, chronic diarrhea with substantial weight loss.
The 22 initial patients reported by the Mayo Clinic were on average 69 years old and had a duration of diarrheal illness for an average of 19 months.
When they discontinued the drug, they gained an average of 27 pounds.
The FDA said it approved the warning on the drug's label after it evaluated its Adverse Event Reporting System, published literature case series, information from the Mini-Sentinel pilot of the Sentinel Initiative, and information from the CMS Medicare database.
"The FDA's evaluation found clear evidence of an association between olmesartan and sprue-like enteropathy," the agency reported in a statement.
The FDA identified 23 serious cases in the Adverse Event Reporting System presenting as late-onset diarrhea with significant weight loss and, in some cases, with intestinal villous atrophy on biopsy.
All patients improved clinically after discontinuation of olmesartan, and a positive rechallenge was seen in 10 of the cases.
The enteropathy may develop months to years after starting olmesartan, and sometimes requires hospitalization.
In May 2013, an article describing patients with villous atrophy and negative serologies for celiac disease reported that some patients without definitive etiologies for villous atrophy were characterized as having unclassified sprue. Some of these patients were later found to have villous atrophy associated with olmesartan use. (Am J Gastroenterol 2013; 108: 647-653).
Olmesartan, made by Daiichi Sankyo, was approved in 2002 for the treatment of high blood pressure, alone or with other antihypertensive agents, and is one of eight marketed ARB drugs.
Sprue-like enteropathy has not been detected with ARB drugs other than olmesartan," according to the FDA.
"Although the mechanism for olmesartan-associated sprue-like enteropathy is uncertain, the long latency before onset of symptoms, findings of lymphocytic or collagenous colitis, and high association with HLA-DQ2/8 suggest a localized delayed hypersensitivity or cell-mediated immune response to the pro-drug olmesartan medoxomil," according to the FDA statement."