Benicar (olmesartan) is a dangerous medication used to treat blood pressure which has been associated with several serious side effects. Dozens of patients have been seriously injured after suffering the grievous consequences of this medication’s adverse reactions. Also known as Olmetec in Europe, this drug is often used in association with several others for the treatment of hypertension. These medications include: Hydrochlorothiazide (Benicar HCT), Amlodipine (Azor), or both (Tribenzor).

Benicar Mechanism of Action

Olmesartan prevents a hormone called Angiotensin II from interacting with its receptor AT1. Angiotensin II is responsible for regulating fluid balance and blood pressure by causing vascular constriction. This hormone acts within a physiological system known as the renin-angiotensin-aldosterone system (RAAS), but when this binding with its receptor is blocked, another hormone called aldosterone is released causing vasodilation. When peripheral vascular resistance is lowered, blood pressure is reduced, explaining Benicar’s antihypertensive action. This drug is prescribed to patients affected by hypertension. Included in a class of medications known as “sartans”, olmesartan is often used together with other medicines that increase its effects, such as Amlodipine and Hydrochlorothiazide. Benicar is the newest sartan approved in America, and it was developed by Daiichi Sankyo. The U.S. Food and Drug Administration (FDA) granted AstraZeneca approval to market olmesartan on April 25, 2002, but the drug was tested for less than three months before it was deemed safe for use in humans. No long-term clinical trials to assess its safety or effectivenes have ever been planned since then.

Gastrointestinal side effects: sprue-like enteropathy and diarrhea

In 2013, another study published in the American Journal of Gastroenterology found evidence of an association between olmesartan and an unclassified sprue-like enteropathy (a severe form of diarrhea). Thes gastrointestinal problem was so severe that some patients lost almost 60 kilograms and required hospitalization, negatively impacting their health and requiring several years to fully recover. Later that same year, the FDA issued an investigation panel to evaluate the medication’s safety and found convincing evidence that correlates this medication with sprue-like enteropathy after a 2-year minimum exposure. The short 3-months long clinical trial that granted approval to this medication was insufficient to adequately evaluate its risks. After one year, in 2014, Benicar’s label was changed to address this new risk, and patients were warned about a chance of suffering from serious intestinal problems. Almost immediately, the Italian counterpart of the American regulator, the Agenzia Italiana del Farmaco (AIFA), issued a closely-related warning about these dangers.

Olmesartan may damage the immune system

A large retrospective study published in 2014 in the Journal of Pharmacy Practice, reviewed the current Pubmed literature and found consistent evidence showing that olmesartan side effects accounted for 22% of previously unclassified sprue cases. Although a potential mechanism mediated by the inhibition of the TGF-β action on the intestine has been suggested, no final answer has yet been found. This mechanism is, in fact, common for all the other sartans, although olmesartan is the only one that causes gastrointestinal problems of this magnitude. Other mechanisms have been suggested, and research showed that Benicar could be responsible for an immuno-mediated response of the intestinal epithelial cells that leads to clinical effects which are very similar to those of gluten in the gut of a subject affected by celiac disease.

Benicar and cardiovascular death risk

Benicar dangers are not limited to just diarrhea and immune-mediated gastrointestinal disorders, though. This antihypertensive agent stands out among its counterparts for a long list of additional side effects, among which cardiovascular death risk is probably the most threatening one. During the last few years, several large clinical trials highlighted Benicar’s controversial role in increasing cardiovascular mortality in diabetic subjects taking high doses of this drug. The FDA issued a safety review after the results of the ROADMAP trial found an unexpected five-fold increase in the risk of cardiovascular death in patients with type 2 diabetes. Although another clinical trial, the ORIENT one also showed similar results, a wider review of other studies led the FDA regulators not to recommend against using this medication in diabetic patients. FDA announced that they found “no clear evidence of increased cardiovascular risks” associated with the use of olmesartan in diabetic patients. Although FDA’s final decision was in favor of this drug’s safety, the controversial results coming from the various studies still raise numerous concerns among doctors and patients.