The Initial Discovery: Linking Olmesartan to Sprue-Like Enteropathy
Olmesartan, an angiotensin II receptor blocker (ARB), was a widely prescribed medication for high blood pressure. While effective at its intended purpose, reports began to emerge in the late 2000s and early 2010s linking the drug to a peculiar and severe gastrointestinal illness.
Medical reports submitted to the FDA's Adverse Event Reporting System (FAERS) and published research, most notably from the Mayo Clinic in 2012, detailed cases of patients suffering from a condition later termed 'sprue-like enteropathy'. These patients presented with severe, chronic diarrhea and significant, unintentional weight loss. Crucially, intestinal biopsies showed damage to the intestinal villi (tiny, finger-like projections that absorb nutrients), a condition called villous atrophy, but blood tests for celiac disease were negative. Many patients had been taking olmesartan for months to years, which is a characteristic of this delayed-onset reaction.
The key finding was that patients' symptoms dramatically improved or disappeared entirely upon discontinuing olmesartan, sometimes within a few weeks. In some cases, symptoms returned upon re-exposure to the drug, confirming the link. This led researchers and the FDA to conclude that olmesartan was the cause, differentiating it from celiac disease, which would not resolve without a gluten-free diet.
Regulatory Action and Legal Fallout
The accumulated evidence and case reports prompted the U.S. Food and Drug Administration (FDA) to take action. In July 2013, the FDA issued an official Drug Safety Communication warning about the intestinal problems linked to olmesartan and required label changes for all products containing the drug, including Benicar, Benicar HCT, Azor, and Tribenzor.
This FDA warning provided concrete evidence that became central to thousands of lawsuits filed against the manufacturer, Daiichi Sankyo. Patients alleged that the company failed to adequately warn them and the medical community about the severe gastrointestinal risks associated with the medication. In 2017, Daiichi Sankyo agreed to a substantial settlement to resolve over 2,300 lawsuits, further underscoring the severity of the issue and the financial burden it imposed on the manufacturer. Ultimately, the commercial viability of olmesartan was severely compromised by these safety concerns and litigation, leading the company to remove the products from the market.
How is Olmesartan-Associated Enteropathy Different from Celiac Disease?
While sharing similar symptoms like severe diarrhea, weight loss, and villous atrophy, olmesartan-associated enteropathy (OAE) has key distinguishing features:
- Negative Celiac Serology: Patients with OAE test negative for the antibodies associated with celiac disease, such as tissue transglutaminase.
- No Response to Gluten-Free Diet: Unlike celiac disease, patients with OAE do not improve with a gluten-free diet. Symptoms only resolve with the discontinuation of olmesartan.
- Drug-Induced Cause: OAE is directly caused by a reaction to the medication itself, whereas celiac disease is an autoimmune reaction to gluten.
Alternative Blood Pressure Medications
With olmesartan and its combination products removed from the market, healthcare providers switched patients to alternative blood pressure treatments. The risk of sprue-like enteropathy is a known issue only with olmesartan among the ARB class, making other ARBs a safe and effective replacement.
Comparison of ARBs Regarding Sprue-Like Enteropathy Risk
| Medication (Examples) | Class | Risk of Sprue-Like Enteropathy | Status |
|---|---|---|---|
| Olmesartan (Benicar) | Angiotensin II Receptor Blocker (ARB) | High | Discontinued |
| Losartan (Cozaar) | Angiotensin II Receptor Blocker (ARB) | No documented risk | Marketed |
| Valsartan (Diovan) | Angiotensin II Receptor Blocker (ARB) | No documented risk | Marketed |
| Candesartan (Atacand) | Angiotensin II Receptor Blocker (ARB) | No documented risk | Marketed |
| Lisinopril (Zestril) | Angiotensin-Converting Enzyme (ACE) Inhibitor | No documented risk | Marketed |
Other alternatives for high blood pressure include different drug classes, such as ACE inhibitors like lisinopril, calcium channel blockers like amlodipine, and diuretics. A healthcare provider will determine the most suitable alternative based on a patient's specific health profile.
Discontinuation of Olmesartan: Guidance for Patients
For patients who were taking olmesartan and need to stop, abrupt discontinuation is not recommended. Suddenly stopping a blood pressure medication can lead to a dangerous spike in blood pressure, increasing the risk of a heart attack or stroke. It is crucial to consult with a healthcare provider to transition safely to an alternative treatment.
The FDA's 2013 safety communication remains a key resource for understanding this issue. The FDA Drug Safety Communication advises patients to contact their doctors if they experience severe, chronic diarrhea with substantial weight loss while on olmesartan.
Conclusion: A Precautionary Measure for Public Safety
In conclusion, why was olmesartan discontinued? The answer is a direct consequence of the drug's association with sprue-like enteropathy, a severe, chronic intestinal disorder. Following significant research, adverse event reporting, an FDA warning, and subsequent legal battles, the manufacturer made the decision to cease production. The availability of safe and effective alternative medications within the same drug class (ARBs) meant that discontinuing olmesartan was a feasible and responsible course of action to protect patient safety. For patients who were on olmesartan, transitioning to an alternative under the guidance of a healthcare professional is the correct and necessary step to manage their blood pressure without the risk of this serious side effect.
