Benicar, also known as olmesartan medoxomil, is a blood pressure medication used to treat hypertension. The drug helps to prevent high blood pressure complications, such as cardiac disease, heart failure, and stroke.
Manufactured by Japanese pharmaceutical company, Daiichi Sankyo, and American drug corporation, Forest Laboratories, Benicar is prescribed to more than 11 million people each year. Despite its popularity, the drug comes with a number of serious gastrointestinal side effects that could lead to hospitalization.
Studies + Science
Benicar treats high blood pressure, a long-term illness that may require multiple medications. High blood pressure affects 1 in 3 Americans, according to the Centers for Disease Control and Prevention.
The medication comes in 5 mg, 20 mg, and 40 mg doses. Benicar medications are available in four combinations, including:
(amlodipine and olmesartan medoxomil)
(olmesartan medoxomil, amlodipine, hydrochlorothiazide)
How Benicar Works
Benicar treats hypertension, also known as high blood pressure. Hypertension is defined as blood pressure above 140/90, but is severe if the pressure is above 180/120.
Benicar is an angiotensin II receptor blocker that targets the cardiovascular system. Benicar works to block the protein angiotensin II, which increases blood pressure by squeezing blood vessels and stressing the heart. The drug works by dilating blood vessels to keep them open, effectively lowering blood pressure.
Side Effects of Celiac | Benicar side effects are often misdiagnosed as celiac disease.
According to the Mayo Clinic, symptoms of celiac disease include:
- Pain in the abdomen or joints
- Gastrointestinal issues, such as belching, diarrhea, fat in stool, heartburn, indigestion, nausea, vomiting, or flatulence
- Bone loss, fatigue, or malnutrition
- Delayed development, puberty, or slowed growth
- Cramping, itching, lactose intolerance, skin rash, or weight loss
However, once celiac is ruled out, symptoms will be referred to as sprue-like enteropathy, or villous atrophy. When Benicar damages the intestine, the body is no longer able to absorb nutrients. Individuals who take Benicar may experience such side effects as:
- Chronic diarrhea
- Weight loss
- Intestinal issues
Additional Benicar side effects include:
- Chest pain
- Abdominal pain
- Hair loss
- Irregular heartbeat
- Liver impairment
- Kidney issues
In The Data
A study published in the National Library of Medicine illustrated that Benicar may cause drug-induced enteropathy, which can develop months to years after the therapy begins. The more severe Benicar side effects can lead to hospitalization.
Case Study 1
A patient arriving from another facility after a stay of 15 days had experienced up to five episodes of bilious emesis and five to 10 episodes of large, watery stools each day. Her medical history included hypertension and gastroesophageal reflux disease (GERD), for which she was taking olmesartan, amlodipine (e.g., Norvasc), bisoprolol (e.g., Zebeta, Duramed/Barr), hydrochlorothiazide, and omeprazole (Prilosec, AstraZeneca).
She was given a trial of empirical antibiotics, but her symptoms did not resolve. Studies to detect infected stool and colonoscopy were negative. Total parental nutrition, which had been initiated at a previous facility, was continued. Endoscopic biopsy revealed sprue-like enteropathy with diffuse villous blunting, crypt hyperplasia, and an increase in intraepithelial lymphocytes. Olmesartan had been withheld during her hospitalization because it was not on the formulary. While she was awaiting IgA tTGA testing, her symptoms began to improve. Additional test results were negative for the HLA DQ2/8 gene associated with celiac disease.
The patient continued to improve. By the day 6, she was tolerating oral intake and ready for discharge by hospital day 7. Two weeks after discharge, although enteroscopy was not performed, the patient reported complete resolution of symptoms and olmesartan had not been reinitiated.
Case Study 2
A middle-aged man presented to our hospital with diarrhea and a weight loss of more than 4 kg (10 pounds). He was admitted for an evaluation of celiac disease because he was experiencing numerous episodes of watery, nonbloody diarrhea several times a day. He denied any other symptoms of infection, recent travel, ill contacts, or change in diet or medications.
The patient’s medical history included hypertension. Recent colonoscopy results did not show evidence of microscopic colitis or inflammatory bowel disease. He was taking olmesartan 40 mg daily for hypertension.
Dehydration developed as a result of the diarrhea, and his serum creatinine level rose to 1.7 mg/dL. No medications were used to control his diarrhea during hospitalization; however, olmesartan was discontinued.
Esophagogastroduodenoscopy revealed villous blunting and atrophy, with increased intraepithelial lymphocytes. Abdominal and pelvic computed tomography did not suggest a pancreatic abnormality or malignancy. An IgA tTGA level and HLA-DQ2 genetic testing were performed in order to confirm a diagnosis of celiac disease.
Upon a later review, all of his serologic markers were negative. No clear cause of his diarrhea was established. On hospital day 3 (i.e., 2 days after olmesartan was discontinued), his GI symptoms continued to improve. Testing was continued to determine a cause of the diarrhea. Within 2 days, the patient’s symptoms completely resolved.
Case Study 3
A 71-year-old woman presented with watery diarrhea, nighttime fecal incontinence, and abdominal pain, along with a weight loss of 27 kg over a period of 5 years. Duodenal biopsies showed villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. She did not respond to a gluten-free diet. Numerous GI tests showed an inflamed and edematous bowel. Capsule endoscopy revealed villous atrophy along 75% to 90% of the small intestinal mucosa.
The patient received a 10-day course of tetracycline for bacterial overgrowth in the small intestine without resolution of symptoms. Follow-up biopsy results at 1 and 2.5 years were unchanged. It was recommended that she stop taking valsartan (Diovan). Within days, the diarrhea, bloating, and abdominal pain resolved. A year later, the villous architecture had normalized. There was no rechallenge; however, drug-induced sprue-like enteropathy, similar to that reported with olmesartan, was suspected to be the cause.
“An association between olmesartan and sprue-like enteropathy has been observed in several case series and reports. Patients 57 to 81 years of age, irrespective of gender, have experienced weight loss of up to 40 kg while taking this drug,” researchers concluded.
A portion of the study data came from Mayo Clinic, which discovered the gastrointestinal side effects linked to Benicar by analyzing data from 2008 and 2011. Researchers examined 22 patients who seemed to be suffering from Celiac disease, but the testing showed that they were not, in fact, afflicted with this particular disease.
“Although the mechanism precipitating this adverse effect remains uncertain, it is essential to consider olmesartan-associated enteropathy in patients with biopsy-proven villous atrophy when no other cause can be found.”
The Food and Drug Administration (FDA) approved Benicar on April 25, 2002. The drug has since been prescribed to millions of Americans, existing on the market for more than a decade.
In 2012, doctors wrote an estimated 10.6 million prescriptions for olmesartan. Nearly 2 million patients filled prescriptions for the single or the combination product from community pharmacies in the U.S., according to researchers.
Cases of olmesartan-induced sprue-like enteropathy have been reported only since 2012, leaving the drug on the market for more than 10 years without a clear association to gastrointestinal side effects.
2014 FDA Safety Communication
In 2014, the FDA released a safety communication stating that there was not sufficient evidence to link Benicar to cardiovascular problems in diabetic problems. The FDA stated, “As a result, our recommendations for use of olmesartan (Benicar, Benicar HCT, Azor, Tribenzor, and generics) will remain the same, but we will require information about some of the studies to be included in the drug labels.”
2017 Drug Update
In 2017, the FDA updated their previous safety communication regarding the connection between Benicar and diabetic heart issues stating:
“The ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) clinical trial examined the effects of olmesartan in patients with type 2 diabetes, to see whether olmesartan could delay kidney damage. There was an unexpected finding of increased risk of cardiovascular death in the olmesartan group compared to the group taking a placebo, or sugar pill. However, the risk of non-fatal heart attack was lower in the olmesartan-treated patients.”
Despite these indications, the FDA pulled back from outright declaring Benicar as dangerous, instead noting, “While data from the ROADMAP trial and the Medicare study have suggested that high-dose olmesartan may increase cardiovascular risk in diabetic patients, when considering the data from all trials and studies, they are not conclusive.”
In conclusion, the FDA stated, “Do not stop taking olmesartan or any blood pressure medication without first discussing it with your health care professional.”
Black Box Warning
In March 2012, the FDA added a fetal toxicity warning to Benicar’s labeling. The Black Box warning is the agency’s most stringent safety notification, which illustrates that patients should use the drug with serious caution.
- 5.1 Fetal toxicity
Pregnancy Category D
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Benicar as soon as possible [see Use in specific Populations (8.1)].
- 5.2 Morbidity in Infants
Children <1 year of age must not receive Benicar for hypertension. Drugs that act directly on the renin-angiotensin aldosterone system (RAAS) can have effects on the development of immature kidneys [see Use in Specific Populations (8.4)].
The FDA classifies Benicar under pregnancy category D, representing serious potential to harm an unborn child. Pregnant women should not take Benicar and should immediately discontinue use if they become pregnant.
2013 + 2014 Updated Labeling
The research prompted the FDA to update the label to include development of villous atrophy as an adverse event in July 2013. The FDA released two safety announcements.
“Severe, chronic diarrhea with substantial weight loss has been reported in patients taking olmesartan months to years after drug initiation. Intestinal biopsies of patients often demonstrated villous atrophy,” according to the FDA.
In April 2014, the FDA updated Benicar’s warning label to inform consumers of a potential increased cardiovascular risk in diabetic patients.
The Next Steps
Individuals who have developed Benicar side effects have begun to speak out, working to inform others of the drug’s potential risks. According to legal documents, a patient by the name of George Williams developed Benicar side effects so severe they destroyed his gastrointestinal tract and he must gain nutrients through a feeding tube.
Treatment for Benicar side effects resulted in more than 100 days in the hospital, Williams became first of many individuals to pursue legal action against the manufacturers of Benicar.