The FDA approved Benicar (olmesartan medoxomil) in 2002 to treat high blood pressure (hypertension). It is manufactured and marketed by Japanese drug maker Daiichi Sankyo. Benicar can be used alone or in combination with other drugs to help lower a patient’s blood pressure by keeping blood vessels dilated (open).
Benicar is part of the angiotensin II receptor blocker (ARB) drug class. This class of drugs helps to lower blood pressure by blocking the hormone that tightens blood vessels. Blood pressure rises as vessels constrict. While it’s normal for blood pressure to rise and fall throughout the day, health problems can develop for individuals whose blood pressure remains high for a longer period of time.
For patients suffering from high blood pressure, taking a medication, such as Benicar, can reduce the risk of heart attack and stroke. High blood pressure usually has no accompanying symptoms, so many people are unaware that there’s even a problem. But high blood pressure left unchecked greatly increases a person’s risk for heart disease and stroke, the first and third leading causes of death in the United States, respectively.
Centers for Disease Control and Prevention (CDC) estimated that 75 million adults are dealing with high blood pressure in the United States. It affects approximately one in every three adults, or 29 percent of the overall American adult population. Only half of those individuals are controlling their condition. Seven in ten of those adults are controlling their blood pressure by using some sort of medication to treat it. These individuals are sometimes prescribed a medication such as Benicar, or one of its sister drugs containing the ingredient olmesartan.
But in 2013, over a decade following its approval, the FDA released a safety announcement warning the public that Benicar also has the potential to cause intestinal problems known as sprue-like enteropathy. Symptoms of sprue-like enteropathy are usually more commonly associated with celiac disease, an immune disorder that results in sensitivity to gluten and contributes to malabsorption and gastrointestinal (GI) problems. But drug-induced enteropathy is also a possibility, as is the case with olmesartan-induced enteropathy, resulting in severe, chronic diarrhea and substantial weight loss within months to years after beginning use of the medication.
What Does Benicar Treat?
Benicar is indicated for the treatment of hypertension (high blood pressure) and is used to lower blood pressure. Elevated blood pressure levels put an individual at a greater risk of experiencing heart attack and stroke.
Additional approved indications include:
- Heart failure
- Diabetic kidney disease
Who Does Not Benefit from Treatment?
Benicar can result in complications for fetuses, especially in the second and third trimesters, and some of these complications can be fatal. Also, the drug has not been tested on children under one year of age. Other individuals can experience
adverse reactions when taking Benicar.
Benicar is not recommended for the following groups of people:
- Pregnant women
- Nursing mothers
- Children under one year of age
- Patients with blood volume or salt depletion
- Patients with narrowing of arteries
Benicar Side Effects
Medications containing olmesartan, such as Benicar, and used to treat high blood pressure, do not come without risks. Benicar has been linked to health problems, including some severe side effects, such as sprue-like enteropathy (demonstrated in patients as severe, chronic diarrhea and substantial weight loss). Benicar can also result in fetal toxicity and is not recommended for women who are pregnant, especially in the second and third trimesters. The most common side effect in individuals taking Benicar is dizziness.
Common Side Effects
- Back pain
- Increase of creatinine phosphokinase (CPK)
- Blood in urine
- High blood sugar
- Elevated triglyceride levels (fat in the blood)
- Flu-like symptoms
- Inflammation of pharynx or back of throat
- Inflammation of mucous membrane inside the nose
Less Common Side Effects
- Chest pain
- Peripheral edema
- Abdominal pain
- diarrhea/abdominal pain
- Heart palpitations
- Very high levels of cholesterol in blood
- Abnormally high concentration of fats in blood
- Excess of uric acid in blood
- Joint pain
- Muscle pain
Rare Side Effects
- Facial swelling
- Swelling below the skin’s surface
- Small decreases in hemoglobin and hematocrit
- Infrequent elevations of liver enzymes and/or serum bilirubin
Post-Marketing (Voluntarily Reported) Side Effects
- Physical weakness/lack of energy
- Life-threatening allergic reaction
- High blood potassium
- Rapid destruction of skeletal muscle
- Acute kidney failure
- Increased blood creatinine levels
- Hair loss
- Severe itching of skin
Severe Gastrointestinal Side Effects
In 2013, the FDA issued a safety announcement that the blood pressure drug Benicar (olmesartan medoxomil), as well as similar drugs such as Benicar HCT, Azor, Tribenzor and generic versions, can cause severe intestinal complications with side effects collectively known as sprue-like enteropathy. Patients experiencing olmesartan-induced sprue-like enteropathy exhibit signs and symptoms similar to individuals suffering from celiac disease.
These signs and symptoms include:
- Severe, chronic diarrhea
- Substantial weight loss
- Abdominal pain
This condition can develop months or even years after the patient first starts taking Benicar or other medications containing olmesartan. In severe cases, patients can end up hospitalized and/or suffer from permanent intestinal damage, or villous atrophy (the destruction of intestinal villa that helps with the absorption of nutrients from food).
Black Box Warning – Fetal Toxicity
A black box warning appears on a prescription drug’s label when the FDA wants to call attention to serious or life-threatening risks associated with its use. Benicar (olmesartan medoxomil) contains one of these warnings for fetal toxicity advising that when pregnancy is detected, Benicar should be discontinued as soon as possible. It further warns that drugs that act directly on the physiological system that regulates blood pressure, such as Benicar, can cause injury and death to the developing fetus.
The prescribing information goes into more detail about the adverse reactions that can occur with the use of Benicar during pregnancy; specifically pointing out the greater risks associated with use during the second and third trimesters, which can result in the reduction of fetal renal function and increase in fetal and neonatal morbidity and death. The potential for a deficiency in amniotic fluid can result in fetal lung underdevelopment and skeletal deformations.
Potential neonatal adverse effects include:
- Skull underdevelopment
- Failure of kidneys to produce urine
- Low blood pressure
- Kidney failure
Benicar comes in tablet form in three different prescription strengths: 5 milligrams (yellow/round pill),20 milligrams (white/round pill),40 milligrams (white/oval). This drug can be taken with or without food, and it can also be administered with a diuretic and/or other antihypertensive medications.
Benicar comes in 5 mg (yellow/round pill), 20 mg (white/round pill),40 mg (white/oval) dosages.
Dosage Information for Adults
- Recommended starting dosage of 20 milligrams once daily
- Patients requiring further blood pressure reduction after two weeks of taking Benicar may increase the dose to 40 milligrams.
- Doses above 40 milligrams have not been shown to have any greater effect in patients.
- Twice-daily dosages do not appear to offer any advantage over the same total dose taken once daily.
Dosage Information for Children
- Dosing must be individualized
- Recommended starting dosage in children 6 to 16 years of age and weighing 44 to 77 pounds is 10 milligrams once daily
- Patients requiring a further reduction in blood pressure after two weeks of taking Benicar may increase the dose to a maximum of 20 milligrams once daily for those weighing under 77 pounds
- Patients requiring a further reduction in blood pressure after two weeks of taking Benicar may increase the dose to a maximum of 40 milligrams for those weighing over 77 pounds
- For children who cannot swallow pills, Benicar may be taken as a suspension.
Drug Interactions with Benicar
It is possible for Benicar to cause adverse reactions when taken concurrently with certain drugs (both prescription and nonprescription). These adverse reactions may include unfavorable side effects and/or lessened effectiveness of Benicar or the other drugs.
- Aliskiren (Brand Name – Tekturna): It is recommended that Benicar is not given in conjunction with aliskiren (antihypertensive drug) in patients with diabetes.
- NSAIDs (Selective COX-2 Inhibitors): Initial dose of 10 mg or 20 mg/day. After 1 week at 10 mg, increase to 20 mg.
- Dual Blockade of the Renin-Angiotensin System (RAS): Taking Benicar with other ARBs, ACE (angiotensin-converting enzyme) inhibitors (such as Captopril, Ramipril, Lisinopril, Quinapril and others) or aliskiren is associated with increased risks of low blood pressure, high potassium and changes in kidney function.
- Colesevelam Hydrochloride (Brand Name – Welchol): Taking colesevelam hydrochloride with Benicar reduces its effectiveness. It is recommended that olmesartan is taken at least four hours prior to taking a dose of colesevelam hydrochloride in order to decrease the effect of the drugs’ interaction.
Mayo Clinic Case Series Confirms Olmesartan-Induced Enteropathy
All 22 patients involved in a case series to determine the link between olmesartan and unexplained sprue-like enteropathy, were seen at the Mayo Clinic between August 2008 and August 2011. Olmesartan is an active ingredient in Benicar.
To be included in the study, patients had to first have chronic diarrhea (lasting more than four weeks) while taking olmesartan. Second, the cause of the enteropathy could not be explained by another disorder, such as celiac disease; and finally, discontinuing the drug had to result in clinical improvement.
Mayo Clinic’s 2012 Report
In 2012, Mayo Clinic researchers published a case series of sprue-like enteropathy associated with patients’ use of olmesartan.
- The 22 subjects involved in the series presented similar clinical results to individuals of 23 adverse event reports identified by the FDA through its FDA’s Adverse Event Report System (FAERS).
- Of the 22 patients from 17 states treated by the Mayo Clinic between the years of 2008 to 2011, 14 required hospitalization with weight losses averaging almost 40 pounds, and one patient losing a total of about 125 pounds.
- None of the patients responded to gluten free diets (used for celiac disease sufferers), but all of the patients shared one similarity; they were all taking daily doses of olmesartan ranging from 10 to 40 mg.
- When olmesartan was discontinued, the patients’ symptoms improved and they all experienced some degree of weight gain.
Mayo Clinic’s 2013 Report
In May of 2013, an article was published describing patients with villous atrophy and negative blood tests for celiac disease.
- The article reported that some patients without definitive causes for villous atrophy were categorized as having unclassified sprue.
- It was later discovered that some of these patients had villous atrophy associated with their use of olmesartan.
Olmesartan-induced enteropathy was further investigated and confirmed by Mini-Sentinel and CMS Medicare assessments, which showed that at a two-year minimum exposure to the ARB class of drugs, patients using olmesartan had a higher rate of subsequent celiac disease diagnoses than users of other ARBs.
FDA-Initiated Label Change and “Warning Letter” to Benicar Manufacturer
Although olmesartan-containing drugs such as Benicar had been on the market for over a decade, the FDA did not issue its safety announcement about the potential for occurrences of sprue-like enteropathy until 2013. This decision came following its evaluation of FAERS, the Mayo Clinic case series and information from the CMS database. The FDA also ordered the drug manufacturer to change its labeling on the blood pressure medication to include a warning about this.
In premarketing clinical trials, the incidence of adverse effects reported by Daiichi Sankyo related to olmesartan was similar to those of placebo, and the only negative effect linked directly to olmesartan with greater frequency than the placebo, as reported in the prescribing information, was dizziness. While millions of individuals have been prescribed olmesartan over the last several years, reports of severe gastrointestinal reactions associated with its use are claimed to not have surfaced until later in 2012.
In 2006, while not related to the gastrointestinal effects of olmesartan, the Department of Health & Human Services (DOH) submitted a “Warning Letter” to Sankyo Pharma Inc. through its Division of Drug Marketing, Advertising and Communications (DDMAC). The letter requested that Sankyo immediately cease its promotion of certain sales and marketing materials that contained unsubstantiated effectiveness and superiority claims, and omitted or minimalized information on the risks associated with the use of Benicar.
The omitted or minimalized risk information included:
- Serious pregnancy-related risks
- Renal artery stenosis (narrowing of arteries that carry blood to one or both of the kidneys) precautions
- Risk information regarding the use of Benicar HCT in patients with impaired liver function or systemic lupus erythematosus (the most common form of lupus characterized by extreme fatigue and joint pain)
- Lithium interactions