In this section, we will talk about the prescribing information of Benicar (Olmesartan medoximil), as well as the side effects, dosage and indications when it’s used alone or in combination with other medications. This drug indicated for the treatment of hypertension. Pertaining to a category of medications known as “sartans”, olmesartan is an Angiotensin II Receptor Blocker (ARB) that acts by preventing excessive vasoconstriction that could lead to high blood pressure. This drug is often used in association with other medications such as Hydrochlorothiazide and Amlodipine (1, 2). Benicar has been developed by Daiichi Sankyo and is the newest ARB in the market since it received FDA approval in 2002.
Benicar Mechanism of Action
Olmesartan blocks the interaction between a hormone called Angiotensin II and its receptor AT1. Angiotensin II is the principal polypeptide involved in the renin-angiotensin-aldosterone system (RAAS), a hormone system that plays a critical role in the regulation of blood pressure and fluid balance. Activation of the AT1 receptors by Angiotensin II causes vascular constriction, while the prevention of this hormonal binding causes vasodilation and release of another hormone called aldosterone. This combined action reduces peripheral vascular resistance, leading to a generalized reduction of blood pressure that explains Benicar antihypertensive effect (3, 4).
Benicar Indications and Use
Sartans are often recommended as first-line therapy for hypertension to lower and control high blood pressure. They are used as a primary alternative to the most known category of antihypertensive medications, the ACE inhibitors, in patients who are intolerant to their adverse reactions. Benicar side effects do not include, in fact, the persistent coughing and angioedema that often prevents patients from using ACE inhibitors (5).
Just like many other antihypertensive medications, olmesartan and the other ARBs aren’t just used for short-term treatment of symptoms. Instead, they are used as a lifelong treatment to reduce the risk of fatal and nonfatal cardiovascular events. Although it is reasonable to say that this drug may be as effective as the other ones in its class, no controlled trials demonstrated a risk reduction in cardiovascular accidents in patients taking this specific drug. Nonetheless, Benicar received its approval from the US Food and Drugs Administration (FDA) after a very short 3-months long clinical trial that didn’t evaluate possible long-term risks associated with this drug (2).
Benicar Dangers and Side Effects
Although other ARBs are often used to treat congestive heart failure, Benicar never received approval from FDA for this indication. A recent study published in the European Heart Journal led by the Japanese Dr. Yasuhiko Sakata, found that treatment with olmesartan in combination with ACE inhibitors and β-blockers was associated with increased adverse cardiac events including strokes, myocardial infarction and longer hospitalization (6).
Other studies showed an association between Benicar and an increased cardiovascular mortality in diabetic patients. However, after the FDA issued an investigation panel to review the data coming from several clinical trials, they determined that the drug is still safe to use in diabetic subjects (7, 8, 9). The most commonly reported Benicar side effects are dizziness, upper respiratory tract infections, hyperuricemia, and nausea.
However, what makes Benicar stand out among the other ARBs is one unexpectedly dangerous side effect that led many people to file Benicar lawsuits, asking Daiichi Sankyo to compensate them for the injuries they sustained. This drug’s adverse reactions include a dangerous sprue-like enteropathy characterized by severe diarrhea and malabsorption. Patients who suffered from this unique diarrhea type reported a weight loss of about 20-40 kilograms, with consequent symptoms such as malnutrition (10, 11, 12). In 2014, a large retrospective study found that 22% of previously unclassified intestinal disorders that showed significant similarities with Celiac Disease, were indeed cases of Benicar sprue-like enteropathy (13).
Olmesartan can be used in therapy as a single agent or in combination with other drugs (1). Benicar is the single-agent version that contains just Olmesartan. A prodrug that requires metabolization inside the gastrointestinal tract, Benicar can be taken with or without food, and comes in three different dosages:
- Benicar (Olmesartan medoximil) 5 mg
- Benicar (Olmesartan medoximil) 20 mg
- Benicar (Olmesartan medoximil) 40 mg
Benicar HCT is a combination of Olmesartan with a Hydrochlorothiazide (HCTZ), a thiazide diuretic. Benicar HCT is an FDA Pregnancy Category D, and should never be used during pregnancy as it could be associated with fetal toxicity (14). Benicar HCT comes in three different dosages:
- Benicar HCT (Olmesartan medoximil + Hydrochlorothiazide) 20 mg/12.5 mg
- Benicar HCT (Olmesartan medoximil + Hydrochlorothiazide) 40 mg/12.5 mg
- Benicar HCT (Olmesartan medoximil + Hydrochlorothiazide) 40 mg/25 mg
Azor is a combination of Olmesartan with Amlodipine, a dihydropyridine calcium receptor blocker (CRB). Azor is indicated for all those patients who need a combination therapy with multiple antihypertensive agents to reach their blood pressure goals (15). Azor comes in four different dosages:
- Azor (Amlodipine + Olmesartan medoximil) 5/20 mg
- Azor (Amlodipine + Olmesartan medoximil) 10/20 mg
- Azor (Amlodipine + Olmesartan medoximil) 5/40 mg
- Azor (Amlodipine + Olmesartan medoximil) 10/40 mg
Tribenzor is a combination of all three drugs (Olmesartan, Amlodipine and Hydrochlorothiazide) in a single tablet. Tribenzor is indicated for all those patients who cannot obtain adequate pressure control by using two antihypertensive agents at their maximally tolerated dose. Tribenzor comes in five different dosages:
- Tribenzor (Olmesartan medoximil + Amlodipine + Hydrochlorothiazide) 20/5/12.5 mg
- Tribenzor (Olmesartan medoximil + Amlodipine + Hydrochlorothiazide) 40/5/12.5 mg
- Tribenzor (Olmesartan medoximil + Amlodipine + Hydrochlorothiazide) 40/5/25 mg
- Tribenzor (Olmesartan medoximil + Amlodipine + Hydrochlorothiazide) 40/10/12.5 mg
- Tribenzor (Olmesartan medoximil + Amlodipine + Hydrochlorothiazide) 40/10/25 mg
Article written by: Dr. Claudio Butticè, Pharm.D.
- Full Prescribing Information. (Accessed January 2016).
- U.S. Food and Drugs Administration (FDA). Olmesartan (marketed as Benicar) Information. (Accessed January 2016).
- Van Zwieten PA. Angiotensin II receptor antagonists (AT1-blockers, ARBs, sartans): similarities and differences. Netherlands Heart Journal. 2006;14(11):381-387.
- Izzo JL Jr, Neutel JM, Silfani T, Dubiel R, Walker F. Efficacy and safety of treating stage 2 systolic hypertension with olmesartan and olmesartan/HCTZ: results of an open-label titration study. J Clin Hypertens (Greenwich). 2007;9;36-44
- James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427.
- Yasuhiko Sakata, Nobuyuki Shiba, et al. Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial. European Heart Journal Apr 2015, 36 (15) 915-923; DOI: 10.1093/eurheartj/ehu504
- Haller H, Ito S, Izzo JL, et al. Olmesartan for the delay or prevention of microalbuminuria in Type 2 Diabetes. N Engl J Med 2011; 364: 907-17.
- Imai E, Chan JC, Ito S, et al. Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia 2011; 54: 2978-86.
- Zhou EH, Gelperin K, Levenson MS, et al. Risk of acute myocardial infarction, stroke, or death in patients initiating olmesartan or other angiotensin receptor blockers – a cohort study using the Clinical Practice Research Datalink. Pharmacepidemiol Drug Saf 2014; 23: 340-7.
- Rubio-Tapia A, Herman ML, Ludvigsson JF, et al. Severe spruelike enteropathy associated with olmesartan. Mayo Clin Proc 2012;87:732-8.
- DeGaetani M, Tennyson CA, Lebwohl B, et al. Villous atrophy and negative celiac serology: A diagnostic and therapeutic dilemma. Am J Gastroenterol 2013;108:647-53.