Benicar - Drug Monograph

Introduction

Benicar (olmesartan medoxomil) is an angiotensin II receptor blocker (ARB) approved by the FDA in 2002 for the treatment of hypertension. It works by selectively blocking the binding of angiotensin II to the AT1 receptor, resulting in vasodilation and reduced blood pressure. Benicar is available as oral tablets and is typically used as monotherapy or in combination with other antihypertensive agents.

Mechanism of Action

Olmesartan medoxomil is a prodrug that undergoes rapid hydrolysis to its active form, olmesartan, during absorption from the gastrointestinal tract. Olmesartan selectively blocks the binding of angiotensin II to the AT1 receptor found in vascular smooth muscle and the adrenal gland. This blockade inhibits angiotensin II-induced vasoconstriction and aldosterone secretion, resulting in decreased systemic vascular resistance and blood pressure reduction without affecting heart rate.

Indications

• Treatment of hypertension, alone or in combination with other antihypertensive agents
• Not indicated for heart failure or diabetic nephropathy (unlike some other ARBs)

Dosage and Administration

• Initial dose: 20 mg once daily
• Maintenance dose: 20-40 mg once daily
• Maximum dose: 40 mg daily

• Renal impairment: No initial dosage adjustment necessary
• Hepatic impairment: Consider starting with lower dose (10 mg)
• Geriatric patients: No dosage adjustment required
• Pediatric patients (6-16 years): Weight-based dosing (starting dose: 20 mg for ≥35 kg, 10 mg for <35 kg)

• Can be taken with or without food
• Tablets should be swallowed whole with water

Pharmacokinetics

• Bioavailability: ~26%
• Peak plasma concentration: 1-2 hours
• Food does not significantly affect absorption

• Protein binding: >99%
• Volume of distribution: 17 L

• Undergoes minimal hepatic metabolism via conjugation
• No significant cytochrome P450 metabolism

• Half-life: 10-15 hours
• Excretion: Primarily fecal (50-65%) and renal (35-50%)
• Not removed by hemodialysis

Contraindications

• Hypersensitivity to olmesartan or any component of the formulation
• Concomitant use with aliskiren in patients with diabetes
• Pregnancy (second and third trimesters)

Warnings and Precautions

• Use in pregnancy: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus when used during second and third trimesters

• Sprue-like enteropathy: Cases of severe, chronic diarrhea with substantial weight loss have been reported
• Hypotension: May occur in volume-depleted patients
• Impaired renal function: Monitor renal function in patients with renal artery stenosis
• Hyperkalemia: May occur, particularly in patients with renal impairment or diabetes
• Hepatic impairment: Use with caution in patients with biliary obstruction

Drug Interactions

• NSAIDs: May reduce antihypertensive effect and increase risk of renal impairment
• Lithium: Increased lithium concentrations and toxicity
• Potassium-sparing diuretics/potassium supplements: Increased risk of hyperkalemia
• ACE inhibitors/aliskiren: Increased risk of hyperkalemia, hypotension, and renal impairment
• Colesevelam: May decrease olmesartan absorption (administer at least 4 hours apart)

Adverse Effects

• Dizziness (3%)
• Headache (2%)
• Upper respiratory infection (2%)
• Influenza-like symptoms (2%)
• Diarrhea (2%)

• Sprue-like enteropathy (may present with severe, chronic diarrhea and weight loss)
• Acute renal failure
• Hyperkalemia
• Hypotension
• Angioedema (rare compared to ACE inhibitors)
• Elevated liver enzymes

Monitoring Parameters

• Blood pressure: Regular monitoring, especially after initiation or dosage changes
• Renal function: Serum creatinine and BUN at baseline and periodically
• Electrolytes: Serum potassium, particularly in patients at risk for hyperkalemia
• Signs/symptoms of enteropathy: Chronic diarrhea, weight loss, abdominal pain
• Hepatic function: In patients with pre-existing liver disease
• Pregnancy test: In women of childbearing potential

Patient Education

• Take medication exactly as prescribed at the same time each day
• Do not stop taking abruptly without consulting your healthcare provider
• Report any signs of pregnancy immediately
• Notify your doctor if you experience severe or chronic diarrhea, weight loss, or abdominal pain
• Rise slowly from sitting or lying position to prevent dizziness
• Avoid potassium supplements or salt substitutes without medical supervision
• Inform all healthcare providers about all medications you're taking
• Regular blood pressure monitoring is important
• Report any swelling of face, lips, or difficulty breathing immediately

References

1. FDA Prescribing Information: Benicar (olmesartan medoxomil) tablets. Revised 2020. 2. Chrysant SG, Weber MA, Wang AC, et al. Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide. Am J Hypertens. 2004;17(3):252-259. 3. Brunner HR. Olmesartan medoxomil: current status of its use in monotherapy. Vasc Health Risk Manag. 2006;2(4):327-340. 4. Rubenstein JH, et al. Olmesartan drugs and severe sprue-like enteropathy: a population-based case-control study. Aliment Pharmacol Ther. 2014;40(3):277-284. 5. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JNC 8 Guidelines for the Management of High Blood Pressure in Adults. JAMA. 2014;311(5):507-520.