Olmesartan - Drug Monograph

Introduction

Olmesartan medoxomil is an angiotensin II receptor blocker (ARB) used primarily in the management of hypertension. As a selective AT1 receptor antagonist, it represents a cornerstone therapy in cardiovascular medicine with well-established efficacy and safety profiles. First approved by the FDA in 2002, olmesartan has become an important option in the antihypertensive armamentarium.

Mechanism of Action

Olmesartan selectively blocks the binding of angiotensin II to the AT1 receptor found in vascular smooth muscle, adrenal cortex, and other tissues. By inhibiting angiotensin II-mediated vasoconstriction, aldosterone secretion, and sympathetic nervous system activation, olmesartan produces potent vasodilation, reduced peripheral resistance, and decreased blood pressure. Unlike ACE inhibitors, olmesartan does not affect bradykinin metabolism, which may contribute to its different side effect profile.

Indications

• Hypertension: First-line treatment for essential hypertension, either as monotherapy or in combination with other antihypertensive agents
• Off-label uses may include:

- Heart failure with reduced ejection fraction (as an alternative to other ARBs) - Diabetic nephropathy protection in patients with type 2 diabetes

Dosage and Administration

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

• Renal impairment: No initial dosage adjustment necessary, but monitor closely
• Hepatic impairment: Consider lower starting dose (10 mg) in moderate to severe impairment
• Geriatric patients: No dosage adjustment required based on age alone
• Pediatric patients: Not recommended for children under 6 years; 6-16 years: 20-35 kg: 10 mg daily, >35 kg: 20 mg daily

Pharmacokinetics

• Absorption: Rapidly converted to active olmesartan during absorption; bioavailability approximately 26%
• Distribution: Volume of distribution ~17 L; 99% protein-bound
• Metabolism: Undergoes minimal hepatic metabolism via esterase-mediated hydrolysis
• Elimination: Primarily excreted unchanged in feces (50-65%) and urine (35-50%); terminal elimination half-life ~13 hours
• Onset of action: 1-2 hours; peak effect at 6-8 hours; duration ~24 hours

Contraindications

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

Warnings and Precautions

• Pregnancy: Category D in second and third trimesters; can cause fetal injury or death
• Hypotension: May occur in volume-depleted patients or those on diuretics
• Renal function: May cause acute renal failure in susceptible patients
• Hyperkalemia: May occur, particularly in patients with renal impairment or diabetes
• Sprue-like enteropathy: Rare but serious gastrointestinal condition reported with long-term use
• Hepatic impairment: Use with caution in patients with severe hepatic dysfunction

Drug Interactions

• Potassium-sparing diuretics/potassium supplements: Increased risk of hyperkalemia
• NSAIDs: May reduce antihypertensive effect and increase renal risk
• Lithium: Increased lithium concentrations possible
• ACE inhibitors: Increased risk of hyperkalemia, hypotension, and renal impairment
• Aliskiren: Contraindicated in patients with diabetes

Adverse Effects

• Dizziness (3%)
• Headache (2%)
• Fatigue (1%)
• Diarrhea (1%)
• Upper respiratory infection (1%)

• Angioedema (rare)
• Acute renal failure
• Severe hypotension
• Hyperkalemia
• Sprue-like enteropathy (rare but serious)
• Rhabdomyolysis (rare)

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 at baseline and periodically
• Pregnancy testing: In women of childbearing potential
• Signs/symptoms of enteropathy: Chronic diarrhea with weight loss
• Hepatic function: In patients with pre-existing liver disease

Patient Education

• Take medication at the same time each day, with or without food
• Do not discontinue abruptly without medical supervision
• Report any signs of pregnancy immediately to healthcare provider
• Notify physician if experiencing dizziness, lightheadedness, or fainting
• Report persistent diarrhea or unexplained weight loss
• Avoid potassium supplements or salt substitutes without medical advice
• Regular blood pressure monitoring is essential
• Inform all healthcare providers about olmesartan use before any procedures

References

1. FDA Prescribing Information: Benicar (olmesartan medoxomil) 2. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018;71(19):e127-e248. 3. Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet. 2000;355(9204):637-645. 4. Rubio-Tapia A, Herman ML, Ludvigsson JF, et al. Severe spruelike enteropathy associated with olmesartan. Mayo Clin Proc. 2012;87(8):732-738. 5. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104. 6. Drugdex® Drug Evaluations: Olmesartan. Micromedex Solutions. Truven Health Analytics.