Olmesartan

Generic Name: Olmesartan
Full Name: Olmesartan medoxomil
Brand Names: Benicar (US), Olmetec (UK, EU), Olmy, Olmax, Olsar, Vocado (with amlodipine), Sevikar (olmesartan + amlodipine + hydrochlorothiazide)
Drug Class: Angiotensin II Receptor Blocker (ARB)
Formulation: Oral tablets
Strengths Available: 5 mg, 10 mg, 20 mg, 40 mg
Route of Administration: Oral (by mouth)

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Therapeutic Indications and Approved Uses

Olmesartan is a selective AT1 receptor antagonist approved for managing high blood pressure (hypertension). It blocks the action of angiotensin II, a vasoconstrictor, helping to relax blood vessels and reduce blood pressure. By lowering blood pressure, olmesartan helps prevent heart attacks, strokes, kidney damage, and other cardiovascular complications.

Indications:

1. Essential Hypertension
   – Approved as monotherapy or in combination with other antihypertensives.
   – Can be used in adults and children ≥6 years (in some regions).

2. Hypertension with Left Ventricular Hypertrophy or Proteinuria (off-label):
   – Preferred in patients with diabetic nephropathy or renal protection needs.

3. Heart Failure (off-label):
   – May be used where ACE inhibitors are not tolerated.

4. Chronic Kidney Disease (CKD) (off-label):
   – Slows the progression of renal impairment in hypertensive patients with proteinuria.

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Mechanism of Action

Olmesartan is a prodrug, converted in the intestinal wall to olmesartan, its active metabolite. It selectively blocks angiotensin II type 1 (AT1) receptors, preventing angiotensin II from binding and exerting its vasoconstrictive and aldosterone-secreting effects.

Key pharmacological effects:

• Vasodilation (reduces systemic vascular resistance)

• Reduction in aldosterone levels (less sodium and water retention)

• Decreased sympathetic activity

• No significant effect on heart rate

• No bradykinin accumulation (unlike ACE inhibitors, so fewer cough and angioedema risks)

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Dosage and Administration

Adults (General Hypertension):

• Initial Dose: 20 mg once daily

• Maintenance Dose: 20–40 mg once daily

• Max Dose: 40 mg once daily

If blood pressure is not controlled by 20 mg, dose may be titrated to 40 mg after 2 weeks. May be used with diuretics, calcium channel blockers, or beta-blockers.

Pediatric Use (6–16 years):

• Weight <35 kg: 10 mg once daily (max 20 mg/day)

• Weight ≥35 kg: 20 mg once daily (max 40 mg/day)

Renal Impairment:

• No initial dose adjustment in mild to moderate renal impairment (CrCl ≥20 mL/min)

• Use with caution in severe impairment or end-stage renal disease

Hepatic Impairment:

• Use cautiously; no formal dose adjustment recommended but initiate at the lower end

Elderly Patients:

• No dose adjustment generally required; monitor renal function and BP

Administration Instructions:

• Taken once daily with or without food

• Consistency in time of administration improves effectiveness

• Do not crush or chew; swallow whole

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Pharmacokinetics

• Bioavailability: ~26% (as active form after conversion)

• Time to peak plasma concentration: ~1–2 hours

• Protein binding: ~99% (mainly albumin)

• Metabolism: Not metabolized by cytochrome P450 enzymes

• Elimination half-life: 13 hours

• Excretion:
  – Feces (50–60%)
  – Urine (35–40%)

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Contraindications

• Known hypersensitivity to olmesartan or any component of the formulation

• Pregnancy (especially second and third trimester) — may cause fetal toxicity

• Bilateral renal artery stenosis or severe hypotension

• Anuria (absence of urine production)

• Co-administration with aliskiren in patients with diabetes or renal impairment (eGFR <60 mL/min/1.73m²) is contraindicated

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Precautions and Warnings

1. Fetal Toxicity (Boxed Warning):
   – ARBs can cause fetal harm when used in pregnancy
   – Discontinue immediately upon detection of pregnancy

2. Hypotension:
   – Particularly in patients who are volume- or salt-depleted (e.g., those on diuretics or dialysis)
   – May need correction of volume status before starting

3. Hyperkalemia:
   – Monitor serum potassium, especially in elderly or those taking potassium-sparing diuretics, ACE inhibitors, or potassium supplements

4. Renal Function Impairment:
   – May worsen renal function in susceptible individuals
   – Monitor serum creatinine and eGFR periodically

5. Sprue-like Enteropathy:
   – Rare but serious chronic diarrhea with weight loss (resembles celiac disease)
   – Usually resolves upon discontinuation

6. Aortic Stenosis or Hypertrophic Cardiomyopathy:
   – Use with caution in patients with outflow tract obstruction

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Adverse Effects

Common (≥1%):

• Dizziness

• Headache

• Fatigue

• Back pain

• Nausea

• Upper respiratory tract infection

• Diarrhea

• Hyperuricemia

• Hematuria

Serious/Rare:

• Hypotension

• Hyperkalemia

• Acute kidney injury

• Angioedema (rare)

• Sprue-like enteropathy (chronic severe diarrhea)

• Hepatic enzyme elevation

• Rhabdomyolysis (rare)

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Drug Interactions

1. Potassium supplements, potassium-sparing diuretics (e.g., spironolactone):
   – Increased risk of hyperkalemia
   – Monitor potassium regularly

2. NSAIDs:
   – May reduce antihypertensive effect
   – Risk of renal impairment and hyperkalemia increases with concomitant use

3. Lithium:
   – Increased risk of lithium toxicity; monitor levels

4. Diuretics (esp. loop and thiazide):
   – Volume depletion may enhance risk of hypotension on initiation
   – Often used together for additive BP control

5. Other antihypertensives:
   – Additive effects on lowering BP
   – Beneficial for combination therapy (e.g., with amlodipine)

6. Aliskiren:
   – Contraindicated in diabetic patients or those with renal impairment due to risk of renal dysfunction, hypotension, and hyperkalemia

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Monitoring Parameters

• Blood pressure (monitor regularly)

• Renal function (serum creatinine, BUN, eGFR at baseline and periodically)

• Serum potassium (especially in those on diuretics or potassium supplements)

• Watch for symptoms of sprue-like enteropathy (chronic diarrhea, weight loss)

• Signs of hypotension or syncope during dose initiation or titration

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Patient Counseling Information

• Take at the same time every day

• Can be taken with or without food

• Do not use salt substitutes containing potassium unless directed

• Report persistent diarrhea, dizziness, or signs of swelling

• Avoid during pregnancy—inform your doctor if you become pregnant

• Do not stop abruptly without consulting your doctor

• Monitor blood pressure regularly at home if advised

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Comparative Overview vs. Other ARBs

ARB	Half-life (hrs)	Onset (hrs)	Dosing	Sprue-like Enteropathy Risk	Clopidogrel Interaction
Olmesartan	13	~1–2	Once daily	Yes (rare but reported)	No known interaction
Losartan	2 (active metabolite ~6–9)	~1	Once or twice daily	No	Possible (mild)
Valsartan	6	~2	Once or twice daily	No	Minimal
Telmisartan	24	~1	Once daily	No	None
Irbesartan	11–15	~2	Once daily	No	None

Storage and Handling

• Store at room temperature (15–30°C)

• Protect from moisture and heat

• Keep out of reach of children

• Tablets should be stored in original packaging until use

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Regulatory Status

• Prescription-only medication

• Approved by FDA (2002), EMA, MHRA, TGA, and other national agencies

• Available globally under numerous brand and generic labels

• Included in multiple hypertension treatment guidelines (e.g., JNC 8, ESC/ESH, NICE)