Olmesta

Approved Indications (Adults and Children ≥6 years):

• Hypertension (Primary/Essential):
• Treatment of mild to moderate hypertension in adults and pediatric patients (≥6 years), to lower blood pressure and reduce the risk of cardiovascular events such as stroke and myocardial infarction.
• Hypertensive Patients with Left Ventricular Hypertrophy (LVH):
• May reduce the risk of stroke, particularly in patients with comorbid conditions like diabetes or chronic kidney disease.

Important Off-Label/Clinically Accepted Uses:

• Heart Failure with Reduced Ejection Fraction (HFrEF):
• Used off-label in select patients intolerant to ACE inhibitors.
• Diabetic Nephropathy (Type 2 Diabetes Mellitus):
• Occasionally used off-label in patients with proteinuria and hypertension.

Route: Oral.

Adults:

• Initial Dose: 20 mg once daily.
• Maintenance Dose: 20–40 mg once daily.
• Maximum Dose: 40 mg once daily.
• If blood pressure is not controlled with 20 mg daily, increase to 40 mg after 2 weeks.

Pediatrics (6–16 years):

• Weight <35 kg: Start with 10 mg once daily; maximum 20 mg/day.
• Weight ≥35 kg: Start with 20 mg once daily; maximum 40 mg/day.

Elderly (≥65 years):

• No initial dose adjustment required. Monitor renal function and blood pressure closely.

Renal Impairment:

• Mild to Moderate (CrCl 30–60 mL/min): Start with 10 mg once daily; maximum 20 mg/day.
• Severe (CrCl <30 mL/min): Use cautiously; limited data.

Hepatic Impairment:

• Mild to Moderate: Start with 10 mg once daily.
• Severe Impairment: Use with caution; not extensively studied.

Administration Notes:

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

Olmesartan medoxomil is a prodrug that is hydrolyzed in the gastrointestinal tract to its active form, olmesartan, a selective angiotensin II receptor blocker (ARB). It specifically blocks the binding of angiotensin II to the AT1 receptor in vascular smooth muscle and the adrenal gland. This results in vasodilation, reduced secretion of aldosterone, and decreased blood volume, ultimately leading to lower blood pressure. Unlike ACE inhibitors, it does not affect the bradykinin pathway, reducing the risk of cough or angioedema.

• Absorption: Rapid; prodrug is hydrolyzed to active form during absorption.
• Bioavailability: ~26% (active olmesartan).
• Peak Plasma Time (Tmax): ~1–2 hours after oral administration.
• Distribution: Volume of distribution ~17 L; ~99% plasma protein-bound.
• Metabolism: Minimal hepatic metabolism; primarily excreted unchanged.
• Half-life: ~13 hours; allows once-daily dosing.
• Excretion:
• ~35–50% in urine
• ~50–60% in feces (via bile)

• Pregnancy:
• Category D (second and third trimester):
• Can cause fetal injury or death when used in the second or third trimester.
• Discontinue as soon as pregnancy is detected.
• Lactation:
• Unknown whether olmesartan is excreted in human milk.
• Use with caution; consider alternative antihypertensive therapy, especially in nursing newborns or preterm infants.

• Primary Class: Antihypertensive Agent
• Subclass: Angiotensin II Receptor Blocker (ARB)
• Generation: Second-generation ARB

• Known hypersensitivity to olmesartan or any component of the formulation
• Pregnancy (second and third trimesters)
• Concomitant use with aliskiren in patients with diabetes mellitus
• Severe renal impairment with bilateral renal artery stenosis

• Fetal Toxicity: Discontinue immediately if pregnancy is detected. Can cause oligohydramnios, fetal hypotension, renal failure, or death.
• Hypotension: Particularly in patients with volume or salt depletion (e.g., those on diuretics or dialysis).
• Hyperkalemia: Monitor potassium, especially in patients with renal impairment or on potassium-sparing agents.
• Renal Function Impairment: Monitor renal function periodically; risk of azotemia and worsening renal failure in high-risk populations.
• Sprue-like Enteropathy: Chronic diarrhea with weight loss has been reported; may appear months to years after initiation.
• Angioedema: Although rare, monitor closely; discontinue if it occurs.

Common (≥1%):

• Gastrointestinal: Diarrhea, nausea, abdominal pain
• Cardiovascular: Hypotension, dizziness
• Musculoskeletal: Back pain
• Respiratory: Upper respiratory tract infection, pharyngitis
• General: Fatigue

Serious and Rare:

• Sprue-like enteropathy (chronic diarrhea, weight loss, villous atrophy)
• Hyperkalemia
• Acute renal failure
• Hypotension in volume-depleted individuals
• Angioedema (rare, less frequent than ACE inhibitors)

Onset:

• Adverse effects may occur within days to weeks; sprue-like enteropathy may develop after long-term use.

• Potassium-Sparing Diuretics (e.g., Spironolactone): Risk of hyperkalemia.
• NSAIDs: May reduce antihypertensive effect; increase risk of renal dysfunction.
• Lithium: Increased serum lithium levels and toxicity risk.
• Aliskiren: Contraindicated in diabetics due to risk of renal impairment, hyperkalemia, hypotension.
• Diuretics: Enhanced risk of hypotension when used concurrently.
• CYP450 Interactions: Olmesartan is not significantly metabolized by CYP enzymes and has low potential for drug-drug interactions via CYP450.

• FDA (Latest Review):
• Continued safety monitoring for sprue-like enteropathy; warning added to prescribing information.
• NICE & ESC Hypertension Guidelines:
• Olmesartan is recommended as a first-line option in young adults or non-black hypertensive patients.
• Recent Meta-analyses:
• Suggest similar efficacy and safety to other ARBs such as losartan and valsartan; however, entero-damage risk unique to olmesartan noted.

• Temperature Range: Store at 20°C to 25°C (68°F to 77°F)
• Excursions permitted between 15°C and 30°C (59°F to 86°F).
• Humidity & Light: Protect from moisture and excessive light.
• Packaging: Keep tablets in original blister packs or containers.
• Handling: No special precautions required; do not crush or split film-coated tablets unless scored.