Olmesartan medoxomil (Benicar) is an ARB (angiotensin II receptor blocker) that is used in the treatment of hypertension, angina, and proteinuria.

Olmesartan medoxomil uses:

• Hypertension:

  •  In adults and pediatric patients ≥6 years of age, management of hypertension.

• Off Label Use of Olmesartan (Benicar) in Adults:

  • Non-ST-elevation acute coronary syndrome.
  • Proteinuric chronic kidney disease (diabetic or non-diabetic).
  • ST-elevation myocardial infarction

Olmesartan medoxomil Dose in Adults

Olmesartan medoxomil Dose in the treatment of acute coronary syndromes:

Note:

• May be used in patients as an alternative who cannot tolerate an ACE inhibitor (eg, due to cough).
• In patients with prior angiotensin-converting enzyme (ACE) inhibitor-associated angioedema (ie, without urticaria or other signs of hypersensitivity), an angiotensin II receptor blocker (ARB) can also be an alternative.
• ARBs do not appear to elevate the risk of angioedema.
• However, patients must be educated that due to an ACE inhibitor, angioedema can sometimes reoccur within months following discontinuation.
• Referral to an allergist may be appropriate.

Olmesartan medoxomil dose in the treatment of Non-ST-elevation acute coronary syndrome (alternative agent) (off-label):

Note:

• Before initiation, patients should be hemodynamically stable.
• Use as a component of an appropriate medical regimen, which may also include an antiplatelet agent(s), a beta-blocker & a statin.
• Continue ARB therapy indefinitely for patients with concurrent diabetes, left ventricular ejection fraction ≤40%, hypertension, or stable chronic kidney disease.
• In the manufacturer's labeling, dosing is based on the general dosing range.
• Initial:
  • 20 mg orally once daily.
  • Increase dose as tolerated up to 40 mg/day under close monitoring to avoid hypotension.

Olmesartan medoxomil dose in the treatment of ST-elevation myocardial infarction (alternative agent) (off-label):

Note:

• Before initiation, patients should be hemodynamically stable.
• Use as a component of an appropriate medical regimen, which may also include an antiplatelet agent(s), a beta-blocker, and a statin.
• Continue ARB therapy indefinitely.
• In the manufacturer's labeling, dosing is based on general dosing range.
• Initial:
  • 20 mg orally once daily.
  • Increase dose as tolerated up to 40 mg per day under close monitoring to avoid hypotension.

Olmesartan medoxomil Dose in the treatment of Hypertension:

Note:

• For initial treatment in patients with blood pressure, ≥20/10 mm Hg above goal, the drug may be used in combination with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker, thiazide diuretic).
• For patients <20/10 mm Hg above goal, some experts recommend an initial trial of monotherapy.
• However, over time, many patients will need combination therapy.
• Initial:
  • 20 mg orally once daily.
  • Evaluate response every 4-6 weeks and increase the dose as needed up to 40 mg once daily.

Olmesartan Dose in the treatment of Proteinuric chronic kidney disease (diabetic or nondiabetic) (off-label):

Note:

• An ARB or an ACE inhibitor may be used in nondiabetic and type 2 diabetic proteinuric chronic kidney disease (CKD).
• In type 1 diabetic proteinuric CKD, in patients who cannot tolerate an ACE inhibitor, an ARB may be used as an alternative  (eg, due to cough).
• Olmesartan may be an alternative in patients with prior ACE inhibitor-associated angioedema (ie, without urticaria or other signs of hypersensitivity).
• To elevate the risk of angioedema, ARBs do not appear.
• However, patients must be educated that angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation.
• Referral to an allergist may be appropriate.
• In the manufacturer's labeling dosing is based on the general dosing range.
• Initial:
  • 20 mg orally once daily.
  • Based on blood pressure response and tolerability can be increased to 40 mg once daily.
  • Target to an appropriate blood pressure goal and a proteinuria goal of <1 g/day.

• IgA nephropathy:

  • In addition to an appropriate blood pressure goal, a proteinuria goal of <1 g/day is also generally recommended.
  • Some experts treat to a proteinuria goal of <500 mg/day.
  • If proteinuria goal is not met with monotherapy at the max dose, consider adding other modalities & agents.

Olmesartan medoxomil Dose in Childrens

Note: Consider a lower starting dose in patients with possible depletion of intravascular volume (eg, patients receiving diuretics).

Olmesartan Dose in the treatment of Hypertension:

• Children (age 1 - 5 years, weight > 5 Kgs):

  • Initial:
  • 0.3 mg/kg/dose orally once daily;
  • if the initial response is inadequate after 2 weeks, the dose may be increased to 0.6 mg/kg/dose once daily.
  • Dosing was evaluated in a double-blind, placebo-controlled study of 59 patients & some efficacy was demonstrated.
  • However, statistically, results were not significant.

• Children and Adolescents 6 to 16 years:

  • 20 to <35 kg:
    • 10 mg orally once daily.
    • If the initial response inadequate after 2 weeks, the dose may be increased.
  • Max daily dose:
    • 20 mg/day
  • ≥35 kg:
    • 20 mg once daily.
    • The dose may be increased if the initial response inadequate after 2 weeks.
  • Max daily dose:
    •  40 mg/day

• Adolescents >16 years:

  • Initial:
    • 20 mg orally once daily.
    • After 2 weeks, if the initial response is inadequate, the dose may be increased to 40 mg once daily.

Pregnancy Risk Factor D

[US Boxed Warning]

• Drugs that affect the renin/angiotensin system may cause injury and death in the developing fetus.
• Stop having a baby if you are pregnant.
• The use of drugs that affect the renin/angiotensin system can be associated with oligohydramnios.
• Oligohydramnios can cause fetal lung hypoplasia and skeletal malformations due to reduced fetal renal function.
• Also, use is associated with hypotension, anuria, renal failure, skull hypoplasia, and death in the fetus/neonate.
• Examine the exposed fetus for signs of fetal growth, amniotic liquid volume and organ formation.
• Children exposed in utero to hyperkalemia, hypotension and oliguria should be checked (exchange transfusions may be necessary).
• These adverse events are usually associated with maternal use during the second and third trimesters.
• Chronic maternal hypertension, which is not treated, can also be associated with adverse events in the mother, infant, or foetus.
• Pregnant women should not use angiotensin II receptor blocking drugs to manage chronic uncomplicated hypertension.

Olmesartan use during breastfeeding:

• It is unknown if breast milk contains olmesartan or not.
• The manufacturer recommends that the mother decide whether to stop breastfeeding or discontinue using the drug. This is in consideration of the risk of serious adverse reactions.

Olmesartan Dose in Kidney Disease:

• CrCl ≥40 mL/min:

  • No dosage adjustment is necessary.

• CrCl <40 mL/min:

  • No initial dosage adjustment is necessary.
  • AUC is increased 3-fold in patients with CrCl <20 mL/min and a max dose of 20 mg/day have been recommended for these patients.

Olmesartan medoxomil Dose in Liver Disease:

• Mild impairment:

  • No dosage adjustment is necessary.

• Moderate to severe:

  • No initial dosage adjustment is necessary.
  • In moderate impairment, total drug exposure increased ~60%.

Side Effects of Olmesartan medoxomil:

• Central Nervous System:

  • Dizziness
  • Headache

• Endocrine & Metabolic:

  • Hyperglycemia
  • Hypertriglyceridemia

• Gastrointestinal:

  • Diarrhea

• Genitourinary:

  • Hematuria

• Neuromuscular & Skeletal:

  • Back Pain
  • Increased Creatine Phosphokinase

• Respiratory:

  • Bronchitis
  • Flu-Like Symptoms
  • Pharyngitis
  • Rhinitis
  • Sinusitis

Rare side effects of Olmesartan medoxomil:

• Hematologic & oncologic:

  • Decreased hematocrit
  • Decreased hemoglobin

Contraindications to Olmesartan medoxomil:

• In patients with diabetes mellitus, concomitant use with aliskiren.

Canadian labeling:Additional contraindications not listed in the US labeling:

• Hypersensitivity to olmesartan and any component of the formulation
• In patients with moderate to severe renal impairment, concomitant use with aliskiren (GFR <60 mL/min/1.73 m2).
• There is not much evidence of an allergenic cross-reactivity between angiotensin II receptor blocking agents and angiotensin II receptor blocksers.
• Cross-sensitivity is possible due to similarities in chemical structure and pharmacologic effects.

Warnings and precautions

• Angioedema

  • Angiotensin II receptor inhibitor antagonists (ARBs), are not recommended to increase the risk of angioedema.
  • Patients with a history of angioedema due to an angiotensin-converting enzyme (ACE) inhibitor must be educated that following discontinuation sometimes there can be recurrence within months (Beltrami 2011).
  • Angioedema can be caused by any number of causes.
  • It is important to have frequent examinations, especially if the tongue, glottis or larynx are involved.
  • They are often associated with obstruction of the airways.
  • Stop all therapy immediately if angioedema develops
  • It is crucial to be aggressive in early management.
  • IM administration of epinephrine might be required.
  • Patients who develop angioedema due to this medication should not be given the ARB.

• Gastrointestinal effects:

  • There have been reports of symptoms of sprue-like Enteropathy (i.e. severe, chronic diarrhea with significant weight gain).
  • Villous atrophy is a condition that may develop after treatment. It is often found in intestinal biopsy.
  • Once all other causes have been ruled out, discontinue treatment and look into other antihypertensive treatments.
  • A series of 22 patients was examined and found that there was a clinical and histologic improvement after discontinuing treatment.

• Hyperkalemia:

  • It may happen.
  • risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements & potassium-containing salts.
  • These agents should be used with caution.

• Hypotension

  • Hypotension can occur when patients are severely salt- or volume-depleted (eg those who have been treated with high dose diuretics).
  • Correct volume depletion must be done before administration.
  • This temporary hypotensive response does not mean that you should be unable to receive olmesartan.

• Renal function deterioration:

  • This may be linked to deterioration in renal function and increases in serum creatinine in patients with low renal flow (eg, kidney artery stenosis or heart failure) whose GFR depends on angiotensin II efferent arterial vasoconstriction.
  • A deterioration can lead to oliguria and acute renal failure.
  • After initiation, small increases in serum creatinine might occur.
  • Patients with significant and progressive impairment of renal function should be considered for discontinuation.

• Mitral and aortic stenosis:

  • Patients with severe aortic/mitralstenosis should be cautious

• Ascites:

  • Patients with cirrhosis and refractory ascites should be avoided.
  • Patients with ascites from cirrhosis should not be used. To avoid rapid renal failure, it is important to examine blood pressure and renal function.

• Renal artery stenosis

  • Use olmesartan cautiously in patients with unstented unilateral/bilateral kidney artery stenosis.
  • If unstented bilateral renal arterial stenosis exists, it is best to avoid use unless the potential benefits outweigh the risks.

• Renal impairment

  • Pre-existing renal impairments should be avoided.

Monitoring Parameters:

• Baseline & periodic blood pressure.
• Electrolytes, renal function.

Hypertension:

The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2018]):

• Confirmed hypertension and known CVD or 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%:
  • Target blood pressure <130/80 mm Hg is recommended.
• Confirmed hypertension without markers of increased ASCVD risk:
  • Target blood pressure <130/80 mm Hg may be reasonable.

Diabetes and hypertension:

The American Diabetes Association (ADA) guidelines (ADA 2019):

• Patients 18-65 years of age, without ASCVD, and 10-year ASCVD risk <15%:
  • Target blood pressure <140/90 mm Hg is recommended.
• Patients 18 to 65 years of age and known ASCVD or 10-year ASCVD risk >15%:
  • Target blood pressure <130/80 mm Hg may be appropriate if it can be safely attained.
• Patients >65 years of age (healthy or complex/intermediate health):
  • Target blood pressure <140/90 mm Hg is recommended.
• Patients >65 years of age (very complex/poor health):
  • Target blood pressure <150/90 mm Hg is recommended.

How to administer Olmesartan medoxomil?

• P/O:
• Administer with or without food.

Mechanism of action of Olmesartan medoxomil:

• As a selective and competitive, nonpeptide angiotensin II receptor antagonist, olmesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II.
• Olmesartan reacts in a reversible manner with the AT1 or AT2 receptors in many tissues. It also has slow dissociation rates.
• Its affinity for AT1 receptors is 12,500x greater than that of the AT2 receptor.
• Angiotensin II receptor antagonists may induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, they do not affect the response to bradykinin, and are less likely to be associated with non-renin-angiotensin effects (eg, cough and angioedema).
• Olmesartan is a natriuretic/kaliuretic that increases the urinary flow and increases excretion of calcium, magnesium, and phosphate.

Distribution:

• 17 L.
• Does not cross the blood-brain barrier (animal studies)

Protein binding:

• 99%

Metabolism:

• In the GI tract to active olmesartan, Olmesartan medoxomil is hydrolyzed.
• No further metabolism occurs.

Bioavailability:

• 26%

Half-life elimination:

• Terminal:
• 13 hours

Time to peak:

• 1-2 hours

Excretion:

• All as unchanged drug:
  • Feces (50% to 65%).
  • Urine (35% to 50%)
• Clearance:
  • 1.3 L/hour.
  • Similar data reported in children (1-16 years) when adjusted by body weight

International Brands of Olmesartan Medoxomil:

• Benicar
• ACT Olmesartan
• AG-Olmesartan
• APO-Olmesartan
• Auro-Olmesartan
• GLN-Olmesartan
• JAMPOlmesartan
• Olmetec
• PMS-Olmesartan
• RIVA-Olmesartan
• SANDOZ Olmesartan
• Abetis
• Almetec
• Alteis
• Alzor
• Angiosartan
• Ao Tan
• Arb-S
• Belsar
• Benetor
• Cardioplus
• Cardosal
• Cresart
• Dolezine
• Erastapex
• Esatec
• Iltux
• Ixia
• Kaportan
• Lezberg
• Macolme
• Mesar
• Normesar
• Olartan
• Oldesar
• Ole
• Olesta
• Olimestra
• Olme
• Olmec
• Olmecor
• Olmepas
• Olmertan
• Olmes
• Olmesan
• Olmesta
• Olmetec
• Olmetel
• Olmezar
• Olsart
• Omecor
• Omesar
• Openvas
• Orion
• Osaver
• Presulock
• Tenzar
• Vivactra
• Votum

Olmesartan Brand Names in Pakistan: