Olmisart

Uses

Olmisart is used for the treatment of mild to moderate essential hypertension. Olmisart may be used alone or in combination with thiazide diuretic.

Olmisart is also used to associated treatment for these conditions: Diabetic Nephropathy, High Blood Pressure (Hypertension), Severe Hypertension, Moderate Hypertension

How Olmisart works

Olmisart belongs to the angiotensin II receptor blocker (ARB) family of drugs, which also includes telmisartan, candesartan, losartan, valsartan, and irbesartan. ARBs selectively bind to angiotensin receptor 1 (AT1) and prevent the protein angiotensin II from binding and exerting its hypertensive effects. As the principal pressor agent of the renin-angiotensin system, Angiotensin II causes vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal reabsorption of sodium. Olmisart blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle. Its action is, therefore, independent of the pathways for angiotensin II synthesis. Overall, olmesartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium.

Olmisart also effects on the renin-angiotensin aldosterone system (RAAS) plays an important role in hemostasis and regulation of kidney, vascular, and cardiac functions. Pharmacological blockade of RAAS via AT1 receptor blockade inhibits negative regulatory feedback within RAAS, which is a contributing factor to the pathogenesis and progression of cardiovascular disease, heart failure, and renal disease. In particular, heart failure is associated with chronic activation of RAAS, leading to inappropriate fluid retention, vasoconstriction, and ultimately a further decline in left ventricular function. ARBs have been shown to have a protective effect on the heart by improving cardiac function, reducing afterload, increasing cardiac output and preventing ventricular hypertrophy and remodelling.

Dosage

Olmisart dosage

Adult:Dosage must be individualized. The usual initial dose is 10 mg once daily. In patients whose blood pressure is not adequately controlled at this dose, the dose may be increased to 20 mg once daily as the optimal dose. For patients requiring further reduction in blood pressure after 2 weeks of therapy, the dose of Olmisart may be increased to 40 mg. Doses above 40 mg do not appear to have greater effect.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Of the total number of hypertensive patients receiving Olmisart Medoxomil in clinical studies, more than 20% were 65 years of age and over, while more than 5% were 75 years of age and older. No overall differences in effectiveness or safety were observed between elderly patients and younger patients.

Side Effects

Common or very common: Arthritis, chest pain, cough, fatigue, gastro-intestinal disturbances, haematuria, hypertriglyceridaemia, hyperuricaemia, influenza-like symptoms, musculoskeletal pain, peripheral edema, pharyngitis, rhinitis, urinary-tract infection.

Uncommon: Angina, rash, vertigo.

Very rare: Headache, myalgia, pruritus, thrombocytopenia, urticaria.

Toxicity

The reported LD50 of olmesartan in dogs was reported to be greater of 1500 mg/kg. Overdose is expressed as hypotension, tachycardia, and bradycardia when there is parasympathetic stimulation. In case of overdose, supportive treatment is recommended.

Olmisart was shown to be safe on carcinogenic and fertility studies. However, in in vitro mutagenic studies showed a potential to induce chromosomal aberrations in cells and it tested positive for thymidine kinase mutations in the mouse lymphoma assay.

Precaution

Fetal/Neonatal Morbidity and Mortality: Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature of patients who were taking angiotensin converting enzyme inhibitors. When pregnancy is detected, Olmisart Medoxomil should be discontinued as soon as possible.

Hypotension in Volume- or Salt-Depleted Patients: In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with Olmisart Medoxomil. Treatment should start under close medical supervision. If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline.

Interaction

No significant drug interactions were reported in studies in which Olmisart Medoxomil was co-administered with digoxin or warfarin in healthy volunteers. The bioavailability of Olmisart was not significantly altered by the co-administration of antacids [Al(OH)3/Mg(OH)2]. Olmisart Medoxomil is not metabolized by the cytochrome P450 system and has no effects on P450 enzymes; thus, interactions with drugs that inhibit, induce or are metabolized by those enzymes are not expected.

Food Interaction

• Take with or without food. Food does not affect absorption.

[Moderate] GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs).

ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion.

Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician.

If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended.

Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

Olmisart Drug Interaction

Moderate: aspirin, aspirin, empagliflozin, pregabalin, alprazolamUnknown: nebivolol, ubiquinone, rosuvastatin, duloxetine, apixaban, omega-3 polyunsaturated fatty acids, atorvastatin, metoprolol, metoprolol, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, cetirizine

Olmisart Disease Interaction

Major: angioedema, hypotensionModerate: CHF, hyperkalemia, renal artery stenosis, renal impairment, renal/liver disease

Volume of Distribution

17 L[L5566]

Elimination Route

When taken orally, the prodrug olmesartan medoxomil is rapidly absorbed in the gastrointestinal tract and metabolized to olmesartan. The esterification with medoxomil was created with the intention of increasing olmesartan bioavailability from 4.5% to 28.6%.

Oral administration of 10-160 mg of olmesartan has been shown to reach peak plasma concentration of 0.22-2.1 mg/L after 1-3 hours with an AUC of 1.6-19.9mgh/L. The pharmacokinetic profile of olmesartan has been observed to be nearly linear and dose-dependent under the therapeutic range. The steady-state level of olmesartan is achieved after once a day dosing during 3 to 5 days.[L5566]

Half Life

The mean plasma olmesartan half-life is reported to be from 10-15 hours after multiple oral administration.

Clearance

Total plasma clearance is 1.3 L/h and the renal clearance is 0.6 L/h.[L5566]

Elimination Route

The main elimination route of olmesartan is in the unchanged form through the feces. From the systemically bioavailable dose, about 10-16% is eliminated in the urine.

Pregnancy & Breastfeeding use

Pregnancy Categories C (first trimester) and D (second and third trimesters).

Nursing Mothers: It is not known whether Olmisart is excreted in human milk, but Olmisart is secreted at low concentration in the milk of lactating rats. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Contraindication

Olmisart is contraindicated in patients who are hypersensitive to any component of this product.

Special Warning

Hepatic Impairment: Dose should not exceed 20 mg daily in moderate impairment.

Renal Impairment: Max. 20 mg daily if eGFR 20–60 mL/minute/1.73 m2. Avoid if eGFR less than 20 mL/minute/1.73 m2.

Acute Overdose

Only limited information is available regarding overdosage in humans. The most likely effect of overdosage is hypotension. In the event of overdosage, the patient should be carefully monitored and treatment should be symptomatic and supportive. No information is available regarding the dialysability of olmesartan.

Storage Condition

Keep out of the reach of children. Keep in the original package in a cool & dry place. Protect from light and moisture.

Innovators Monograph

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