Olimestra^® (Tablets) Instructions for Use

Marketing Authorization Holder

Krka d.d., Novo mesto (Slovenia)

ATC Code

C09CA08 (Olmesartan medoxomil)

Active Substance

Olmesartan medoxomil (Rec.INN registered by WHO)

Dosage Forms

	Olimestra®	Film-coated tablets, 10 mg: 28, 30, 56, 60, 80 or 90 pcs.
		Film-coated tablets, 20 mg: 28, 30, 56, 60 or 90 pcs.
		Film-coated tablets, 40 mg: 28, 30, 56, 60 or 90 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, slightly biconvex, with an engraving “S1” on one side.

Excipients: lactose monohydrate, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate.

Film coating composition: Opadry 85F28751 II HP white (polyvinyl alcohol, titanium dioxide (E171), macrogol 3000, talc).

10 pcs. – blisters (3) – carton packs.
10 pcs. – blisters (6) – carton packs.
10 pcs. – blisters (9) – carton packs.
14 pcs. – blisters (2) – carton packs.
14 pcs. – blisters (4) – carton packs.
15 pcs. – blisters (2) – carton packs.
15 pcs. – blisters (4) – carton packs.
15 pcs. – blisters (6) – carton packs.

Film-coated tablets white, round, slightly biconvex, with an engraving “S2” on one side.

Excipients: lactose monohydrate, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate.

Film coating composition: Opadry 85F28751 II HP white (polyvinyl alcohol, titanium dioxide (E171), macrogol 3000, talc).

10 pcs. – blisters (3) – carton packs.
10 pcs. – blisters (6) – carton packs.
10 pcs. – blisters (9) – carton packs.
14 pcs. – blisters (2) – carton packs.
14 pcs. – blisters (4) – carton packs.
15 pcs. – blisters (2) – carton packs.
15 pcs. – blisters (4) – carton packs.
15 pcs. – blisters (6) – carton packs.

Film-coated tablets white, oval, biconvex, with an engraving “S3” on one side.

Excipients: lactose monohydrate, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate.

Film coating composition: Opadry 85F28751 II HP white (polyvinyl alcohol, titanium dioxide (E171), macrogol 3000, talc).

7 pcs. – blisters (4) – carton packs.
7 pcs. – blisters (8) – carton packs.
10 pcs. – blisters (3) – carton packs.
10 pcs. – blisters (6) – carton packs.
10 pcs. – blisters (9) – carton packs.

Clinical-Pharmacological Group

Angiotensin II receptor antagonist

Pharmacotherapeutic Group

Angiotensin II receptor antagonist

Pharmacological Action

Antihypertensive agent, angiotensin II receptor blocker. It has high selectivity for angiotensin II type 1 (AT₁) receptors, through which the main effects of angiotensin II are realized. By blocking these receptors, Olmesartan medoxomil prevents and eliminates the vasoconstrictive action of angiotensin II, causes a secondary increase in plasma renin activity due to the elimination of negative feedback during renin release and a direct decrease in aldosterone secretion.

In arterial hypertension, olmesartan medoxomil causes a dose-dependent, prolonged decrease in blood pressure.

There are no data regarding the development of arterial hypotension after the first dose of olmesartan medoxomil, tachyphylaxis during long-term treatment, and withdrawal syndrome.

When olmesartan medoxomil is used once a day, it provides effective and smooth reduction of blood pressure over 24 hours. The maximum antihypertensive effect is achieved after 8 weeks from the start of therapy, although a significant blood pressure reduction effect is noted after 2 weeks of treatment.

Pharmacokinetics

Olmesartan medoxomil is a prodrug. It is rapidly converted into the pharmacologically active metabolite olmesartan by the action of esterases in the intestinal mucosa and in the portal vein blood during absorption from the gastrointestinal tract. Unchanged Olmesartan medoxomil or the unchanged side chain of the medoxomil group was not detected in plasma or excreta. The C_max of olmesartan in plasma is reached on average approximately 2 hours after oral administration and increases almost linearly with increasing dose up to 80 mg. Concurrent food intake has practically no effect on the bioavailability of olmesartan.

The binding of olmesartan to plasma proteins is 99.7%, however, the potential for a clinically significant shift in protein binding during the interaction of olmesartan with other drugs that have a high degree of protein binding is low (this is confirmed by the absence of a clinically significant interaction between olmesartan and warfarin). Olmesartan is excreted in the urine (approximately 40%) and bile (approximately 60%), T_1/2 is 10-15 hours. No accumulation of olmesartan was noted.

Indications

Essential arterial hypertension.

ICD codes

Dosage Regimen

Take orally, daily. The initial dose is 10 mg/day. If the effect is insufficient, the dose is increased to the optimal dose – 20 mg/day. If necessary, the dose can be increased to the maximum – 40 mg/day.

For elderly patients, dose adjustment is not required. If it is necessary to increase the daily dose to the maximum of 40 mg/day, the increase should be carried out under careful blood pressure monitoring.

For patients with mild or moderate renal impairment (creatinine clearance 20-60 ml/min), the maximum daily dose is 20 mg.

Adverse Reactions

From the cardiovascular system arterial hypotension, angina pectoris.

From the hematopoietic system thrombocytopenia.

From the central nervous system vertigo, dizziness, headache, asthenic syndrome (increased fatigue, drowsiness, general malaise).

From the respiratory system bronchitis, pharyngitis, rhinitis, cough.

From the digestive system diarrhea, dyspepsia, gastroenteritis, abdominal pain, nausea, vomiting, increased liver enzyme activity.

Dermatological reactions skin itching, rash, angioedema, allergic dermatitis, facial edema, urticaria.

From the musculoskeletal system arthritis, back pain, bone pain, muscle cramps, myalgia, increased CPK activity.

From the urinary system hematuria, urinary tract infection.

From metabolism: hypertriglyceridemia, hyperuricemia, hyperkalemia, increased serum creatinine and urea levels, peripheral edema.

Other chest pain, flu-like symptoms.

Contraindications

Biliary tract obstruction, pregnancy, breastfeeding period, children and adolescents under 18 years of age, hypersensitivity to olmesartan medoxomil.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during lactation (breastfeeding).

Use in Hepatic Impairment

Due to the lack of sufficient clinical experience, the use of olmesartan medoxomil in patients with impaired liver function is not recommended.

Use in Renal Impairment

Due to the lack of sufficient clinical experience, the use of olmesartan medoxomil in patients with severe renal failure (creatinine clearance ≤20 ml/min) is not recommended.

Olmesartan medoxomil should be used with caution in patients with kidney disease, with stenosis of the renal artery of both or a single kidney, since there is a risk of developing acute hypotension, azotemia, oliguria, acute renal failure.

When treating patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

For elderly patients, dose adjustment is not required. If it is necessary to increase the daily dose to the maximum of 40 mg/day, the increase should be carried out under careful blood pressure monitoring.

Special Precautions

Due to the lack of sufficient clinical experience, the use of olmesartan medoxomil in patients with severe renal failure (creatinine clearance ≤20 ml/min), in patients with impaired liver function is not recommended.

Use with caution in patients with aortic or mitral valve stenosis or with obstructive hypertrophic cardiomyopathy.

In case of prior intensive diuretic therapy, adherence to a salt-free diet, diarrhea and/or vomiting, then after taking the first dose, arterial hypotension may develop as a result of a decrease in circulating blood volume. Therefore, it is necessary to eliminate the possibility of hypovolemia before starting treatment with olmesartan medoxomil.

Olmesartan medoxomil should be used with caution in patients with heart failure, kidney disease, with stenosis of the renal artery of both or a single kidney, since there is a risk of developing acute hypotension, azotemia, oliguria, acute renal failure.

When treating patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended.

It is not recommended to use Olmesartan medoxomil in patients with primary hyperaldosteronism.

It should be borne in mind that an excessive decrease in blood pressure in patients with coronary artery disease or cerebral atherosclerosis may lead to the development of myocardial infarction or ischemic stroke.

Effect on the ability to drive vehicles and operate machinery

When using olmesartan medoxomil, dizziness or increased fatigue may occasionally occur, which must be taken into account when used in patients driving vehicles and/or engaged in other potentially hazardous activities.

Drug Interactions

With the simultaneous use of olmesartan medoxomil with other antihypertensive agents, an enhancement of the hypotensive effect is possible.

With the simultaneous use of olmesartan medoxomil with NSAIDs, a decrease in the hypotensive effect and an increase in the risk of developing acute renal failure are possible.

After therapy with antacids (magnesium aluminum hydroxide), a decrease in the bioavailability of olmesartan medoxomil was noted.

With the simultaneous use of olmesartan medoxomil with lithium preparations, the toxicity of the latter increases (the combination is not recommended).

The risk of hyperkalemia increases with the simultaneous use of olmesartan medoxomil with potassium-sparing diuretics, potassium-containing drugs, or with other drugs that can cause an increase in serum potassium levels, for example, with heparin (the combination is not recommended).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.