Olimestra - instructions for use, dose, side effects, contraindications

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Dosage form: & nbspfilm-coated tablets

Composition:

1 tablet 10 mg, film-coated, contains:

core: active substance: olmesartan medoxomil 10.00 mg; Excipients: lactose monohydrate 57.50 mg, microcrystalline cellulose 26.00 mg, low-substituted giprolose 10.00 mg, magnesium stearate 1.50 mg;

film sheath: Opadrai 85F28751 II HP white * 4.00 mg.

1 tablet 20 mg, film-coated, contains:

core: dActive substance: olmesartan medoxomil 20.00 mg; Excipients: lactose monohydrate 115.00 mg, microcrystalline cellulose 52.00 mg, low-substituted giprolose 20.00 mg, magnesium stearate 3.00 mg;

film sheath: Opadrai 85F28751 II HP white * 8.00 mg.

1 tablet 40 mg, film-coated, contains:

core: active substance: olmesartan medoxomil 40.00 mg; atExcipients: lactose monohydrate 230.00 mg, microcrystalline cellulose 104.00 mg, low-substituted giprolose 40.00 mg, magnesium stearate 6.00 mg;

film sheath: Opadrai 85F28751 II HP white * 16.00 mg.

* Failure 85F28751 II HP white: polyvinyl alcohol 40.00%, titanium dioxide (E171) 25.00%, macrogol-3000 20.20%, talc 14.80%.

Description:

Tablets 10 mg and 20 mg: round, slightly biconvex tablets, covered with a film coating of white color.

Tablets 40 mg: oval, biconvex tablets, covered with a film shell of white color.

Pharmacotherapeutic group:angiotensin II receptor antagonist

Pharmacodynamics:

Olmesartan medoxomil is a selective angiotensin II receptor antagonist (type AT₁), which blocks all the actions of angiotensin II, mediated AT₁-receptors, regardless of the source or route of synthesis of angiotensin II. Angiotensin II is the main vasoactive hormone of the renin-angiotensin-aldosterone system (RAAS), increases the activity of renin, reduces the concentration of aldosterone in the blood plasma and plays an important role in the pathophysiology of hypertension by AT₁receptors. There is no evidence of the development of arterial hypotension after taking the first dose of the drug, tachyphylaxis during long-term use and the "withdrawal" syndrome (a sharp increase in BP after drug withdrawal).

With arterial hypertension, olmesartan causes a dose-dependent prolonged decrease in blood pressure (BP).

Taking olmesartan medoxomil once a day provides an effective and smooth decrease in blood pressure within 24 hours, and the effect after a single dose is similar to the effect of taking the drug 2 times a day in the same daily dose.

With prolonged therapy, the maximum reduction in blood pressure is achieved by the 8th week after the start of treatment, although a significant reduction in blood pressure is observed after 2 weeks of olmesartan.

When used simultaneously with hydrochlorothiazide, the antihypertensive effect is enhanced and the simultaneous use of these drugs is well tolerated.

Pharmacokinetics:

Suction and distribution

Olmesartan medoxomil is a prodrug that is rapidly converted by enzymes into a pharmacologically active metabolite of olmesartan in the intestinal mucosa and in the blood of the portal vein when absorbed from the gastrointestinal tract (GI tract).

Olmesartan medoxomil is not found in the blood plasma. The average absolute bioavailability of olmesartan is 25.6%. The maximum concentration of olmesartan in the blood plasma (C_mOh) is achieved within 2 hours after ingestion, the concentration of olmesartan in the blood plasma increases linearly with a single dose increase to 80 mg when ingested.

Food intake has minimal effect on the bioavailability of olmesartan, and therefore olmesartan medoxomil can be taken regardless of food intake. There are no clinically significant differences depending on sex in the pharmacokinetic parameters of olmesartan.

The association with plasma proteins is high (99.7%).However, the potential for a clinically significant shift in the degree of binding to plasma proteins in the interaction of olmesartan with other drugs that have a high degree of binding to plasma proteins is low. This is confirmed by the absence of a clinically significant interaction between olmesartan and warfarin. The association of olmesartan with erythrocytes is insignificant.

Metabolism and excretion

The total plasma clearance is 1.3 l / h (coefficient of variation (CV) - 19%) and relatively low in comparison with hepatic blood flow (approximately 90 l / h). Olmesartan is excreted as by the kidneys (approximately 40%), and with bile through the intestine (about 60%). The intestinal and hepatic recirculation of olmesartan is minimal. Since most of the olmesartan is excreted in the bile, its use in patients with bile duct obstruction is contraindicated.

The half-life (T_1/2) of olmesartan varies from 10 to 15 hours. The equilibrium concentration is achieved after the first few doses are applied, further cumulation is not observed after 14 days of olmesartan application. Kidney clearance is approximately 0.5-0.7 l / h and does not depend on the dose of olmesartan.

Pharmacokinetics in selected patient groups

Elderly patients

In patients with arterial hypertension, the area under the concentration-time curve (AUC) in the equilibrium state increased by approximately 35% in elderly patients (65-75 years) and by 44% in patients older than 75 years compared with young patients. Perhaps this is partly due to impairment of renal function in this group of patients.

Impaired renal function

In patients with impaired renal function AUC 62%, 82% and 179% in patients with mild, moderate and severe renal failure, respectively, in comparison with a group of healthy volunteers.

Impaired liver function

After a single oral intake AUC olmesartan were 6% and 65% higher in patients with mild and moderate impairment of liver function than in healthy volunteers in the control group. Unbound olmesartan fraction 2 hours after application by healthy volunteers, patients with mild and moderate impairment of liver function were 0.26%, 0.34%, and 0.41%, respectively. After repeated use of the drug by patients with moderate impairment of liver function, the mean AUC Olmesartan was approximately 65% higher than in healthy volunteers in the control group. The average value of C_mOhOlmesartan in blood plasma is similar in patients with hepatic insufficiency and healthy volunteers.

Indications:Arterial hypertension.

Contraindications:

Hypersensitivity to the active substance or any of the auxiliary components of the drug, pregnancy, breastfeeding period, severe renal failure (creatinine clearance less than 20 ml / min), condition after kidney transplantation (no experience of clinical use), bile duct obstruction, simultaneous use with aliskiren in patients with diabetes mellitus or renal dysfunction (CC less than 60 ml / min), age under 18 years (safety and efficacy not established), lactase deficiency, intolerant Lactose, glucose-galactose malabsorption syndrome.

Carefully:

- Stenosis of the aortic and / or mitral valves;

- hypertrophic obstructive cardiomyopathy (GOKMP);

- primary hyperaldosteronism; hyperkalemia;

- hyponatremia;

- renal failure (CK> 20 ml / min);

- Chronic heart failure (CHF);

- bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney;

- ischemic heart disease and cerebrovascular disease; use in elderly patients (over 65 years);

- conditions accompanied by a decrease in the volume of circulating blood (bcc) (as a result of diuretic therapy, while limiting consumption of table salt, diarrhea and vomiting);

- violations of the liver function of non-biliary origin without the phenomena of cholestasis (see the dosing regimen in the section "Method of administration and dose").

Pregnancy and lactation:

Olimestrra® is not recommended during the first trimester of pregnancy. The available data on the teratogenicity of angiotensin-converting enzyme (ACE) inhibitors in the first trimester of pregnancy are not convincing, but this risk can not be completely ruled out. Controlled epidemiological data on the risk of angiotensin II receptor antagonists (APA II) in the first trimester of pregnancy are not present, however, it can not be excluded with the use of drugs of this group.

Olimestrra® is contraindicated in the II-III trimesters of pregnancy,because the use of pregnancy in II-III trimesters can cause fetotoxic effects (decreased kidney function, low blood pressure, slowing ossification of the fetal bones) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). If nevertheless used the drug in the II-III trimesters of pregnancy, then it is necessary to perform ultrasound examination of the kidneys and bones of the fetal skull.

Olimestrra®, like any other drug directly affecting RAAS, should not be used during pregnancy, as well as in women planning pregnancy. When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile. When using agents that affect RAAS, it is necessary to inform women of childbearing age of the potential risk of adverse effects of these drugs on the fetus during pregnancy. When confirming a pregnancy, Olimestrra® should be discontinued as soon as possible.

It is not known whether olmesartan is excreted in breast milk.If it is necessary to use Olimestrra®, breastfeeding should be discontinued.

Dosing and Administration:

Inside, daily, preferably at the same time (for example, during breakfast), regardless of the meal.

The tablet should be washed down with a sufficient amount of liquid (for example, a glass of water), not chew.

Adults

The recommended initial dose is 10 mg once a day.

Patients to whom the initial dose does not provide a targeted reduction in blood pressure, the dose of the drug can be increased to 20 mg once a day.

If you need to further reduce blood pressure, the dose of Olimestrra® can be increased to a maximum daily dose of 40 mg.

The maximum antihypertensive effect is achieved within 2-8 weeks after the beginning of application of Olmitestra®.

A patient can be transferred to a combined therapy with hydrochlorothiazide.

Special patient groups

Elderly patients

Correction of the dose is not required. If you need to increase the dose to 40 mg per day, you need to monitor blood pressure.

Impaired renal function

The maximum daily dose of Olimestrra® for mild and moderate renal dysfunction (KK 20-60 ml / min) is 20 mg once a day.

The use of Olimestrra® in patients with severe renal impairment (CC <20 mL / min) is not recommended, due to lack of experience.

Impaired liver function

Patients with moderate impairment of liver function: the recommended initial dose is 10 mg once a day and the maximum dose should not exceed 20 mg once a day. Patients with impaired liver function who simultaneously take diuretics or other antihypertensive drugs need constant monitoring of blood pressure and kidney function.

Side effects:

With the use of olmesartan the following side effects are most often observed: headache (7.7%), flu-like symptoms (4.0%) and dizziness (3.7%).

Classification of the frequency of development of side effects of the World Health Organization (WHO): very often (≥ 1/10), often (≥ 1/100, <1/10), infrequently (≥ 1/1000, <1/100); rarely (≥ 1/10 000, <1/1000), very rarely (<1/10 000), the frequency is unknown - can not be estimated from the available data.

In each group, undesirable effects are presented in order of decreasing severity.

Violations of the blood and lymphatic system: infrequently: thrombocytopenia.

Immune system disorders: infrequently: anaphylactic reactions.

Disorders from the metabolism and nutrition: often: hypertriglyceridemia, hyperuricemia; rarely: hyperkalemia.

Disturbances from the nervous system: often: dizziness, headache.

Hearing disorders and labyrinthine disorders: infrequently: vertigo.

Heart Disease: infrequently: angina pectoris.

Vascular disorders: rarely: marked decrease in blood pressure.

Disturbances from the respiratory system, chest and mediastinal organs: often: bronchitis, pharyngitis, cough, rhinitis.

Disorders from the gastrointestinal tract: often: nausea, indigestion, gastroenteritis, diarrhea, abdominal pain; infrequently: vomiting.

Disturbances from the skin and subcutaneous tissues: infrequently: exanthema, allergic dermatitis, urticaria, skin rash, itchy skin; rarely: angioedema.

Disturbances from musculoskeletal and connective tissue: often: arthritis, back pain, bone pain; infrequently: myalgia; rarely: muscle spasms.

Disorders from the kidneys and urinary tract: often: urinary tract infections, hematuria; rarely: renal failure, including acute renal failure.

General disorders and disorders at the site of administration: often: pain, chest pain, flu-like symptoms, peripheral edema, increased fatigue; infrequently: swelling of the face, asthenia, malaise; rarely: drowsy.

Laboratory violations and instrumental data: often: increased activity of "liver" enzymes, increased urea concentration in blood serum, increased activity of creatine phosphokinase (CK); rarely: increased serum creatinine concentration.

Individual cases of rhabdomyolysis, which coincide with the use of ARA II, were recorded.

Overdose:

Symptoms: marked decrease in blood pressure.

Treatment: with a marked decrease in blood pressure, it is necessary to put the patient on his back, lifting his legs. Recommended gastric lavage and / or reception of activated carbon, then - therapy aimed at replenishment of bcc and violations of water-electrolyte metabolism.

Interaction:

Effects of other medications on olmesartan medoxomil

Double blockade of RAAS

In some patients, double blockade of RAAS was accompanied by the development of arterial hypotension, syncope, hyperkalemia and impaired renal function (including acute renal failure (ARF)).

The simultaneous use of ARA II, including olmesartan, with drugs that affect RAAS is not recommended, if necessary, the combination of a careful evaluation of kidney function.

The simultaneous use of olmesartan with aliskiren is contraindicated in patients with diabetes mellitus and renal dysfunction (KC less than 60 ml / min) and is not recommended in other patients.

Potassium-sparing diuretics, potassium preparations, potassium-containing food supplements and other drugs and substances that increase the potassium content in the blood serum (for example, heparin)

Simultaneous use of olmesartan with drugs that affect the potassium content, can lead to an increase in potassium in the serum.

Other antihypertensives

The antihypertensive effect of olmesartan can be enhanced with simultaneous use with other antihypertensive agents.

Non-steroidal anti-inflammatory drugs (NSAIDs)

ARA II and NSAIDs, including selective inhibitors of cyclooxygenase-2 (COX-2) and nonselective NSAIDs (acetylsalicylic acid in a dose of more than 3 g / day), can act synergistically by reducing glomerular filtration. With the simultaneous use of NSAIDs and ARA II, there is a risk of acute arterial hypertension.At the beginning of therapy it is recommended to evaluate the function of the kidneys, as well as adjust the violations of the water-electrolyte balance.

In addition, with simultaneous use, it is possible to attenuate the antihypertensive effect.

Other

After using antacids (magnesium / aluminum hydroxide), a moderate decrease in the bioavailability of olmesartan is possible.

The simultaneous use of warfarin and digoxin has no effect on the pharmacokinetics of olmesartan.

Effects of olmesartan medoxomil on other drugs

Lithium

Simultaneous use with lithium preparations is not recommended, since a reversible increase in the lithium content in the blood plasma and the development of intoxication are possible. If it is necessary to simultaneously apply with lithium preparations, you should carefully monitor the lithium content in blood plasma.

With simultaneous use of lithium drugs and ACE inhibitors, cases of reversible increase of lithium content in serum and development of intoxication were noted. A similar effect is possible with simultaneous use of lithium and ARA II preparations.

Other

The studies conducted in healthy volunteers did not show a clinically significant interaction of olmesartan withwarfarin, digoxin, antacids (aluminum / magnesium hydroxide), hydrochlorothiazide and pravastatin. In particular, olmesartan did not significantly affect the pharmacodynamics and pharmacokinetics of warfarin and the pharmacokinetics of digoxin.

There was also no clinically significant inhibitory effect of olmesartan in humans under conditions in vitro on cytochrome P450 isoenzymes: CYP1A1/2, CYP2A6, CYP2C8/9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and a minimal or zero induced effect was observed with respect to cytochrome P450 in rats. Therefore, studies on the study of drug interactions in conditions in vivo with known inhibitors and inducers of cytochrome P450 isoenzymes not performed, clinically significant interaction of olmesartan with drugs, the metabolism of which is provided by the above isoenzymes of cytochrome P450, is not expected.

Special instructions:

Arterial hypotension

Perhaps the development of symptomatic arterial hypotension, especially after taking the first dose, in patients with reduced bcc, for example, when using large doses of diuretics, while limiting consumption of table salt, diarrhea and vomiting.At the beginning of therapy, care must be taken and, if necessary, compensated for BCC.

Other conditions accompanied by RAAS stimulation

In patients whose vascular tone and renal function depend on RAAS activity (eg, severe CHF or kidney failure), treatment with other drugs that affect RAAS (eg, ACE inhibitors) is associated with the possible development of acute arterial hypotension, oliguria, augmentation of azotemia or, in very rare cases, the development of OPN. The probability of development of these states can not be ruled out with the use of APA II.

Stenosis of the renal artery

Since other arterial hypotension and renal insufficiency may occur in patients with other drugs that affect RAAS, patients with bilateral renal artery stenosis or arterial stenosis of a single kidney should be monitored for serum creatinine and urea concentrations as a precautionary measure.

Kidney Transplantation

The experience of using Olimestrra® in patients who have recently undergone kidney transplantation is absent.

Impaired renal function

When administering Olimestrra® to patients with renal insufficiency (CK> 20 ml / min), periodic monitoring of potassium and serum creatinine concentrations is recommended. The use of olimestrra® is not recommended for patients with severe renal insufficiency (CC <20 ml / min). There is no experience with Olimestrra® in patients with end-stage renal disease (CC <12 mL / min).

Hyperkalemia

With the use of drugs that affect RAAS, it is possible to develop hyperkalemia, the risk of which increases in elderly patients, with renal insufficiency and in patients with diabetes mellitus, while using drugs that lead to hyperkalemia and / or in the presence of intercurrent diseases. In some cases, hyperkalemia can lead to death of the patient.

Before the simultaneous use of other drugs that affect RAAS, you should carefully evaluate the ratio of the likely benefits and risks of this therapy and consider alternative therapies.

The main risk factors for hyperkalemia include renal failure,use in elderly patients (65 years and older), diabetes mellitus, certain intercurrent conditions (decreased bcc, decompensated CHF, metabolic acidosis, impaired renal function (for example, against infectious diseases), conditions accompanied by tissue ischemia / necrosis for example, acute limb ischemia, rhabdomyolysis, extensive trauma)), simultaneous use of drugs that affect RAAS (eg, ACE inhibitors, ARA II), potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), as well as potassium or potassium supplements, as well as NSAIDs (including selective inhibitors of COX-2), heparin, immunosuppressants, such as ciclosporin or tacrolimus, trimethoprim.

In patients who have such risk factors, it is recommended to regularly monitor the potassium content in the blood plasma.

Lithium

As in the case of other ARA II, simultaneous use of lithium preparations and Olimestra® is not recommended.

Stenosis of aortic and mitral valves, GOKMP

As with the use of other vasodilators, the Olimestrra® preparation should be used with caution in patients with stenosis of the aortic and mitral valves, GOKMP.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism usually do not respond to therapy with antihypertensive drugs that inhibit RAAS. Therefore, the use of olimestrra® in patients with primary hyperaldosteronism is not recommended.

Ethnic Features

The antihypertensive effect of Olimestrra® in patients of the Negroid race is less pronounced than in patients of other races, and, therefore, an increase in the dose of Olimestrra® is more often required, as well as simultaneous use with other antihypertensive medications.

Other

As with other antihypertensive drugs, excessive reduction in blood pressure in patients with coronary heart disease or ischemic cerebrovascular disease can lead to myocardial infarction or stroke.

Olimestrra® contains lactose, so do not use it for patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

Effect on the ability to drive transp. cf. and fur:

Care must be taken when driving vehicles and occupying others,potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, as dizziness and weakness are possible.

Form release / dosage:

Tablets, film-coated, 10 mg, 20 mg, 40 mg.

Packaging:

Tablets 10 mg and 20 mg: 10, 14 or 15 tablets are placed in a blister of the combined material OPA / Al / PVC - aluminum foil. For 3, 6 or 9 blisters (a blister of 10 tablets), or 2 or 4 blisters (a blister of 14 tablets), or 2, 4 or 6 blisters (a blister of 15 tablets) is placed in a cardboard box along with instructions for use .

For hospitals: for 20 or 56 blisters (blister for 10 tablets) or 40 blisters (blister for 14 tablets) are placed in a pack of cardboard along with instructions for use.

Tablets 40 mg: 7 or 10 tablets are placed in a blister of the combined material OPA /Al/ PVC - aluminum foil. For 4 or 8 blisters (a blister for 7 tablets), or for 3, 6 or 9 blisters (a blister of 10 tablets) is placed in a pack of cardboard along with instructions for use.

For hospitals: for 20 or 56 blisters (blister for 10 tablets) or for 80 blisters (a blister for 7 tablets) is placed in a pack of cardboard along with instructions for use.

Storage conditions:

At temperatures not higher than 30 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002160

Date of registration:26.07.2013

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp17.08.2015

Illustrated instructions

Instructions

Olimestra® (Olmestra® )