Attento pills 5mg+20mg, 28pcs

Composition

Core:

Active ingredients:

olmesartan medoxomil – 20.00 mg,

amlodipine bezylate-6.944 mg (based on amlodipine base-5.00 mg).

Auxiliary substances:

pregelatinized starch-35,000 mg,

microcrystalline silicanized cellulose* – 32,656 mg,

croscarmellose sodium-5.0 mg,

magnesium stearate-0.400 mg.

Film shell:

Opadray II white 85F18422, consisting of: polyvinyl alcohol-2.0000 mg,

titanium dioxide (E 171) – 1.2500 mg,

macrogol-1.0100 mg,

talc-0.7400 mg

. * consists of 98% microcrystalline cellulose and 2% colloidal silicon dioxide.

Pharmacological action

Pharmacotherapeutic group:

combined antihypertensive agent (BMCC+angiotensin II receptor antagonist)

ATX:

Olmezartan medoxomil and amlodipine

Pharmacodynamics :

The drug Attento® is a combined antihypertensive drug, which includes an angiotensin II receptor antagonist (ARA II) – olmesartan medoxomil and a slow calcium channel blocker (BMCC) – amlodipine. The combination of the two active substances has a synergistic antihypertensive effect, as a result of which blood pressure (BP) decreases to a greater extent than when taking each of them separately.

In an 8-week, double-blind, randomized, placebo-controlled study involving 1,940 patients, the antihypertensive effect of Attento® was shown to develop, as a rule, during the first 2 weeks of therapy. As shown in three studies, the antihypertensive effect of the drug Attento® persists for 24 hours when used once a day, while the residual / peak ratio for systolic blood pressure (SBP) and diastolic blood pressure (DBP) varied from 71% to 82%. The antihypertensive effect was confirmed by outpatient blood pressure monitoring and did not depend on age and gender, as well as on the presence of diabetes mellitus in patients. In two open-label, non-randomized, extended-release studies, sustained efficacy of 5 mg + 40 mg of Attento® was shown in 49-67% of patients within one year of use.

In a double-blind, randomized, placebo-controlled study, the addition of 5 mg amlodipine when the previous 8-week olmesartan medoxomil 20 mg monotherapy was ineffective resulted in a reduction in SBP and DBP by 16.2 and 10.6 mm Hg after 8 weeks (p = 0.0006), respectively. Percentage of patients who achieved the target BP values (< 140/90 mm Hg for patients without diabetes mellitus and

In another study, the addition of 20 mg (40 mg) of olmesartan medoxomil with insufficient effectiveness of previous monotherapy with amlodipine at a dose of 5 mg (for 8 weeks) led to a decrease in SBP and DBP by 15.3 and 9.3 mm Hg, respectively, after 8 weeks (the addition of 40 mg of olmesartan medoxomil – by 16.7 and 9.5 mm Hg). In patients who continued to receive 5 mg amlodipine monotherapy, SBP and DBP decreased by 9.9 and 5.7 mm Hg, respectively, after 8 weeks.

The proportion of patients who had achieved target blood pressure values (< 140/90 mm Hg. art for patients without diabetes and < 130/80 mm Hg. art for patients with diabetes),29.9% in the group of monotherapy with amlodipine at a dose of 5 mg of 53.5% in the group of drug Attento® at a dosage of 5 mg + 20 mg and 50.5% in the group of drug Attento® at a dosage of 5 mg + 40 mg.

In an 8-week double-blind, randomized, placebo – controlled study involving 1,940 patients (71% Caucasian and 29% non – Caucasian), the use of Attento® (with any combination of doses of its components) resulted in a significantly more pronounced decrease in SBP and DBP compared to monotherapy. The degree of SBP/DBP reduction depended on the amlodipine/olmesartan medoxomil doses used: -24 / -14 mmHg (5 mg + 20 mg), -25/-16 mmHg (5 mg + 40 mg), and -30/-19 mmHg (10 mg + 40 mg).

When using the drug Attento® in a dosage of 5 mg + 40 mg, there was an additional decrease in SBP/DBP in the “sitting” position by 2.5/1.7 mm Hg compared to the use of the drug Attento® in a dosage of 5 mg + 20 mg. Similarly, the use of the drug Attento® in a dosage of 10 mg + 40 mg resulted in an additional decrease in SBP/DBP in the “sitting” position by 4.7/3.5 mm Hg compared with the use of the drug Attento® in a dosage of 5 mg + 40 mg. Percentage of patients who managed to reach the target blood pressure values (< 140/90 mm Hg for patients without diabetes mellitus and

Olmesartan medoxomil, which is part of the drug Attento®, is a powerful specific ARA II (type AT 1). Angiotensin II is the primary vasoactive component of the renin-angiotensin-aldosterone system and plays a significant role in the pathophysiology of arterial hypertension by acting on AT1 receptors. Olmesartan inhibits the binding of angiotensin II to AT1 receptors in tissues (including vascular smooth muscle and adrenal glands) and blocks its vasoconstrictive effect, as well as the effects associated with the effect of angiotensin II on aldosterone secretion. Specific antagonism of olmesartan against AT1-receptors leads to an increase in the activity of renin, angiotensin I and II in blood plasma, and also contributes to a decrease in the plasma concentration of aldosterone.

In patients with hypertension, olmesartan medoxomil causes a dose-dependent prolonged decrease in blood pressure. There are no data on the development of arterial hypotension after taking the first dose of olmesartan medoxomil, on tachyphylaxis during long-term treatment, or on the “withdrawal” syndrome (a sharp increase in blood pressure after discontinuation of olmesartan medoxomil).

Taking olmesartan medoxomil once a day provides an effective and gentle reduction in blood pressure for 24 hours. Dividing the daily dose into two doses has an antihypertensive effect similar to that of taking the same daily dose at the same time. The antihypertensive effect of olmesartan medoxomil usually occurs as early as 2 weeks, and the maximum effect develops approximately 8 weeks after the start of therapy.

Currently, there are no data on the effect of olmesartan medoxomil on mortality and morbidity.

A randomized ROADMAP trial involving 4,447 patients with type 2 diabetes mellitus, normoalbuminuria, and at least one additional cardiovascular risk factor evaluated the ability of olmesartan to increase the time to microalbuminuria. During the study period (median follow-up was 3.2 g), patients received olmesartan or placebo in addition to other antihypertensive agents (with the exception of angiotensin converting enzyme (ACE) inhibitors or other ARA II drugs). The study showed a 23% reduction in risk for the primary endpoint (time to microalbuminuria) in favor of olmesartan (HR 0.770; 95.1% CI: 0.630-0.941; p=0.0104). Cardiovascular events (secondary endpoints) were reported in 96 patients (4.3%) in the olmesartan group and in 94 patients (4.2%) in the placebo group.

The ORIENT randomized trial, conducted in Japan and China, examined the effect of olmesartan on renal and cardiovascular outcomes in 577 patients with type 2 diabetes mellitus and severe nephropathy. During the study (median follow-up was 3.1 years), patients received olmesartan or placebo in addition to other antihypertensive drugs, including ACE inhibitors.

The primary combined endpoint (time to the first event to occur: doubling of plasma creatinine, development of end-stage chronic kidney disease, death from all causes) was reported in 116 patients in the olmesartan group (41.1%) and 129 patients in the placebo group (45.4%) (HR 0.97; 95% CI: 0.75-1.24; p = 0.791).

Amlodipine, which is part of the drug Attento®, is a BMCC that blocks the incoming transmembrane current of calcium ions into cardiomyocytes and vascular smooth muscle cells through potential-dependent L-type channels. Experimental data indicate that amlodipine interacts with both dihydropyridine and non-dihydropyridine binding sites. Amlodipine has a relative vasoselectivity and has a greater effect on vascular smooth muscle cells than on cardiomyocytes. The mechanism of antihypertensive action of amlodipine is associated with a direct relaxing effect on vascular smooth muscles, causing a decrease in peripheral vascular resistance and a decrease in blood pressure.

Amlodipine causes a dose-dependent long-term decrease in blood pressure in patients with arterial hypertension. There are no data on the development of arterial hypotension after the first dose of amlodipine, on tachyphylaxis during long-term treatment, or on the “withdrawal”syndrome.

When used in therapeutic doses in patients with arterial hypertension, amlodipine causes vasodilation, leading to a decrease in blood pressure (in the patient’s “lying”, “sitting” and “standing”positions). With prolonged use, a decrease in blood pressure is not accompanied by a significant change in heart rate (HR) and the concentration of catecholamines in blood plasma.In hypertensive patients with normal renal function, the use of amlodipine in therapeutic doses leads to a decrease in renal vascular resistance, an increase in glomerular filtration rate, and an increase in effective renal blood flow without changing the filtration fraction and level of proteinuria.

In hemodynamic studies in patients with heart failure, as well as in clinical studies involving patients with heart failure (NYHA functional class II-IV), when performing a stress test, amlodipine did not worsen the patient’s condition, which was assessed by exercise tolerance, left ventricular ejection fraction, and clinical signs and symptoms.

In a placebo-controlled trial (PRAISE) involving patients with heart failure (NYHA functional class III-IV) treated with digoxin, diuretics, and ACE inhibitors, it was shown that amlodipine does not increase the risk of complications and / or mortality (general and from cardiovascular causes) in patients with heart failure.

In a long-term placebo-controlled trial (PRAISE-II) involving patients with heart failure (NYHA functional class III-IV) without clinical symptoms or objective evidence of coronary heart disease, taking ACE inhibitors, digoxin and diuretics, it was shown that the use of amlodipine did not affect overall mortality and mortality from cardiovascular causes.

In a double-blind randomized trial (ALLHAT), the efficacy of amlodipine 2.5-10 mg/day or lisinopril 10-40 mg/day as the first-choice therapy was compared with that of the thiazide diuretic chlortalidone 12.5-25 mg/day for mild to moderate hypertension. A total of 33,357 hypertensive patients aged 55 years and older were included in the study and followed up for an average of 4.9 years. The combined primary endpoint included death in patients with coronary artery disease or non-fatal myocardial infarction. There were no statistically significant differences in the effect on the primary endpoint of the study in the amlodipine and chlortalidone groups. There was also no significant difference in all-cause mortality between these groups.

Pharmacokinetics:

After oral use of the drug Attento®, the maximum concentration (Cmax) of olmesartan and amlodipine in blood plasma is reached in 1.5-2 hours and 6-8 hours, respectively. The rate and degree of absorption of olmesartan medoxomil and amlodipine in the composition of the drug Attento ® correspond to the rate and degree of absorption of these components in the form of monopreparations. Simultaneous food intake does not affect the bioavailability of olmesartan medoxomil and amlodipine.

Olmesartan medoxomil

Absorption and distribution: olmesartan medoxomil is a prodrug. It is rapidly converted to the pharmacologically active metabolite olmesartan by the action of enzymes (esterases) in the intestinal mucosa and portal blood during absorption from the gastrointestinal tract. Olmesartan medoxomil in unchanged form or with an intact medoxomil fragment is not detected in blood plasma and / or feces. The average bioavailability of olmesartan is 25.6%. Simultaneous food intake does not significantly affect the bioavailability of olmesartan, so olmesartan medoxomil can be taken regardless of food intake.

Cmax of olmesartan in blood plasma is reached on average 2 hours after oral use of olmesartan medoxomil and increases approximately linearly with an increase in a single dose to 80 mg.

Olmesartan is characterized by a high degree of binding to plasma proteins (99.7%), but the potential for a clinically significant shift in the value of protein binding in the interaction of olmesartan with other highly binding and simultaneously used drugs is low (this is confirmed by the absence of a clinically significant interaction between olmesartan and warfarin). The association of olmesartan with blood cells is insignificant. The average volume of distribution after intravenous use is low (16-29 l).

Metabolism and elimination: total plasma clearance is usually 1.3 l / h (coefficient of variation-19%) and is relatively low compared to hepatic blood flow (approximately 90 l/h).

The elimination of olmesartan is carried out in two ways. After a single oral dose of olmesartan medoxomil labeled with the 14C isotope,10-16% of the radioactive substance was excreted by the kidneys (most of it within 24 hours after taking olmesartan medoxomil), and the remaining radioactive substance was excreted through the intestine. Taking into account the systemic bioavailability of 25.6%, it can be calculated that approximately 40% of absorbed olmesartan is excreted through the kidneys, and about 60% – through the hepatobiliary system. The released radioactive substance was represented by olmesartan. No other metabolites were detected. Intestinal-hepatic recirculation of olmesartan is minimal. Since most of olmesartan is excreted through the hepatobiliary system, its use in patients with biliary tract obstruction is contraindicated (see section “Contraindications”). The half-life of olmesartan (T 1/2) is 10-15 hours after repeated oral use. The equilibrium state is reached after taking the first few doses of the drug, after 14 days of repeated use, further accumulation is not observed. Renal clearance is approximately 0.5-0.7 l / h and does not depend on the dose of the drug.

There were no clinically significant differences in the pharmacokinetic parameters of olmesartan depending on gender.

Amlodipine

Absorption and distribution: after oral use in therapeutic doses, amlodipine is well absorbed, the time to reach the maximum concentration (TMAX) is 6-12 hours after use. Absolute bioavailability is about 64-80%. The volume of distribution is about 21 l / kg. In vitro plasma protein binding for circulating amlodipine is approximately 97.5%. Simultaneous food intake does not significantly affect the absorption of amlodipine.

Metabolism and elimination: after a single dose, T 1/2 from the blood plasma in the terminal phase is about 35-50 h. Amlodipine is largely metabolized in the liver with the formation of inactive metabolites,10% of the starting substance and 60% of the metabolites are excreted by the kidneys.

Pharmacokinetics in patients aged 65 years and older

In elderly (65-75 years) and senile (75 years and older) patients with hypertension, the area under the concentration-time curve (AUC) (at steady state) for olmesartan is 35% and approximately 44% larger, respectively, compared to the AUC of olmesartan in younger patients, which may be partly due to age-related decreased renal function.

The time to reach the Cmax of amlodipine in blood plasma does not differ between elderly and young patients. In elderly patients, there is a tendency to decrease the clearance of amlodipine, which leads to an increase in AUC and an elongation of T 1/2.

Pharmacokinetics in patients with renal insufficiency

Olmesartan AUC increases by approximately 62%,82%, and 179%, respectively, in patients with mild, moderate, and severe renal insufficiency compared to healthy volunteers.

Renal insufficiency does not significantly affect the pharmacokinetics of amlodipine. Changes in the concentration of amlodipine in blood plasma do not correlate with the degree of impaired renal function. Amlodipine is not eliminated from the body during dialysis.

Pharmacokinetics in patients with hepatic insufficiency

After a single oral dose, the AUC values of olmesartan were 6% and 65% higher in patients with mild and moderate hepatic insufficiency, respectively, compared with healthy volunteers. The unbound fraction of olmesartan 2 hours after oral use of a single dose of the drug in healthy volunteers, in patients with mild and moderate hepatic insufficiency, was 0.26%,0.34% and 0.41%, respectively. With repeated oral use, the AUC of olmesartan in patients with moderate hepatic insufficiency was 65% higher than in healthy volunteers from the control group. The mean Cmax values of olmesartan in patients with hepatic insufficiency and healthy volunteers were similar. The pharmacokinetics of olmesartan medoxomil in patients with severe hepatic insufficiency have not been studied.

Clinical experience with amlodipine in patients with hepatic insufficiency is limited. Patients in this group show a decrease in amlodipine clearance and an elongation of T 1/2, which leads to an increase in AUC by approximately 40-60%.

Indications

Essential hypertension (if olmesartan monotherapy with medoxomil or amlodipine is ineffective).

Contraindications

Hypersensitivity to olmesartan medoxomil, amlodipine and other derivatives of dihydropyridine or to other components of the drug;

– liver failure severe severity (more than 9 points on a scale child-Pugh);

– obstruction of the bile ducts and cholestasis;

– severe hypotension (SBP less than 90 mm Hg. calendar);

– shock (including cardiogenic);

– hemodynamically unstable heart failure after myocardial infarction;

renal failure severe severity (creatinine clearance (CC) of less than 20 ml/min, the clinical application is not available);

– condition after kidney transplantation (clinical experience missing);

– state, accompanied by a pronounced violation of the outflow of blood from the left ventricle (e. g., stenosis of the mouth of the aorta, severe);

– pregnancy;

– the period of breastfeeding;

– age under 18 years (effectiveness and safetConcomitant use with potassium-sparing diuretics, potassium supplements, dietary salt substitutes containing potassium, or other drugs that increase the level of potassium in the blood plasma (for example, nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 (COX-2) inhibitors), immunosuppressants (for example, cyclosporine or tacrolimus), trimethoprim, angiotensin-converting enzyme inhibitors) is not recommended. enzyme replacement factor (ACE), heparin). If the simultaneous use of these drugs and olmesartan medoxomil is necessary, careful monitoring of the potassium content in the blood plasma is necessary.

Data from clinical studies show that double blockade of the renin-angiotensin-aldosterone system (RAAS) with simultaneous use of ACE inhibitors, ARA II or aliskiren, is associated with a higher incidence of side effects such as hypotension, hyperkalemia and decreased renal function (including the development of acute renal failure) than with the use of only one drug that affects the RAAS. Therefore, concomitant use of ACE inhibitors, ARA II or aliskiren is not recommended.

Concomitant use of olmesartan medoxomil and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and renal insufficiency (with a glomerular filtration rate of less than 60 ml / min/1.73 m2 of body surface area) (see section “Contraindications”).

ACE inhibitors and ARA II inhibitors should not be used simultaneously in patients with diabetic nephropathy.

In cases where the simultaneous use of two drugs that affect the RAAS is necessary, their use should be carried out under the supervision of a doctor and accompanied by regular monitoring of renal function, blood pressure and electrolyte levels in blood plasma.

When used concomitantly with antacids (magnesium and aluminum hydroxide), a moderate decrease in the bioavailability of olmesartan medoxomil is observed.

When olmesartan is co-administered, medoxomil has no clinically significant effect on the pharmacokinetics and pharmacodynamics of warfarin or the pharmacokinetics of digoxin.

The concomitant use of olmesartan medoxomil with pravastatin in healthy volunteers did not have clinically significant effects on the pharmacokinetics of each of the drugs.

There are reports of a reversible increase in the concentration of lithium in blood plasma and the manifestation of toxicity with the simultaneous use of lithium preparations with ACE inhibitors and with ARA II, so the use of olmesartan medoxomil in combination with lithium preparations is not recommended. If appropriate combination therapy is necessary, regular monitoring of the lithium concentration in the blood plasma is recommended.

Clinically significant inhibiting effect of olmesartan on isoenzymes CYP1A1/2, CYP2A6, CYP2C8/9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 cytochrome P-450 human in vitro was not observed in the ratio of cytochrome P-450 in rats observed zero or minimal inducing effects, suggesting no clinically significant interactions with concomitant use of olmesartan medoxomil and drugs metabolized with the participation of the above isoenzymes of cytochrome P-450.

Concomitant use of NSAIDs, including non-selective NSAIDs, selective COX-2 inhibitors, acetylsalicylic acid (at a dose of more than 3 g / day), and ARA II may increase the risk of acute renal failure, so it is recommended to monitor renal function, especially at the beginning of use, as well as regular intake of sufficient fluids by the patient.

At the same time, concomitant use of NSAIDs and ARA II may lead to a weakening of the antihypertensive effect of ARA II, leading to a partial loss of their therapeutic effectiveness.

Colesevelam (bile acid sequestrant)

With the simultaneous use of colesevelam hydrochloride (bile acid sequestrant) and olmesartan medoxomil, there is a weakening of the systemic effect of olmesartan medoxomil, a decrease in its Cmax and T 1/2. Taking olmesartan medoxomil at least 4 hours before taking colesevelam hydrochloride leads to a weakening of this interaction. Olmesartan medoxomil should be taken at least 4 hours before taking colesevelam hydrochloride.

Amlodipine

When amlodipine and other antihypertensive drugs are used simultaneously, their antihypertensive effects are summed up.

Concomitant use of amlodipine with potent or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, azole antifungal drugs, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may significantly increase the concentration of amlodipine in blood plasma. The clinical manifestations of this interaction may be more pronounced in elderly patients, which may require additional monitoring of the patient’s condition and dose adjustment.

There are no data on the effect of inducers of the CYP3A4 isoenzyme on the pharmacokinetics of amlodipine. However, it should be borne in mind that when used simultaneously with inducers of the CYP3A4 isoenzyme (such as rifampicin, St. John’s wort), the concentration of amlodipine in blood plasma may decrease. Caution should be exercised when using amlodipine concomitantly with inducers of the CYP3A4 isoenzyme.

In animal studies, after taking BMCC (verapamil) and intravenous use of dantrolene (a drug for the treatment of malignant hyperthermia) against the background of hyperkalemia, cases of ventricular fibrillation and the development of cardiovascular insufficiency with a fatal outcome were noted.

Due to the risk of hyperkalemia in patients prone to malignant hyperthermia, as well as against the background of the use of dantrolene in malignant hyperthermia, it is recommended to avoid the use of BMCC, such as amlodipine. Despite the fact that amlodipine usually does not have a negative inotropic effect, some BMCs may increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause prolongation of the QT interval (for example, amiodarone, quinidine).

A single 100 mg dose of sildenafil in patients with essential hypertension does not affect the pharmacokinetics of amlodipine. Single and repeated use of amlodipine at a dose of 10 mg does not affect the pharmacokinetics of ethanol.

Antiviral agents (e. g. ritonavir) increase plasma concentrations of BMCC, including amlodipine.

Neuroleptics and isoflurane enhance the antihypertensive effect of BMCC dihydropyridine derivatives.

Calcium supplements may reduce the effect of BMCC.

Cimetidine does not affect the pharmacokinetics of amlodipine.

Concomitant use of aluminum-or magnesium-containing antacids does not significantly affect the pharmacokinetics of amlodipine.

No effect of amlodipine on the pharmacokinetics of atorvastatin, digoxin, warfarin, or cyclosporine has been observed in clinical drug interaction studies.

Concomitant use of amlodipine (10 mg) and simvastatin (80 mg) for a long time resulted in an increase in the concentration of simvastatin in blood plasma by 77% compared to taking simvastatin alone. The dose of simvastatin in patients taking amlodipine should not exceed 20 mg per day.

Concomitant use of amlodipine and grapefruit juice is not recommended, as some patients may have increased bioavailability and increased antihypertensive effects of amlodipine.

When used concomitantly, amlodipine may increase the toxic effect of tacrolimus or cyclosporine, so it is necessary to monitor the concentration of cyclosporine and tacrolimus in blood plasma and adjust the dose if necessary.

How to take, course of use and dosage

Inside. The drug Attento® is taken orally 1 time a day, at the same time, regardless of the time of food intake, without chewing, with a sufficient amount of liquid (for example, a glass of water).

To select the optimal dosage regimen, it is advisable to use the most appropriate dosage of the drug.

Prior to prescribing the combined drug Attento®, it is recommended to pre-select the doses of each of the active substances separately (i. e. olmesartan medoxomil and amlodipine). In the presence of clinical indications, it is allowed to transfer the patient from monotherapy immediately to the use of a combined drug.

Patients receiving combination therapy with monopreparations of olmesartan medoxomil and amlodipine can be transferred to the drug Attento® containing olmesartan medoxomil and amlodipine in similar doses.

Recommended dose:

Daily 1 tablet of the drug Attento® in a dosage of 5 mg + 20 mg, containing 20 mg of olmesartan medoxomil and 5 mg of amlodipine, in the absence of adequate blood pressure reduction against the background of monotherapy with olmesartan medoxomil in a dose of 20 mg or amlodipine in a dose of 5 mg.

In the absence of an adequate reduction in blood pressure against the background of taking the drug Attento in a dosage of 5 mg + 20 mg, it is possible to use the drug Attento® in a dosage of 5 mg + 40 mg (1 tablet) per day, containing 40 mg of olmesartan medoxomil and 5 mg of amlodipine.

If there is no adequate reduction in blood pressure while taking the drug Attento® in a dosage of 5 mg + 40 mg, it is possible to use the drug Attento® in a dosage of 10 mg + 40 mg (1 tablet) per day, containing 40 mg of olmesartan medoxomil and 10 mg of amlodipine.

The maximum daily dose of olmesartan medoxomil is 40 mg. The maximum daily dose of amlodipine is 10 mg.

Use in patients aged 65 years and older

In patients aged 65 years and older with normal renal function, no dose adjustment is required.

When increasing the dose of olmesartan medoxomil to the maximum (40 mg per day) in elderly patients, it is necessary to carefully monitor blood pressure.

Use in patients with renal insufficiency

When using Attento® in patients with mild to moderate renal insufficiency (creatinine clearance 20-60 ml/min), it is recommended to periodically monitor the content of potassium and creatinine in blood plasma. The maximum dose of olmesartan medoxomil for patients with mild to moderate renal insufficiency is 20 mg once a day, since the experience of using higher doses in this category of patients is limited.

In patients with severe renal insufficiency (creatinine clearance less than 20 ml/min), the use of Attento® is contraindicated.

Use in patients with hepatic insufficiency

In patients with mild or moderate hepatic insufficiency (less than 9 points on the Child-Pugh scale), Attento® should be used with caution.

In patients with mild or moderate hepatic insufficiency, the maximum dose of olmesartan medoxomil is 20 mg once a day. The use of amlodipine in patients with impaired liver function should begin with a minimum dose (5 mg).

When used concomitantly with diuretics and/or other antihypertensive drugs in patients with impaired liver function, careful monitoring of blood pressure and renal function is recommended.

The use of the drug Attento® is contraindicated in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale) (no experience of use) (see the section “Contraindications”).

Overdose

No cases of overdose of the drug Attento® have been reported.

Symptoms:

an overdose of olmesartan medoxomil is most likely to cause symptoms such as a marked decrease in blood pressure and tachycardia; bradycardia may develop in the case of parasympathetic stimulation (vagus nerve).

In case of overdose of amlodipine, the most characteristic symptoms are: a pronounced decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation. The risk of developing a pronounced and prolonged decrease in blood pressure, up to the development of shock and death, should be taken into account.

Treatment

It is recommended to use activated charcoal, especially during the first 2 hours after overdose, gastric lavage (in some cases). Taking activated carbon for 2 hours after oral use of amlodipine significantly reduces its absorption.

With a marked decrease in blood pressure, it is recommended to put the patient in a horizontal position, raise his legs and conduct therapy aimed at replenishing the volume of circulating blood, maintaining the function of the cardiovascular system and correcting violations of the water-electrolyte balance. It is necessary to monitor the performance of the heart and lungs, control the volume of circulating blood and diuresis. Vasoconstrictor medications may be prescribed to restore vascular tone and blood pressure in the absence of contraindications.

Intravenous use of calcium gluconate is recommended to eliminate calcium channel blockage.

Since amlodipine is largely bound to plasma proteins, hemodialysis is ineffective. There are no data on the elimination of olmesartan during hemodialysis.

Special instructions

In patients with chronic heart failure, in whom renal function may be significantly affected by RAAS activity (for example, in patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney), the use of drugs that affect RAAS, such as ARA II, can lead to the development of acute arterial hypotension, oliguria, azotemia or, in rare cases, acute renal failure. Therefore, in patients with heart failure, Atteno® should be used with caution.

Since the drug Attento contains amlodipine, which, like other vasodilators, should be used with caution in patients with aortic and / or myrtal stenosis, as well as in patients with hypertrophic obstructive cardiomyopathy.

BMCs should be used with caution in patients with chronic heart failure, as there is evidence that they may increase the risk of cardiovascular complications and mortality. However, studies involving patients with heart failure have shown that amlodipine does not increase the risk of complications and/or mortality.

In a long-term placebo-controlled study of amlodipine in patients with severe heart failure (NYHA class III and IV), there was an increase in the number of reports of pulmonary edema in the amlodipine group compared to the placebo group.

As with any antihypertensive medication, excessive lowering of blood pressure in patients with CHD and cerebrovascular diseases can lead to the development of a heart attack or ischemic stroke.

Patients with hypovolemia and/or hyponatremia resulting from intensive diuretic therapy, restriction of salt intake with food, diarrhea or vomiting may experience symptomatic hypotension, especially after taking the first dose of the drug. These conditions should be corrected before prescribing the drug Attento® or the patient should be closely monitored at the initial stage of therapy.

As with other ARA II and ACE inhibitors, hyperkalemia may occur with the use of Attento®, especially in patients with impaired renal function and / or heart failure. When prescribing the drug Attento® to patients in this group, careful monitoring of the content of potassium and creatinine in blood plasma is recommended. The use of the drug Attento® is contraindicated in severe renal insufficiency (creatinine clearance less than 20 ml / min).

There is no experience with the use of Attento® in patients who have recently undergone a kidney transplant, or in patients with end-stage renal insufficiency (creatinine clearance less than 12 ml/min).

In patients with hepatic insufficiency, the effect of amlodipine and olmesartan medoxomil may increase. Atteno® should be used with caution in patients with mild or moderate hepatic insufficiency (less than 9 points on the Child-Pugh scale). In patients with moderate hepatic insufficiency, the dose of olmesartan medoxomil should not exceed 20 mg. In patients with hepatic insufficiency, the use of amlodipine should be started with the lowest dose and caution should be exercised both at the beginning of treatment and when increasing the dose. The use of Attento® is contraindicated in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale).

Atteno® should be used with caution in combination with potassium supplements, potassium-sparing diuretics, food salt substitutes containing potassium, or other medications that may increase the potassium content (heparin, etc. ); regular monitoring of blood potassium levels is recommended.

Patients with primary aldosteronism usually do not respond to antihypertensive drugs that suppress RAAS. Therefore, the use of the drug Attento® is inappropriate for patients in this category.

As with other ARA II drugs, the antihypertensive effect of Attento® in black patients may be slightly less than in other patients, possibly due to the greater prevalence of low renin levels in this population.

Reversible biochemical changes in the sperm head have been reported in patients taking BMCC. There is insufficient clinical evidence regarding the potential effects of amlodipine on fertility.

Given the presence of amlodipine in the composition of the drug Attento®, during the use of the drug Attento®, it is necessary to monitor the following parameters: body weight, the amount of table salt consumed, oral hygiene and dental supervision (to prevent soreness, bleeding and gum hyperplasia).

Sprue-like enteropathy

In very rare cases, severe chronic diarrhea accompanied by significant weight loss has been reported in patients treated with olmesartan medoxomil for several months to several years. It is possible that these effects are based on a local delayed hypersensitivity reaction. According to the results of the biopsy, atrophy of the intestinal villi was often observed in these cases. If the above symptoms occur during the use of olmesartan medoxomil, other possible causes of diarrhea should be excluded. If it is not possible to determine the possible causes, the use of drugs containing olmesartan medoxomil should be discontinued. If a biopsy confirms the presence of sprue-like enteropathy, the use of drugs containing olmesartan medoxomil should not be resumed, even after the symptoms disappear.

Influence on the ability to drive vehicles and fur. :

During treatment with Attento®, care should be taken when driving vehicles and other mechanisms, when engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions (since side effects such as headache, dizziness, nausea and increased fatigue may develop, especially at the beginning of treatment).

Form of production

Film-coated tablets,5 mg + 20 mg,5 mg + 40 mg,10 mg + 40 mg.

Storage conditions

Store at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 5 years.

Do not use after the expiration date indicated on the package.

Active ingredient

Amlodipine, Olmesartan medoxomil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension