Attento tabs 10mg + 40mg #28

Attento instruction

You can buy Attento here

The composition of one tablet

Tablets 10 mg + 40 mg
Core:
Active ingredients: olmesartan medoxomil - 40.00 mg, amlodipine besilate -13.888 mg (in terms of amlodipine base - 10.00 mg).
Excipients: pregelatinized starch - 70,000 mg, microcrystalline silicized cellulose * - 65.312 mg, croscarmellose sodium - 10,000 mg, magnesium stearate - 0.800 mg.
Film shell:
Opadry II red 85F25467, consisting of: polyvinyl alcohol - 3.2000 mg, titanium dioxide (Е 171) - 1.4920 mg, macrogol - 1.6160 mg, talc - 1.1840 mg, dye iron oxide yellow (Е 172) - 0.1080 mg, dye iron oxide red (E 172) - 0.4000 mg.
* consists of 98% microcrystalline cellulose and 2% colloidal silicon dioxide.

Description

Tablets 10 mg + 40 mg: round, biconvex tablets, film-coated, reddish-brown, embossed "C77" on one side; in cross section, the core is white.
Pharmacotherapeutic group: antihypertensive agent combined (blocker of “slow” calcium channels + angiotensin II receptor antagonist)
ATX Code: C09DA02

Pharmacodynamics

The drug Attento is a combined antihypertensive drug, which consists of an angiotensin II receptor antagonist (ARA II) - olmesartan medoxomil and a “slow” calcium channel blocker (BMCC) - amlodipine. The combination of two active substances has a synergistic antihypertensive effect, as a result of which the arterial pressure (BP) decreases to a greater extent than when each of them is taken separately.
In the 8-week double-blind, randomized, placebo-controlled study involving 1940 patients, it was shown that the antihypertensive effect of Attento develops, as a rule, during the first 2 weeks of therapy. As was shown in three studies, when using Attento 1 time per day, the antihypertensive effect of Attento is maintained for 24 hours, while the residual / peak ratio for systolic blood pressure (MAP) and diastolic blood pressure (DAD) varied from 71% to 82%. . The antihypertensive effect was confirmed during outpatient monitoring of blood pressure and was not dependent on age and gender, as well as on the presence of diabetes in patients. In two open non-randomized extended studies, the sustained efficacy of Attento at a dosage of 5 mg + 40 mg was shown for 49-67% of patients within one year of use.
In a double-blind, randomized, placebo-controlled study, the addition of amlodipine at a dose of 5 mg with insufficient effectiveness of the previous (within 8 weeks) monotherapy of olmesartan with medoxomil at a dose of 20 mg resulted in 8.2 and 10.6 decrease in GAD and DBP. mm Hg Art. (p = 0.0006), respectively. The proportion of patients in whom target blood pressure values ​​were achieved (<140/90 mmHg for patients without diabetes and <130/80 mmHg for patients with diabetes) was 44.5% in combination therapy olmesartan medoxomil at a dose of 20 mg and amlodipine at a dose of 5 mg compared to 28.5% with monotherapy with 20 mg of olmesartan medoxomil.
In another study, the addition of 20 mg (40 mg) of olmesartan medoxomil with insufficient effectiveness of the previous monotherapy with amlodipine at a dose of 5 mg (for 8 weeks) resulted in 8 weeks of a decrease in GARDEN and DBP by 15.3 and 9.3 mm Hg. Art., respectively (the addition of 40 mg of olmesartan medoxomil - 16.7 and 9.5 mm Hg. Art.). In patients who continued to receive monotherapy with amlodipine at a dose of 5 mg, GARDEN and DBP decreased by 9.9 and 5.7 mm Hg after 8 weeks. Art., respectively.
The proportion of patients who achieved target blood pressure (<140/90 mmHg for patients without diabetes and <130/80 mmHg for patients with diabetes) was 29.9% in the monotherapy group amlodipine in a dose of 5 mg, 53.5% in the Attento group at a dosage of 5 mg + 20 mg and 50.5% in the Attento group at a dosage of 5 mg + 40 mg.
In an 8-week, double-blind, randomized, placebo-controlled study involving 1940 patients (71% of Caucasians and 29% of other races), Attento (with any combination of doses of its components) resulted in a significantly more pronounced decrease in CAD and DBP compared to monotherapy. The degree of reduction in CAD / DAP depended on the doses of amlodipine / olmesartan medoxomil used: -24 / -14 mm Hg. Art. (5 mg + 20 mg), -25 / -16 mm Hg. Art. (5 mg + 40 mg) and -30 / -19 mm. Hg Art. (10 mg + 40 mg).
At use of the drug Attento in a dosage of 5 mg + 40 mg, an additional decrease in SBP / DBP in the sitting position by 2.5 / 1.7 mm Hg was noted. Art. in comparison with use of the drug Attento in a dosage of 5 mg + 20 mg. Similarly, the use of Attento at a dosage of 10 mg + 40 mg resulted in an additional decrease in SBP / DBP in the sitting position by 4.7 / 3.5 mmHg. Art. in comparison with the use of Attento at a dosage of 5 mg + 40 mg. The proportion of patients who managed to achieve target BP values ​​(<140/90 mmHg for patients without diabetes and <130/80 mmHg for patients with diabetes) was 42.5%, 51, 0% and 49.1% for Attento drugs at a dosage of 5 mg + 20 mg, 5 mg + 40 mg and 10 mg + 40 mg, respectively.
Olmesartan medoxomil, which is a part of Attento, is a powerful specific APA II (AT1 type). 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 affecting AT1 receptors. Olmesartan, preventing the binding of angiotensin II to AT1 receptors in tissues (including vascular smooth muscle and adrenal glands), blocks its vasoconstrictor action, as well as the effects associated with the effect of angiotensin II on aldosterone secretion. The specific antagonism of olmesartan in relation to AT1 receptors leads to an increase in the activity of renin, angiotensin I and II in the blood plasma, and also helps to reduce the plasma concentration of aldosterone.
In case of arterial hypertension of olmesartan, medoxomil causes a dose-dependent, prolonged reduction in blood pressure. There is 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 mild decrease in blood pressure for 24 hours. Dividing the daily dose into two doses has an antihypertensive effect similar to that seen when taking the same daily dose at a time. The antihypertensive effect of olmesartan medoxomil occurs, as a rule, already after 2 weeks, and the maximum effect develops approximately 8 weeks after the start of therapy.
To date, data on the effect of olmesartan medoxomil on mortality and morbidity are not available.
In a randomized ROADMAP study involving 4447 patients with type 2 diabetes mellitus, normoalbuminuria and at least one additional cardiovascular risk factor, the ability of olmesartan to increase the time to microalbuminuria was assessed. During the study period (median follow-up was 3.2 g), patients took olmesartan or placebo in addition to other antihypertensive drugs (with the exception of angiotensin-converting enzyme (ACE) or other APA II inhibitors). The study showed a 23% reduction in risk with respect to the primary endpoint (time until microalbuminuria appeared) in favor of olmesartan (ODF 0.770; 95.1% CI: 0.630-0.941; p = 0.0104). Cardiovascular complications (secondary endpoints) were reported in 96 patients (4.3%) in the olmesartan group and in 94 patients (4.2%) in the placebo group.
In a randomized ORIENT study conducted in Japan and China, the effect of olmesartan on renal and cardiovascular outcomes was studied in 577 patients with type 2 diabetes 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 event that will occur first: a doubling of plasma creatinine concentration, development of end-stage chronic kidney disease, death from all causes) was recorded in 116 patients in the olmesartan group (41.1%) and in 129 patients in the placebo group (45.4%) (FIR 0.97; 95% CI: 0.75-1.24; p = 0.791).
Amlodipine, which is part of Attento, is BMCA, blocking the incoming transmembrane current of calcium ions into cardiomyocytes and vascular smooth muscle cells through potential-dependent L-type channels. Experimental data suggest that amlodipine interacts with both the 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 muscle, causing a decrease in peripheral vascular resistance and a decrease in blood pressure.
Amlodipine causes a dose-dependent, prolonged decrease in blood pressure in patients with arterial hypertension. There is no data on the development of arterial hypotension after taking 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 dilation of blood vessels, leading to a decrease in blood pressure (in the patient's position "lying", "sitting" and "standing"). With prolonged use, a decrease in blood pressure is not accompanied by a significant change in heart rate (HR) and catecholamine concentration in the blood plasma. In hypertension in 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 the level of proteinuria.
In hemodynamic studies in patients with heart failure, as well as in clinical studies involving patients with heart failure (NYHA Class II-IV functional class) during the stress test, amlodipine did not worsen the patient's condition, which was assessed by exercise tolerance, ejection fraction left ventricular, as well as on clinical signs and symptoms.
In a placebo-controlled study (PRAISE) involving patients with heart failure (III-IV functional class according to NYHA classification) who received digoxin, diuretics and ACE inhibitors, it was shown that amlodipine does not increase the risk of complications and / or mortality (total and from cardiovascular causes) in patients with heart failure.
In a long-term placebo-controlled study (PRAISE-II) involving patients with heart failure (NYHA Class III-IV functional class) 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 the overall mortality and mortality from cardiovascular causes.
In a double-blind, randomized study (ALLHAT), we compared the efficacy of amlodipine at a dose of 2.5-10 mg / day or lisinopril at a dose of 10-40 mg / day as the first choice therapy, and the use of thiazide diuretic chlortalidone at a dose of 12.5 - 25 mg / day with mild to moderate hypertension. A total of 33,357 patients with hypertension aged 55 years and older were included in the study and were followed up for an average of 4.9 years. The combined primary endpoint included death in patients with ischemic heart 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 chlorthalidone groups. There was also no significant difference in all-cause mortality between these groups.

Pharmacokinetics

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

Olmesartana Medoxomil

Absorption and distribution: olmesartan medoxomil is a prodrug. It quickly turns into a pharmacologically active metabolite of olmesartan under the action of enzymes (esterases) in the intestinal mucosa and in the portal blood during absorption from the gastrointestinal tract. Olmesartan medoxomil unchanged or with an intact medoxomil fragment is not detected in blood plasma and / or feces. The bioavailability of olmesartan is on average 25.6%. Simultaneous ingestion of food does not have a significant effect on the bioavailability of olmesartan, so olmesartan medoxomil can be taken regardless of the meal.
Cmax of olmesartan in plasma is, on average, achieved 2 hours after taking olmesartan medoxomil by mouth 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%), however, the potential for a clinically significant shift in protein binding when olmesartan interacts with other highly binding and simultaneously used drugs is low (a confirmation of this is the absence of clinically significant interaction between olmesartan and warfarin). Communication olmesartan with blood cells is negligible. The average volume of distribution after intravenous administration 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 with hepatic blood flow (approximately 90 l / h).
Removal of olmesartan is carried out in two ways. After a single intake of olmesartan medoxomil labeled with the 14C isotope, 10–16% of the radioactive substance was excreted by the kidneys (most within 24 hours after taking olmesartan medoxomil), and the remaining radioactive substance was secreted through the intestine. Taking into account the systemic bioavailability equal to 25.6%, it can be calculated that approximately 40% of the absorbed olmesartan is eliminated through the kidneys, and about 60% through the hepatobiliary system. The released radioactive substance was represented by olmesartan. No other metabolites were detected. The enterohepatic recirculation of olmesartan is minimal. Since most of olmesartan is excreted through the hepatobiliary system, its use in patients with obstruction of the biliary tract is contraindicated (see the section "Contraindications"). The elimination half-life of olmesartan (T1 / 2) is 10-15 hours after repeated ingestion. The equilibrium state is achieved after taking the first few doses of Attento, after 14 days of repeated use, further cumulation is not observed. Renal clearance is approximately 0.5-0.7 l / h and does not depend on the dose of Attento.
There were no clinically significant differences in pharmacokinetic parameters of olmesartan depending on gender.

Amlodipine

Absorption and distribution: after oral administration in therapeutic doses, amlodipine is well absorbed, the time to reach the maximum concentration (Tx) is 6-12 hours after administration. Absolute bioavailability is about 64-80%. The volume of distribution is about 21 l / kg. In vitro plasma protein binding for circulating amlodipine in the blood is approximately 97.5%. A simultaneous meal does not have a significant effect on the absorption of amlodipine.
Metabolism and excretion: after a single dose of T1 / 2 from blood plasma in the terminal phase is about 35-50 hours. Amlodipine is largely metabolized in the liver to form inactive metabolites, 10% of the original substance and 60% of metabolites excreted by the kidneys.
Pharmacokinetics in patients aged 65 and over
In patients of elderly (65-75 years) and senile age (75 years and older) with hypertension, the area under the concentration-time curve (AUC) (in equilibrium) for olmesartan is 35% more and about 44%, respectively compared with the AUC of olmesartan in younger patients, which may be partly due to the age-related decline in renal function.
The time to achieve Cmax amlodipine in plasma does not differ in elderly patients and in young patients. In elderly patients, there is a tendency to a decrease in the clearance of amlodipine, which leads to an increase in AUC and a prolongation of T1 / 2.

Pharmacokinetics in Patients with Renal Insufficiency

Compared to healthy volunteers, patients with mild, moderate, and severe severity of renal insufficiency of AUC olmesartan increase by approximately 62%, 82%, and 179%, respectively.
Renal failure has no significant effect on the pharmacokinetics of amlodipine. Changes in the concentration of amlodipine in the blood plasma do not correlate with the degree of renal dysfunction. Amlodipine is not excreted during dialysis.

Pharmacokinetics in Patients with Hepatic Insufficiency

After a single oral administration, the values ​​of AUC 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 h after ingestion of a single dose of Attento in healthy volunteers, in patients with mild and moderate hepatic insufficiency was 0.26%, 0.34% and 0.41%, respectively. With repeated intake of AUC olmesartan in patients with moderately severe liver failure was 65% higher than in healthy volunteers from the control group. The mean Cmax values ​​of olmesartan in patients with liver failure and healthy volunteers were similar. The pharmacokinetics of olmesartan medoxomil have not been studied in patients with severe hepatic insufficiency.
Experience with the clinical use of amlodipine in patients with hepatic insufficiency is limited. In patients of this group, there is a decrease in the clearance of amlodipine and a prolongation of T1 / 2, which leads to an increase in AUC by approximately 40-60%.

Indications for use

Essential hypertension (with the ineffectiveness of olmesartan monotherapy with medoxomil or amlodipine).

Contraindications

- hypersensitivity to olmesartan medoxomil, amlodipine and other dihydropyridine derivatives or to other components of the drug;
- liver failure severe severity (more than 9 points on the Child-Pugh scale);
- obstruction of the biliary tract and cholestasis;
- severe arterial hypotension (MAP less than 90 mmHg);
- shock (including cardiogenic);
- hemodynamically unstable heart failure after myocardial infarction;
- renal failure severe severity (creatinine clearance (CC) less than 20 ml / min, no clinical experience);
- condition after kidney transplantation (no clinical experience);
- conditions accompanied by severe impaired outflow of blood from the left ventricle (for example, severe aortic stenosis);
- pregnancy;
- breastfeeding period;
- age up to 18 years (efficacy and safety have not been established);
- simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes and / or impaired renal function (glomerular filtration rate less than 60 ml / min / 1.73 m of body surface area).

Carefully

- Aortic and mitral valve stenosis;
- hypertrophic obstructive cardiomyopathy;
- simultaneous use with lithium preparations (see also the section "Interaction with other medicinal preparations");
- hyperkalemia, hyponatremia;
- hypovolemia (including due to diarrhea, vomiting, or the simultaneous use of diuretics), as well as in patients on a diet with restriction of salt intake;
- renal failure of mild and moderate severity (CC 20-60 ml / min);
- primary aldosteronism;
- renovascular hypertension (bilateral renal artery stenosis or arterial stenosis of a single kidney);
- other conditions accompanied by activation of the renin-angiotensin-aldosterone system;
- chronic heart failure (CHF) (III-IV functional class according to the classification NUNA);
- chronic forms of coronary heart disease;
- acute forms of coronary heart disease (acute myocardial infarction, including within one month after it; unstable stenocardia);
- Sick sinus syndrome;
- arterial hypotension;
- cerebrovascular diseases;
- hepatic failure mild to moderate severity (less than 9 points on the Child-Pugh scale);
- age over 65 years;
- use in patients of the Negroid race.

Use during pregnancy and during breastfeeding

There are no data on the use of Attento during pregnancy. However, due to the existing reports of severe teratogenic effects of drugs acting directly on the renin-angiotensin-aldosterone system, the use of Attento during pregnancy is contraindicated.
In the case of the use of APA II in the second and third trimesters of pregnancy, it is necessary to conduct an ultrasound study to assess kidney function and ossification of the fetal bones. Newborns whose mothers took ARA II should be monitored for possible development of arterial hypotension and impaired renal function.
The data obtained during observations of a limited number of pregnant women did not show that amlodipine or other BMCC have a negative effect on the fetus. However, there is a risk of increasing the length of labor.
Patients planning a pregnancy are recommended to be transferred to antihypertensive drugs of other groups, the safety of which is proven during pregnancy, unless Attento is prescribed for life reasons. In the event of pregnancy during treatment with Attento, the drug should be immediately discontinued and, if necessary, prescribe an alternative treatment with a proven safety profile of use during
It was shown that olmesartan medoxomil penetrates into breast milk in rats, but similar data for humans are not available. Due to the lack of reliable data, the use of Attento during breastfeeding is contraindicated.

Dosage and administration

Inside Attento is taken orally once a day, at the same time, regardless of the time of the meal, without chewing, drinking 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 Attento.
Prior to the appointment of the combined drug Attento, it is recommended to pre-select the doses of each of the active ingredients separately (ie, olmesartan medoxomil and amlodipine). In the presence of clinical indications it is allowed to transfer the patient from monotherapy immediately to the use of the combined drug.
Patients receiving the combination therapy with olmesartan medoxomil and amlodipine monopreparations can be transferred to Attento containing olmesartan medoxomil and amlodipine in similar doses.

Recommended Dose

Daily, 1 tablet of Attento at a dosage of 5 mg + 20 mg, containing 20 mg of olmesartan medoxomil and 5 mg of amlodipine, in the absence of an adequate reduction in blood pressure during the monotherapy of olmesartan with medoxomil at a dose of 20 mg or amlodipine at a dose of 5 mg.
In the absence of an adequate reduction in blood pressure while taking Attento at a dosage of 5 mg + 20 mg, Attento may be used at a dosage of 5 mg + 40 mg (1 tablet) per day, containing 40 mg of olmesartan medoxomil and 5 mg of amlodipine.
In the absence of an adequate reduction in blood pressure while taking Attento at a dosage of 5 mg + 40 mg, Attento may be used at 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 and over

Patients aged 65 years and older with normal renal function do not require dose adjustment.
With an increase in the dose of olmesartan medoxomil to the maximum (40 mg per day), in elderly patients it is necessary to exercise careful control of blood pressure.

Use in patients with renal failure

In the case of Attento in patients with mild to moderate renal insufficiency (CK 20–60 ml / min), it is recommended to periodically monitor the content of potassium and creatinine in the blood plasma.
The maximum dose of olmesartan medoxomil for patients with mild to moderate renal insufficiency is 20 mg once a day, since experience with higher doses in this category of patients is limited.
In patients with severe renal insufficiency (CC less than 20 ml / min), Attento is contraindicated.

Use in patients with hepatic impairment

In patients with mild to moderate hepatic insufficiency (less than 9 points on the Child-Pugh scale), Attento should be used with caution.
In case of hepatic insufficiency of mild or moderate severity, the maximum dose of olmesartan medoxomil is 20 mg once a day. The use of amlodipine in patients with impaired liver function should be started with a minimum dose (5 mg).
With simultaneous use with diuretics and / or other antihypertensive drugs in patients with impaired liver function, careful control of blood pressure and kidney function is recommended.
The use of Attento is contraindicated in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale) (no experience) (see the section “Contraindications”).

Side effect

Possible side effects are listed below in accordance with the classification of the World Health Organization (WHO) by descending frequency of occurrence: very often (≥ 1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, < 1/100), rarely (≥1 / 10000, <1/1000), very rarely, including individual messages (<1/10000), the frequency is unknown (it is impossible to determine the frequency from the available data).
The combination of amlodipine and olmesartan medoxomil
The immune system
Seldom: allergic reactions, hypersensitivity reactions.
The nervous system
Often: dizziness, headache;
Infrequently: hypesthesia, paresthesia, postural dizziness, drowsiness;
Rarely: syncope.
Mental disorders
Infrequently: decrease in a libido.
Since the cardiovascular system
Infrequently: feeling of heartbeat, tachycardia, pronounced decrease in blood pressure, orthostatic hypotension;
Rarely: "tides" of blood to the face.
The respiratory system, organs of the chest and mediastinum
Infrequently: cough, dyspnea.
On the part of the organ of hearing and labyrinth disorders
Infrequently: vertigo.
From the gastrointestinal tract
Infrequently: dryness of the oral mucosa, abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting.
Skin and Subcutaneous Tissues
Infrequently: skin rash.
Rarely: urticaria.
From the musculoskeletal system
Infrequently: back pain, muscle cramps, pain in the limbs.
Kidney and urinary tract
Infrequently: pollakiuria.
From the genitals and mammary glands
Infrequently: erectile dysfunction / impotence.
General violations
Often: increased fatigue, peripheral edema, soft tissue swelling;
Infrequently: asthenia;
Rarely: swelling of the face.
From the laboratory indicators
Infrequently: an increase / decrease in the content of potassium in the blood plasma, an increase in the concentration of uric acid in the blood plasma, an increase in the concentration of creatinine in the blood plasma, an increase in the activity of gamma-glutamyltransferase.

Olmesartan medoxomil (monotherapy)

Blood and lymphatic system
Infrequently: thrombocytopenia.
The immune system
Infrequently: anaphylactic reactions.
Metabolism and nutrition
Often: an increase in plasma triglyceride concentration, an increase in plasma uric acid concentration
Seldom: increase of content of potassium in a blood plasma.
The nervous system
Often: dizziness, headache.
The respiratory system, organs of the chest and mediastinum
Often: pharyngitis, rhinitis, bronchitis, cough.
On the part of the organ of hearing and labyrinth disorders
Infrequently: vertigo.
From the digestive organs
Often: diarrhea, dyspepsia, gastroenteritis, abdominal pain, nausea;
Infrequently: vomiting.
Very rare: spru-like enteropathy.
Liver and biliary tract
Often: increased activity of "liver" enzymes.
Skin and Subcutaneous Tissues
Infrequently: rash, allergic dermatitis, urticaria, skin rash, itching;
Rarely: angioedema.
From the musculoskeletal system
Often: back pain, bone pain, arthritis;
Infrequently: myalgia.
Seldom: muscle cramps.
Kidney and urinary tract
Often: hematuria, urinary tract infections;
Rarely: acute renal failure, renal failure.
Since the cardiovascular system
Infrequently: stenocardia;
Rarely: pronounced decrease in blood pressure.
General violations
Often: chest pain, peripheral edema, flu-like symptoms, fatigue, pain of unspecified location;
Infrequently: swelling of the face, asthenia, general malaise.
Seldom: drowsiness.
From the laboratory indicators
Often: an increase in urea concentration in the blood plasma, an increase in the activity of creatine phosphokinase;
Seldom: increase in concentration of creatinine in a blood plasma.
It was also reported on isolated cases of rhabdomyolysis, which in time of development was associated with the reception of antagonists of receptors AT-II.

Amlodipine (monotherapy)

Blood and lymphatic system
Very rare: leukopenia, thrombocytopenia, thrombocytopenic purpura
The immune system
Very rare: hypersensitivity reactions.
Metabolism and nutrition
Very seldom: increase in concentration of glucose in a blood plasma.
From the psyche
Infrequently: depression, insomnia, irritability, mood lability (including anxiety);
Seldom: confusion of consciousness.
The nervous system
Often: dizziness, headache, drowsiness;
Infrequently: a violation of taste, sleep disturbance, hypesthesia, paresthesia, syncope, tremor, ataxia, amnesia, peripheral neuropathy;
Very rarely: hypertonus, parosmia, apathy, agitation.
From the organ of vision
Infrequently: blurred vision (including diplopia), xerophthalmia, conjunctivitis, eye pain.
On the part of the organ of hearing and labyrinth disorders
Infrequently: tinnitus.
Since the cardiovascular system
Often: "flushes" of blood to the face, feeling of heartbeat;
Infrequently: angina (including exacerbation of coronary heart disease), marked reduction in blood pressure.
Very rarely: cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), development or worsening of CHF, orthostatic hypotension, myocardial infarction, vasculitis.
The respiratory system, organs of the chest and mediastinum
Infrequently: dyspnea, rhinitis, epistaxis;
Very rarely: cough.
From the digestive organs
Often: abdominal pain, nausea.
Infrequently: functional disorders of the intestine (including diarrhea and constipation), dryness of the oral mucosa, dyspepsia, vomiting.
Very rare: gastritis, gingival hyperplasia, pancreatitis.
Liver and biliary tract
Very rarely: increased activity of liver enzymes (in most cases against the background of cholestasis), hepatitis, jaundice, hyperbilirubinemia.
Skin and Subcutaneous Tissues
Infrequently: alopecia, rash, increased sweating, pruritus, skin rash (including hemorrhagic), disorders of skin pigmentation;
Very rarely: angioedema, erythema polymorphic, exfoliative dermatitis, photosensitivity, angioedema, Stevens-Johnson syndrome, urticaria.
From the musculoskeletal system
Often: swelling in the ankles;
Infrequently: arthralgia (pain in the joints), back pain, myalgia, muscle cramps.
Rarely: myasthenia.
Kidney and urinary tract
Infrequently: frequent urination, painful urge to urinate, nocturia.
Very rare: dysuria, polyuria.
Reproductive system and mammary glands
Infrequently: erectile dysfunction / impotence, gynecomastia.
General violations
Often: increased fatigue, edema;
Infrequently: asthenia, chest pain, general malaise, pain of unspecified localization.
Other violations
Infrequently: decrease / increase in body weight.
In patients taking amlodipine, it was also reported on isolated cases of extrapyramidal syndrome.

Overdose

Cases of overdose of the drug Attento are not registered.
Symptoms: in case of an overdose of olmesartan medoxomil, the most likely occurrence of such symptoms as a pronounced decrease in blood pressure and tachycardia; bradycardia may develop in case of parasympathetic stimulation (vagus nerve).
With an 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. You should consider the risk of a pronounced and prolonged decrease in blood pressure up to the development of shock and death.

Treatment

The use of activated carbon is recommended, especially during the first 2 hours after an overdose, gastric lavage (in some cases). The intake of activated carbon within 2 hours after ingestion of amlodipine orally substantially reduces its absorption.
With a pronounced decrease in blood pressure, it is recommended to place the patient in a horizontal position, raising his legs and carry out therapy aimed at filling the circulating blood volume, maintaining the function of the cardiovascular system and correcting impaired water-electrolyte balance. It is necessary to monitor the performance of the heart and lungs, control the volume of circulating blood and diuresis. To restore vascular tone and blood pressure in the absence of contraindications may appoint vasoconstrictor drugs.
Intravenous administration of calcium gluconate is recommended to eliminate the blockade of calcium channels.
Since amlodipine is largely bound to plasma proteins, hemodialysis is ineffective. Data on the removal of olmesartan with hemodialysis are not available.

Interaction with other drugs

The combination of amlodipine and olmesartan medoxomil
The antihypertensive effect of Attento may be enhanced while being used with other antihypertensive drugs (for example, alpha blockers, diuretics).

Olmesartana Medoxomil

Simultaneous use with potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, or other drugs that increase the potassium content in blood plasma (for example, nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 inhibitors (COX-2)) is not recommended. ), immunosuppressants (for example, cyclosporine or tacrolimus), trimethoprim, angiotensin converting enzyme (ACE) inhibitors, heparin). If necessary, the simultaneous use of these drugs and olmesartan medoxomil requires careful monitoring of the content of potassium in the blood plasma.
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 kidney function (in .ch., the development of acute renal failure) than when using only one drug acting on the RAAS. Thus, the simultaneous use of ACE inhibitors, ARA II or aliskiren is not recommended.
The simultaneous use of olmesartan medoxomil and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and renal insufficiency (at a glomerular filtration rate of less than 60 ml / min / 1.73 m of body surface area) (see section "Contraindications").
Patients with diabetic nephropathy should not simultaneously use ACE inhibitors and ARA II.
In the case when the simultaneous use of two agents acting on the RAAS is necessary, their use should be carried out under the supervision of a physician and be accompanied by regular monitoring of renal function, blood pressure indicators and electrolytes in the blood plasma.
With simultaneous use with antacids (magnesium and aluminum hydroxide), a moderate decrease in the bioavailability of olmesartan medoxomil is observed.
With simultaneous use of olmesartan, medoxomil does not have a clinically significant effect on the pharmacokinetics and pharmacodynamics of warfarin or digoxin pharmacokinetics.
The simultaneous use of olmesartan medoxomil with pravastatin in healthy volunteers had no clinically significant effects on the pharmacokinetics of each of the drugs.
There are reports of a reversible increase in plasma concentration of lithium and the manifestation of toxicity with simultaneous use of lithium preparations with ACE inhibitors and with APA II, therefore the use of olmesartan medoxomil in combination with lithium preparations is not recommended. If necessary, the use of appropriate combination therapy is recommended to regularly monitor the concentration of lithium in the blood plasma.
Clinically significant inhibitory effect of olmesartan on isoenzymes CYP1A1 / 2, CYP2A6, CYP2C8 / 9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 of the human cytochrome P450 system in vitro was not detected, in relation to cytochrome P450, rats underwent human cytochrome P450 in vitro; significant interactions with the simultaneous use of olmesartan medoxomil and drugs metabolized with the participation of the above isoenzymes of the cytochrome P450 system.
With simultaneous 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, you may increase the risk of developing acute renal failure, therefore, it is recommended to monitor kidney function, especially at the beginning of use, and also regular patient intake of a sufficient amount of fluid.
However, the simultaneous use of NSAIDs and ARA II can lead to a weakening of the antihypertensive effect of ARA II, leading to a partial loss of their therapeutic efficacy.
Coleveleam (bile acid sequestrant)
With the simultaneous use of wheelevalera hydrochloride (bile acid sequestrant) and olmesartan medoxomil, a weakening of the systemic effect of olmesartan medoxomil, a decrease in its Cmax and T1 / 2, is observed. Taking olmesartan medoxomil at least 4 hours before taking the wheel of hydrochloride leads to a weakening of this interaction. Olmesartan medoxomil should be taken at least 4 hours before taking the wheel of hydrochloride.

Amlodipine

With the simultaneous use of amlodipine and other antihypertensive drugs, their antihypertensive effects are summarized.
With simultaneous use of amlodipine with potent or mild inhibitors of the isoenzyme SURZA4 (protease inhibitors, azole antifungal drugs, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem), a significant increase in plasma amlodipine levels is possible. 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.
Data on the effect of inducers of isoenzyme SURZA4 on the pharmacokinetics of amlodipine is not available. However, it should be borne in mind that when used simultaneously with inducers of the isoenzyme SURZA4 (such as rifampicin, St. John's wort), a decrease in the concentration of amlodipine in the blood plasma is possible. Amlodipine should be used simultaneously with inducers of the CYP3A4 isoenzyme with caution.
In animal studies after taking BMCC (verapamil) and intravenous dantrolene (a drug for treating malignant hyperthermia) amid the development of hyperkalemia, cases of ventricular fibrillation and the development of cardiovascular insufficiency with a lethal outcome were noted.
In connection with the risk of developing hyperkalemia, in patients prone to malignant hyperthermia, as well as against the background of dantrolene use for malignant hyperthermia, it is recommended to avoid using BMCC, such as amlodipine.
Despite the fact that the use of amlodipine negative inotropic action is usually not observed, some BMCC may increase the severity of the negative inotropic action of antiarrhythmic drugs that cause prolongation of the QT interval (for example, amiodarone, quinidine).
A single dose of sildenafil in a dose of 100 mg in patients with essential hypertension does not affect the parameters of amlodipine pharmacokinetics.
A single and repeated administration of amlodipine at a dose of 10 mg does not affect the pharmacokinetics of ethanol.
Antiviral agents (for example, ritonavir) increase plasma concentrations of BCCA, including amlodipine.
Neuroleptics and isoflurane increase the antihypertensive effect of BMCA of dihydropyridine derivatives.
Calcium preparations can reduce the effect of BCCA.
Cimetidine does not affect the pharmacokinetics of amlodipine.
The simultaneous use of aluminum- or magnesium-containing antacids has no significant effect on the pharmacokinetics of amlodipine.
In clinical studies on drug interactions, no effect of amlodipine on the pharmacokinetics of atorvastatin, digoxin, warfarin or cyclosporine was noted.
The simultaneous use of amlodipine (10 mg) and simvastatin (80 mg) for a long time led to an increase in the concentration of simvastatin in the blood plasma by 77% compared to taking only simvastatin. The dose of simvastatin in patients taking amlodipine should not exceed 20 mg per day.
The simultaneous use of amlodipine and grapefruit juice is not recommended, since in some patients it is possible to increase the bioavailability, and enhance the antihypertensive effect of amlodipine.
With simultaneous use of amlodipine can enhance the toxic effect of tacrolimus or cyclosporine, therefore, it is necessary to control the concentration of cyclosporine and tacrolimus in the blood plasma and adjust the dose if necessary.

special instructions

In patients with chronic heart failure, in whom renal function may largely depend on the activity of the RAAS (for example, in patients with bilateral renal artery stenosis or arterial stenosis of the only functioning kidney), the use of drugs that affect the RAAS, such as ARA II, can lead to the development of acute arterial hypotension, oliguria, azotemia, or, in rare cases, acute renal failure. Thus, in patients with heart failure, Attento should be used with caution.
Since Attento contains amlodipine, which, like other vasodilators, should be used with caution in patients with aortic and / or myrtle stenosis, as well as in patients with hypertrophic obstructive cardiomyopathy.
BCCA 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, in studies involving patients with heart failure, it has been shown that amlodipine does not increase the risk of complications and / or mortality.
In the long-term placebo-controlled study of amlodipine in patients with severe heart failure (Grade III and IV according to NYHA classification), an increase in the number of reports of pulmonary edema in the amlodipine group was observed compared with the placebo group.
As with any antihypertensive drugs, an excessive reduction in blood pressure in patients with coronary artery disease and with cerebrovascular diseases can lead to the development of a heart attack or ischemic stroke.
In patients with hypovolemia and / or hyponatremia resulting from intensive diuretic therapy, restriction of salt intake from food, diarrhea or vomiting, symptomatic hypotension may occur, especially after taking the first dose of Attento. These conditions must be corrected before prescribing Attento, or the patient must be carefully monitored at the initial stage of therapy.
As with the use of other ARA II and ACE inhibitors, hyperkalemia may develop with Attento, especially in patients with impaired renal function and / or heart failure. When prescribing Attento, patients in this group are recommended to carefully monitor the content of potassium and creatinine in the blood plasma. The use of Attento is contraindicated in severe renal insufficiency (creatinine clearance less than 20 ml / min).
The experience of using Attento in patients who recently underwent kidney transplantation or in patients with terminal renal insufficiency (creatinine clearance less than 12 ml / min) is absent.
In patients with hepatic insufficiency, the effect of amlodipine and olmesartan medoxomil may be enhanced. Attento should be used with caution in patients with mild to moderate hepatic insufficiency (less than 9 points on the Child-Pugh scale). In patients with moderately severe hepatic insufficiency, the dose of olmesartan medoxomil should not exceed 20 mg. In patients with hepatic impairment, the use of amlodipine should be started at the lowest dose and care should be taken both at the beginning of treatment and when increasing the dose. Use of Attento is contraindicated in patients with severely severe liver failure (more than 9 on the Child-Pugh scale).
Attento should be used with caution simultaneously with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium or other drugs that can increase the potassium content (heparin, etc.); it is recommended that regular monitoring of potassium in the blood.
Patients with primary aldosteronism usually do not respond to hypnotic drugs that suppress RAAS. Therefore, the appointment of the drug Attento is inappropriate for patients in this category.
As with the use of other APA II, the antihypertensive effect of Attento on members of the Negroid race may be somewhat less than on other patients, possibly due to the greater prevalence of low renin levels in this population.
Cases have been reported in patients taking AMCC, reversible biochemical changes have occurred in the sperm head. Clinical data regarding the potential effects of amlodipine on fertility are insufficient.
Taking into account the presence of amlodipine in the Attento preparation, the following parameters should be monitored during Attento use: body weight, the amount of salt consumed, oral hygiene and monitoring by a dentist (to prevent pain, bleeding and gum hyperplasia).

Spru-like enteropathy

In very rare cases, severe chronic diarrhea has been reported, with significant weight loss in patients taking olmesartan medoxomil for several months to several years. It is possible that the basis of these effects is a local delayed hypersensitivity reaction. According to the results of biopsy, atrophy of the villi of the intestine was often observed in these cases. In the event that the above symptoms occur while using olmesartan medoxomil, other possible causes of diarrhea should be excluded. If it is not possible to establish the possible causes, the use of drugs containing olmesartan medoxomil should be discontinued. If biopsy confirms the presence of spru-like enteropathy, the use of drugs containing olmesartan medoxomil should not be resumed, even after the symptoms have disappeared.
Impact on ability to drive vehicles and other mechanisms
During the period of treatment with Attento, care must be taken when driving vehicles and other mechanisms, while engaging in potentially hazardous activities that require increased concentration and psychomotor speed of reaction (because side effects like headache, dizziness, nausea and fatigue, especially at the beginning of treatment).

Release form

Tablets, film coated, 5 mg + 20 mg, 5 mg + 40 mg, 10 mg + 40 mg.
On 14 tablets in the blister strip packaging (blister) from aluminum foil / aluminum foil.
On 1, 2 or 4 blisters with the application instruction in a cardboard pack.

Storage conditions

Store at a temperature not higher than 25 ° С.
Keep out of the reach of children!
Shelf life - 5 years.
Do not use after the expiration date printed on the package.

Terms of sell

The prescription is not required to buy Attento.