Alotendin tab. 5mg/5mg in blister. in pack No. 10x3 (bisoprolol+amlodipine)

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

A combination drug containing a calcium channel blocker ( amlodipine ) and a β1-adrenergic receptor ( bisoprolol ).

Amlodipine has a hypotensive and antianginal effect. It blocks the flow of calcium into the myocardial cells and vascular muscles. The hypotensive effect is due to the relaxing effect on the vascular muscles. The antianginal effect is realized by dilating peripheral arterioles and coronary arteries. Dilatation increases oxygen access to the myocardium. In case of hypertension, a decrease in blood pressure throughout the day. The onset of action of amlodipine is slow, so there is no sharp decrease in blood pressure.

For angina pectoris , it reduces the frequency of attacks, lengthens the time of physical activity, and reduces the need for nitrates. Does not affect changes in lipid levels, can be used for concomitant diabetes mellitus , asthma and gout .

Bisoprolol also has a hypotensive and antianginal effect. By blocking adrenergic receptors , it reduces the myocardial for oxygen and eliminates the severity of ischemia . The hypotensive effect is achieved after 2 weeks of administration.

Pharmacokinetics

When taken orally, amlodipine Cmax is determined after 6–12 hours . Bioavailability 65–80%. About 95–98% is protein bound. Metabolized in the liver. T½ from the blood - 35–50 hours. Administered mainly by the kidneys.

Bisoprolol is almost completely absorbed from the gastrointestinal tract . Bioavailability - about 90%. The half-life is 10–12 hours. Protein binding is 30%. Half the dose of bisoprolol is metabolized in the liver and excreted as metabolites by the kidneys. The remaining half unchanged is also excreted by the kidneys.

ALOTENDIN 5/10MG TAB No. 30

Instructions

composition
active ingredients : amlodipine, bisoprolol;

1 tablet Alotendin 5 mg / 5 mg 5 mg bisoprolol fumarate 5 mg amlodipine, which corresponds to 6.95 mg amlodipine besilate;

1 tablet of Alotendin 10 mg / 5 mg contains 10 mg of bisoprolol fumarate and 5 mg of amlodipine, which corresponds to 6.95 mg of amlodipine besilate;

1 tablet Alotendin 5 mg / 10 mg 5 mg bisoprolol fumarate and 10 mg amlodipine, which corresponds to 13.9 mg amlodipine besilate;

1 tablet of Alotendin 10 mg / 10 mg contains 10 mg of bisoprolol fumarate and 10 mg of amlodipine, which corresponds to 13.9 mg of amlodipine besilate;

Excipients : microcrystalline cellulose, sodium starch (type A), colloidal silicon dioxide, magnesium stearate.

Dosage form

Pills.

Basic physical and chemical properties:

5 mg / 5 mg tablets: white or almost white, oblong, slightly biconvex, odorless, scored on one side and MS engraved on the other side; tablets 10 mg / 5 mg: white or almost white, oval, slightly biconvex, odorless, scored on one side and MS engraved on the other side; tablets 5 mg / 10 mg: white or almost white, round, flat, beveled tablets, odorless, scored on one side and MS engraved on the other side; 10 mg / 10 mg tablets: white or almost white, round, slightly biconvex, odorless, scored on one side and MS engraved on the other side. Pharmacological group

Selective beta-blockers and other antihypertensive agents. ATX code C07 FB.

Pharmacological properties

Pharmacological.

Amlodipine is a calcium antagonist (slow calcium channel blocker), which blocks the transmembrane flow of calcium ions into myocardial and vascular smooth muscle cells. The mechanism of the antihypertensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle. The antianginal effect of amlodipine is achieved by two mechanisms:

• expansion of peripheral arterioles and, as a result, a decrease in total peripheral resistance (afterload). Since the heart rate does not change, reducing the load on the heart reduces myocardial energy consumption and its oxygen demand;

• expansion of the main coronary arteries and arterioles in both unchanged and ischemic areas of the myocardium. This dilation increases the supply of oxygen to the myocardium

• in patients with vasospastic angina (Prinzmetal's angina or variant angina).

In patients with arterial hypertension, taking amlodipine once a day provides a clinically significant reduction in blood pressure over 24 hours. Due to the slow onset of action of amlodipine, a sharp decrease in blood pressure is not observed.

In patients with angina pectoris, amlodipine prolongs the total time of physical activity, the time before the onset of an angina attack and increases the time until significant ST segment depression occurs, and also reduces the frequency of angina attacks and the need for nitroglycerin.

Amlodipine does not cause undesirable metabolic effects or changes in plasma lipid levels, so it can be used in patients with bronchial asthma, diabetes mellitus and gout.

Bisoprolol is a selective β 1 -adrenergic receptor blocker without BCA, and it also does not have significant membrane-stabilizing properties.

Blocks beta 1-adrenergic receptors and reduces the effect of catecholamines on them. Has hypotensive and antianginal effects.

The mechanism of antihypertensive action is carried out by reducing cardiac output, reducing sympathetic stimulation of peripheral vessels and inhibiting the release of renin by the kidneys.

The antianginal effect is associated with the blockade of β 1 -adrenergic receptors, which leads to a decrease in myocardial oxygen demand due to negative chronotropic and inotropic effects. Thus, bisoprolol eliminates or reduces the symptoms of ischemia.

The maximum effect appears 3-4 hours after oral administration. Typically, the maximum hypertensive effect occurs after 2 weeks of use.

Pharmacokinetics.

Amlodipine.

After administration in therapeutic doses, amlodipine is well absorbed and reaches maximum concentration in the blood 6-12 hours after administration. Food intake does not affect the bioavailability of amlodipine. Bioavailability ranges from 64% to 80%. The volume of distribution is approximately 21 l/kg. In vitro studies have shown that approximately

93-98% of circulating amlodipine is bound to plasma proteins.

Amlodipine is metabolized in the liver to form inactive metabolites, 10% is excreted unchanged in the urine, 60% in the form of metabolites, 20-25% in feces.

The plasma half-life is approximately 35-50 hours, which allows the drug to be administered once a day.

Bisoprolol is almost completely (up to 90%) absorbed from the gastrointestinal tract. The effect of the first passage through the liver is insignificant (about 10%), bioavailability is about 90%. The plasma half-life is 10-12 hours, which provides a therapeutic effect within 24 hours after a single daily dose.

Distribution volume - 3.5 l / kg. Binding to blood plasma proteins is 30%.

Bisoprolol is excreted from the body in two ways. 50% is metabolized by the liver to inactive metabolites, which are then excreted by the kidneys. The remaining 50% is excreted unchanged by the kidneys. Active metabolites are not formed in the human body.

readings

Arterial hypertension, as monotherapy or in combination with other antihypertensive drugs.

Chronic stable angina, as monotherapy or in combination with other antianginal drugs.

As replacement therapy in patients whose blood pressure and/or chronic stable angina is adequately controlled by the simultaneous use of amlodipine and bisoprolol in the same dosages.

Contraindications

For amlodipine/bisoprolol tablets: hypersensitivity to amlodipine, dihydropyridine derivatives, bisoprolol and/or any excipient.

For amlodipine.

• Unstable angina.

• Severe arterial hypotension.

• Shock (including cardiogenic shock).

• Obstruction of the left ventricular outflow tract (eg, severe aortic stenosis).

• Hemodynamically unstable heart failure after acute myocardial infarction.

Bisoprolol:

• acute heart failure or decompensated heart failure, which requires inotropic therapy • cardiogenic shock

• AV blockade of II-III degrees;

• sick sinus syndrome;

• sinoatrial blockade, bradycardia (heart rate less than 60 per minute), before treatment, arterial hypotension (systolic blood pressure <100 mm Hg)

• bronchial asthma, chronic obstructive pulmonary disease;

• severe peripheral circulatory disorders, Raynaud's syndrome;

• untreated pheochromocytoma;

• metabolic acidosis.

Interaction with other drugs and other types of interactions

For amlodipine.

Drugs whose simultaneous use requires caution with thiazide diuretics, beta blockers, long-acting nitrates, sublingual nitroglycerin, NSAIDs, antibiotics and oral hypoglycemic drugs.

The simultaneous use of amlodipine with digoxin does not lead to a change in the concentration of digoxin in the blood plasma and does not affect its renal clearance.

Concomitant use of amlodipine with cimetidine does not affect the pharmacokinetics of amlodipine.

Concomitant use of amlodipine with warfarin does not significantly affect prothrombin time.

The effect of other drugs on amlodipine.

CYP3A4 inhibitors.

Concomitant use of amlodipine and strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may lead to a significant increase in amlodipine exposure, which may lead to an increased risk of hypotension. The clinical significance of such changes may be more pronounced in elderly patients. Clinical monitoring of the patient's condition and dose adjustment may be required.

The simultaneous use of amlodipine and grapefruits or grapefruit juice is not recommended, since in some patients the bioavailability of amlodipine may increase, which, in turn, leads to increased hypotensive effects.

CYP3A4 inducers.

There is no information on the effect of CYP3A4 inducers on amlodipine. The simultaneous use of amlodipine and substances that are CYP3A4 inducers (for example, rifampicin, St. John's wort) may lead to a decrease in the concentration of amlodipine in the blood plasma, so such combinations should be used with caution.

Dantrolene (infusion).

Fatal ventricular fibrillation and cardiovascular collapse, associated with hyperkalemia, were observed in animals after administration of verapamil and dantrolene. Due to the risk of developing hyperkalemia, it is recommended to avoid the use of calcium channel blockers such as amlodipine in patients prone to malignant hyperthermia and in the treatment of malignant hyperthermia.

Effect of amlodipine on other drugs.

The hypotensive effect of amlodipine potentiates the hypotensive effect of other antihypertensive drugs.

Tacrolimus.

There is a risk of increased tacrolimus blood levels when administered concomitantly with amlodipine, but the pharmacokinetic mechanism of this interaction has not been fully established. To avoid tacrolimus toxicity during concomitant use of amlodipine, regular monitoring of tacrolimus blood levels and, if necessary, dosage adjustment are necessary.

Cyclosporine.

Interaction studies between cyclosporine and amlodipine have not been conducted in healthy volunteers or other groups, with the exception of use in kidney transplant patients in whom a variable increase in trough concentrations of cyclosporine has been observed.

Contraindications

Combine contraindications for the use of two components.

For amlodipine :

• severe aortic stenosis ;
• angina .

For bisoprolol :

• cardiogenic shock;
• bradycardia (60 beats/min);
• AV block;
• sinoatrial block;
• bronchial asthma and COPD ;
• Raynaud's syndrome;
• metabolic acidosis.

As well as general contraindications:

• increased sensitivity;
• age under 18 years;
• lactation.

Side effects

Most common adverse reactions:

• swelling of the legs;
• bradycardia;
• fatigue, asthenia ;
• headache;
• tides;
• drowsiness , dizziness ;
• nausea, abdominal pain.

Less common adverse reactions:

• increased fatigue;
• nausea, abdominal pain;
• leukopenia , thrombocytopenia ;
• peripheral neuropathy , hypoesthesia , tremor ;
• visual impairment;
• shortness of breath , rhinitis ;
• tinnitus;
• dyspepsia , pancreatitis , dry mouth, gastritis ;
• frequent urination, nocturia ;
• hyperhidrosis , skin depigmentation, rashes, itching, erythema and urticaria ;
• arthralgia , myalgia , convulsions;
• hyperglycemia;
• vasculitis;
• asthenia , weight gain;
• cholestasis , hepatitis ;
• AV conduction disorder ;
• decreased tear secretion;
• hearing impairment;
• bronchospasm;
• rashes, itching;
• muscle weakness, cramps.

Alotendin tablet 5/10mg N3x10

ALOTENDIN Egis C07F B07

COMPOSITION AND FORM OF RELEASE:

table 5 mg/5 mg blister, No. 28, No. 30, No. 56, No. 90

Bisoprolol fumarate 5 mg Amlodipine 5 mg

1 tablet contains 5 mg of bisoprolol fumarate and 5 mg of amlodipine, which corresponds to 6.95 mg of amlodipine besilate.

No. UA/11609/01/01 from 08/03/2011 to 08/03/2016

table 5 mg/10 mg blister, No. 28, No. 30, No. 56, No. 90

Bisoprolol fumarate 5 mg Amlodipine 10 mg

1 tablet contains 5 mg of bisoprolol fumarate and 10 mg of amlodipine, which corresponds to 6.95 mg of amlodipine besilate.

No. UA/11609/01/03 from 08/03/2011 to 08/03/2016

table 10 mg/5 mg blister, No. 28, No. 30, No. 56, No. 90

Bisoprolol fumarate 10 mg Amlodipine 5 mg

1 tablet contains 10 mg of bisoprolol fumarate and 5 mg of amlodipine, which corresponds to 13.9 mg of amlodipine besilate.

No. UA/11609/01/04 from 08/03/2011 to 08/03/2016

table 10 mg/10 mg blister, No. 28, No. 30, No. 56, No. 90

Bisoprolol fumarate 10 mg Amlodipine 10 mg

1 tablet contains 10 mg of bisoprolol fumarate and 10 mg of amlodipine, which corresponds to 13.9 mg of amlodipine besilate.

No. UA/11609/01/02 from 08/03/2011 to 08/03/2016

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics. Amlodipine is a slow calcium channel blocker that blocks the transmembrane flow of calcium ions into myocardial and vascular smooth muscle cells. The mechanism of the antihypertensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle. The antianginal effect of amlodipine is due to two mechanisms:

• expansion of peripheral arterioles and, as a result, a decrease in peripheral vascular resistance (afterload). Since heart rate does not change, reducing the load on the heart reduces myocardial energy consumption and its oxygen demand;
• expansion of the main coronary arteries and arterioles in both unchanged and ischemic areas of the myocardium. This dilation increases the supply of oxygen to the myocardium in patients with vasospastic angina (Prinzmetal's angina or variant angina).

In patients with hypertension, taking amlodipine once a day provides a clinically significant decrease in blood pressure over 24 hours. Due to the slow onset of action of amlodipine, a sharp decrease in blood pressure is not observed. In patients with angina pectoris, amlodipine prolongs the total time of physical activity, the time until the onset of an angina attack and the time until the onset of significant ST segment depression, and also reduces the frequency of angina attacks and reduces the need for nitroglycerin. Amlodipine does not cause undesirable metabolic effects or changes in plasma lipid levels, so it can be used in patients with asthma, diabetes mellitus and gout. Bisoprolol is a selective β1-adrenergic receptor blocker, without BCA, and also without pronounced membrane-stabilizing properties. Blocks β1-adrenergic receptors and reduces the effect of catecholamines on them. Has antihypertensive and antianginal effects. The mechanism of antihypertensive action is carried out by reducing cardiac output, sympathetic stimulation of peripheral vessels and the release of renin by the kidneys. The antianginal effect is associated with blockade of β1-adrenergic receptors, which leads to a decrease in myocardial oxygen demand through negative chronotropic and inotropic effects. Thus, bisoprolol eliminates or reduces the severity of ischemic symptoms. The maximum effect occurs 3–4 hours after oral administration. Typically, the maximum hypotensive effect is achieved after 2 weeks of use. Pharmacokinetics Amlodipine After oral administration in therapeutic doses, amlodipine is well absorbed and reaches Cmax in the blood 6-12 hours after administration. Food intake does not affect the bioavailability of amlodipine. Absolute bioavailability is 64–80%. The volume of distribution is about 21 l/kg. In vitro studies revealed that about 93–98% of circulating amlodipine is bound to plasma proteins. Amlodipine is metabolized in the liver to form inactive metabolites, 10% of the drug is excreted unchanged in the urine and 60% in the form of metabolites, 20–25% in feces. T½ from blood plasma is about 35–50 hours, which allows you to take the drug once a day. Bisoprolol is almost completely (up to 90%) absorbed from the gastrointestinal tract. The effect of the first passage through the liver is insignificant (about 10%), absolute bioavailability is about 90%. T½ from blood plasma is 10–12 hours, which provides a therapeutic effect for 24 hours after a single daily dose. Volume of distribution - 3.5 l/kg. Binding to blood plasma proteins is 30%. Bisoprolol is excreted from the body in two ways. 50% is metabolized in the liver to inactive metabolites, which are excreted by the kidneys. The remaining 50% is excreted unchanged by the kidneys. Active metabolites are not formed in the human body.

INDICATIONS:

Hypertension, as monotherapy or in combination with other antihypertensive drugs. Stable angina, as monotherapy or in combination with other antianginal drugs. As replacement therapy in patients whose blood pressure and/or stable angina are adequately controlled by the simultaneous use of amlodipine and bisoprolol in the same doses.

APPLICATION:

The recommended daily dose is 1 tablet of the appropriate dosage, which should preferably be taken in the morning, regardless of meals, without chewing. The maximum daily dose is 1 tablet of Alotendin 10 mg/10 mg/day. The dosage range of the drug allows you to flexibly select the ratio of components depending on the clinical need. Treatment should not be stopped suddenly as this may lead to a temporary deterioration of the clinical condition. This is especially true for patients with coronary artery disease. A gradual dose reduction is recommended. Impaired liver and kidney function In liver failure, the elimination of amlodipine slows down. There are no specific recommendations regarding the dosage of amlodipine, so the drug should be prescribed with caution in patients with impaired liver function. In case of severe liver failure, the daily dose of bisoprolol should not exceed 10 mg. There is no need to change the dosage in patients with mild or moderate renal impairment. In case of severe renal failure (creatinine clearance), the usual doses of the drug can be prescribed to elderly patients. The combination drug amlodipine/bisoprolol is not recommended for use in children under the age of 18 years due to the lack of data regarding the safety and effectiveness of the drug.

CONTRAINDICATIONS:

amlodipine: unstable angina, severe aortic stenosis. Bisoprolol: acute heart failure, cardiogenic shock, AV block II-III degree, sick sinus syndrome, sinoatrial block, bradycardia (heart rate Amlodipine/bisoprolol: hypersensitivity to amlodipine, dihydropyridine derivatives, bisoprolol and/or any excipient, period breastfeeding, children under 18 years of age.

SIDE EFFECTS:

may be caused by each of the components of the drug and are presented according to the frequency of occurrence: very often (≥1/10), often (≥1/100, Amlodipine In placebo-controlled studies in patients with hypertension and angina pectoris, the following adverse reactions more often occurred: headache, swelling (especially in the lower legs), increased fatigue, drowsiness, nausea, abdominal pain, hot flashes, palpitations, dizziness. Laboratory tests: very rarely - increased activity of liver enzymes. From the heart: often - increased heart rate. From the blood system and lymphatic system: infrequently - leukopenia, thrombocytopenia, purpura. From the nervous system: often - headache, dizziness, drowsiness; infrequently - peripheral neuropathy, syncope, hypoesthesia, paresthesia, taste disturbance, tremor. From the organ of vision: infrequently - disturbance vision. On the part of the hearing and vestibular apparatus: infrequently - ringing in the ears. From the respiratory system: infrequently - shortness of breath, cough, rhinitis. From the gastrointestinal tract: often - nausea, abdominal pain; uncommon - dyspepsia, gingival hyperplasia, pancreatitis, dry mouth, gastrointestinal motility disorders; very rarely - gastritis. From the kidneys and urinary system: infrequently - frequent urination, urinary dysfunction, nocturia. From the skin and subcutaneous tissues: infrequently - hyperhidrosis, alopecia, skin depigmentation; rarely - allergic reactions, rashes, itching, angioedema, exudative erythema multiforme; very rarely - urticaria. From the musculoskeletal system: uncommon - arthralgia, myalgia, back pain, muscle cramps. Metabolic disorders: uncommon - hyperglycemia. From the side of blood vessels: often - hot flashes; uncommon - vasculitis; rarely - arterial hypotension. General disorders: often - edema, peripheral edema, fatigue; infrequently - exhaustion, asthenia, increase or decrease in body weight. From the hepatobiliary system: very rarely - cholestasis, jaundice, hepatitis. From the reproductive system: infrequently - impotence, gynecomastia. Mental disorders: uncommon - mood changes. Similar to other calcium antagonists, the following adverse reactions have been reported: myocardial infarction, arrhythmia (including ventricular tachycardia and atrial fibrillation), angina pectoris, but it is almost impossible to determine the causal relationship with the underlying disease. Bisoprolol Cardiac disorders: often - bradycardia; infrequently - impaired AV conduction, increased manifestations of heart failure. From the nervous system: often - headache, dizziness; infrequently - sleep disturbance. On the part of the organ of vision: rarely - decreased secretion of tear fluid, which must be taken into account when using contact lenses; very rarely - conjunctivitis. From the organ of hearing and vestibular apparatus: rarely - hearing impairment. From the respiratory system: infrequently - bronchospasm (especially in patients with asthma or with a history of obstructive bronchial diseases); rarely - allergic rhinitis. From the gastrointestinal tract: often - nausea, vomiting, diarrhea, constipation. From the skin and subcutaneous tissues: rarely - allergic reactions, rashes, itching; very rarely - alopecia, psoriatic rashes. From the musculoskeletal system: infrequently - muscle weakness, cramps. Metabolic disorders: rarely - increased TG levels. From the side of blood vessels: often - deterioration of peripheral circulation (feeling of cold in the extremities); infrequently - arterial hypotension. General disorders: often - fatigue, asthenia. From the hepatobiliary system: rarely - increased levels of liver enzymes (ALAT, AST), hepatitis. From the reproductive system: infrequently - impotence. Mental disorders: infrequently - depression; rarely - nightmares, hallucinations. Symptoms such as dizziness, headache, fatigue, asthenia are typical at the beginning of treatment and often disappear within 1–2 weeks.

SPECIAL INSTRUCTIONS:

Amlodipine Patients with impaired liver function. As with other calcium antagonists, the half-life of amlodipine is prolonged in patients with impaired liver function. Therefore, amlodipine should be prescribed to such patients with caution and careful monitoring of liver enzyme levels. Amlodipine should be prescribed with caution in patients with heart failure. For elderly patients, there is no need to change the dosage, but dose increases should be done with caution. Bisoprolol Especially in patients with coronary artery disease, sudden cessation of treatment with bisoprolol, unless clearly indicated, can lead to an exacerbation of the disease. Bisoprolol should be administered with caution to patients with hypertension or angina associated with heart failure. Bisoprolol should be used with caution in the following conditions:

• diabetes mellitus with significant fluctuations in blood glucose levels; symptoms of hypoglycemia may be masked;
• strict fasting or dieting;
• concomitant desensitizing therapy. Bisoprolol may increase sensitivity to allergens and the severity of anaphylactoid reactions;
• AV block of the first degree;
• Prinzmetal's angina;
• peripheral vascular occlusive disease;
• in patients with psoriasis or with a history of psoriasis, use only after a thorough assessment of the benefit/risk ratio;
• when treated with bisoprolol, the symptoms of thyrotoxicosis may be masked;
• in patients with pheochromocytoma, bisoprolol can be used only after therapy with α-adrenergic receptor blockers;
• Before performing general anesthesia, the doctor must be informed about the patient's use of β-adrenergic receptor blockers. If it is necessary to discontinue the use of bisoprolol before surgery, this must be done 48 hours before anesthesia;
• for asthma and other chronic obstructive respiratory diseases, β-adrenergic receptor blockers are used in minimal doses in combination with bronchodilators. Sometimes, in patients with asthma, airway resistance may increase, which may require increasing the dose of β2-agonists.

The drug contains an active substance that leads to a positive result during anti-doping control. Period of pregnancy and lactation Amlodipine Due to insufficient clinical experience regarding the use of the drug during pregnancy and lactation, amlodipine can be prescribed only according to strict indications, provided that the benefit to the mother outweighs the possible risk to the fetus; also in women of reproductive age who do not use effective contraception during treatment. In the absence of alternative therapy, it is recommended to stop breastfeeding. Bisoprolol β-adrenergic receptor blockers reduce placental perfusion, which can lead to growth retardation, fetal death, spontaneous abortion, and premature birth. The fetus/newborn may experience hypoglycemia and bradycardia. If treatment with β-adrenergic blockers is necessary, the use of selective β1-adrenergic blockers is preferable. Bisoprolol should not be used during pregnancy unless there are clear indications for this. If treatment with bisoprolol is necessary, placental circulation and fetal development should be monitored. In case of a negative effect on the course of pregnancy or the fetus, it is necessary to decide on alternative treatment. Newborns should be closely monitored. Hypoglycemia and bradycardia can usually develop in the first 3 days. It is not known whether the drug passes into breast milk and whether bisoprolol is harmful to the baby. In this regard, the use of amlodipine/bisoprolol tablets during breastfeeding is not recommended. Children. Alotendine is not recommended for use in children. The ability to influence reaction speed when driving vehicles and working with other mechanisms. Given the varying individual patient responses, the ability to influence reaction time when driving or operating machinery may be impaired, especially at the beginning of treatment, when treatment is changed, or in the case of simultaneous use of alcohol.

INTERACTIONS:

Amlodipine Drugs whose simultaneous use requires caution: thiazide diuretics, beta-adrenergic blockers, long-acting nitrates, sublingual nitroglycerin, NSAIDs, antibiotics and oral hypoglycemic drugs. The simultaneous use of amlodipine with digoxin does not lead to a change in the concentration of digoxin in the blood plasma and does not affect its renal clearance. Concomitant use of amlodipine with cimetidine does not affect the pharmacokinetics of amlodipine. Concomitant use of amlodipine with warfarin does not significantly affect prothrombin time. Drinking grapefruit juice may lead to a slight increase in plasma concentrations of amlodipine, but this does not lead to clinically significant changes in blood pressure. Bisoprolol Concomitant use with calcium antagonists (verapamil and, to a lesser extent, diltiazem) is not recommended: they negatively affect contractility, atrioventricular conduction and blood pressure. IV administration of verapamil in patients using beta-adrenergic blockers can lead to severe arterial hypotension and AV blockade; centrally acting antihypertensive drugs (clonidine, methyldopa, moxonodine, rilmenidine): simultaneous administration of these drugs can lead to a decrease in heart rate, cardiac output and vasodilation. Sudden discontinuation of the drug may increase the risk of developing withdrawal syndrome in the form of hypertension. Drugs whose simultaneous use requires caution:

• calcium antagonists of the dihydropyridine type, such as nifedipine: due to an increased risk of arterial hypotension and heart failure;
• class I antiarrhythmic drugs (for example, disopyramide, quinidine, lidocaine, phenytoin, flecainide, propafenone): due to an increased negative effect on myocardial inotropic function, AV conduction;
• class III antiarrhythmic drugs (eg amiodarone): due to an increased effect on atrioventricular conduction;
• parasympathomimetics: when used concomitantly, atrioventricular conduction time may increase and therefore increase the risk of bradycardia;
• local agents containing beta-adrenergic blockers (eye drops for the treatment of glaucoma) can complement the systemic action of bisoprolol;
• insulin and oral antidiabetic agents: increased hypoglycemic effect. β-adrenergic receptor blockade may mask signs of hypoglycemia;
• cardiac glycosides: decrease in heart rate, prolongation of AV conduction;
• NSAIDs: decreased antihypertensive effect;
• β-sympathomimetics (isoprenaline, dobutamine): combination with bisoprolol can reduce the severity of the effects of both drugs;
• tricyclic antidepressants, barbiturates, phenothiazines, and other antihypertensive drugs: increase the risk of developing arterial hypotension.

Inhalation anesthetics, hydrocarbon derivatives (chloroform, cyclopropane, halothane, methoxyflurane, etc.): when used simultaneously with beta-adrenergic receptor blockers, the risk of inhibition of myocardial function and the development of hypotensive reactions increases. The effect of non-depolarizing blockers of neuromuscular transmission can be enhanced and prolonged by the influence of beta-adrenergic receptor blockers. Drugs whose simultaneous use requires discussion:

• mefloquine: increased risk of bradycardia;
• MAO inhibitors (except for MAO-B inhibitors): enhancing the hypotensive effect of beta-adrenergic receptor blockers, as well as increasing the risk of a hypertensive crisis.

OVERDOSE:

Amlodipine Due to slow absorption, gastric lavage is an effective procedure. Overdose (high dose intake) of amlodipine can lead to excessive peripheral vasodilation and prolonged arterial hypotension and possibly reflex tachycardia. In case of clinically significant arterial hypotension, it is necessary to actively maintain the function of the cardiovascular system, monitor cardiac and respiratory activity, elevate the lower limbs, monitor blood volume and diuresis, and conduct intensive supportive therapy. It is recommended to use vasoconstrictors to normalize vascular tone and blood pressure, unless there are contraindications to their use. IV administration of calcium gluconate helps neutralize the blockade of calcium channels. Amlodipine is not eliminated by hemodialysis. Bisoprolol The most common symptoms of overdose are bradycardia, arterial hypotension, acute heart failure, bronchospasm, hypoglycemia. In case of overdose, supportive and symptomatic treatment is indicated. Bradycardia is treated with intravenous atropine. If this is not sufficient, isoprenaline or another drug with a positive chronotropic effect can be administered with caution. In some circumstances it may be necessary to install a pacemaker. Arterial hypotension: intravenous infusions, vasopressors. Administration of glucagon may also be helpful. AV block (2nd or 3rd degree): Patients should be under close medical supervision, isoprenaline should be administered, or a pacemaker may need to be installed. Acute heart failure: IV diuretics, drugs with a positive chronotropic effect, and vasodilators should be used. Bronchospasm: use bronchodilators such as isoprenaline, β2-sympathomimetics and/or aminophylline. Hypoglycemia: intravenous administration of glucose solution. There is limited evidence that bisoprolol is almost not eliminated by hemodialysis.

STORAGE CONDITIONS:

at a temperature not exceeding 30 °C.

Alotendin, instructions for use (Method and dosage)

The tablets are taken in the morning without chewing. The daily dose is one tablet of the appropriate dosage. Treatment is started with the minimum dose - Alotendin 5/5 mg, which is gradually increased if necessary. The dosage range makes it possible to select the dose depending on the clinical picture and the prevalence of certain symptoms.

The maximum daily dose is Alotendin 10/10 mg once a day.

In case of severe liver and kidney failure, the dose of bisoprolol should not exceed 10 mg; Alotendin 5/10 mg tablets may be used.

Treatment should not be stopped suddenly, as this may worsen the condition (angina pain appears).

Alotendin tablets 5mg/5mg No. 10x3

Name

Alotendin tab. 5mg/5mg per bl. in pack №10x3

Description

Appearance: Alotendine tablets 5/5 mg: white or off-white, oblong, slightly biconvex, odorless tablets, scored* on one side and MS engraved on the other side. Alotendine tablets 5/10 mg: white or almost white, round, flat, beveled, odorless tablets, scored* on one side and MS engraved on the other side. Alotendine tablets 10/5 mg: white or off-white oval, slightly biconvex, odorless tablets, scored* on one side and MS engraved on the other side. Alotendine tablets 10/10 mg: white or off-white, round, slightly biconvex, odorless tablets, scored* on one side and MS engraved on the other side. *The risk is intended only for the convenience of taking the tablet.

Main active ingredient

Bisoprolol and amlodipine

Release form

7 or 10 tablets in a blister made of a combined “cold” film: (polyamide/aluminum foil/PVC)//aluminum foil. 4 or 8 blisters (7 tablets each) or 3 or 9 blisters (10 tablets each) are placed in a cardboard box along with instructions for medical use for patients.

Dosage

5mg/5mg per bl. in pack №10x3

Indications for use

Alotendine tablets are indicated for the treatment of high blood pressure (hypertension). Alotendine can be used as replacement therapy if your symptoms are adequately controlled by the combined use of amlodipine tablets and bisoprolol tablets at the same doses as in the combination drug.

Directions for use and doses

This medication should be taken strictly as prescribed by your doctor. If you have any questions, ask your doctor or pharmacist. Dosage regimen The usual recommended dose is one tablet of the specific dosage prescribed to you. Special groups of patients Impaired liver and kidney function Usually, with mild to moderate functional failure of the liver and kidneys, there is no need for dose adjustment. In case of severe impairment of liver and kidney function, the dosage may be changed. Elderly patients In elderly patients, no dosage adjustment is required; caution when increasing the dose. Children and adolescents under the age of 18 Alotendin tablets are not recommended for use in children, since the safety and effectiveness of this drug in this category of patients have not been confirmed. Directions for use It is advisable to take Alotendin tablets in the morning, regardless of meals, with a small amount of liquid and without chewing. The risk is intended only for the convenience of taking the tablet. You can use it to break the tablet if you find it difficult to take it whole. If you think that the therapeutic effect of Alotendin tablets is excessive or insufficient, consult your doctor or pharmacist. If you take more tablets than prescribed If you take more Alotendin tablets than you should, consult your doctor immediately. If you forget to take a pill, try to take the missed dose as soon as possible. If it is already time for your next dose, do not take a double dose to make up for the missed dose because you will not make up for it and may increase the risk of overdose. If you stop taking the drug Do not suddenly stop taking the drug or change the recommended dose without checking with your doctor, as this may cause your heart failure to temporarily worsen. Treatment should not be stopped abruptly, which is especially true for patients with diseases of the coronary arteries of the heart. If discontinuation of treatment is required, the dose should be reduced gradually. If you have any additional questions about the use of this drug, contact your doctor or pharmacist.

Use during pregnancy and lactation

If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, tell your doctor or pharmacist before using this drug. Pregnancy Considering the fact that there is no adequate clinical experience with the use of the drug in pregnant women, it can be prescribed only after a thorough individual assessment of the risk/benefit ratio by the attending physician, so warn your attending physician about a possible pregnancy or its planning. If the drug is prescribed during pregnancy, careful monitoring of the condition of the fetus and newborn may be required. Breastfeeding Due to the lack of relevant clinical experience, this drug is not recommended for use in nursing mothers. Check with your healthcare provider before taking any medicine if you are pregnant or breastfeeding.

Precautionary measures

Talk to your doctor or pharmacist before starting to use Alotendin. If you have any of the following conditions, Alotendin tablets should be taken with caution, so be sure to tell your doctor if you have any of the following conditions: old age; heart failure; diabetes mellitus with large fluctuations in blood sugar levels; strict diet; parallel antiallergic (desensitizing) treatment (for example, to prevent allergic rhinitis); minor disturbances of the conduction system of the heart (first degree AV block); impaired perfusion of the coronary arteries (Prinzmetal's angina); vascular diseases of the extremities, characterized by decreased perfusion; psoriasis; hyperthyroidism; liver and kidney diseases; treated pheochromocytoma, which is a rare tumor of the adrenal medulla; bronchial asthma or chronic obstructive pulmonary disease; If you are planning to have surgery, tell the anesthesiologist that you are taking Alotendine tablets. If you have any of the abnormalities listed above, your doctor may decide that you need special help (for example, prescribing additional medications). Children and adolescents under 18 years of age This medicine should not be used in children under 18 years of age due to the lack of data on safety and effectiveness in this age category of patients.

Interaction with other drugs

The therapeutic and side effects of this drug may be changed by other drugs taken at the same time. Interactions may occur even if other drugs are taken for a short period of time. Tell your doctor or pharmacist about any medicines you are taking, have recently taken, or might take, including those taken without a prescription. Co-prescribing of the following drugs is not recommended: Calcium channel blockers such as verapamil and diltiazem: These drugs are used to treat high blood pressure and chronic stable angina. Centrally acting antihypertensives (eg, clonidine, methyldopa, moxonodine, rilmenidine): Do not stop taking these medications without first consulting your doctor. The following drugs may only be co-administered in certain situations, with extreme caution and subject to medical supervision: Certain drugs that affect heart rhythm (quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone, amiodarone). These drugs are used to treat arrhythmias and other heart rhythm disorders. Topical dosage forms of beta blockers (for example, eye drops for the treatment of glaucoma). Parasympathomimetics. These drugs are used to enhance smooth muscle function in diseases of the stomach, small intestine, bladder, and glaucoma. Insulin and oral antidiabetic agents. Sleeping pills and painkillers. Cardiac glycosides (digitalis preparations), drugs used to treat heart failure. Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs may be prescribed to treat joint inflammation, pain, or arthritis. Sympathomimetics (eg, isoprenaline, dobutamine, norepinephrine, epinephrine). These drugs are used to treat serious circulatory problems in emergency situations. Any drugs that cause a decrease in blood pressure due to their therapeutic or undesirable effects (for example, antihypertensive drugs, tricyclic antidepressants, barbiturates, phenothiazines). Dantrolene infusion for the treatment of severe changes in body temperature. Tacrolimus, cyclosporine - immunosuppressants - drugs that suppress the activity of the immune system. Simvastatin is a drug to lower blood cholesterol. Your doctor will decide whether to prescribe the following drugs with the tablets: Mefloquine, used to prevent or treat malaria. Monoamine oxidase inhibitors (MAOIs), used to treat depression. Drugs that affect the metabolism of amlodipine or bisoprolol (for example, rifampicin, ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, indinavir, nelfinavir and drugs containing St. John's wort). Ergotamine derivatives (drugs for the treatment of gynecological bleeding). Interactions with food, drinks and alcohol Alcohol may potentiate the hypotensive (blood pressure-lowering) effect of this drug. The tablets can be taken regardless of meals.

Contraindications

If you are allergic to amlodipine, bisoprolol (active ingredients), digyropyridine derivatives or any of the excipients of Alotendin tablets; If you have a serious obstruction of blood ejection from the left ventricle (severe narrowing of the aorta); If you have acute heart failure, or heart failure after an acute myocardial infarction, requiring intravenous administration of drugs to increase the force of contraction of the heart muscle; If you have shock caused by abnormal heart function (extremely low blood pressure with collapse of the circulatory system); If you have a heart condition characterized by a very slow or irregular heartbeat (2nd or 3rd degree atrioventricular block, sinoatrial block, sick sinus syndrome); If you have a pronounced decrease in blood pressure (the first value is consistently below .Hg); If you have severe bronchial asthma or chronic obstructive pulmonary disease; If you have serious pathology of peripheral arteries; If you have Raynaud's syndrome, which is characterized by numbness, buzzing, and paleness of your fingers and toes when exposed to cold; If you have pheochromocytoma, which is a rare tumor of the adrenal medulla for which you have not received treatment; During metabolic changes, when the pH of the blood changes towards acidification. If you think you have any of the above conditions, talk to your doctor about whether you can take this drug.

Compound

Active ingredients: bisoprolol and amlodipine Excipients: anhydrous colloidal silicon dioxide, magnesium stearate, sodium starch glycolate (type A), microcrystalline cellulose.

Side effect

Like all medicines, this drug may cause side effects, although not everyone gets them. If any of the following occur, consult your doctor: Very common side effects (occurs in more than 1 in 10 patients): Swelling of the ankles. Common side effects (occurs in less than 1 patient in 10): headache, dizziness, drowsiness (especially at the beginning of treatment), visual disturbances (including double vision), palpitations, hot flashes, shortness of breath, abdominal pain, swelling of the ankles, muscle cramps, fatigue, asthenia, feeling of chilliness and numbness in the extremities, gastrointestinal disorders: nausea, vomiting, digestive disorders, irregular bowel movements (including diarrhea and constipation). Uncommon side effects (occurs in less than 1 in 100 patients): insomnia, mood changes (including anxiety), depression, momentary loss of consciousness (syncope), hypoesthesia, paresthesia, changes in taste, tremor, tinnitus, cardiac arrhythmia , decreased blood pressure (hypotension), cough, runny nose, dry mouth, minor hemorrhages in the skin and mucous membranes (purpura), change in skin color, increased sweating, itching, skin rashes, exanthema, urticaria, arthralgia (joint pain), myalgia (muscle pain), back pain, frequent urination, urination disorder, nocturia (nighttime urination), impotence, breast enlargement in men, chest pain, pain, feeling unwell, weight gain or loss, sleep disorders, disorders cardiac conduction, worsening of existing heart failure, slow heart rate (less than 50 beats per minute), bronchospasm in patients with bronchial asthma or a history of obstructive pulmonary disease, muscle weakness, exhaustion*. *This symptom is mainly observed at the beginning of treatment and is usually mild and often goes away within 1-2 weeks. Rare side effects (occurs in no more than 1 patient in 1000): confusion, increased concentration of triglycerides in the blood, nightmares, hallucinations (false perception that appears in the absence of detectable stimuli, similar to the real sensation and appears real to the person), decreased secretion of tear fluid (this should be taken into account if you wear contact lenses), hearing loss, allergic rhinitis, hepatitis, hypersensitivity reactions such as itching, hot flashes, rash, increased levels of liver enzymes. Very rare side effects (occurs in less than 1 in 10,000 patients): low white blood cell and platelet counts, allergic reactions, increased blood sugar, hypertension, peripheral neuropathy, myocardial infarction, focal inflammation of small vessels (vasculitis ), gastritis, gingival hyperplasia, pancreatitis, jaundice, angioedema (acute swelling of the skin or mucous membranes, most often on the eyelids, lips, joints, genitals, glottis, pharynx and tongue), severe inflammation of the skin or mucous membranes with the formation of red blisters (erythema multiforme), severe redness and peeling of the skin (exfoliative dermatitis), blisters on the skin or mucous membranes of the mouth, genitals and anal area, with fever, sore throat and fatigue (Stevens-Johnson syndrome), photosensitivity, conjunctivitis; drugs with a mechanism of action similar to bisoprolol (the active ingredient of the drug) can cause psoriasis (a chronic skin disease in which itchy, flaky red spots appear on the skin) or worsen its course, or cause psoriasis-like skin changes. Such drugs may cause extrapyramidal symptoms (a combination of involuntary movements, muscle rigidity and contractions, and tremors (shaking)). Reporting side effects If you notice any side effects, including those not mentioned in this leaflet, please contact your doctor or pharmacist. By reporting side effects you can help get more information about the safety of this medicine.

Storage conditions

Store at a temperature not exceeding 30°C, out of the reach of children!

Overdose

An overdose of amlodipine is manifested by severe peripheral vasodilation and arterial hypotension , as well as reflex tachycardia . If arterial hypotension is severe, treatment is aimed at maintaining the cardiovascular system. Vasoconstrictors are used intravenous administration of calcium gluconate to neutralize amlodipine . An overdose of bisoprolol is manifested by bradycardia , bronchospasm , arterial hypotension and hypoglycemia . When AV blockade isoprenaline is administered bronchodilators are used to eliminate bronchospasm , hypoglycemia glucose solution .

Interaction

Drinking grapefruit juice leads to increased concentrations of amlodipine .

Prescribe with caution simultaneously with thiazide diuretics, long-acting nitrates, nitroglycerin , NSAIDs , and hypoglycemic drugs.

The use of amlodipine with digoxin , cimetidine , warfarin does not affect the pharmacokinetic parameters of amlodipine .

The simultaneous use of bisoprolol with verapamil and diltiazem negatively affects conductivity and contractility.

Alotendin is prescribed with caution with Nifedipine (due to the high risk of heart failure and hypotension), with quinidine , phenytoin , lidocaine , flecainide , amiodarone .

Local β-adrenergic receptor in the form of eye drops may enhance the effect of bisoprolol .

An increase in the hypoglycemic effect is observed with the use of insulin and hypoglycemic drugs.

NSAIDs cause a decrease in the hypotensive effect.

The risk of arterial hypotension is increased by tricyclic antidepressants, phenothiazines, and barbiturates.

The simultaneous use of cardiac glycosides aggravates bradycardia and prolongs AV conduction .

Inhibition of myocardial function is observed when using inhalation anesthesia, and hypotension .

Alotendin 5 mg/5 mg No. 30 tablet.

Instructions for medical use of the drug ALOTENDIN Trade name Alotendin International nonproprietary name No Dosage form Tablets, 5 mg/5 mg, 10 mg/5 mg, 5 mg/10 mg, 10 mg/10 mg Composition Composition One tablet 5 mg/5 mg contains the active substance - bisoprolol fumarate 5 mg amlodipine 5 mg (in the form of 6.95 mg amlodipine besylate), One 10 mg/5 mg tablet contains the active substance - bisoprolol fumarate 10 mg amlodipine 5 mg (in the form of 6.95 mg amlodipine besylate), One 5 mg/10 mg tablet contains the active substance - bisoprolol fumarate 5 mg amlodipine 10 mg (in the form of 13.9 mg amlodipine besilate), One 10 mg/10 mg tablet contains the active substance - bisoprolol fumarate 10 mg amlodipine 10 mg (in the form of 13 .9 mg amlodipine besylate), excipients: microcrystalline cellulose sodium starch glycolate (type A), magnesium stearate, colloidal anhydrous silicon dioxide Description 5/5 mg tablets: white or almost white, oblong, slightly biconvex, odorless tablets, scored on one side and engraved with a stylized letter E and the number 571 on the other side of the tablet. 5/10 mg tablets: white or off-white oval, slightly biconvex, odorless tablets, scored on one side of the tablet and engraved with a stylized letter E and the number 572 on the other side of the tablet. 10/5 mg tablets: white or off-white, round, flat, bevelled tablets, odorless, scored on one side of the tablet and engraved with a stylized letter E and the number 573 on the other side of the tablet. 10/10 mg tablets: white or off-white, round, slightly biconvex, odorless tablets, scored on one side and engraved with a stylized letter E and the number 574 on the other side of the tablet. Pharmacotherapeutic group Selective beta-blockers in combination with other antihypertensive drugs. ATC code C07FB Pharmacological properties Pharmacokinetics After oral administration, amlodipine is well absorbed and peak blood levels are reached 6-12 hours after administration. Food intake does not affect its bioavailability. Absolute bioavailability is 64-80%. Volume of distribution 21 l/kg. Equilibrium plasma concentration (5-15 ng/ml) is achieved after 7-8 days of daily dosing. In vitro studies have shown that 93-98% of amlodipine circulating in the bloodstream is bound to plasma proteins. Amlodipine is rapidly metabolized (approximately 90%) by the liver to inactive pyridine derivatives. 10% of the parent compound and 60% of inactive metabolites are excreted in the urine, 20-25% in the feces. The decrease in plasma concentration is biphasic. The terminal elimination half-life from blood plasma is approximately 35-50 hours, and corresponds to once daily dosing. The total clearance is 7 ml/min/kg (for a patient weighing 60 kg - 25 l/hour). In elderly patients, this value is 19 l/hour. The pharmacokinetics of amlodipine does not undergo significant changes in renal failure and with increasing age of patients. In case of liver failure - due to decreased clearance - a reduction in the initial dose is recommended. Bisoprolol is almost completely (> 90%) absorbed from the gastrointestinal tract. Due to the very low first-pass effect through the liver (approximately 10%), the absolute bioavailability of the drug after oral administration is about 90%. The volume of distribution is 3.5 l/kg. Bisoprolol binding to plasma proteins is 30%. Bisoprolol is excreted from the body in two ways: 50% is metabolized by the liver to inactive metabolites, which are then excreted by the kidneys. The remaining 50% is excreted unchanged by the kidneys. Since elimination occurs equally in the kidneys and liver, no dosage adjustment is required in patients with mild to moderate hepatic or renal impairment. The total clearance is approximately 15 l/h. The elimination half-life from plasma is about 10 hours. The kinetics of bisoprolol is linear and does not depend on age. Pharmacodynamics Alotendin is a combined antihypertensive drug that contains a slow calcium channel blocker (amlodipine) and a selective beta-blocker (bisoprolol). The drug has an antihypertensive effect. Amlodipine inhibits the transmembrane transition of calcium ions into myocardial and smooth muscle vascular cells (slow calcium channel blocker or calcium ion antagonist). The mechanism of antihypertensive action is associated with a direct relaxing effect on vascular smooth muscle, which leads to a decrease in peripheral vascular resistance. The exact mechanism by which angina symptoms are relieved is not fully established, but may involve: 1) dilatation of peripheral arterioles, thereby reducing total peripheral resistance (afterload). Since this does not lead to reflex tachycardia, myocardial energy expenditure and oxygen demand are reduced. 2) due to the expansion of the main coronary arteries and arterioles, both in normal and ischemic areas, oxygen supply is improved. Due to this, the supply of oxygen to the myocardium increases, even in the case of spasm of the coronary arteries (variant angina or Prinsmetal angina). In patients with arterial hypertension, a single dose of the drug throughout the day provides a clinically significant decrease in blood pressure, both in the supine and standing positions. Due to the slow onset of action, sudden arterial hypotension is not common. In patients with angina pectoris, with a single dose per day, the total time of tolerance to physical activity, the time until the development of an angina attack and the time until significant depression of the ST segment increases, and the frequency of angina attacks and the number of glyceryl trinitrate tablets consumed decreases. This was not associated with adverse metabolic effects: the drug had no effect on plasma lipids, blood sugar or serum uric acid levels, and was beneficial in patients with asthma. Bisoprolol is a potent, highly selective β1-adrenergic blocker, lacking intrinsic sympathomimetic activity (ISA), and it does not have significant membrane-stabilizing properties. It has low affinity for β2 receptors of bronchial and vascular smooth muscle, as well as β2 receptors related to metabolic regulation. For this reason, it is unlikely that bisoprolol has an overall effect on airway resistance and β2-mediated metabolic effects. β1 selectivity extends beyond the therapeutic dosage range. Bisoprolol does not have a clear negative inotropic effect. The maximum effect of bisoprolol develops 3-4 hours after its oral administration. The elimination half-life from plasma (10-12 hours) provides 24-hour effectiveness after once daily dosing of the drug. Typically, the maximum antihypertensive effect develops after 2 weeks. When administered acutely to patients with coronary heart disease without chronic heart failure, bisoprolol reduces heart rate and stroke volume and, thus, cardiac output and oxygen consumption. With prolonged administration, the initially increased peripheral resistance decreases. The antihypertensive effect of β-blockers is, among other things, associated with a decrease in renin activity. Bisoprolol inhibits the response to sympathoadrenergic activation by blocking β-receptors in the heart. This leads to a decrease in heart rate and suppression of myocardial contractility, which leads to a decrease in the oxygen demand of the heart muscle. Indications for use - arterial hypertension in the form of monotherapy or, if necessary, as part of combination therapy with other antihypertensive drugs - chronic stable angina in the form of monotherapy or, if necessary, as part of combination therapy with other antianginal drugs - as replacement therapy in patients blood pressure and/or chronic stable angina pectoris in which can be adequately controlled by the simultaneous use of amlodipine and bisoprolol in the same doses. Method of administration and doses The drug is used strictly as prescribed by the doctor! Alotendine is indicated for patients in whom high blood pressure or coronary vascular pathology can be adequately controlled by separate administration of monocomponent drugs in the same doses as in the recommended fixed combinations. The recommended daily dose is 1 tablet of a certain dosage. Alotendine is recommended to be taken in the morning, regardless of meals, without chewing. Treatment should not be stopped suddenly, as this may lead to a temporary deterioration of the clinical condition. Especially treatment should not be abruptly stopped in patients suffering from coronary heart disease. A gradual dose reduction is recommended. In case of liver failure, elimination of amlodipine may be delayed. There are no precise dosing recommendations for amlodipine, so the drug should be prescribed with caution in these patients. In case of severe liver failure, the daily dose of bisoprolol should not exceed 10 mg. In patients with mild to moderate renal impairment, no dosage change is required. In case of severe renal failure (creatinine clearance less than 20 ml/min), the daily dose of bisoprolol should not exceed 10 mg. Elderly patients can be prescribed the usual doses of the drug. Side effects Often (³1/100 - <1/10) - palpitations, bradycardia - headache, dizziness, drowsiness, fatigue - nausea, vomiting, diarrhea, constipation, abdominal pain - "hot flashes" - swelling, peripheral edema - feeling of coldness and numbness of the extremities Uncommon (³1/1,000 - <1/100) - leukopenia, thrombocytopenia, purpura - visual disturbances, sleep disorders, depression - peripheral neuropathy, syncope, hypoesthesia, paresthesia, taste perversion, tremor - arterial hypotension, AV disorders conductivity, worsening of existing heart failure - shortness of breath, cough, rhinitis, bronchial asthma or bronchospasm with a history of obstructive pulmonary disease - pollakiuria, urination disorder, nocturia - arthralgia, myalgia, muscle cramps, back pain, muscle weakness, cramps - dryness in the mouth, gingival hyperplasia, dyspepsia, pancreatitis - increased sweating, alopecia, skin discoloration - hyperglycemia - vasculitis - exhaustion, asthenia, increase or decrease in body weight - impaired potency, gynecomastia - mood changes Rarely (³1/10,000 - <1/1,000 ) - allergic skin reactions, itching, rash, angioedema, exudative erythema multiforme - hypersensitivity reactions such as itching, hot flashes, rash - arterial hypotension - decreased secretion of tear fluid (this should be taken into account if the patient wears contact lenses) - hearing impairment, nightmares, hallucinations - increased triglyceride levels - allergic rhinitis - increased levels of liver enzymes (ALAT, AST), hepatitis - impaired potency Very rare (<1/10,000), unknown (cannot be assessed based on available data) - urticaria - gastritis - increased levels of liver enzymes - cholestasis, jaundice, hepatitis* Very rare (<1/10,000), - conjunctivitis - alopecia - β-blockers can provoke or worsen the course of psoriasis, or can cause psoriasis-like changes on the skin Mental disorders As well as In the case of other calcium antagonists, undesirable effects have been reported (myocardial infarction, arrhythmia (for example, ventricular tachycardia and atrial fibrillation) and angina), on the basis of which it is impossible to decide whether they are related to the underlying disease or not. * These symptoms are especially typical at the beginning of treatment. In general, they are mildly expressed and most often disappear within 1-2 weeks. Contraindications - hypersensitivity to amlodipine, dihydropyridine derivatives, bisoprolol and/or any of the excipients - unstable angina - severe aortic stenosis - acute heart failure or episodes of heart failure requiring intravenous drugs with inotropic action - cardiogenic shock - AV block II or III degree (without pacemaker) - sick sinus syndrome - sinoatrial block - bradycardia (heart rate less than 60 beats/min) before treatment - arterial hypotension (systolic blood pressure < 100 mmHg) - severe bronchial asthma or severe chronic obstructive pulmonary disease - late stages of occlusive peripheral arterial disease and severe Raynaud's syndrome - untreated pheochromocytoma - metabolic acidosis - breastfeeding Drug interactions Drug interactions are not yet fully known. Caution must be exercised when using the drug together with thiazide diuretics, β-blockers, long-acting nitrates, sublingual glyceryl trinitrate preparations, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs. Co-administration of Alotendin with digoxin did not lead to changes in serum digoxin levels and did not affect the renal clearance of digoxin. Co-administration of the drug with cimetidine did not affect the pharmacokinetics of amlodipine. Amlodipine does not affect the binding of digoxin, phenytoin, coumarin and indomethacin to plasma proteins. Co-administration of Alotendin and warfarin did not cause a significant effect on prothrombin time. Drinking grapefruit juice may result in a slight increase in serum amlodipine levels but does not produce clinically significant changes in blood pressure. Not recommended combinations: - calcium antagonists such as verapamil and, to a lesser extent, such as diltiazem, have a negative effect on contractility, atrioventricular conduction and blood pressure. Intravenous administration of verapamil in patients receiving treatment with beta-blockers can lead to severe hypotension and atrioventricular block; - simultaneous use with centrally acting antihypertensive drugs (for example, clonidine, methyldopa, moxonodine, rilmenidine) can lead to a decrease in heart rate, cardiac output and vasodilation. Abrupt discontinuation of the drug may result in an increased risk of “withdrawal syndrome in the form of hypertension.” Combinations of Alotendine with the following drugs should be used with extreme caution: - calcium antagonists of the dihydropyridine type, such as nifedipine, may increase the risk of arterial hypotension, and in patients with heart failure the risk of increased further deterioration of ventricular pumping function cannot be excluded; - class I antiarrhythmic drugs (for example, disopyramide, quinidine, lidocaine, phenytoin, flecainide, propafenone) may potentiate the effect on atrioventricular conduction time and may enhance the negative inotropic effect; - class III antiarrhythmic drugs (for example, amiodarone) can potentiate the effect on atrioventricular conduction time; - parasympathomimetic drugs can cause an increase in atrioventricular conduction time and, thus, increase the risk of developing bradycardia; - topical preparations containing a beta-blocker (for example, eye drops for the treatment of glaucoma) may alter the systemic effects of the drug; - Insulin and oral antidiabetic drugs may increase the hypoglycemic effect. β-adrenergic receptor blockade may mask symptoms of hypoglycemia; — digitalis glycosides can cause a decrease in heart rate and an increase in atrioventricular conduction time; - non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of the drug; - β-sympathomimetic drugs (for example, isoprenaline, dobutamine) can reduce the effect of both drugs; - antihypertensive drugs, as well as other drugs that have a hypotensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) may increase the risk of arterial hypotension. In patients undergoing general anesthesia, β-blockade reduced the incidence of arrhythmia and myocardial ischemia during induction of anesthesia and intubation, as well as in the postoperative period. It is currently recommended that β-blockade be maintained perioperatively. The anesthesiologist should be aware of β-blockade due to the potential for interaction with other drugs, which can cause bradyarrhythmia, weakening of reflex tachycardia and inhibition of the reflex ability to compensate for blood loss. If it is necessary to discontinue a beta blocker prior to surgery, this should be done gradually and completed within approximately 48 hours prior to anesthesia. Combinations of alotentin with drugs requiring consideration: - Meplokin can increase the risk of bradycardia; -Monoaminoxidase inhibitors (with the exception of Mao-B inhibitors): they can enhance the hypotensive effect of β-blockers, as well as increase the risk of hypertensive crisis. Special instructions in patients with heart failure of the II/III class according to NYHA Alothentin did not cause deterioration in the clinical state with respect to the tolerance of physical exertion, changes in the fraction of the release of the left ventricle and clinical symptoms. In patients with heart failure of the III/IV class, Nyha, using ACE inhibitors, diuretics and digoxin, the addition of alotentin to the treatment regimen did not cause an increase in the frequency of cardiovascular pathology or cardiovascular mortality. Since vasodilation, induced by the technique of alotentin, is characterized by a gradual beginning, cases of acutely developing arterial hypotension were rarely reported. Especially in the case of coronary heart disease, treatment should not be stopped suddenly, unless there are clear indications for the cancellation of the drug, since this can lead to a temporary deterioration in cardiac pathology. Alotentin should be prescribed with particular caution to patients with arterial hypertension or angina pectoris associated with heart failure. The drug should be used with caution in the following conditions: - diabetes mellitus with large fluctuations in blood glucose levels, symptoms of hypoglycemia can be disguised; - strict starvation/diet; -at the same time, the desensitizing therapy (as in the case of taking other β-blockers, the drug can cause an increase in sensitivity to allergens and weighting anaphylactic reactions. The use of adrenaline cannot always give the expected therapeutic effect); -AB-block of I degree; - angina pectoris Princes; - occlusal diseases of the peripheral arteries (increased complaints can be especially pronounced at the beginning of treatment); -psoriasis or its presence in a history-in this case, only β-blockers (bisoprolol) should be used after a thorough consideration of benefits and risks; - in the treatment of alotentin, symptoms of hyperthyroidism can be erased; -patients with pheochromocytoma of alotentin should be prescribed only after the blockade of α-receptors; -Before the general anesthesia, the anesthetist should receive information about the patient’s admission of β-blockers. If it is necessary to cancel the β-blocker before surgical intervention, this should be completed gradually and completed about 48 hours before anesthesia; - with bronchial asthma and other chronic obstructive lung diseases that can cause symptoms, bronze -based therapy should be carried out at the same time. In some cases, patients with bronchial asthma may develop an increase in the resistance in the respiratory tract, and for this reason an increase in the dose of β2-stimulators may require. The use of Alotentin in pediatrics is not recommended for children and adolescents under the age of 18 due to the lack of security and efficiency of use in this category of patients. Pregnancy and breastfeeding in toxicological tests in the effect of amlodipine on reproductive function, any effect on fertility or general reproductive ability was not noted. Like other β-blockers, maternal toxicity and embryonic/ neonatal toxicity were shown in relation to bisoprolol, but no teratogenic effect was observed. Due to the lack of sufficient clinical experience in the use of the drug during pregnancy and lactation, in case of pregnancy or in the case of a question of therapy in women with childbearing potential, not applying effective methods of contraception, amlodipine can only be prescribed for very strict indications after a thorough consideration of the correlation Risk/benefit. In the absence of other alternatives, in the case of alotentin therapy, lactation is recommended. Bisoprolol has pharmacological effects that can cause a harmful effect on pregnancy and/or fetus/newborn. In general, β-blockers reduce placental perfusion, which causes growth retardation, intrauterine death, spontaneous abortion and early birth. In the fetus and a newborn, undesirable effects (hypoglycemia and bradycardia) can be observed. If treatment with β-blockers is necessary, selective β1-blockers are preferred. Alotentin should not be used during pregnancy, unless there are strict indications for that. If treatment with alotentin is considered necessary, careful monitoring of uterine-placental blood flow and fetal growth is required. In case of negative impact on pregnancy or fetus, the issue of alternative treatment should be solved. Newborns should be carefully observed. Symptoms of hypoglycemia and bradycardia are generally expected during the first 3 days. There is no data on the excretion of the drug into breast milk, so the appointment of alotentin when breastfeeding is not recommended. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms. Based on clinical experience, we can assume the lack of influence on these abilities. Nevertheless, given the variability of individual reactions to the drug, the ability to drive vehicles and mechanisms can be violated. Such an effect is most often noted at the beginning of treatment, with a change in treatment and in case of simultaneous use of alcohol. Overdose symptoms: bradycardia, arterial hypotension, bronchospasm, acute heart failure and hypoglycemia. There is wide interpersonal variability in sensitivity and in reaction to a single high dose of bisoprolol: patients with heart pathology are more sensitive to the effects of bisoprolol. With a massive overdose, excess peripheral vasodilation with severe and persistent arterial hypotension and, possibly, reflex tachycardia, is possible. There are data on very rare cases of deliberate overdose. Treatment: with an overdose, the drug should be canceled, and supportive and symptomatic treatment has begun. Taking into account the slow absorption of the drug, gastric lavage. In the case of clinically significant arterial hypotension, active cardiovascular support, monitoring of the heart and breathing, lifting the lower extremities, control over the volume of circulating fluid and diuresis, as well as intense supporting therapy are necessary. The use of vasoconstrictors may be useful in restoring vascular tone and blood pressure, provided that there are no contraindications to their use. Intravenous administration of gluconate calcium can contribute to the regression of the effects of blockade of calcium channels. With bradycardia: intravenous administration of atropine. If the answer is insufficient, isoprenaline or other drugs with a positive chronotropic effect can be prescribed with caution. In some cases, a transvenous installation of an artificial rhythm driver may be required. With arterial hypotension: intravenous infusions and vasopressors; Intravenous introduction of a glucagon. With AB-blockade (II or III degree): carefully monitoring the patient's condition, infusion of isoprenaline or may require implantation of an artificial rhythm driver. With a sudden deterioration of heart failure: intravenous administration of diuretics, drugs with a positive inotropic effect, vasodilators. In bronchospasm: the use of bronchodilators (for example, isoprenaline, β2-sympatomymetics and/or aminophylline). With hypoglycemia: intravenous administration of glucose. Since the drug has a high degree of binding with blood plasma proteins, dialysis will not give tangible benefits. The form of release and packaging tablets 5 mg/5 mg, 10 mg/5 mg, 5 mg/10 mg, 10 mg/10 mg. 7 or 10 tablets in contour cell packages, consisting of a combined film "COLD" (polyamide / aluminum foil / PVC) / aluminum foil. 3 and 9 contour cell packages of 10 tablets, and 4 and 8 contour cell packages of 7 tablets along with instructions for medical use in the state and Russian languages ​​are placed in a pack of cardboard. Shelf life 3 years Do not use after expiration date. Storage conditions Store at a temperature not exceeding 25°C. Keep out of the reach of children! Conditions for the vacation from pharmacies according to the recipe manufacturer OJSC Pharmaceutical Plant EGIS 1106 Budapest, ul. Keresturi, 30-38 Hungary phone: (36-1) 803-5555, fax: (36-1) 803-5529 Address of the organization receiving in the territory of the Republic of Kazakhstan claims from consumers on the quality of products (goods) Representative in the Republic of Kazakhstan OJSC Pharmaceutical Plant AGIS 050060, Almaty, st. Zharokova 286 g of bodies: +, +, fax: +7 (727) 299 79 95, e-mail

Reviews about Alotendin

There are few reviews about the drug, since it is rarely found in the pharmacy chain. All of them are positive and there is little information about side effects. Patients note that the drug was prescribed for a combination of hypertension, angina pectoris and severe tachycardia , with preserved sinus rhythm, resistant to other drugs. This drug was prescribed at first in small doses, and after 2 weeks, under the supervision of a doctor, the dose was increased. This is especially true for the dose of bisoprolol - it was increased to 10 mg over several weeks.

• “... I take Alotendin tablets for high blood pressure. These pills suit me and don’t cause any side effects, my tachycardia has calmed down.”
• “... When I took amlodipine alone, my blood pressure decreased at a high dose, but swelling appeared in my legs. This drug can reduce blood pressure with a lower dose and without swelling.”
• “... I found my drug - it keeps my blood pressure normal, calms my heart and doesn’t bother me with heart pain.”

Instructions for use ALOTENDIN®

— Diabetes mellitus with large fluctuations in blood glucose levels; symptoms of hypoglycemia (tachycardia, palpitations, increased sweating) may be masked.

— Strict fasting/diet.

— Simultaneously carried out desensitizing therapy. Like other beta blockers, bisoprolol can cause increased sensitivity to allergens and worsening anaphylactic reactions. The use of adrenaline may not always give the expected therapeutic effect.

— AV block of the first degree.

- Prinzmetal's angina.

- Occlusive diseases of peripheral arteries (increased complaints can be especially pronounced at the beginning of treatment).

- Psoriasis or a history of it - in this case, beta blockers (for example, bisoprolol) should be used only after a careful assessment of the balance of benefits and risks.

— When treated with bisoprolol, the symptoms of hyperthyroidism may be erased.

— In patients with pheochromocytoma, bisoprolol should be prescribed only after blockade of alpha receptors.

— In patients undergoing general anesthesia, beta blockade reduced the incidence of arrhythmia and myocardial ischemia during induction of anesthesia and intubation, as well as in the postoperative period. It is currently recommended that beta blockade be maintained perioperatively. The anesthesiologist should be aware of beta blockade due to the potential for interaction with other drugs, which can cause bradyarrhythmia, weakening of reflex tachycardia and inhibition of the reflex ability to compensate for blood loss. If it is necessary to discontinue a beta blocker before surgery, this should be done gradually, and completed approximately 48 hours before anesthesia.

- Although cardioselective (β1-selective) beta blockers have a lesser effect on pulmonary function than non-selective beta blockers, their use should be avoided in patients with obstructive pulmonary disease, as with other beta blockers. For bronchial asthma and other chronic obstructive pulmonary diseases that may cause symptoms, bronchodilator therapy should be carried out in parallel. Sometimes patients with bronchial asthma may develop increased airway resistance, and for this reason an increase in the dose of β2-stimulants may be required.

Preclinical safety data

Amlodipine

Reproductive toxicity:

Reproductive toxicity studies in rats and mice have demonstrated delayed onset of labor, delayed delivery, and poorer offspring survival at doses approximately 50 times the maximum recommended human dose on a mg/kg body weight basis.

Carcinogenesis:

In rats and mice fed amlodipine maleate in food for up to two years, at concentrations calculated to provide daily dosing levels of 0.5, 1.25 and 2.5 mg amlodipine/kg/day, there was no evidence of carcinogenicity. effect of the drug. For mice, the highest dose expressed on a mg/m2 basis was similar to the maximum recommended human dose of 10 mg amlodipine/day. For rats, the highest dose on a mg/m2 basis was twice the maximum recommended dose in humans.

Mutagenesis:

Mutagenic studies conducted with amlodipine maleate did not reveal drug-related effects at either the genetic or chromosomal levels.

Fertility:

Fertility problems:

Standard fertility tests showed that amlodipine maleate did not affect the fertility of rats (males - 64 days, females 14 days before mating) treated with this drug in doses up to 10 mg / kg / day, which is 8 times the maximum recommended dose in humans, corresponding to 10 mg/day calculated as mg/m2). However, in another published study, male rats received amlodipine besylate for 30 days at a dose comparable to the human dose on a mg/kg basis; At the same time, a decrease in the levels of follicle-stimulating hormone and testosterone was observed, as well as a decrease in sperm density, the number of mature spermatids and Sertoli cells.

Bisoprolol

Preclinical data did not reveal any particular hazard to humans when conducting traditional studies on pharmacological safety, repeated dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity.

In toxicological tests on the effect of bisoprolol on reproductive function, no effect on fertility or general reproductive capacity was noted.

Like other beta-blockers, bisoprolol caused maternal toxicity (reduced feed intake and decreased body weight gain) and embryonic/fetotoxicity (increased incidence of fetal resorption, decreased body weight of newborn animals, delayed physical development), but did not exhibit teratogenic properties.

Impact on the ability to drive vehicles and operate machinery

Amlodipine may have a slight or moderate effect on the ability to drive vehicles and use machines. If patients taking amlodipine complain of dizziness, headache, fatigue or nausea, their reactivity may be impaired. In a study involving patients with coronary artery disease, bisoprolol did not affect the ability to drive vehicles or operate machines. However, given the variability of individual reactions to this drug, the influence of the drug on the ability to drive vehicles and machinery cannot be ruled out. This effect is most often observed at the beginning of treatment, during changes in treatment, and in the case of concomitant alcohol use.

Alotendin price, where to buy

At the moment, it is impossible to buy Alotendin in the pharmacy chain of the Russian Federation. An analogue is offered - Niperten Combi, the cost of 30 tablets is 307-445 rubles.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine
• Online pharmacies in KazakhstanKazakhstan

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