Bisoprolol AML

Arterial hypertension: replacement of therapy with monocomponent drugs amlodipine and bisoprolol in the same doses.

Inside, without chewing, regardless of the meal, in the morning.

The recommended daily dose is 1 tablet. on the day of a certain dosage.

The selection and titration of the dose individually for each patient is carried out by the doctor during the appointment of monocomponent drugs containing active substances that are part of the drug Bisoprolol AML.

Duration of treatment. Treatment with Bisoprolol AML is usually long-term.

Special patient groups

Impaired liver function. In patients with impaired liver function, the elimination of amlodipine may be slowed. A special dosage regimen for this group of patients is not defined, but the drug in this case should be prescribed with caution. For patients with severe hepatic impairment, the maximum daily dose of bisoprolol is 10 mg.

Impaired renal function. Patients with mild or moderate renal impairment usually do not need to adjust the dosage regimen. Amlodipine is not eliminated by dialysis. Patients undergoing dialysis should be prescribed amlodipine with extreme caution. For patients with severe renal impairment (creatinine Cl <20 ml/min), the maximum daily dose of bisoprolol is 10 mg.

Old age. Elderly patients may be prescribed regular doses of the drug. Caution is only required when increasing the dose.

Children. The drug is not recommended for use in children under the age of 18 years due to the lack of data on efficacy and safety.

Treatment should not be stopped abruptly, as this may lead to a temporary deterioration of the clinical condition.

Especially treatment should not be abruptly discontinued in patients with CHD. A gradual dose reduction is recommended.

Amlodipine

unstable angina (with the exception of Prinzmetal angina),

hemodynamically unstable heart failure after myocardial infarction,

clinically significant aortic stenosis.

Bisoprolol

acute heart failure or chronic decompensated heart failure requiring inotropic therapy,

atrioventricular block of II and III degree, without pacemaker,

sinus node weakness syndrome (SSS),

sinoatrial blockade,

severe bradycardia (heart rate <60 beats / min),

severe forms of bronchial asthma or chronic obstructive pulmonary disease,

severe peripheral arterial circulation disorders or Raynaud's syndrome,

pheochromocytoma (without simultaneous use of alpha-blockers),

metabolic acidosis.

Combination of amlodipine bisoprolol

hypersensitivity to amlodipine, other dihydropyridine derivatives, bisoprolol, and / or any of the excipients,

severe arterial hypotension (sBP <100 mmHg).),

shock (including cardiogenic),

children under 18 years of age (efficacy and safety have not been established).

With caution: chronic heart failure (including non-ischemic etiology of the III–IV functional class according to the classification NYHA), hepatic insufficiency, renal insufficiency, hyperthyroidism, diabetes mellitus with significant fluctuations in blood glucose concentration, atrioventricular block of the first degree, Prinzmetal angina, occlusive diseases of the peripheral arteries, psoriasis (in t.tsch. in anamnesis), fasting (strict diet), pheochromocytoma (with simultaneous use of alpha-blockers), bronchial asthma and chronic obstructive pulmonary disease, simultaneously conducted desensitizing therapy, general anesthesia, elderly age, hypotension, type 1 diabetes, aortic stenosis, mitral stenosis, acute myocardial infarction (after the first 28 days)

Adverse side effects observed when using the active ingredients separately are presented according to the following frequency grouping criteria: very often ≥1/10, often ≥1/100 — <1/10, infrequently ≥1/1000 — <1/100, rarely ≥1/10000 — <1/1000, very rarely <1/1000, unknown (an assessment based on available data cannot be made).

Amlodipine

From the blood and lymphatic system: very rarely — leukopenia, thrombocytopenia.

On the part of the immune system: very rarely — allergic reactions.

From the side of metabolism and nutrition: very rarely — hyperglycemia.

Mental disorders: infrequently-insomnia, mood changes (including anxiety), depression, rarely-confusion.

From the nervous system: often-headache, dizziness, drowsiness (especially at the beginning of treatment), infrequently-fainting, hypesthesia, paresthesia, dysgeusia, tremor, very rarely-muscle hypertension, peripheral neuropathy.

On the part of the visual organ: infrequently-visual impairment (including diplopia).

On the part of the organ of hearing and labyrinth disorders: infrequently-tinnitus.

From the gastrointestinal tract: often-nausea, abdominal pain, infrequently-vomiting, changes in the mode of defecation (including constipation or diarrhea), dyspepsia, dryness of the oral mucosa, very rarely-gastritis, gum hyperplasia, pancreatitis.

From the liver and biliary tract: very rarely-hepatitis*, jaundice*.

From the heart: often-a feeling of palpitation, very rarely-myocardial infarction, arrhythmia (bradycardia, ventricular tachycardia, atrial fibrillation).

From the side of the vessels: often-flushes of blood to the face, infrequently-a marked decrease in blood pressure, very rarely-vasculitis.

From the respiratory system, chest and mediastinal organs: infrequently-shortness of breath, rhinitis, very rarely — cough.

From the kidneys and urinary tract: infrequently-pollakiuria, painful urge to urinate, nocturia.

From the genitals and breast: infrequently-impotence, gynecomastia.

General disorders and disorders at the injection site: often-peripheral edema, increased fatigue, infrequently-chest pain, asthenia, pain, general malaise.

From the musculoskeletal system and connective tissue: often-swelling of the ankles, infrequently-arthralgia, myalgia, muscle cramps, back pain.

From the skin and subcutaneous tissues: infrequently — alopecia, purpura, skin discoloration, increased sweating, itching, rash, exanthema, very rarely-angioedema, erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, Quincke's edema, photosensitivity.

Laboratory and instrumental data: infrequently-an increase in body weight, a decrease in body weight, very rarely-an increase in the activity of liver enzymes*.

Bisoprolol

From the side of metabolism and nutrition: rarely-an increase in the concentration of triglycerides.

Mental disorders: infrequently-depression, rarely-hallucinations, nightmares.

From the nervous system: often-headache**, dizziness**, infrequently-insomnia, rarely-fainting.

On the part of the visual organ: rarely-reduced lacrimation (should be taken into account when wearing contact lenses), very rarely-conjunctivitis.

On the part of the organ of hearing and labyrinth disorders: rarely-hearing disorders.

From the heart: infrequently-violation of AV-conduction, bradycardia, aggravation of symptoms of CHF.

From the side of the vessels: often-a feeling of coldness or numbness in the extremities, a pronounced decrease in blood pressure, infrequently-orthostatic hypotension.

From the respiratory system, chest and mediastinal organs: infrequently-bronchospasm in patients with a history of bronchial asthma or airway obstruction, rarely-allergic rhinitis.

From the gastrointestinal tract: often — nausea, vomiting, diarrhea, constipation.

From the liver and biliary tract: rarely-hepatitis.

From the skin and subcutaneous tissues: rarely-hypersensitivity reactions, such as itching, rash, hyperemia of the skin, very rarely-alopecia. Beta-blockers can exacerbate the symptoms of psoriasis or cause a psoriasis-like rash.

From the musculoskeletal system and connective tissue: infrequently-muscle weakness, muscle cramps.

From the genitals and breast: rarely-impotence.

General disorders and disorders at the injection site: often-increased fatigue**, infrequently-exhaustion**.

Laboratory and instrumental data: rarely-increased activity of hepatic transaminases in the blood (ACT, ALT).

*In most cases with cholestasis.

**These symptoms appear especially often at the beginning of the course of treatment. Usually, these phenomena are mild and pass, as a rule, within 1-2 weeks after the start of treatment.

Amlodipine

Symptoms: a marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of developing severe and persistent arterial hypotension, including with the development of shock and death).

Treatment: gastric lavage, administration of activated charcoal, maintenance of CCC function, monitoring of heart and lung function, elevated position of the limbs, control of BCC and diuresis. Intensive symptomatic therapy. To restore vascular tone — the use of vasoconstrictive drugs (in the absence of contraindications to their use), to eliminate the effects of calcium channel blockade-intravenous administration of calcium gluconate. Hemodialysis is ineffective.

Bisoprolol

Symptoms: AV block, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia. Sensitivity to a single dose of high-dose bisoprolol varies greatly among individual patients, and it is likely that patients with CHF have a high sensitivity.

Treatment: if an overdose occurs, first of all, it is necessary to stop taking the drug and start supportive symptomatic therapy.

In severe bradycardia: intravenous administration of atropine. If the effect is insufficient, with caution, you can enter a tool that has a positive chronotropic effect. Sometimes it may be necessary to temporarily set up an artificial pacemaker.

With a pronounced decrease in blood pressure: intravenous administration of plasma-substituting solutions and vasopressors. It may also be indicated in / in the administration of glucagon.

For AV block: patients should be constantly monitored and treated with adrenomimetics such as epinephrine. If necessary — setting up an artificial pacemaker.

In case of exacerbation of the course of CHF: intravenous administration of diuretics, drugs with a positive inotropic effect, as well as vasodilators.

With bronchospasm: the appointment of bronchodilators, including beta₂- adrenomimetics and / or aminophylline.

In hypoglycemia: intravenous administration of dextrose (glucose). Bisoprolol practically does not respond to dialysis.

This drug has pronounced antihypertensive and antianginal effects due to the complementary action of two active ingredients: BCC-amlodipine and selective beta₁- an adrenoblocker-bisoprolol.

The mechanism of action of amlodipine. Amlodipine blocks calcium channels, reduces the transmembrane transfer of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes).

The antihypertensive effect of amlodipine is due to the direct relaxing effect on vascular smooth muscle cells, which leads to a decrease in the resistance of peripheral vessels.

The mechanism of antianginal action is not fully understood, perhaps it is associated with the following two effects:

1. The expansion of peripheral arterioles reduces OPSS, i.e. post-loading. Since amlodipine does not cause reflex tachycardia, the energy and oxygen consumption of the myocardium is reduced.

2. The expansion of large coronary arteries and coronary arterioles improves the oxygen supply to both normal and ischemic areas of the myocardium. These effects improve the oxygen supply to the myocardium, even in cases of coronary artery spasm (Prinzmetal angina or unstable angina).

In patients with arterial hypertension, taking the drug once a day causes a clinically significant decrease in blood pressure in the lying and standing position throughout the 24-hour interval between doses of the drug. Due to the slow development of the antihypertensive effect of amlodipine, it does not cause acute arterial hypotension.

In patients with angina, the drug 1 time per day increases the total execution time for exercise, time to development of angina, and time to a significant reduction in the ST interval, and reduces the frequency of angina attacks and the need of receiving sublingual nitroglycerin. No negative effect of amlodipine on the metabolism of plasma lipids, blood glucose and serum uric acid was found.

The mechanism of action of bisoprolol. Bisoprolol is a selective beta₁- an adrenoblocker without its own sympathomimetic activity-does not have a membrane-stabilizing effect.

It has only a slight affinity for beta₂- adrenoreceptors of the smooth muscles of the bronchi and blood vessels, as well as to beta₂- adrenoreceptors involved in the regulation of metabolism. Therefore, bisoprolol in general does not affect the resistance of the respiratory tract and the metabolic processes in which beta-beta is involved₂- adrenergic receptors.

Selective effect of the drug on beta₁adrenergic receptors and stored outside the therapeutic range. Bisoprolol does not have a pronounced negative inotropic effect.

The maximum effect of the drug is achieved in 3-4 hours after oral administration. Even when bisoprolol is prescribed once a day, its therapeutic effect persists for 24 hours due to a 10-12-hour T_1/2 from the blood plasma.

As a rule, the maximum antihypertensive effect is achieved 2 weeks after the start of treatment.

Bisoprolol reduces the activity of the sympathoadrenal system( SAS) by blocking beta₁- adrenoreceptors of the heart. With a single oral administration in patients with CHD without signs of CHF, bisoprolol reduces the heart rate, reduces the stroke volume of the heart and, as a result, reduces the ejection fraction and the need for oxygen in the myocardium. With long-term therapy initially elevated peripheral vascular resistance is reduced. A decrease in the activity of renin in the blood plasma is considered as one of the components of the hypotensive effect of beta-blockers.

Amlodipine

Suction. Amlodipine is well absorbed after oral administration. C_max in the blood plasma, it is noted after 6-12 hours. Taking the drug with food does not affect its absorption. The absolute bioavailability is 64-80%.

Distribution. Visible V_d it is 21 l / kg. C_ss in the blood plasma (5-15 ng / ml) is reached in 7-8 days after the start of the drug.

Researches in vitro It was shown that circulating amlodipine is approximately 93-98% bound to plasma proteins.

Metabolism and excretion. Amlodipine undergoes intensive metabolism in the liver. Approximately 90% of the dose is converted to inactive pyridine derivatives. Approximately 10% of the dose taken is excreted unchanged in the urine. Approximately 60% of the amount of inactive metabolites is excreted by the kidneys and 20-25% through the intestine. The decrease in the concentration in the blood plasma has a two-phase character.

Final T_1/2 it is approximately 35-50 hours, which allows you to administer the drug once a day. The total clearance is 7 ml / min / kg (25 l / h in patients weighing 60 kg). In elderly patients, it is 19 l/h.

In elderly patients and patients with renal insufficiency, no significant changes in the pharmacokinetics of amlodipine were observed.

Due to the decrease in clearance in patients with hepatic insufficiency should be assigned a lower initial dose.

Amlodipine penetrates through the BBB.

Bisoprolol

Suction. Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability due to insignificant metabolism at the first pass through the liver (at a level of about 10%) is about 90% after oral administration. Food intake does not affect bioavailability. Bisoprolol demonstrates linear kinetics, and its plasma concentrations are proportional to the dose taken in the range from 5 to 20 mg. C_max in the blood plasma, it is reached after 2-3 hours.

Distribution. Bisoprolol is distributed quite widely. V_d it is 3.5 l/kg. The binding to plasma proteins reaches about 30%.

Metabolism. It is metabolized by the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and are excreted by the kidneys. The main metabolites found in blood plasma and urine do not show pharmacological activity.

Data obtained from experiments with human liver microsomes in vitro, show that bisoprolol is primarily metabolized by the CYP3A4 isoenzyme (about 95%), while the CYP2D6 isoenzyme plays only a minor role.

Output. The clearance of bisoprolol is determined by the balance between excretion by the kidneys in unchanged form (about 50%) and metabolism in the liver (about 50%) to metabolites that are also excreted by the kidneys. The total clearance is 15 l / h. T_1/2 - 10-12 hours —

• Antihypertensive agent combined (β₁- adrenoblocker selective blocker of "slow" calcium channels (BMCC) [Beta-blockers in combinations]
• Antihypertensive agent combined (β₁- adrenoblocker selective blocker of "slow" calcium channels (BMCC) [Calcium channel blockers in combinations]

Amlodipine

Concomitant use of amlodipine with thiazide diuretics, beta-blockers, long-acting nitrates, sublingual nitroglycerin preparations, NSAIDs, antibiotics and hypoglycemic agents for oral administration is considered safe.

Inhibitors of CYP3A4. Amlodipine should be used with caution in combination with CYP3A4 inhibitors.

Strong and moderate inhibitors of CYP3A4 (for example, protease inhibitors, antifungal agents of the azole group, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) can increase the concentration of amlodipine in the blood plasma to clinically significant values.

Inducers of CYP3A4. Concomitant use with inducers of CYP3A4 (including rifampicin, St. John's wort) may lead to a decrease in the concentration of amlodipine in the blood plasma. Amlodipine should be used with caution simultaneously with CYP3A4 inducers.

Simvastatin. Concomitant use with amlodipine may lead to an increase in the concentration of simvastatin in the blood plasma.

Patients taking amlodipine are not recommended to use simvastatin at a dose of more than 20 mg / day.

Grapefruit juice, cimetidine, aluminum / magnesium (as part of antacids) and sildenafil do not affect the pharmacokinetics of amlodipine.

Amlodipine may enhance the antihypertensive effect of other antihypertensive agents.

Amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, ethanol (beverages containing alcohol), warfarin or cyclosporine.

Bisoprolol

Not recommended combinations

BCC of the verapamil type and to a lesser extent diltiazem, when used simultaneously with bisoprolol, can lead to a decrease in the contractility of the myocardium, a pronounced decrease in blood pressure and a violation of AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe hypotension and AV block.

Hypotensive agents of central action (such as clonidine, methyldopa, moxonidine, rilmenidine), when used simultaneously with bisoprolol, can lead to a decrease in heart rate and a decrease in cardiac output, as well as to vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal, especially before the withdrawal of beta-blockers, may increase the risk of developing rebound hypertension.

Combinations that require caution

BCC derivatives of dihydropyridine (for example, nifedipine) when used concomitantly with bisoprolol may increase the risk of hypotension. In patients with CHF, the risk of subsequent deterioration of the contractile function of the heart cannot be excluded.

Antiarrhythmic agents of class I (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), when used simultaneously with bisoprolol, can reduce AV conduction and myocardial contractility.

Class III antiarrhythmic agents (for example, amiodarone) can increase the violation of AV conduction.

Parasympathomimetics, when used concomitantly with bisoprolol, may increase the violation of AV conduction and increase the risk of developing bradycardia.

The action of beta-blockers for topical use (for example, eye drops for the treatment of glaucoma) may enhance the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate).

The hypoglycemic effect of insulin or hypoglycemic agents for oral administration may increase. The symptoms of hypoglycaemia, in particular tachycardia can be masked. Such interactions are more likely when using non-selective beta-blockers.

General anaesthetic agents may reduce reflex tachycardia and increase the risk of hypotension (see "Special instructions").

Cardiac glycosides when used concomitantly with bisoprolol can lead to an increase in the time of the pulse and the development of bradycardia.

NSAIDs may reduce the antihypertensive effect of bisoprolol.

Concomitant use of bisoprolol with beta-adrenomimetics (for example, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs.

The combination of bisoprolol with adrenomimetics that affect beta-and alpha-adrenoreceptors (for example, norepinephrine, epinephrine) can enhance the vasoconstrictor effects of these drugs that occur with the participation of alpha-adrenoreceptors, leading to an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers.

Antihypertensive agents, as well as other agents with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines), can enhance the antihypertensive effect of bisoprolol.

Combinations that need to be considered

Mefloquine, when used concomitantly with bisoprolol, may increase the risk of bradycardia.

MAO inhibitors (with the exception of MAO-B inhibitors) may enhance the antihypertensive effect of beta-blockers. Simultaneous use can also lead to the development of a hypertensive crisis.

Rifampicin slightly shortens T_1/2 bisoprolol. As a rule, no dose adjustment is required. Ergotamine derivatives, when used concomitantly with bisoprolol, increase the risk of developing peripheral circulatory disorders.

In a place protected from light, at a temperature not exceeding 25 °C.

Keep out of reach of children.

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

Tablets, 5 mg 5 mg, 5 mg 10 mg, 10 mg 5 mg and 10 mg 10 mg. According to 10 tables. in a contour cell package. According to 30 tables. in a polymer jar or in a polymer bottle.

Each jar or bottle, 3, 5, 6 contour cell packs of 10 tablets, 2, 3 contour cell packs of 30 tablets. they are placed in a cardboard box.

Amlodipine

In experimental studies, the fetotoxic and embryotoxic effects of the drug have not been established, but use during pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus.

There are no data indicating the excretion of amlodipine in breast milk. However, other BCC derivatives of dihydropyridine are known to be excreted in breast milk. In this regard, if it is necessary to prescribe amlodipine during lactation, the issue of stopping breastfeeding should be resolved.

Bisoprolol

The use of bisoprolol during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. Beta-blockers reduce blood flow to the placenta and may affect fetal development.

You should monitor the blood flow in the placenta and uterus, as well as monitor the growth and development of the unborn child, and in case of adverse events in relation to pregnancy and/or the fetus, take alternative therapies. Newborns should be carefully examined after delivery. In the first 3 days of life, symptoms of bradycardia and hypoglycemia may occur.

There are no data on the release of bisoprolol into breast milk. Therefore, its use is not recommended for women during breastfeeding. If taking bisoprolol during lactation is necessary, breastfeeding should be discontinued.

According to the recipe.

Amlodipine

In patients with impaired liver function T_1/2 amlodipine increases. When prescribing the drug to such patients, care should be taken and the activity of liver enzymes should be regularly monitored.

When prescribing amlodipine to patients with CHF, caution should be exercised.

In patients with CHF (including non-ischemic etiology of functional class III-IV according to the classification NYHA) amlodipine increases the risk of pulmonary edema, which is not associated with an aggravation of the symptoms of CHF.

During amlodipine therapy, it is necessary to control body weight and salt intake, and the appropriate diet is indicated.

It is necessary to maintain oral hygiene and follow up with a dentist (to prevent soreness, bleeding and gum hyperplasia).

IVF. In isolated cases, during IVF, against the background of the use of BCC, reversible biochemical changes were noted in the head of spermatozoa, which led to a violation of their functions.

If IVF attempts are unsuccessful and other causes of infertility are excluded, the probability of BCC affecting sperm cells (when used) should be taken into account.

Bisoprolol

Monitoring the condition of patients taking bisoprolol should include measuring heart rate and blood pressure, conducting an ECG, determining the concentration of blood glucose in patients with diabetes mellitus (1 time every 4-5 months).

In elderly patients, it is recommended to monitor kidney function (once every 4-5 months).

The patient should be trained in the method of calculating heart rate and instructed about the need for medical advice with a heart rate of less than 60 beats / min.

Before starting treatment, it is recommended to conduct a study of the function of external respiration in patients with a burdened bronchopulmonary history.

Patients who use contact lenses should take into account that against the background of treatment with the drug, it is possible to reduce the production of tear fluid.

When using bisoprolol in patients with pheochromocytoma, there is a risk of developing paradoxical arterial hypertension (if an effective blockade of alpha-adrenoreceptors is not previously achieved).

In hyperthyroidism, bisoprolol may mask certain clinical signs of hyperthyroidism (for example, tachycardia).

Abrupt discontinuation of the drug in patients with hyperthyroidism should be avoided in order to avoid increased symptoms.

In diabetes mellitus, it can mask tachycardia caused by hypoglycemia. Unlike non-selective beta-blockers, it practically does not increase insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentration to normal values.

With the simultaneous use of clonidine, its reception can be discontinued only a few days after the withdrawal of bisoprolol.

It is possible to increase the severity of hypersensitivity reactions and the lack of effect from the usual doses of epinephrine (epinephrine) against the background of a burdened allergic history.

If it is necessary to carry out planned surgical treatment, bisoprolol should be discontinued 48 hours before general anesthesia. If the patient took bisoprolol before surgery, he should choose a drug for general anesthesia with minimal negative inotropic effect.

Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg).

Drugs that deplete the depot of catecholamines (including reserpine) can enhance the effect of beta-blockers, so patients taking such combinations of drugs should be under constant medical supervision for the detection of a pronounced decrease in blood pressure or the development of bradycardia.

In patients with bronchospastic diseases, cardioselective beta-blockers can be used with caution in case of intolerance and / or ineffectiveness of other antihypertensive agents against the background of simultaneous use of bronchodilators.

Against the background of taking beta-blockers in patients with concomitant bronchial asthma, airway resistance may increase. If the dose of bisoprolol is exceeded, such patients are at risk of developing bronchospasm.

In the case of patients with increasing bradycardia (heart rate less than 60 beats/min), a pronounced decrease in blood pressure (sBP less than 100 mm Hg), AV block, it is necessary to reduce the dose or discontinue treatment.

It is recommended to stop therapy with bisoprolol in the development of depression.

You can not abruptly interrupt treatment due to the risk of developing severe arrhythmias and myocardial infarction. Withdrawal of the drug is carried out gradually, reducing the dose for 2 weeks or more (by 25% in 3-4 days).

The drug should be discontinued before testing the concentration of catecholamines, normetanephrine, vanillylmindalic acid, and antinuclear antibody titers in the blood and urine.

In smokers, the effectiveness of beta-blockers is lower.

The effect of the drug on the ability to drive vehicles, work with moving mechanisms. During treatment with the drug, care must be taken when driving vehicles and working with technically complex mechanisms.

C07FB Beta-blockers, selective in combination with other antihypertensive agents

• I10 Essential (primary) hypertension
• I15 Secondary hypertension

Tablets 5 5 mg and 5 10 mg: white or almost white, round, flat-cylindrical, with a chamfer.

Tablets 10 5 mg and 10 10 mg: white or almost white in color, round, flat-cylindrical, with a chamfer and a risk on one side.