Description
Description
Tablets are white or almost white, round, flat-cylindrical with a bevel.
Pharmacological action
This drug has pronounced antihypertensive and antianginal effects due to the complementary effect of two active ingredients: BMKK – amlodipine and selective beta1-blocker – bisoprolol.
Amlodipine mechanism of action:
Amlodipine blocks calcium channels, reduces the transmembrane transition of calcium ions to the cell (more to vascular smooth muscle cells than to cardiomyocytes).
The antihypertensive effect of amlodipine is due to the direct relaxing effect on vascular smooth muscle cells, which leads to a decrease in peripheral vascular resistance. The mechanism of antianginal action has not been fully studied, perhaps it is associated with the following two effects:
1. The expansion of peripheral arterioles reduces the overall peripheral resistance, i.e. afterload Since amlodipine does not cause reflex tachycardia, myocardial energy and oxygen consumption is reduced.
1 Enlargement of the large coronary arteries and coronary arterioles improves oxygen supply to both normal and ischemic myocardial zones. Thanks to these effects, myocardial oxygen supply improves, even with spasm of the coronary arteries (Prinzmetal angina pectoris or unstable angina pectoris).
In patients with arterial hypertension, taking the drug once a day causes a clinically significant decrease in blood pressure in the lying and standing positions throughout the entire 24-hour interval between doses of the drug. Due to the slow development of the antihypertensive effect of amlodipine, it does not cause acute hypotension . In patients with angina pectoris, taking the drug once a day increases the total exercise time, the time before the development of an attack of angina pectoris, as well as the time to significantly reduce the ST interval, and also reduces the frequency of angina attacks and the need for sublingual administration of nitroglycerin. No negative effect of amlodipine on the exchange of blood plasma lipids, blood glucose and uric acid of blood serum was found.
Mechanism of action of bisoprolol:
Bisoprolol is a selective beta1-blocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect.
It has only a slight affinity for the beta2-adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for the beta2-adrenergic receptors involved in the regulation of metabolism.Therefore, bisoprolol as a whole does not affect the resistance of the respiratory tract and metabolic processes in which beta 2-adrenergic receptors are involved.
The selective effect of the drug on beta1-adrenergic receptors remains outside the therapeutic range. Bisoprolol does not have a pronounced negative inotropic effect
The maximum effect of the drug is achieved 3-4 hours after ingestion. Even with the appointment of bisoprolol once a day, its therapeutic effect persists for 24 hours due to the 10-12 hour half-life from 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 (CAS) by blocking the beta1-adrenergic receptors of the heart.
With a single oral administration in patients with coronary heart disease (CHD) without signs of chronic heart failure (CHF), bisoprolol reduces heart rate (HR), reduces stroke volume and, as a result, reduces the ejection fraction and myocardial oxygen demand. With prolonged therapy, initially elevated total peripheral vascular resistance (OPSS) decreases. A decrease in plasma renin activity is considered as one of the components of the hypotensive effect of beta-blockers. Pharmacokinetics Amlodipine:
Absorption:
Amlodipine is well absorbed after oral administration. The maximum concentration in the blood plasma is observed after 6-12 hours. Taking the drug with food does not affect its absorption. Absolute bioavailability is 64 – 80%.
Distribution:
The apparent volume of distribution is 21 l / kg. Equilibrium plasma concentration (5-15 ng / ml) is achieved 7-8 days after the start of the drug.
In vitro studies have shown that circulating amlodipine is approximately 93-98% bound to plasma proteins.
Metabolism and excretion:
Amlodipine undergoes extensive metabolism in the liver. Approximately 90% of the dose taken is converted to inactive pyridine derivatives. About 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 intestines. The decrease in plasma concentration is biphasic. The final half-life is approximately 35-50 hours, which allows the drug to be administered 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 / hour.
In elderly patients and patients with renal failure, no significant changes in the pharmacokinetics of amlodipine were observed. Due to reduced clearance, patients with hepatic insufficiency should be given lower initial doses.
Amlodipine crosses the blood-brain barrier. Bisoprolol:
Suction. Bisoprolol is almost completely absorbed (more than 90%) from the gastrointestinal tract. Its bioavailability due to insignificant metabolism at the first passage through the liver (at the level of about 10%) is about 90% after ingestion. Eating 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. The maximum concentration in blood plasma is reached after 2-3 hours.
distribution. Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l / kg. Communication with plasma proteins reaches approximately 30%.
Metabolism. It is metabolized via the oxidative pathway without subsequent conjugation. All metabolites are polar (water soluble) and excreted by the kidneys. Major metabolites found in blood plasma and urine, do not show pharmacological activity. The data obtained from experiments with human liver microsomes in vitro show that bisoprolol is metabolized primarily by
using the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role.
Withdrawal. Bisoprolol clearance is determined by the equilibrium between excretion by the kidneys unchanged (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. The elimination half-life is 10-12 hours.
Indications
Arterial hypertension: replacement of therapy with monocomponent preparations of amlodipine and bisoprolol in the same doses.
Contraindications
Ampodipine:
– unstable angina (except for Prinzmetal angina)
– hemodynamically unstable heart failure after myocardial infarction
– clinically significant aortic stenosis.
For bisoprolol:
– acute heart failure or chronic heart failure (CHF) in the decompensation stage, requiring inotropic therapy
– atrioventricular (AV) block II and III degree, without pacemaker
– sinus node weakness syndrome (SSS)
– sinoatrial blockade
– severe bradycardia (heart rate less than 60 beats / min – severe asthma or srdlk chronic obstructive pulmonary disease (COPD)
– severe peripheral arterial circulatory disorders or Raynaud’s syndrome
– pheochromocytoma (without the simultaneous use of alpha-blockers)
– metabolic acidosis
amlodipine / bisoprolol combinations:
– hypersensitivity to amlodipine, other derivatives of dihydropyridine, bisoprolol and / or any of the excipients
– severe arterial hypotension (systolic blood pressure less than 100 mm RT. c)
– shock (including cardiogenic)
– children under 18 years of age (efficacy and safety have not been established).
CAUTION
CHF (including non-ischemic etiology of functional class III-IV according to NYHA classification), liver failure, renal failure, hyperthyroidism, diabetes mellitus with significant fluctuations in blood glucose concentration, AV block I, degree, Prinzmetal angina, peripheral arterial occlusion diseases, psoriasis (including history), starvation (strict diet), pheochromocytoma (with the simultaneous use of alpha-blockers), bronchial asthma and COPD, while desensitizing I therapy, general anesthesia, elderly, hypotension, type 1 diabetes, aortic stenosis, mitral stenosis, acute myocardial infarction (after the first 28 days).
APPLICATION DURING PREGNANCY AND BREAST-FEEDING
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 outweighs the potential risk to the fetus. There is no evidence of excretion of amlodipine with breast milk. However, it is known that other BMCC – derivatives of dihydropyridine, are excreted in breast milk. In this connection, if necessary, the appointment of amlodipine during lactation should decide on the termination of breastfeeding.
For bisoprolol:
The use of bisoprolol during pregnancy is possible only if when the intended benefit to the mother outweighs the potential risk to the fetus. Beta-blockers reduce blood flow in the placenta and can affect fetal development.
Blood flow in the placenta and uterus should be monitored, as well as the growth and development of the unborn baby, and in case of adverse events regarding pregnancy and / or the fetus, take alternative methods of therapy. You should carefully examine the newborn after childbirth. In the first three days of life, symptoms of bradycardia and hypoglycemia may occur.
There is no data on the release of bisoprolol into breast milk. Therefore, its intake is not recommended for women during breastfeeding. If bisoprolol is required during lactation, breast-feeding should be discontinued.
Directions for use
Tablets for oral administration. Tablets should be taken in the morning, regardless of food intake, without chewing.
Recommended daily dose -1 tablet per day of a certain dosage. The selection and titration of the dose for each patient individually is carried out by the doctor during the appointment of monocomponent preparations containing the active substances that make up Bisoprolol AML.
Duration of treatment
Treatment with bisoprolol AML is usually a long-term therapy.
Impaired liver function
In patients with impaired liver function, amlodipine excretion may be slowed down. 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 severely impaired liver function, the maximum daily dose of bisoprolol is 10 mg. Renal dysfunction
Patients with impaired renal function of mild or moderate severity of dosage regimen are usually not required. Amlodipine is not excreted by dialysis. Dialysis patients should be given amlodipine with extreme caution.
For patients with severe renal impairment (creatinine clearance (CC) less than 20 ml / min), the maximum daily dose of bisoprolol is 10 mg.
Elderly patients
Elderly patients may be given normal doses of the drug Caution is required only with increasing doses.
Children
The drug is not recommended for use in children under the age of 18 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 stopped in patients with IBS. A gradual dose reduction is recommended.
Special instructions
Amlodipine
In patients with impaired hepatic function, T | / 2 of amlodipine increases. When prescribing the drug to such patients, caution should be exercised and regular monitoring of the activity of “liver” enzymes.
When prescribing amlodipine to patients with chronic heart failure, caution should be exercised. In patients with heart failure (including the non-ischemic etiology of functional class III-IV according to NYHA classification), amlodipine increases the risk of pulmonary edema, which is not associated with an aggravation of symptoms of heart failure.
During the period of amlodipine therapy, it is necessary to control body weight and salt intake, the appointment of an appropriate diet is indicated. It is necessary to maintain oral hygiene and supervision by a dentist (to prevent soreness, bleeding and gingival hyperplasia).
In Vitro Fertilization (IVF)
In rare cases, when IVF was performed while BMKK was used, reversible biochemical changes were noted in the sperm head, which led to impaired function.
In case of unsuccessful IVF attempts and with the exclusion of other causes of infertility, one should take into account the likelihood of influence on the sperm BMCC if they are used.
Bisoprolol
Monitoring the status 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 (once every 4-5 months). In elderly patients, it is recommended to monitor renal function (1 time in 4-5 months).
The patient should be trained in the method of calculating heart rate and instructed on the need for medical advice for heart rate less than 60 beats / min. Before starting treatment, it is recommended to study the function of external respiration in patients with a burdened bronchopulmonary history. Patients using contact lenses should take into account that, against the background of treatment with the drug, a decrease in the production of tear fluid is possible.
When using bisoprolol in patients with pheochromocytoma, there is a risk of developing paradoxical hypertension (unless effective blocking of a-adrenergic receptors has been previously achieved). With hyperthyroidism, bisoprolol may mask certain clinical signs of hyperthyroidism (e.g., tachycardia). Abrupt withdrawal of the drug in patients with hyperthyroidism should be avoided in order to avoid increased symptoms.
With diabetes, it can mask tachycardia caused by hypoglycemia. In contrast to non-selective p-adrenergic blockers, it practically does not enhance insulin-induced hypoglycemia and does not delay the restoration of blood glucose concentration to normal values.
With the simultaneous use of clonidine, its administration can be stopped only a few days after the withdrawal of bisoprolol. It is possible to increase the severity of the hypersensitivity reaction and the lack of effect of the usual doses of epinephrine (adrenaline) against the background of a burdened allergic history.
If routine surgical treatment is necessary, bisoprolol should be discontinued 48 hours before general anesthesia. If the patient has taken bisoprolol before surgery, he should choose a drug for general anesthesia with a minimally negative inotropic effect.
Reciprocal vagus nerve activation can be eliminated by intravenous administration of atropine (1-2 mg).
Medicines that deplete the catecholamine depot (including reserpine) can enhance the effect of P-blockers, therefore, patients taking such combinations of drugs should be under constant medical supervision to detect a pronounced decrease in blood pressure or bradycardia.
Patients with bronchospastic diseases can be prescribed cardioselective p-blockers with caution in case of intolerance and / or ineffectiveness of other antihypertensive drugs against the background of the simultaneous use of bronchodilating agents. While taking p-adrenergic blocking agents in patients with concomitant bronchial asthma, airway resistance may increase. If the dose of bisoprolol is exceeded, such patients have a 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 (systolic blood pressure less than 100 mm Hg), AV block, it is necessary to reduce the dose or stop treatment.
It is recommended that bisoprolol therapy be discontinued if depression develops.
Do not abruptly interrupt treatment because of the danger of developing severe arrhythmias and myocardial infarction. Drug withdrawal is carried out gradually, reducing the dose for 2 weeks or more (reduce the dose by 25% in 34 days). The drug should be discontinued before examining the concentration in the blood and urine of catecholamines, normetanephrine, vanilla lindic acid, titers of antinuclear antibodies.
In smokers, the effectiveness of p-blockers is lower.
Composition
1 tablet contains: dosage 5 mg + 5 mg:
active ingredients: 5 mg amlodipine besilate (in terms of amlodipine) and 5 mg bisoprolol fumarate: excipients: microcrystalline cellulose – 132.5 mg carboxymethyl starch sodium 0 mg of magnesium stearate – 1.5 mg of silicon anhydrous colloidal dioxide (Aerosil anhydrous) – 1.0 mg.
Side effects of
Undesirable side reactions observed when using the active ingredients separately, are presented in accordance with the following criteria for frequency grouping:
Very frequent> 1/10 frequent> 1/100 – <1/10 infrequent> 1/1 LLC – <1/100 rare and 1/10 000 - <1/1 LLC very rare (<1/10 000), unknown (assessment based on available data cannot be carried out). According to amlodipine: Disorders from the blood and lymphatic system: very rarely – leukopenia, thrombocytopenia. Disorders of the immune system: very rarely – allergic reactions. Disorders from metabolism and nutrition: very rarely – hyperglycemia. Mental disorders: infrequently – insomnia, mood changes (including anxiety), depression rarely – confusion. Disorders of 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 Disorders of the organ of vision: infrequently – impaired vision vision (including diplopia). Hearing disorders and labyrinth disorders: infrequently – tinnitus. Disorders of the gastrointestinal tract: often – nausea, abdominal pain infrequently – vomiting, change in bowel movement (including constipation or diarrhea), dyspepsia, dry oral mucosa very rarely – gastritis, gingival hyperplasia, pancreatitis. Violations of the liver and biliary tract: very rarely – hepatitis *, jaundice *. Disturbances from the heart: often – palpitations very rarely – myocardial infarction, arrhythmia (bradycardia, ventricular tachycardia, atrial fibrillation). Vascular disorders: often: flushing of the face, infrequently – a marked decrease in blood pressure is very rare – vasculitis. Disorders from the respiratory system, chest and mediastinal organs: infrequently – shortness of breath, rhinitis is very rare – cough. Disorders from the kidneys and urinary tract: infrequently – pollakiuria, painful urination, nocturia. Violations of the genital organs and mammary gland: infrequently – impotence, gynecomastia. General disorders and disorders at the injection site: often – peripheral edema, increased fatigue infrequently – chest pain, asthenia, pain, general malaise. Violations of the musculoskeletal and connective tissue: often – swelling of the ankles infrequently – arthralgia, myalgia, muscle cramps, back pain. Violations of the skin and subcutaneous sheets: infrequent – Alopecia, purpura, skin discoloration, excessive sweating, itching, rash, rash, very rarely – angioneurotic edema, exudative erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, angioedema , photosensitivity. Laboratory and instrumental data: infrequently – an increase in body weight, a decrease in body weight is very rare – an increase in the activity of “liver” enzymes *. * In most cases with cholestasis. By bisoprolol Metabolic and nutritional disorders: rarely – increased triglyceride concentrations. Mental disorders: infrequently – depression rarely – hallucinations, nightmares. Disorders of the nervous system: often – headache, dizziness infrequently – insomnia rarely – fainting. Violations of the organ of vision: rarely – a decrease in lacrimation (should be taken into account when wearing contact lenses), very rarely – conjunctivitis. Hearing impairment and labyrinth disorders: rarely – hearing impairment. Disturbances from the heart: infrequently – violation of AV conduction, bradycardia, aggravation of symptoms of chronic heart failure. Disorders from the vessels: often – a feeling of cooling or numbness in the limbs, a marked decrease in blood pressure infrequently – orthostatic hypotension. Disorders of the respiratory system, chest and mediastinal organs: infrequently – bronchospasm in patients with bronchial asthma or airway obstruction rarely has a history of allergic rhinitis. Disorders of the gastrointestinal tract: often: nausea, vomiting, diarrhea, constipation. Disorders from the liver and biliary tract: rarely – hepatitis. Disorders of the skin and subcutaneous integument: rarely – hypersensitivity reactions, such as skin itching, rash, redness of the skin very rarely – alopecia. Beta-blockers can exacerbate the symptoms of psoriasis or cause a psoriasis-like rash. Disorders of the musculoskeletal and connective tissue: infrequently – muscle weakness, muscle cramps. Disorders of the genitals and mammary gland: rarely – impotence. General disorders and disorders at the injection site: often – increased fatigue infrequently – exhaustion **. Laboratory and instrumental data are rare – increased activity of hepatic transaminases in the blood (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)). ** Especially often, these symptoms appear at the beginning of treatment. Typically, these phenomena are mild and go away, usually within 1-2 weeks after the start of treatment. Drug interaction For amlodipine: The simultaneous use of amlodipine with thiazide diuretics, beta-blockers, long-acting nitrates, sublingual nitroglycerin drugs, non-steroidal anti-inflammatory drugs, hypoglymic antibiotics is considered safe. CYP3A4 Inhibitors: Amlodipine should be used with caution in conjunction with CYP3A4 inhibitors. Strong and moderate CYP3A4 inhibitors (for example, protease inhibitors, antifungals of the azole group, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) can increase the concentration of amlodipine in blood plasma to clinically significant values. Inductors CYP3A4: Simultaneous use with inducers CYP3A4 (incl. rifampicin, Hypericum perforatum) can lead to a decrease in the concentration of amlodipine in blood plasma. Amlodipine should be used with caution concurrently with CYP3A4 inducers. Simvastatin: Concomitant use with amlodipine may lead to an increase in plasma concentrations of simvastatin. Patients taking amlodipine are not recommended to use simvastatin in a dose of more than 20 mg per day. G rapefruit 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 drugs. Amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, ethanol (beverages containing alcohol), warfarin, or cyclosporine. Amlodipine has no effect on laboratory parameters. According to bisoprolol: Not recommended combinations Slow calcium channel blockers (BMKKs) such as verapamil and, to a lesser extent, diltiazem, when used with bisoprolol, can lead to a decrease in myocardial contractility, a marked decrease in blood pressure and impaired AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV block. Antihypertensive drugs of a central action (such as clonidine, methyldopa, moxonidine, rilmenidine), when used together with bisoprolol, can lead to a reduction in heart rate and a decrease in cardiac output, as well as to vasodilation due to a decrease in central sympathetic tone. Abrupt cancellation especially before the abolition of beta-blockers may increase the risk of developing “rebound” arterial hypertension. Combinations that require caution BMCC derivatives of dihydropyridine (eg, nifedipine) when used concomitantly with bisoprolol may increase the risk of hypotension. In patients with heart failure, the risk of a subsequent deterioration in cardiac contractile function cannot be ruled out. Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), while used with bisoprolol, can reduce AV conductivity and myocardial contractility. Class III antiarrhythmic drugs (e.g., amiodarone) may increase impairment of AV conduction. Parasympathomimetics when used simultaneously with bisoprolol can increase the violation of AV conduction and increase the risk of developing bradycardia. Topical beta-blockers (for example, eye drops for glaucoma) can enhance the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate). The hypoglycemic effect of insulin or hypoglycemic agents for oral administration may be enhanced. Signs of hypoglycemia – in particular tachycardia – may be masked. Such interactions are more likely when using non-selective beta-blockers. Means for general anesthesia can weaken reflex tachycardia and increase the risk of developing hypotension (see the section “Special Instructions”). Cardiac glycosides, when used concomitantly with bisoprolol, can lead to an increase in the duration of the pulse and to the development of bradycardia. Nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the antihypertensive effect of bisoprolol. The simultaneous use of bisoprolol with beta-adrenergic agonists (for example, isoprenaline, dobutamine) can lead to a decrease in the effect of both drugs. The combination of bisoprolol with adrenergic agonists affecting beta and alpha adrenergic receptors (for example, norepinephrine, epinephrine) can enhance the vasoconstrictor effects of these agents that occur with the participation of alpha adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers. antihypertensive drugs, 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 needs to be considered Mefloquine while used with bisoprolol can increase the risk of developing 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 the half-life (T, / 2) of bisoprolol. As a rule, dose adjustment is not required. Ergotamine derivatives when used simultaneously with bisoprolol increase the risk of peripheral circulation disturbance. Overdose Ampopipine Symptoms: a marked decrease in blood pressure with possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent arterial hypotension, including with the development of shock and years). Treatment: gastric lavage, administration of activated charcoal, maintenance of the cardiovascular system, monitoring of heart and lung function, elevated limbs, control of circulating blood volume and diuresis. Intensive symptomatic therapy. To restore vascular tone – the use of vasoconstrictor drugs (in the absence of contraindications to their use) to eliminate the effects of calcium channel blockade – intravenous administration of calcium gluconate. Hemodialysis is not effective. By bisoprolol Symptoms: AV block, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure, and hypoglycemia. Sensitivity to a single dose of a high dose of bisoprolol varies greatly among individual patients and probably patients with heart failure have a high sensitivity. Treatment: in case of an overdose, first of all, it is necessary to stop taking the drug and start supporting 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 a temporary setting of an artificial pacemaker may be required. With a pronounced decrease in blood pressure: intravenous administration of plasma substituting solutions and vasopressor drugs. Intravenous administration of glucagon may also be indicated. For AV blockade: Patients should be constantly monitored and treated with beta-adrenergic agonists such as epinephrine. If necessary, staging an artificial pacemaker. With exacerbation of CHF: intravenous administration of diuretics, drugs with a positive inotropic effect, as well as vasodilators. For bronchospasm: administration of bronchodilators, including beta2-adrenergic agonists and / or aminophylline. For hypoglycemia: intravenous administration of dextrose (glucose). Bisoprolol practically does not respond to dialysis Storage conditions In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children. Term hodnosty 3 years Active ingredient Amlodipine, bisoprolol Pharmacy terms Prescription Form of Treatment tablets Appointment for Adults on purpose doctor, Beremenn m doctor prescribing Indications Hypertension
