Bicard AM pills 5mg/10mg №10×3

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Bicard AM tab. 5mg/10mg per col. cell pack. No. 10×3
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Tablets 5 mg + 10 mg: pink flat-cylindrical tablets with a bevel and a notch. Inclusions are allowed. The main active ingredient Bisoprolol + amlodipine Release form Tablets Dosage 5 mg / 10 mg Pharmacological action Pharmacodynamics This drug has pronounced antihypertensive and antianginal effects due to the complementary action of two active ingredients: BMCC – amlodipine and selective beta 1-blocker – bisoprolol. The mechanism of action of amlodipine: Amlodipine blocks calcium channels reduces the trans-membrane transition 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 a direct relaxing effect on vascular smooth muscle cells, which leads to a decrease in peripheral vascular resistance. The mechanism of anti-anginal action is not fully understood, perhaps it is associated with the following two effects: 1. The expansion of peripheral arterioles reduces the total peripheral resistance, i.e. afterload. Since amlodipine does not cause reflex tachycardia, myocardial energy and oxygen consumption is reduced. 2. The expansion of large coronary arteries and coronary arterioles improves the supply of oxygen to both normal and ischemic areas of the myocardium. Thanks to these effects, the supply of oxygen to the myocardium improves, even with spasm of the coronary arteries (Prinzmetal’s angina 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 arterial hypotension. In patients with angina pectoris, taking the drug once a day increases the total time of exercise, the time to the development of an angina attack, and the time to a significant decrease in the ST interval, and also reduces the frequency of angina attacks and the need for sublingual nitroglycerin. No negative effect of amlodipine on the metabolism of blood plasma lipids, blood glucose and serum uric acid was found. The 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 beta2-adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for beta2-adrenergic receptors involved in the regulation of metabolism. Therefore, bisoprolol generally does not affect airway resistance and metabolic processes in which beta2-adrenergic receptors are involved. The selective effect of the drug on beta1-adrenergic receptors persists 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 1 time per day, its therapeutic effect persists for 24 hours due to the 10-12 hour half-life from 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 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 slows down the heart rate (HR), reduces the stroke volume of the heart and, as a result, reduces the ejection fraction and myocardial oxygen demand. With long-term therapy, initially increased total peripheral vascular resistance (OPVR) decreases. A decrease in plasma renin activity is considered as one of the components of the hypotensive action of beta-blockers. Pharmacokinetics Amlodipine Absorption Amlodipine is well absorbed after oral administration. The maximum concentration in 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. Steady-state plasma concentration (5-15 ng/ml) is reached 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 is extensively metabolized in the liver. Approximately 90% of the dose taken is converted into inactive pyridine derivatives. Approximately 10% of the dose taken is excreted in the urine unchanged. 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 terminal 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 a patient 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 reduced clearance, patients with hepatic insufficiency should be given lower initial doses. Bisoprolol Absorption Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability due to negligible first pass metabolism by the liver (at about 10%) is about 90% after oral administration. Eating does not affect bioavailability. Bisoprolol demonstrates linear kinetics, and its concentration in blood plasma is proportional to the dose taken in the range from 5 to 20 mg. The maximum plasma concentration is reached after 2-3 hours. Distribution Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l/kg. Communication with blood plasma proteins reaches approximately 30%. Metabolism Metabolized by the oxidative pathway without subsequent conjugation. All metabolites are polar (water soluble) and 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 metabolized primarily by the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role. Withdrawal The clearance of bisoprolol is determined by the balance between excretion by the kidneys unchanged (about 50%) and metabolism in the liver (about 50%) to metabolites, which are also excreted by the kidneys. The total clearance is 15 l / h. The half-life is 10-12 hours. Indications for use The drug Bicard AM is indicated for the treatment of arterial hypertension. Can be used as replacement therapy in patients whose symptoms have been adequately controlled by the combined use of amlodipine tablets and bisoprolol tablets in the same doses as in the combined drug. Dosage and administration Tablets for oral administration. Tablets should be taken in the morning, regardless of the meal, without chewing. The score on the tablets is intended solely to facilitate taking one tablet (by breaking the tablet into two halves), and not to divide the tablet into two doses. The recommended daily dose is 1 tablet per 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 preparations containing active ingredients that are part of the Bicard AM preparation. Duration of treatment Treatment with Bicard AM is usually long-term therapy. Impaired liver function In patients with impaired liver function, the excretion of amlodipine may be slowed down. A special dosing regimen for this group of patients is not defined, however, the drug in this case should be administered with caution. For patients with severely impaired liver function, the maximum daily dose of bisoprolol is 10 mg. Impaired renal function Patients with impaired renal function of mild or moderate severity dosing regimen adjustment, as a rule, is not required. Amlodipine is not excreted by dialysis. Patients undergoing dialysis 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 the usual doses of the drug. Caution is required only when increasing the dose. Children The drug is not recommended for use in children under the age of 18 due to lack of data on efficacy and safety. Treatment should not be stopped abruptly, as this may lead to a temporary worsening of the clinical condition. In particular, treatment should not be abruptly discontinued in patients with CAD. A gradual dose reduction is recommended. Use during pregnancy and lactation The drug Bicard AM is not recommended for use during pregnancy, unless there are strict indications for this. If treatment with Bicard AM is necessary, uteroplacental blood flow and fetal growth should be closely monitored. In the event of a negative effect on pregnancy or the fetus, the issue of alternative treatment should be considered. The newborn should be carefully examined after delivery. In the first three days of life, symptoms of bradycardia and hypoglycemia may occur. There are no data indicating the release of bisoprolol and amlodipine into human breast milk. However, some BMCC derivatives of dihydropyridine are known to be excreted in breast milk. In this regard, if it is necessary to prescribe a drug during lactation, breastfeeding should be stopped. Influence on the ability to drive vehicles or potentially dangerous mechanisms During the period of drug treatment, care must be taken in driving vehicles and working with technically complex mechanisms. PrecautionsSee See also the information “With caution” section “Contraindications”. For amlodipine: Patients with heart failure should take amlodipine with caution. In patients with heart failure stage III-IV according to the NYHA classification, amlodipine increases the risk of pulmonary edema, which is not associated with worsening symptoms of CHF. For bisoprolol: Stopping treatment with bisoprolol should not be abrupt, especially in patients with coronary artery disease, unless there are clear indications for discontinuation of the drug. Abrupt withdrawal of bisoprolol can lead to a temporary worsening of cardiac pathology. Bisoprolol should be administered with extreme caution to patients with arterial hypertension or angina pectoris in combination with heart failure. As with other beta-blockers, bisoprolol can cause an increase in sensitivity to allergens and an increase in anaphylactic reactions, so care must be taken when simultaneously conducting desensitizing therapy. The use of adrenaline may not always give the expected therapeutic effect. When using bisoprolol, the symptoms of hyperthyroidism may be masked. In patients with pheochromocytoma, bisoprolol should only be given after blockade of alpha-adrenergic receptors. Before performing general anesthesia, the anesthesiologist should be informed about the patient taking beta-blockers. If it is necessary to stop the beta-blocker before surgery, this should be done gradually, and completed approximately 48 hours before anesthesia. In bronchial asthma or COPD, the simultaneous use of bronchodilators is indicated. In patients with bronchial asthma, an increase in airway resistance is possible, which requires a higher dose of beta2-agonists. Interactions with other drugs For amlodipine: The use of amlodipine with the following drugs was safe: with thiazide diuretics, P-blockers, long-acting nitrates, sublingual preparations of glycerol trinitrate, non-steroidal anti-inflammatory drugs, antibiotics, oral hypoglycemic drugs. Effect of other medicinal products on amlodipine: CYP3A4 inhibitors: when amlodipine is combined with potent or moderate CYP3A4 inhibitors (eg, protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, or verapamil or diltiazem), an increase in concentration can be expected amlodipine in plasma to clinically significant levels. The clinical interpretation of these pharmacokinetic changes may be more pronounced in the elderly, so it is advisable to conduct clinical monitoring and individual dose selection in young patients and with diltiazem in elderly patients, the plasma concentration of amlodipine increased by 22% and 50%, respectively. However, the clinical significance of this observation is unknown. It cannot be excluded that potent inhibitors of CYP3A4 (ketoconazole, itraconazole, ritonavir) may lead to a more significant increase in plasma levels of amlodipine than diltiazem. Amlodipine should be combined with CYP3A4 inhibitors with caution, although no side effects associated with such combinations have been reported. CYP3A4 inducers: There are no data on the effect of CYP3A4 inducers on amlodipine. Co-administration of CYP3A4 inducers (rifampicin, St. John’s wort) may lower plasma concentrations of amlodipine. Amlodipine should be combined with CYP3A4 inducers with caution. In drug interaction studies, grapefruit juice, cimetidine, aluminum/magnesium (an antacid) and sildenafil have not been shown to affect the pharmacokinetics of amlodipine. Dantrolene (infusion): Fatal ventricular fibrillation, cardiovascular failure, and hyperkalemia have been observed in animals when verapamil was co-administered with intravenous dantrolene. Due to the risk of hyperkalemia, concomitant use of dantrolene with calcium channel blockers, such as amlodipine, should be avoided in patients prone to malignant hyperthermia and in the treatment of malignant hyperthermia. Effect of amlodipine on other drugs: The antihypertensive effect of amlodipine enhances the antihypertensive effects of other drugs that lower blood pressure. In drug interaction studies, it was shown that amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, or warfarin. Tacrolimus: when used together with amlodipine, there may be a risk of increasing the level of tacrolimus in the blood plasma, however, the pharmacokinetic mechanism of this interaction has not been fully identified. In order to avoid tacrolimus toxicity, the administration of amlodipine to patients receiving tacrolimus requires regular monitoring of tacrolimus blood levels and adjustment of its dose, if necessary. Cyclosporine: The interaction of amlodipine with cyclosporine has not been studied in healthy volunteers or in other groups, with the exception of patients with a kidney transplant, in which there was an increase in the minimum concentration of cyclosporine of varying degrees (0-40%). It may be appropriate to monitor ciclosporin levels in kidney transplant patients receiving amlodipine and, if necessary, reduce the ciclosporin dose. Simvastatin: Co-administration with amlodipine may increase plasma levels of simvastatin. Doses of simvastatin exceeding 20 mg/day are not recommended in patients receiving amlodipine. Amlodipine does not affect the results of laboratory tests. According to bisoprolol: Non-recommended combinations Blockers of “slow” calcium channels (BCCC) such as verapamil and, to a lesser extent, diltiazem, when used simultaneously with bisoprolol, can lead to a decrease in myocardial contractility, a pronounced 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 blockade. Centrally acting antihypertensive agents (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” arterial hypertension. Combinations requiring caution BMKK-derivatives of dihydropyridine (for example, nifedipine), when used simultaneously with bisoprolol, may increase the risk of arterial hypotension. In patients with CHF, the risk of subsequent worsening of the contractile function of the heart cannot be excluded. Class I antiarrhythmic drugs (for example, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone), when used simultaneously with bisoprolol, can reduce AV conduction and myocardial contractility. Class III antiarrhythmics (eg, amiodarone) may exacerbate AV conduction disturbance. Parasympathomimetics, when used simultaneously with bisoprolol, can increase the disturbance of AV conduction and increase the risk of developing bradycardia. The action of topical beta-blockers (for example, eye drops for the treatment of glaucoma) may enhance the systemic effects of bisoprolol (lowering blood pressure, slowing heart rate). The hypoglycemic effect of insulin or oral hypoglycemic agents may be enhanced. Signs of hypoglycemia – in particular tachycardia – may be masked. Such interactions are more likely with the use of non-selective beta-blockers. Means for general anesthesia can weaken reflex tachycardia and increase the risk of arterial hypotension (see section “Special Instructions”). Cardiac glycosides, when used simultaneously with bisoprolol, can lead to an increase in impulse conduction time and to the development of bradycardia. Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of bisoprolol. The simultaneous use of bisoprolol with beta-agonists (eg, isoprenaline, dobutamine) may lead to a decrease in the effect of both drugs. The combination of bisoprolol with adrenomimetics that affect beta- and alpha-adrenergic receptors (for example, norepinephrine, epinephrine) can enhance the vasoconstrictor effects of these drugs that occur with the participation of alpha-adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely with the use of non-selective beta-blockers. Antihypertensive drugs, as well as other drugs with a possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines), may enhance the antihypertensive effect of bisoprolol. Combinations to be considered Mefloquine, when used simultaneously with bisoprolol, may 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?) of bisoprolol. As a rule, dose adjustment is not required. Ergotamine derivatives, when used simultaneously with bisoprolol, increase the risk of developing peripheral circulatory disorders. Contraindications For amlodipine: unstable angina (with the exception of Prinzmetal’s angina); acute myocardial infarction (within the first 28 days); clinically significant aortic stenosis. For bisoprolol: acute heart failure or chronic heart failure (CHF) in the stage of decompensation, requiring inotropic therapy; atrioventricular (AV) blockade II and III degree, without a pacemaker; sick sinus syndrome (SSS); sinoatrial blockade; severe bradycardia (heart rate less than 60 beats / min); severe forms of bronchial asthma or chronic obstructive pulmonary disease (COPD); severe disorders peripheral arterial circulation or Raynaud’s syndrome; pheochromocytoma (without the simultaneous use of alpha-blockers); metabolic acidosis. According to the combination of amlodipine / bisoprolol: hypersensitivity to amlodipine, other dihydropyridine derivatives, bisoprolol and / or any of the excipients; severe arterial hypotension (systolic blood pressure less than 100 mm Hg); shock (incl. cardiogenic); children under 18 years of age (efficacy and safety have not been established). WITH CAUTION CHF (including non-ischemic etiology III-IV functional class according to the NYHA classification), liver failure, renal failure, hyperthyroidism, diabetes mellitus with significant fluctuations blood glucose levels, AV block I degree, Prinzmetal’s angina, peripheral arterial occlusive disease, psoriasis (including history), starvation (strict diet), pheochromocytoma (with simultaneous use of alpha-blockers), bronchial asthma and COPD, concurrent desensitizing therapy, general anesthesia, old age, arterial hypotension, type 1 diabetes mellitus, aortic stenosis, mitral stenosis, acute myocardial infarction (after the first 28 days). Composition Each 5 mg + 10 mg tablet contains: active substance: 5 mg of bisoprolol fumarate and 10 mg of amlodipine (in the form of 13.86 mg of amlodipine besylate) excipients: microcrystalline cellulose, sodium starch glycolate, magnesium stearate, anhydrous colloidal silicon dioxide, iron oxide red (E172) Overdose For amlodipine: Symptoms: a pronounced decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent arterial hypotension, including with the development of shock and death). Treatment: gastric lavage, administration of activated charcoal, maintenance of the function of the cardiovascular system, control of indicators of heart and lung function, elevated position of the 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. According to bisoprolol: Symptoms: AV blockade, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia. Sensitivity to a single high dose of bisoprolol varies greatly among individual patients and it is likely that patients with CHF are highly sensitive. Treatment: in the event of an overdose, first of all, it is necessary to stop taking the drug and start supportive symptomatic therapy. With severe bradycardia: intravenous atropine. If the effect is insufficient, a remedy with a positive chronotropic effect can be administered with caution. Sometimes temporary placement of an artificial pacemaker may be required. With a pronounced decrease in blood pressure: intravenous administration of plasma-substituting solutions and vasopressor drugs. Intravenous glucagon may also be indicated. For AV block: Patients should be monitored closely and treated with beta-adrenergic agonists such as epinephrine. If necessary, the setting of an artificial pacemaker. With an 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-agonists and / or aminophylline. With hypoglycemia: intravenous administration of dextrose (glucose). Bisoprolol is practically not amenable to dialysis. Side effects When taking the drug, there is a possibility of developing adverse reactions, which are classified by organ systems and frequency of occurrence: very often? 1/10, often from? 1/100 to <1/10, infrequently from? 1/1000 to <1/100 , rarely ≤1/10000 to <1/1000, very rare <1/10000, unknown (estimation based on available data cannot be made). For amlodipine: Blood and lymphatic system disorders: very rare: leukopenia, thrombocytopenia. Immune system disorders: very rare: allergic reactions. Metabolic and nutritional disorders: very rare: hyperglycemia. Mental disorders: infrequently: insomnia, mood changes (including anxiety), depression; rarely: confusion. Nervous system disorders: 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 organ of vision: infrequently: visual impairment (including diplopia). On the part of the organ of hearing and labyrinth disorders: infrequently: tinnitus. Gastrointestinal disorders: often: nausea, abdominal pain; infrequently: vomiting, change in the mode of defecation (including constipation or diarrhea), dyspepsia, dryness of the oral mucosa; very rarely: gastritis, gingival hyperplasia, pancreatitis. Liver and biliary tract disorders: very rare: hepatitis, jaundice. Cardiac disorders: often: palpitations; infrequently: arrhythmia (bradycardia, ventricular tachycardia, atrial fibrillation); very rarely: myocardial infarction. Vascular disorders: often: flushing of blood to the face; infrequently: a pronounced decrease in blood pressure; very rare: vasculitis. Respiratory, thoracic and mediastinal disorders: infrequently: shortness of breath, rhinitis; very rare: cough. Renal and urinary tract disorders: infrequently: pollakiuria, painful urge to urinate, nocturia. On the part of the genital organs and the 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. Musculoskeletal and connective tissue disorders: often: swelling of the ankles; infrequently: arthralgia, myalgia, muscle cramps, back pain. Skin and subcutaneous disorders: infrequently: alopecia, purpura, discoloration of the skin, increased sweating, itching, rash, exanthema; very rarely: angioedema, erythema multiforme exudative, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, angioedema, photosensitivity. Laboratory and instrumental data: infrequently: weight gain, weight loss; very rarely: an increase in the activity of "liver" enzymes *. *In most cases with cholestasis. According to bisoprolol: Metabolic and nutritional disorders: rarely: an increase in the concentration of triglycerides. Mental disorders: infrequently: depression; rarely: hallucinations, nightmares. Nervous system disorders: often: headache**, dizziness**; infrequently: insomnia; rarely: fainting. On the part of the organ of vision: rarely: a decrease in lacrimation (should be taken into account when wearing contact lenses); very rare: conjunctivitis. Hearing disorders and labyrinth disorders: rarely: hearing impairment. Cardiac disorders: infrequently: impaired AV conduction, bradycardia, aggravation of symptoms of CHF. Vascular disorders: often: a feeling of coldness or numbness in the extremities, a pronounced decrease in blood pressure; infrequently: orthostatic hypotension. Respiratory, thoracic and mediastinal disorders: Uncommon: Bronchospasm in patients with asthma or a history of airway obstruction; rarely: allergic rhinitis. From the gastrointestinal tract: often - nausea, vomiting, diarrhea, constipation. Liver and biliary tract disorders: Rare: Hepatitis. Skin and subcutaneous disorders: rarely: hypersensitivity reactions such as pruritus, rash, flushing of the skin; very rare: alopecia. Beta-blockers can exacerbate the symptoms of psoriasis or cause a psoriasis-like rash. Musculoskeletal and connective tissue disorders: Uncommon: muscle weakness, muscle cramps. Violations of the genital organs and mammary gland: rarely: impotence. General disorders and disorders at the injection site: often: increased fatigue**; infrequently: exhaustion **. Laboratory and instrumental data: rarely: increased activity of "liver" transaminases in the blood (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)). Especially often these symptoms appear at the beginning of the course of treatment. Usually these phenomena are mild and disappear, as a rule, within 1-2 weeks after the start of treatment. Storage conditions In a place protected from moisture and light at a temperature not exceeding 25 ° C. Keep out of the reach of children. 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