Carvedilol-MIC capsules 25mg №10×3

Name Carvedilol-MIC caps. I degree blockade, unstable angina, in the treatment of alpha1-blockers or alpha2-adrenergic agonists, with the combined use of MAO inhibitors, pheochromocytoma (only stabilized by the appointment of alpha-blockers), depression, myasthenia gravis, psoriasis, renal failure. Patients with severe heart failure (greater than NYHA grade III), electrolyte imbalance, low blood pressure (less than 100 mm Hg), or elderly patients should be under close medical supervision within 2 hours after the first dose or after taking the first increased dose, due to the risk of developing a sudden drop in blood pressure, orthostatic hypotension and syncope. The risk of these complications can be reduced by prescribing the drug in small initial doses and taking it with food. The drug is not recommended for use in patients with low blood pressure. In patients with heart failure, if their initial SBP is less than 100 mm Hg. Art. or there are concomitant diseases – ischemic heart disease, peripheral vascular disease or impaired renal function, you should check the condition of the urinary system more often, because. treatment may affect kidney function (usually temporarily). If inhibition of renal function is observed, the dose of the drug should be reduced or treatment should be discontinued. Like other beta-blockers, carvedilol may mask the symptoms of hypoglycemia and adversely affect carbohydrate metabolism. Accordingly, the treatment of diabetic patients with carvedilol requires special attention and more frequent measurement of blood sugar. Treatment with carvedilol may mask symptoms of hyperthyroidism. With the sudden withdrawal of the drug, an increase in thyrotoxicosis is likely and a thyrotoxic crisis is possible. Treatment with carvedilol in patients with established pheochromocytoma should not be initiated until appropriate therapeutic alpha-adrenergic blockade has been given. Treatment with carvedilol in patients with psoriasis requires a benefit/risk assessment, as carvedilol may exacerbate the disease or trigger symptoms. The use of carvedilol may reduce the sensitivity of allergy tests. Against the background of the use of carvedilol, general anesthesia should be carried out with caution using drugs with a negative inotropic effect (ether, cyclopropane, trichlorethylene). Before extensive surgical interventions, a gradual withdrawal of the drug is recommended. Care must be taken when using the drug in case of severe metabolic acidosis. Patients using contact lenses should be warned that carvedilol reduces tear production. During the period of drug use, alcohol should be avoided. Stop treatment should be gradual, reducing the dose. Carvedilol can cause bradycardia, with a decrease in heart rate (below 55 beats per minute), the dose of the drug should be reduced. Caution is necessary when prescribing the drug to patients with peripheral vascular disease (including Raynaud’s syndrome), since beta-blockers can increase the symptoms of arterial insufficiency. Non-selective beta-blockers may cause pain in patients with Prinzmetal’s angina. There is no experience of prescribing carvedilol in these patients. Although beta-adrenergic blocking properties can prevent such symptoms, the drug should be prescribed in such cases with caution. This medicinal product contains lactose and therefore patients with rare hereditary problems of lactose intolerance, glucose-galactose intolerance, malabsorption syndrome or sucrose-isomaltase deficiency should not take this medicinal product. Pharmacological properties Pharmacodynamics Pharmacological action – antianginal, hypotensive, antioxidant, vasodilating, antiproliferative. Carvedilol has β-, α1-blocking and antioxidant properties. It reduces afterload on the heart through arteriolar vasodilation and inhibits neurohumoral constrictor activation of blood vessels and the heart. Carvedilol has a prolonged antihypertensive effect. It also has an antianginal effect. It has no intrinsic sympathomimetic activity. Carvedilol inhibits the proliferation and migration of smooth muscle cells, apparently by acting on specific mitogenic receptors. Perhaps Carvedilol is able to prevent the development of atheroma. It does not have a pronounced effect on lipid metabolism and the content of K +, Na + and Mg2 + in plasma. Carvedilol and several of its metabolites have antioxidant properties, as they can inhibit the oxidation of noradrenaline with the subsequent formation of toxic intermediates, including reactive oxygen free radicals, in the myocardium. Thus, Carvedilol has a cardioprotective effect. Due to its antioxidant activity, carvedilol also blocks the expression of several genes, in particular ICAM-1 (intracellular adhesion molecule-1), whose product, the ICAM-1 protein, is a key adhesive molecule responsible for the attachment of neutrophils to endothelial and smooth muscle cells. The ICAM-1 gene is involved in myocardial damage and heart remodeling, and by inhibiting the expression of this gene, carvedilol suppresses neutrophil infiltration into the ischemic myocardium. Carvedilol inhibits the activation of free radical-induced transcription factors, prevents the release of oxygen radicals by neutrophils, and significantly inhibits apoptosis (programmed cell death), possibly through multiple mechanisms, including oxygen radical scavenging, neurohumoral antagonism, and modulation of gene transcription. In arterial hypertension, a decrease in blood pressure is not accompanied by an increase in total peripheral vascular resistance characteristic of beta-blockers and a change in renal blood flow. Long-term antianginal effect in coronary artery disease is associated with a decrease in pre- and afterload. In patients with systolic congestive heart failure, it increases exercise tolerance, reduces heart rate, peripheral vascular resistance, increases left ventricular ejection fraction, cardiac index, and reduces pulmonary capillary wedge pressure. Reduces the risk of death in patients with decompensated heart failure (65%) and the frequency of hospitalizations (by 38%). With moderate chronic heart failure reduces the risk of death by 28%. Efficacy is more pronounced in patients with tachycardia (HR > 82 beats/min) and low ejection fraction (23%). The therapeutic effect is also manifested in ischemic etiology of chronic heart failure and in patients with dilated cardiomyopathy. When treated with carvedilol at a dose of 25 mg once a day for 12 months, almost all patients with mild/moderate hypertension required the addition of the diuretic hydrochlorothiazide (25 mg once a day) to achieve and maintain a diastolic blood pressure of less than 90 mm Hg. Art. Pharmacokinetics When taken orally, it is rapidly and well absorbed from the gastrointestinal tract, undergoes intensive first pass metabolism. Absolute bioavailability is 25-35% (for S(-)-enantiomer 15%, for R(+)-enantiomer 31%). The maximum concentration of carvedilol in blood plasma after administration at a dose of 25 mg is 5-99 μg / ml and is reached on average after 1.46 hours (0.68-3.10 hours). The binding of carvedilol to plasma proteins is 98-99% (mainly due to the R (+)-enantiomer associated with albumin), the specific volume of distribution is 1.5-2.0 l / kg. The metabolism of carvedilol proceeds with demethylation and oxidation of the aromatic ring, followed by glucuronization or sulfation. Non-synthetic metabolic reactions proceed with the participation of cytochrome P450 isoforms CYP2D6 (provides 4′ and 5′-hydroxylation of the phenol ring), CYP2C9 (provides O-demethylation of the S (-)-enantiomer), minor metabolizing isoforms are CYP3A4, CYP2C19, CYP1A2, CYP2E1. In the process of demethylation and hydroxylation, 3 active metabolites are formed that have β-adrenergic blocking activity. The main metabolite, 4′-hydroxyphenylcarvedilol, is 13 times more β-blocking than the parent compound, while its plasma level is 10% of that of carvedilol. The elimination half-life of carvedilol is from 4 to 7 hours (significant fluctuations are possible due to the genetic polymorphism of CYP2D6 and an increase in the elimination half-life to 10 hours in individuals with a defective isoform of the enzyme). It is eliminated mainly with bile, no more than 2% of the administered carvedilol is excreted in the urine. The total clearance of carvedilol is 0.52 l/h×kg. Indications for use arterial hypertension – as monotherapy and in combination with other antihypertensive agents; left ventricular dysfunction after myocardial infarction in clinically stable patients (left ventricular ejection fraction less than 40%); chronic heart failure II-III class according to NYHA, in combination with diuretics, digoxin or ACE inhibitors. Dosage and administration Inside, with a sufficient amount of liquid. The dose is selected individually. Arterial hypertension: the recommended dose during the first days of treatment is 6.25 mg 2 times a day, if necessary, in the next 7-14 days of treatment, increase to 12.5 mg 2 times a day. The recommended maintenance dose is 25 mg carvedilol. With insufficient clinical effect, but not earlier than 14 days of treatment, the dose can be increased to a maximum of 50 mg per day. The maximum single dose is 25 mg, the daily dose should not exceed 50 mg. Left ventricular dysfunction after myocardial infarction: 6.25 mg 2 times a day, if necessary, the dose can be increased at intervals of 3-10 days to 12.5 mg 2 times a day, then up to 25 mg 2 times a day. Chronic heart failure: The recommended maximum daily dose is 25 mg twice daily for all patients with class III CHF and for patients with class I and II CHF weighing less than 85 kg. In patients with CHF class I and II weighing more than 85 kg, the recommended dose is a maximum of 50 mg twice a day. Patients with heart failure in order to prevent orthostatic hypotension, it is recommended to take the drug during meals. If a dose is missed, the drug should be used as soon as possible, but if the time for the next dose is approaching, then take only it, without doubling it. Cancellation of the drug should be done gradually over 1-2 weeks (especially in patients with angina pectoris). If the drug has not been taken for more than 2 weeks, treatment should be resumed, starting with the lowest doses. Should not be given to patients with severe hepatic impairment. Safety and efficacy in children (under 18 years of age) have not been established. In the elderly, an initial dose of 12.5 mg daily is recommended. If the response is inadequate, the dose may be titrated up to the recommended daily dose of a maximum of 50 mg once daily or in divided doses. Use during pregnancy and lactation The drug is contraindicated for use during pregnancy and lactation. Interaction with other drugs In the joint use of carvedilol with agents that deplete catecholamine reserves (reserpine, MAO inhibitors), severe bradycardia and arterial hypotension are possible. Calcium channel blockers (verapamil, diltiazem) and antiarrhythmic drugs (especially class I) while taking carvedilol can provoke severe arterial hypotension and heart failure. In / in the introduction of these drugs in conjunction with taking carvedilol is contraindicated. With alpha- and beta-adrenergic agonists, hypertension, severe reflex bradycardia and asystole may occur, as well as a decrease in the beta-blocking effect of carvedilol. Clonidine and carvedilol may enhance each other’s ability to lower blood pressure and heart rate. When used together, the withdrawal should be made gradually: carvedilol is first excluded, then, after a few days, clonidine can be gradually stopped. With the simultaneous use of carvedilol with digoxin, AV conduction slows down. Insulin and oral hypoglycemic agents increase the hypotensive effect of carvedilol and mask the symptoms of hypoglycemia. Nitrates and antihypertensive drugs (clonidine, guanethidine, alpha-methyldopa, guanfacine, etc.) enhance the hypotensive effect of carvedilol and reduce heart rate. Means for anesthesia increase the negative inotropic effect and the hypotensive effect of carvedilol. Drugs affecting the central nervous system (hypnotics, tranquilizers, tricyclic antidepressants and ethyl alcohol) and carvedilol mutually reinforce each other’s effects. NSAIDs reduce the hypotensive effect of carvedilol due to a decrease in PG production. When carvedilol is co-administered with ergotamine, the vasoconstrictor effect of ergotamine must be taken into account. Xanthine derivatives (aminophylline, theophylline) reduce the beta-adrenergic blocking effect of carvedilol. Since carvedilol undergoes oxidative metabolism, its pharmacokinetics may change with induction or inhibition of the cytochrome P450 enzyme system, so the effect of: rifampicin (a 70% decrease in carvedilol serum concentration occurs); barbiturates (reduce the effect of carvedilol); inhibitors of the CYP2D6 isoenzyme (quinidine, fluoxetine, paroxetine, propafenone; an increase in the concentration of the R (+) enantiomer of carvedilol can be assumed); cimetidine (increases the bioavailability of carvedilol by 30%). Carvedilol delays the metabolism of cyclosporine, increases the concentration of digoxin in the blood plasma. Contraindications chronic obstructive pulmonary disease, bronchial asthma; liver failure; severe bradycardia (heart rate less than 50 beats per minute); conduction disturbances (sick sinus syndrome; sinoatrial blockade, AV block II and III degree), with the exception of patients with an artificial pacemaker; heart failure in the stage of decompensation (IV FC); cardiogenic shock; arterial hypotension (with blood pressure less than 85 mm Hg); bronchial asthma; metabolic acidosis; pregnancy and lactation; children and adolescents under 18 years of age (safety and effectiveness of use have not been established); hypersensitivity to the drug. CompositionCarvedilol OverdoseSymptoms: severe arterial hypotension, bradycardia, respiratory failure (including bronchospasm), heart failure; in severe cases – cardiogenic shock, conduction disturbances up to cardiac arrest; impaired consciousness, up to coma; generalized seizures. Treatment: gastric lavage or administration of emetics if they are carried out within a few hours after taking the drug. If the patient is conscious, it is necessary to lay him on his back with slightly raised legs and lowered head, the unconscious patient should be laid on his side. The beta-blocking effect is eliminated by orciprenaline or isoprenaline 0.5-1 mg IV and / or glucagon at a dose of 1-5 mg (maximum dose 10 mg). Severe hypotension is treated with parenteral fluid and epinephrine at a dose of 5-10 mcg (or its IV infusion at a rate of 5 mcg/min). For the treatment of excessive bradycardia, intravenous atropine is prescribed at a dose of 0.5-2 mg. To maintain heart failure: glucagon – 1-10 mg IV quickly over 30 seconds, after which a constant infusion is carried out at the rate of 2-5 mg / hour. If the peripheral vasodilating effect predominates (warm extremities, in addition to significant hypotension), it is necessary to prescribe norepinephrine in repeated doses of 5-10 micrograms or as an infusion – 5 micrograms / min. For relief of bronchospasm, beta-agonists are prescribed (in the form of an aerosol or IV) or aminophylline IV. If convulsions develop, slow administration of diazepam or clonazepam is recommended. In severe cases of intoxication, when symptoms of shock dominate, treatment with antidotes should continue until the patient’s condition stabilizes, taking into account T1 / 2 carvedilol (6-10 hours). Side effects In recommended doses, the drug is usually well tolerated. From the side of the central nervous system and peripheral nervous system: headache, dizziness, syncope, muscle weakness (more often at the beginning of treatment), sleep disturbances, depression, paresthesia, convulsions, visual impairment, hearing loss, hypesthesia, emotional lability. From the side of the cardiovascular system: bradycardia, orthostatic hypotension, angina attacks, AV blockade; rarely – peripheral circulatory disorders (cold extremities), “intermittent” claudication, progression of heart failure, a pronounced decrease in blood pressure, peripheral edema. On the part of the respiratory system: shortness of breath, bronchospasm; rarely – nasal congestion. From the digestive system: dry mouth, nausea, abdominal pain, diarrhea, melena; rarely – constipation, vomiting, increased activity of hepatic transaminases. From the hemopoietic system: thrombocytopenia, leukopenia, anemia. From the urinary system: renal failure, peripheral edema, difficulty urinating, hypervolemia, fluid retention; albuminuria, hematuria. From the reproductive system: rarely – decreased libido, impotence. On the part of the skin: allergic exanthema, urticaria, itching, exacerbation of psoriatic rashes; very rarely – anaphylactoid reactions. Others: rarely – flu-like effect, pain in the extremities, decreased tearing, eye irritation, urination disorders, impaired renal function, increased levels of alkaline phosphatase, GGTP, hyperuricemia, hyponatremia, hyperkalemia. Storage conditions Do not use after the expiry date indicated on the package. Store in a place protected from moisture and light at a temperature of 15°C to 25°C. Buy Carvedilol-MIC capsules 25mg №10×3