Pharmacological properties of the drug Carvedilol
Combined α1- and non-selective β-adrenergic receptor blocker without BCA; the ratio of α1- and β-adrenergic blocking activity is 1:100. It has antioxidant properties and moderately expressed antagonistic activity against calcium ions. Used for hypertension (arterial hypertension), stable angina pectoris; reduces morbidity and mortality in heart failure. With long-term use, it has a positive effect on the lipid spectrum of blood serum and does not change the level of glucose in the blood. Reduces left ventricular hypertrophy. After oral administration, bioavailability is 25–35% due to first pass metabolism through the liver. Bioavailability increases in patients with liver disease and in the elderly (up to 50%). Concomitant food intake slows down the absorption of carvedilol, but does not reduce its volume. The maximum concentration in blood plasma is reached 1–2 hours after administration and has a linear dependence on the dose taken. Duration of action - more than 15 hours. Extensively metabolized in all tissues of the body; passes into breast milk. 98% of carvedilol binds to plasma proteins. The content in erythrocytes is 69% of the concentration in blood plasma. Metabolized by oxidation of the aromatic ring and glucuronidation with the participation of cytochrome P450 2D6. Forms three main metabolites with β-adrenergic blocking and weak α-antagonistic activity. One of them, 4′-hydroxyphenylcarvedilol, has β-adrenergic blocking activity that is almost 13 times greater than the parent compound. The terminal half-life is 7–11 hours for the S-enantiomer and 5–9 hours for the R-enantiomer. Less than 2% of carvedilol is excreted unchanged in the urine.
Side effects of the drug Carvedilol
At the beginning of treatment (the effect of the first dose) and with increasing doses, a pronounced decrease in blood pressure is possible. Typically, symptomatic hypotension resolves spontaneously and does not require drug correction. When using carvedilol, general weakness, increased fatigue, headache, bradycardia, increased tone and intestinal motility are possible; Less commonly observed are disturbances of peripheral blood flow, attacks of angina pectoris, AV block, episodes of intermittent claudication, as well as allergic exanthema, skin itching, urticaria, reactions resembling lichen planus, the appearance of psoriatic plaques or exacerbation of a pre-existing psoriatic process. In some cases, the following were noted: sleep disturbance, depression, paresthesia, increased manifestations of heart failure, nasal congestion, thrombocytopenia, leukopenia, increased transaminase activity in the blood serum.
Carvedilol tablets 12.5 mg No. 30
Compound
Active substance: carvedilol - 12.5 mg. Excipients: lactose monohydrate - 146 mg, corn starch - 20.5 mg, microcrystalline cellulose - 16 mg, magnesium stearate - 2.5 mg, talc - 1.8 mg, colloidal silicon dioxide - 0.9 mg.
Pharmacokinetics
After oral administration, it is quickly and almost completely absorbed from the gastrointestinal tract. Cmax in blood plasma is achieved within 1 hour. Bioavailability is 25%.
Plasma protein binding is 98-99%. Vd - about 2 l/kg. Penetrates the placental barrier and is excreted in breast milk. Subject to a first-pass effect through the liver. Metabolites have a pronounced antioxidant and adrenergic blocking effect.
T1/2 - 6-10 hours. Plasma clearance - 590 ml/min. It is excreted mainly in bile.
In patients with impaired liver function, bioavailability may increase up to 80%.
Indications for use
- Arterial hypertension.
- IHD: prevention of attacks of stable angina.
- Chronic heart failure (as part of combination therapy).
Contraindications
- hypersensitivity to carvedilol and to any other component of the drug;
- acute and decompensated CHF, requiring intravenous administration of inotropic drugs;
- atrioventricular (AV) block II-III stage (without artificial pacemaker),
- severe bradycardia (heart rate less than 50 beats/min);
- sick sinus syndrome (SSNS);
- cardiogenic shock;
- severe liver failure;
- bronchial asthma or bronchospasm (history);
- severe arterial hypotension (systolic blood pressure less than 85 mm Hg);
- breastfeeding period;
- age under 18 years (safety and effectiveness of use have not been established);
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose);
- pheochromocytoma without simultaneous use of alpha-blockers.
Directions for use and doses
Inside, with a sufficient amount of liquid.
For arterial hypertension, the initial dose is 12.5 mg 1 time per day in the first 2 days, then 25 mg 1 time per day, with a possible gradual increase in dose at intervals of at least 2 weeks. The maximum recommended daily dose of the drug is 50 mg 1 time per day (possibly divided into two doses).
For angina pectoris, the initial dose is 12.5 mg 1 time per day in the first 2 days, then 25 mg 2 times a day (maximum - up to 100 mg, divided into 2 doses).
For CHF (against the background of selected therapy with cardiac glycosides, diuretics and angiotensin-converting enzyme (ACE) inhibitors, start with 3.125 mg (1/2 tablet 6.25 mg (tablet has a risk)) 2 times a day for 2 weeks, then (with good tolerance) this dose is increased to 6.25 mg 2 times a day, then to 12.5 - 25 mg 2 times a day (for patient body weight less than 85 kg - the maximum dose is 25 mg 2 times a day, for body weight patient over 85 kg - 50 mg 2 times a day).
Before each dose increase, you should consult your doctor to avoid an increase in symptoms of CHF or vasodilation.
If symptoms of CHF or fluid retention in the body increase, the dose of diuretics should be increased, or the dose of carvedilol should be reduced or temporarily discontinued.
If treatment with Carvedilol is interrupted for more than 1 week, its administration is resumed at a lower dose and then increased in accordance with the above recommendations. If treatment is interrupted for more than 2 weeks, then its resumption begins with a dose of 3.125 mg (1/2 tablet of 6.25 mg (tablet has a score)) 2 times a day, followed by an increase in dose.
If vasodilation occurs, the dose of diuretics should be reduced. If symptoms persist, the dose of the ACE inhibitor (if the patient is taking one) can be reduced and then, if necessary, the dose of carvedilol. The dose of carvedilol should not be increased until symptoms of worsening heart failure or hypotension have stabilized.
Dosing in special patient groups
For patients with moderate to severe renal impairment, as well as elderly patients, no dosage adjustment of carvedilol is required.
For patients with clinical manifestations of liver dysfunction, carvedilol is contraindicated.
Storage conditions
Store in a dry place, protected from light, at a temperature not exceeding 25°C.
Keep out of the reach of children.
Best before date
2 years. Do not use after the expiration date stated on the package.
special instructions
Use with caution in patients with coronary artery disease and heart failure. Before starting treatment with carvedilol for heart failure, adequate therapy should be carried out to eliminate the symptoms of decompensation.
When using carvedilol in patients with coronary artery disease, it is possible to reduce the myocardial oxygen demand (due to blockade of β1-adrenergic receptors). In this regard, carvedilol should be discontinued gradually to avoid the development of angina attacks.
In patients with endocrine disorders, carvedilol may mask the symptoms of hyperthyroidism and early signs of acute hyperglycemia (which should be warned about in patients with insulin-dependent diabetes mellitus).
During the treatment period, alcohol consumption is not recommended.
There is no clinical experience with the use of carvedilol in pediatrics.
Description
Alpha and beta blocker.
Dosage form
Tablets are white or white with a yellowish tint, marbling is allowed, round, flat-cylindrical, without marks, with a chamfer.
Use in children
There is no clinical experience with the use of carvedilol in pediatrics.
Pharmacodynamics
An antihypertensive drug from the group of alpha- and beta-blockers without internal sympathomimetic activity. Blocks α1-, β1- and β2-adrenergic receptors. As a result of blockade of β1-adrenergic receptors, it moderately reduces the conductivity, strength and frequency of heart contractions without causing severe bradycardia. As a result of blockade of α1-adrenergic receptors, it causes dilatation of peripheral vessels. As a result of blockade of β2-adrenergic receptors, it may slightly increase the tone of the bronchi, some microvasculature vessels, as well as the tone and intestinal motility.
Side effects
From the cardiovascular system: at the beginning of treatment (the effect of the first dose) and as the dose increases, episodes of excessive decrease in blood pressure are possible (usually these phenomena go away on their own and the patient’s condition stabilizes without special correction); With further use of carvedilol, bradycardia is also possible; Peripheral blood flow disorders, angina attacks, AV block, and episodes of intermittent claudication are less common; in some cases - increased manifestations of heart failure.
From the central nervous system and peripheral nervous system: possible weakness, fatigue, headache; in some cases - sleep disturbances, mental depression, paresthesia.
From the digestive system: increased intestinal tone and motility; in some cases - changes in transaminase activity in the blood plasma.
Allergic reactions: rarely - allergic exanthema, itching.
Dermatological reactions: urticaria, reactions resembling lichen planus, the appearance of psoriatic plaques or exacerbation of a pre-existing psoriatic process.
From the respiratory system: in some cases - nasal congestion.
From the hematopoietic system: in some cases - thrombocytopenia, leukopenia.
Use during pregnancy and breastfeeding
Carvedilol is contraindicated for use during pregnancy and lactation (breastfeeding).
Although there are no direct indications of embryo- or fetotoxic effects of carvedilol, it is known that it penetrates the placental barrier and is excreted in breast milk. Blockade of α- and β-adrenergic receptors in the fetus or newborn can induce perinatal or neonatal distress syndrome, manifested by bradycardia, respiratory depression, hypothermia and hypoglycemia.
Interaction
- When used simultaneously with carvedilol, antiarrhythmic drugs, anesthetics, antihypertensive drugs, antianginal drugs, and other beta-blockers (including in the form of eye drops), there is a risk of unwanted drug interaction.
- With simultaneous use of inhibitors of the CYP2D6 isoenzyme, it is theoretically possible to enhance the effect of carvedilol.
- With simultaneous use of inducers of the CYP2D6 isoenzyme system, the effect of carvedilol may be reduced.
- When used simultaneously with verapamil and diltiazem for intravenous administration, severe arterial hypotension may develop.
- When used simultaneously with digoxin, it is possible to increase the concentration of digoxin in the blood plasma and increase the risk of developing severe bradycardia and AV conduction disorders.
- With the simultaneous use of insulin and oral hypoglycemic drugs, the risk of hypoglycemia may increase.
- When used simultaneously with clonidine, severe bradycardia, arterial hypotension, and conduction disturbances are possible. If clonidine is suddenly discontinued in patients receiving carvedilol, a sharp increase in blood pressure may occur.
- When used simultaneously with reserpine and MAO inhibitors, there is a risk of developing severe arterial hypotension and bradycardia.
- When used simultaneously with rifampicin, the AUC and Cmax of carvedilol in the blood plasma decrease.
- Fluoxetine inhibits the CYP2D6 isoenzyme, which leads to inhibition of carvedilol metabolism and its accumulation. This may enhance the cardiodepressive effect (including bradycardia). Fluoxetine and, mainly, its metabolites are characterized by a long T1/2, so the likelihood of drug interactions remains even several days after discontinuation of fluoxetine.
- When used simultaneously with cimetidine, the AUC of carvedilol increases without changing its Cmax in the blood plasma.
- When used simultaneously with cyclosporine, an increase (from small to moderate) in the concentration of cyclosporine in the blood plasma is possible.
- When used simultaneously with ergotamine derivatives, deterioration of peripheral circulation is possible.
Overdose
Symptoms: vomiting, confusion, marked decrease in blood pressure (systolic blood pressure 80 mm Hg and below), bradycardia (less than 50 beats/min), impaired respiratory function (including bronchospasm), heart failure, cardiogenic shock, arrest heart, generalized convulsions.
Treatment: cardiotonics, control of cardiovascular system, respiratory system and kidney functions. Hemodialysis is not effective.
Impact on the ability to drive vehicles and operate machinery
At the beginning of treatment, as well as when increasing the dose of carvedilol during treatment, you should refrain from driving and other activities associated with the need for high concentration and rapid psychomotor reactions.
Special instructions for the use of the drug Carvedilol
Before starting treatment with carvedilol for heart failure, adequate therapy should be carried out to eliminate decompensation. When used in patients with coronary artery disease, carvedilol should be discontinued gradually to avoid the development of angina attacks. In patients with endocrine disorders, carvedilol may mask the symptoms of hyperthyroidism and hypoglycemia. At the beginning of treatment, as well as when increasing the dose of carvedilol during treatment, you should refrain from driving and other activities that require increased concentration and quick reaction. During the treatment period, alcohol consumption should be avoided. Although there is no direct evidence of embryo- or fetotoxic effects of carvedilol, it is known to cross the placenta and is found in breast milk. Blockade of α- and β-adrenergic receptors in the fetus or newborn can induce perinatal or neonatal distress syndrome, manifested by bradycardia, respiratory depression, hypothermia and hypoglycemia. There is no clinical experience with the use of carvedilol in pediatrics.
Instructions for use CARVEDILOL-MIC
The drug should be prescribed with caution in case of bronchospastic syndrome, chronic bronchitis, pulmonary emphysema, Prinzmetal's angina, diabetes mellitus, hypoglycemia, hyperthyroidism, peripheral vascular diseases, AV blockade of the first degree, unstable angina, when treated with alpha1-blockers or alpha2-adrenergic agonists, when combined the use of MAO inhibitors, pheochromocytoma, depression, myasthenia gravis, psoriasis, renal failure.
Patients with severe heart failure (more than III functional class according to the NYHA classification), with electrolyte imbalance, with arterial hypotension (less than 100 mm Hg), as well as elderly patients should be under close medical supervision for 2 hours after administration 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 arterial hypotension.
In patients with heart failure, if their initial blood pressure level is less than 100 mm Hg. Art. or there are concomitant diseases (coronary artery disease, peripheral vascular disease or renal dysfunction), renal function should be monitored more often. If renal dysfunction 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. In this regard, the administration of Carvedilol-MIC to patients with diabetes mellitus should be carried out with extreme caution and with frequent monitoring of blood glucose levels.
The use of the drug may mask the symptoms of hyperthyroidism. If the drug is suddenly discontinued, thyrotoxicosis may increase and a thyrotoxic crisis is possible.
In patients with established pheochromocytoma, Carvedilol-MIC should not be started before appropriate therapeutic blockade of α-adrenergic receptors.
Treatment of patients with psoriasis with Carvedilol-MIC requires a benefit/risk assessment, because the use of carvedilol may worsen the disease or provoke the appearance of its symptoms.
It is possible that the results of allergy tests performed during the use of Carvedilol-MIC may be distorted.
While using carvedilol, general anesthesia should be used with caution using drugs with negative inotropic effects (ether, cyclopropane, trichlorethylene). Before major surgical interventions, gradual withdrawal of the drug is recommended.
Caution must be exercised when using the drug Carvedilol-MIC in case of severe metabolic acidosis.
Patients wearing contact lenses should be warned that carvedilol reduces tear production.
During the period of use of the drug, you should avoid drinking alcohol.
Carvedilol-MIC should be discontinued by gradually reducing the dose.
Use in pediatrics
Safety and effectiveness of the drug Carvedilol-MIC in children and adolescents under 18 years of age
not installed.
Impact on the ability to drive vehicles and operate machinery
During the period of use of the drug Carvedilol-MIC, you should refrain from engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions.
Drug interactions Carvedilol
When using carvedilol, calcium channel blockers (verapamil) and class I antiarrhythmic drugs should be prescribed with caution. It is necessary to avoid intravenous administration of these drugs while using carvedilol. Carvedilol increases the concentration of digoxin in the blood plasma. The hypotensive effect of carvedilol is enhanced by anesthetic agents. The concentration of carvedilol in the blood plasma is reduced by inducers of microsomal liver enzymes (including rifampicin).
List of pharmacies where you can buy Carvedilol:
- Moscow
- Saint Petersburg
