Instructions for use of Coriolus tablets 12.5 mg No. 28
Composition
active ingredient: carvedilol;
1 tablet contains carvedilol 12.5 or 25 mg;
excipients: sucrose, lactose monohydrate, povidone K25, colloidal anhydrous silica, crospovidone, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
12.5 mg tablets: oval, slightly biconvex, white tablets with a score on one side and the marking "S3" on the other side;
25 mg tablets: round, slightly biconvex, white tablets with beveled edges and a score line on one side.
Pharmacotherapeutic group
Blockers of a- and b-adrenergic receptors.
ATX code C07A G02.
Pharmacological properties
Pharmacodynamics
Carvedilol is a non-selective β-blocker with vasodilator activity. It also has antioxidant and antiproliferative properties.
The active ingredient carvedilol is a racemate; the enantiomers differ in their effects and metabolism. The S(–)-enantiomer has activity directed at blocking both α1- and β-adrenoceptors, while the R(+)-enantiomer exhibits activity directed at blocking only α1-adrenoceptors. Due to cardioselective blockade of β-adrenoceptors, it reduces blood pressure, heart rate and cardiac output. Carvedilol reduces pulmonary artery pressure and right atrial pressure. By blocking α1-adrenoceptors, it causes peripheral vasodilation and reduces systemic vascular resistance. Due to these effects, the workload on the heart muscle is reduced and the development of angina is prevented. In patients with heart failure, this leads to an increase in the ejection fraction from the left ventricle and a decrease in the symptoms of the disease. Similar effects have been observed in patients with left ventricular dysfunction. Carvedilol does not exhibit intrinsic sympathomimetic activity and, like propranolol, has membrane-stabilizing properties. Plasma renin activity is reduced and fluid retention is rare. The effect on blood pressure and heart rate is most pronounced 1-2 hours after administration.
In patients with arterial hypertension on the background of healthy kidneys, carvedilol reduces renal vascular resistance. At the same time, there are no significant changes in glomerular filtration, renal blood flow and electrolyte excretion. Due to the maintenance of peripheral blood flow, cooling of the extremities, characteristic of treatment with β-blockers, rarely occurs.
Carvedilol generally does not affect serum lipoprotein levels.
Pharmacokinetics
Carvedilol is rapidly and almost completely absorbed after oral administration. It is almost completely bound to plasma proteins. The volume of distribution is approximately 2 l/kg. The plasma concentration is proportional to the applied dose.
Due to extensive first-pass metabolism in the liver (mainly by the hepatic enzymes CYP2D6 and CYP2C9), the bioavailability of carvedilol is only about 30%. Three active metabolites are formed that exhibit β-blocking activity; one of them (the 4'-hydroxyphenyl derivative) has 13 times the β-blocking activity of carvedilol. Compared with carvedilol, the active metabolites have weak vasodilator activity. Metabolism is stereoselective; therefore, the plasma level of R(+)-carvedilol is 2–3 times higher than that of S(–)-carvedilol. The plasma levels of the active metabolites are about 10 times lower than those of carvedilol. The half-life varies greatly: 5–9 hours for R(+)-carvedilol and 7–11 hours for S(–)-carvedilol.
In elderly patients, an increase in carvedilol levels of approximately 50% is observed.
In patients with cirrhosis of the liver, the bioavailability of carvedilol is increased by 4 times, and the maximum plasma concentration is 5 times higher than in healthy subjects. In patients with impaired liver function, the bioavailability increases to 80% due to reduced first-pass metabolism. Since carvedilol is excreted mainly in the feces, significant accumulation of the drug is unlikely in patients with impaired renal function.
The presence of food in the stomach slows down the rate of absorption of the drug, but this does not affect its bioavailability.
Indication
Essential hypertension (both mono- and as part of combination therapy).
Chronic stable angina.
Chronic heart failure of moderate and severe severity, as adjunctive therapy.
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the medicinal product;
decompensated heart failure – heart failure of class IV according to the NYHA (New York Heart Association) classification, which requires intravenous administration of inotropic agents;
unstable heart failure;
atrioventricular block of the 2nd and 3rd degree (except in cases where a permanent pacemaker is installed);
concomitant intravenous administration of verapamil, diltiazem or other antiarrhythmic drugs (especially class I antiarrhythmic drugs);
severe bradycardia (heart rate (HR) < 50 beats/min);
severe arterial hypotension (systolic pressure below 85 mm Hg);
cardiogenic shock;
uncompensated heart failure requiring intravenous administration of positive inotropic and/or diuretic agents;
pulmonary heart, pulmonary hypertension;
bronchial asthma or obstructive airway diseases accompanied by bronchospasm;
pheochromocytoma (unless adequately controlled with alpha-blockers);
Prinzmetal's angina;
severe liver dysfunction;
concomitant use of monoamine oxidase inhibitors (MAO) (except MAO-B inhibitors);
galactose intolerance, lactase deficiency or glucose-galactose malabsorption;
metabolic acidosis;
pregnancy and lactation, childhood.
Interaction with other medicinal products and other types of interactions
Some antiarrhythmics, narcotics, antihypertensives, drugs for the treatment of angina, other β-blockers (e.g. in the form of eye drops), drugs that reduce the level of catecholamines (e.g. monoamine oxidase inhibitors, reserpine), and cardiac glycosides may enhance the effects of carvedilol. Therefore, the dose of these drugs and Coriolus® should be selected with caution.
Pharmacokinetic interactions.
Digoxin: Increased digoxin exposure (by almost 20%) has been observed in some studies in healthy volunteers and patients with heart failure. A significantly greater effect was observed in male patients compared to female patients. Therefore, it is recommended to monitor digoxin levels when initiating, adjusting or discontinuing carvedilol. Carvedilol did not affect intravenously administered digoxin.
Inducers or inhibitors of P-glycoprotein, CYP2D6, CYP2D9.
Carvedilol is an inhibitor of P-glycoprotein, therefore the bioavailability of drugs transported by P-glycoprotein may be increased when used concomitantly with carvedilol. In addition, the bioavailability of carvedilol may be altered by inducers or inhibitors of P-glycoprotein.
Inhibitors, as well as inducers of CYP2D6 and CYP2D9, can stereoselectively alter the systemic or presystemic metabolism of carvedilol, increasing or decreasing the plasma concentrations of R- and S-carvedilol.
Fluoxetine and Paroxetine.
In a randomized crossover study in 10 patients with heart failure, concomitant administration of fluoxetine, a potent CYP2D6 inhibitor, resulted in stereoselective inhibition of carvedilol metabolism with a 77% increase in mean AUC of the R(+) enantiomer and a non-statistical 35% increase in AUC of the S(–) enantiomer compared to placebo. However, there were no differences in adverse events, blood pressure, or heart rate between treatment groups. The effect of a single dose of paroxetine, a potent CYP2D6 inhibitor, on the pharmacokinetics of carvedilol was studied in 12 healthy subjects after a single oral dose. Despite a significant increase in exposure to R- and S-carvedilol, no clinical effects were observed in these healthy subjects.
β-agonist bronchodilators.
Non-cardioselective β-blockers antagonize the β-agonist effects of bronchodilators, so such patients require close monitoring.
Hepatic Metabolism Inducers and Inhibitors: Rifampicin decreases carvedilol plasma concentrations by approximately 70%. Cimetidine increases AUC by approximately 30% but does not cause any change in Cmax. Caution may be warranted in those taking mixed-function oxidase inducers, such as rifampicin, as serum carvedilol levels may be decreased, or mixed-function oxidase inhibitors, such as cimetidine, as serum levels may be increased. However, based on the relatively small effect of cimetidine on carvedilol drug levels, the likelihood of any clinically significant interaction is minimal.
Catecholamine-depleting drugs: Patients taking both drugs with β-blocking properties and a drug that may deplete catecholamines (e.g., reserpine and monoamine oxidase inhibitors) should be closely monitored for signs of hypotension and/or severe bradycardia.
Ciclosporin: Two studies in renal and cardiac transplant patients receiving oral ciclosporin have shown an increase in plasma ciclosporin concentrations after initiation of carvedilol treatment. Carvedilol is thought to increase the exposure of oral ciclosporin by approximately 10–20%. To maintain therapeutic levels of ciclosporin, a reduction in the ciclosporin dose of 10–20% was required on average. The mechanism of interaction is unknown, but inhibition of intestinal P-glycoprotein by carvedilol may be involved. Due to the significant inter-subject variability in the required dose adjustment, it is recommended that ciclosporin concentrations be carefully monitored after initiation of carvedilol therapy and the ciclosporin dose adjusted accordingly. No interaction with carvedilol is expected when ciclosporin is administered intravenously.
Antiarrhythmic drugs.
Careful monitoring of the patient's condition is necessary when carvedilol is used concomitantly with amiodarone (oral) or class I antiarrhythmic drugs. Bradycardia, cardiac arrest, ventricular fibrillation have been reported shortly after the start of treatment with β-blockers in patients receiving concomitant amiodarone. There is a risk of heart failure in the case of concomitant intravenous therapy with class Ia or Ia antiarrhythmic drugs.
An in vitro study with human liver microsomes showed that amiodarone and desethylamiodarone inhibited the oxidation of R- and S-carvedilol. Trough concentrations of R- and S-carvedilol were significantly increased by 2.2-fold in heart failure patients receiving concomitant carvedilol and amiodarone compared with patients receiving carvedilol monotherapy. The effect on S-carvedilol was attributed to desethylamiodarone, a metabolite of amiodarone, which is a potent inhibitor of CYP2C9. Monitoring of β-blocking activity is recommended in patients receiving the combination of carvedilol and amiodarone.
Other antihypertensive drugs.
Like other drugs with β-blocking activity, carvedilol may enhance the effect of other concomitantly administered drugs that are antihypertensive in action (e.g. β1-receptor antagonists) or may cause hypotension in relation to their side effect profile.
Pharmacodynamic interactions.
Insulin or oral hypoglycemic agents: Drugs with β-blocking properties may enhance the blood sugar-lowering effect of insulin and oral hypoglycemic agents. The symptoms of hypoglycemia may be masked or attenuated (especially tachycardia). Therefore, regular monitoring of blood glucose levels is recommended for patients taking insulin or oral hypoglycemic agents.
Clonidine: Concomitant administration of clonidine with drugs with β-blocking properties may potentiate the blood pressure and heart rate lowering effects. When concomitant treatment with drugs with β-blocking properties and clonidine is terminated, the β-blocking drug should be discontinued first. Then, after a few days, clonidine therapy can be discontinued by gradually reducing the dosage.
Dihydropyridines.
When dihydropyridines and carvedilol are used concomitantly, careful patient monitoring should be ensured, as cases of heart failure and severe arterial hypotension have been reported.
Nitrates.
Enhances the hypotensive effect.
NSAIDs, estrogens, and corticosteroids.
Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), estrogens, corticosteroids, and beta-adrenergic blockers may lead to increased blood pressure and worsening blood pressure control, which results in water and sodium retention.
Sympathomimetics, α-mimetics and β-mimetics.
With simultaneous use, there is a risk of developing arterial hypertension and pronounced bradycardia.
Ergotamine.
With simultaneous use, vasoconstriction increases.
Muscle relaxants.
When carvedilol is combined with muscle relaxants, neuromuscular blockade is enhanced.
Xanthine derivatives.
It should be used with caution with xanthine derivatives (aminophylline, theophylline) due to reduced β-adrenergic blocking effect.
Anesthetics: Extreme caution should be exercised during anesthesia due to the synergistic negative inotropic and hypertensive effects of carvedilol and anesthetics.
Application features
Arterial hypotension.
The drug is not recommended for use in patients with low blood pressure.
Orthostatic hypotension.
Especially at the beginning of treatment with Coriolus® and when the dose is increased, orthostatic hypotension with dizziness and vertigo, sometimes also with fainting, may occur. Patients with heart failure, elderly patients, and patients taking other antihypertensive agents or diuretics are at greatest risk. These effects can be prevented by using a low initial dose of Coriolus®, carefully increasing the maintenance dose and taking the drug after a meal. Patients should be told about measures to avoid orthostatic hypotension (caution when standing up; if dizziness occurs, the patient should sit or lie down).
Discontinuation of treatment.
Carvedilol treatment should not be stopped abruptly, especially in patients suffering from ischemic heart disease.
Abrupt discontinuation of Coriolus® (as with other β-blockers) may cause sweating, tachycardia, dyspnea, and worsening of angina pectoris. Severe exacerbation of angina pectoris and myocardial infarction and ventricular arrhythmias have been reported in patients with angina pectoris after abrupt discontinuation of β-blocker therapy. The dose should be tapered gradually over 1–2 weeks.
If treatment has been temporarily discontinued for more than 2 weeks, it should be resumed starting at the lowest dose.
In most cases, carvedilol should be prescribed in addition to diuretics, angiotensin-converting enzyme (ACE) inhibitors, digitalis and/or vasodilators in patients with chronic heart failure. Treatment should be initiated in a hospital setting under medical supervision. Therapy should only be initiated if the patient has been stable on standard basic therapy for at least 4 weeks. Patients with severe heart failure, salt depletion or dehydration, the elderly or with low baseline blood pressure should be monitored closely for approximately 2 hours after the first dose or after dose increases, as hypotension may develop. Hypotension due to excessive vasodilation is initially treated by reducing the dose of diuretics, and if symptoms persist, the dose of any ACE inhibitor can be reduced. At the beginning of treatment or during dose increase, worsening of heart failure or fluid retention may occur. In this case, it is necessary to increase the dose of the diuretic. However, in some cases, it may be necessary to reduce the dose or cancel the drug. The dose of carvedilol should not be increased until symptoms associated with worsening heart failure or arterial hypotension due to excessive vasodilation are controlled.
Carvedilol should be prescribed with caution to patients with chronic heart failure who are taking digitalis, as this combination prolongs atrioventricular conduction.
Carvedilol may cause bradycardia. If heart rate is < 55 beats/min and symptoms associated with bradycardia occur, the dose of the drug should be reduced.
Because carvedilol has an inherent negative dromotropic effect, it should be administered with caution to patients with first-degree heart block.
Kidney dysfunction.
In patients with heart failure and low blood pressure (systolic < 100 mm Hg), ischemic heart disease or systemic atherosclerosis and/or renal insufficiency, reversible deterioration of renal function has been observed during treatment with carvedilol. In patients with heart failure who have such risk factors, renal function should be monitored during titration of carvedilol. If significant deterioration of renal function is observed, the carvedilol dose should be reduced or treatment discontinued.
Diabetes.
Caution should be exercised when using carvedilol in patients with diabetes mellitus, as blood glucose control may deteriorate or early signs of acute hypoglycemia may be masked or attenuated. For patients with diabetes mellitus, regular monitoring of blood glucose levels is recommended when starting carvedilol or when the dose is increased by titration and appropriate adjustment of hypoglycemic therapy.
Diabetes mellitus and hyperthyroidism.
β-blockers slow the heart rate and therefore may mask hypoglycemia in patients with diabetes mellitus and thyrotoxicosis in patients with thyroid disease. In patients with heart failure and diabetes mellitus, blood glucose levels may decrease or increase.
Antiarrhythmic drugs.
When using carvedilol simultaneously with calcium channel blockers such as verapamil and diltiazem, or other antiarrhythmic drugs, especially amiodarone, blood pressure and ECG should be monitored, so their simultaneous intravenous administration should be avoided.
Thyrotoxicosis.
Carvedilol, like other drugs with β-blocking action, may mask the symptoms of thyrotoxicosis.
General anesthesia.
β-blockers reduce the risk of arrhythmias during anesthesia, but may also increase the risk of hypotension, so some anesthetics should be used with caution.
Liver dysfunction.
Carvedilol may in very rare cases cause deterioration of liver function. If clinical deterioration is suspected, liver function should be checked. In case of liver failure, the patient should stop taking Coriol®. As a rule, liver function normalizes after discontinuation of treatment.
Chronic obstructive pulmonary disease.
β-blockers may increase bronchial obstruction; therefore, these drugs are not recommended for use in patients with chronic lung disease. In exceptional cases, Coriolus® may be prescribed to patients with mild lung disease when other drugs are ineffective; however, careful monitoring is necessary. It is important that these patients take the lowest effective dose of Coriolus®. If signs of airway obstruction appear, treatment with Coriolus® should be discontinued immediately.
Peripheral vascular disease and Raynaud's syndrome.
Carvedilol should be used with caution in patients with peripheral vascular disease and Raynaud's syndrome, as β-blockers may exacerbate the symptoms of the disease.
Psoriasis.
Carvedilol should be used with caution in patients with a history of serious hypersensitivity reactions and in those requiring desensitization, as β-blockers may increase sensitivity to allergens and the severity of anaphylactic reactions. The drug should also be used with caution in patients with psoriasis, as it may exacerbate skin reactions.
Prinzmetal's angina.
In patients with Prinzmetal's angina, nonselective β-blockers may cause chest pain (the α1-adrenoblocking effect of carvedilol may prevent this, but there is insufficient clinical experience with carvedilol in Prinzmetal's angina).
Pheochromocytoma.
Patients with pheochromocytoma should be given an alpha-blocker before any beta-blocker. Although carvedilol has both alpha- and beta-blocking pharmacological activity, there is no experience with carvedilol in this condition. Therefore, caution should be exercised when prescribing carvedilol to patients suspected of having pheochromocytoma.
Hypersensitivity reactions.
Carvedilol should be administered with caution to patients with a history of serious hypersensitivity reactions and those undergoing desensitization, as β-blockers may increase reactivity in allergy tests, increase sensitivity to allergens, and increase the severity of anaphylactic reactions.
Contact lenses: Contact lens wearers should be warned about the possibility of decreased tear production.
The safety and efficacy of Coriolus® in patients under 18 years of age have not been studied, therefore Coriolus® is not recommended for use in such patients.
Important information about excipients.
The medicinal product contains sucrose and lactose. Coriolus® should not be taken by patients with the following disorders: fructose intolerance, lactase deficiency, galactosemia, glucose-galactose malabsorption syndrome or sucrase-isomaltase deficiency.
Patients are not recommended to drink alcoholic beverages during treatment, as alcohol may enhance the effects of carvedilol.
Since the drug contains sucrose, this should be taken into account by patients with diabetes.
Use during pregnancy or breastfeeding
There are insufficient clinical data on the effects of carvedilol during pregnancy. The results of animal experiments do not allow an assessment of the effects during pregnancy, the effects on fetal development and the effects on the child after birth. The potential risk to humans remains unknown.
Beta-blockers have dangerous pharmacological effects on the fetus. They can cause fetal hypotension, bradycardia, and hypoglycemia.
Coriolus® is contraindicated during pregnancy.
Since there is a possibility that carvedilol passes into breast milk, breastfeeding should be discontinued during treatment with Coriolus®.
The ability to influence the reaction speed when driving or working with other mechanisms
At the beginning of treatment with Coriolum®, patients may experience dizziness and increased fatigue, which may indicate the development of postural hypotension and loss of consciousness, so they should refrain from driving vehicles and working with potentially dangerous mechanisms.
Method of administration and doses
To slow down absorption and prevent orthostatic effects, Coriolus® should be taken after meals. The dose should be selected individually. Treatment should be started with low doses, which are gradually increased until the optimal clinical effect is achieved. After the first dose and after each dose increase, it is recommended to measure the patient's blood pressure in a standing position 1 hour after administration to exclude possible arterial hypotension.
Treatment with Coriolum® should be discontinued gradually by reducing the dose over 1 or 2 weeks.
If treatment has been interrupted for more than 2 weeks, its resumption should be started at the lowest dose.
Essential hypertension
The initial dose of Coriolus® is 12.5 mg in the morning after breakfast or 6.25 mg 2 times a day (morning and evening). After 2 days of treatment, the dose should be increased to 25 mg in the morning (1 tablet of 25 mg) or to 12.5 mg 2 times a day. After 14 days of treatment, the dose can be increased again to 25 mg 2 times a day.
The maximum dose of Coriolus® for the treatment of arterial hypertension is 25 mg 2 times a day.
The recommended initial dose of Coriolus® for the treatment of hypertension in patients with heart failure is 3.125 mg* twice daily.
Chronic stable angina
The initial dose of Coriolus® is 12.5 mg 2 times a day after meals. After 2 days of treatment, the dose should be increased to 25 mg 2 times a day.
The maximum dose of Coriolus® for the treatment of chronic angina is 25 mg 2 times a day.
The recommended initial dose of Coriolus® for the treatment of angina in patients with heart failure is 3.125 mg* twice daily.
Coriolus® is recommended for the treatment of stable mild to moderate or severe chronic heart failure as an adjunct to standard therapy such as diuretics, ACE inhibitors or digitalis. Coriolus® can also be used in patients who are intolerant to ACE inhibitors. The patient should only be started on Coriolus® after titration of the diuretic, ACE inhibitor and digitalis (if applicable). The dose should be individualised. Careful medical monitoring is required during the first 2–3 hours after initial administration or after dose increases to check tolerability. If the patient's heart rate slows to less than 55 beats per minute, the dose of Coriolus® should be reduced. If symptoms of hypotension occur, a reduction in the dose of the diuretic or ACE inhibitor should be considered first; if these measures are insufficient, the dose of Coriolus® should be reduced.
At the beginning of treatment with Coriolum® or after increasing the dose, a transient increase in heart failure may occur. In this case, it is necessary to increase the dose of the diuretic. Sometimes it is necessary to temporarily reduce the dose of Coriolum® or even cancel it. After stabilization of the clinical condition, treatment with Coriolum® can be resumed or its dose increased.
The initial dose is 3.125 mg* twice daily. If the patient tolerates this dose well, it can be gradually increased (every 2 weeks) until the optimal dose is reached. Subsequent doses are 6.25 mg twice daily, then 12.5 mg twice daily and 25 mg twice daily. The patient should take the highest dose that is well tolerated. The maximum recommended dose is 25 mg twice daily. For patients weighing more than 85 kg, the dose can be cautiously increased to 50 mg twice daily.
Elderly patients
The dose does not need to be changed.
Patients with hepatic insufficiency
Coriolus® is not recommended for use in patients with severe hepatic impairment.
Patients with renal insufficiency
For patients with systolic blood pressure above 100 mm Hg, no specific dose adjustment is required (see also section "Special warnings and precautions for use").
* If a dose of 3.125 mg is necessary, prescribe other carvedilol preparations in the appropriate dosage form and dosage.
Children
The safety and efficacy of Coriolus® in children have not been established, therefore the use of the drug in children is contraindicated.
Overdose
Symptoms: pronounced decrease in blood pressure (BP), bradycardia, heart failure, cardiogenic shock, cardiac arrest; possible respiratory disorders, bronchospasm, vomiting, confusion and generalized convulsions. Treatment: in addition to general measures, it is necessary to monitor and correct vital signs, if necessary - in the intensive care unit. The following measures can be taken:
lay the patient on his back;
with severe bradycardia – atropine 0.5–2 mg intravenously;
to support cardiovascular activity – glucagon 1–10 mg intravenously by jet, then 2–5 mg per hour as a continuous infusion;
sympathomimetics (dobutamine, isoprenaline, orciprenaline or adrenaline) in different doses, depending on body weight and therapeutic efficacy.
If necessary, the administration of drugs with a positive isotropic effect should be administered with phosphodiesterase inhibitors. If the clinical picture of overdose is dominated by arterial hypotension, administer noradrenaline; it should be administered under conditions of continuous monitoring of blood circulation indicators.
In case of bradycardia resistant to treatment, the use of an artificial pacemaker is indicated.
In case of bronchospasm, administer β-adrenomimetics in the form of an aerosol (if ineffective, intravenously) or aminophylline intravenously. In case of convulsions, slowly administer diazepam or clonazepam intravenously. Since in case of severe overdose with symptoms of shock, the half-life of the drug from the depot may be prolonged, it is necessary to continue supportive therapy for a sufficiently long time. The duration of supportive detoxification therapy depends on the severity of the overdose; it should be continued until the patient's condition stabilizes.
Carvedilol cannot be removed by dialysis.
In the event of a serious overdose, when the patient is in a state of cardiogenic shock, supportive treatment should be provided for a sufficiently long time, since the elimination or redistribution of carvedilol may be slower than usual.
Side effects
The frequency of adverse reactions is estimated as follows:
very common (> 10%), common (> 1%, <10%), uncommon (> 0.1%, <1%), rare (> 0.01%, <1%), very rare, including isolated cases (0.01%).
Infections and infestations:
often - bronchitis, pneumonia, upper respiratory tract infections, urinary tract infections.
On the part of the immune system:
very rarely - hypersensitivity (allergic reaction).
From the central nervous system:
often - headache, dizziness, increased fatigue;
rarely - depression, sleep disorders, paresthesia, vertigo.
From the cardiovascular system:
rarely - peripheral circulatory disorders (cold extremities, peripheral vascular disease, intermittent claudication and Raynaud's disease), orthostatic reactions, peripheral edema, atrioventricular block, worsening of heart failure, angina pectoris.
On the part of the respiratory system:
often - shortness of breath, pulmonary edema, bronchial asthma;
rarely - nasal congestion.
On the part of the digestive system:
often - nausea, diarrhea, abdominal pain;
rarely - dry mouth, constipation, vomiting, periodontitis, melena.
On the skin:
infrequently - rash; itching; urticaria; reactions resembling lichen planus; increased sweating; the appearance of psoriatic plaques or exacerbation of psoriasis; alopecia; allergic exanthema; dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome.
On the part of the organs of vision:
rarely - decreased lacrimation, visual impairment, eye irritation.
Metabolic disorders: weight gain, hypervolemia, fluid retention.
On the part of the musculoskeletal system:
rarely - pain in the extremities, arthralgia, cramps.
From the genitourinary system:
rarely - urination disorders, impotence;
very rarely - renal dysfunction in patients with diffuse peripheral arterial disease, renal failure, hematuria, albuminuria, urinary incontinence in women.
From the hepatobiliary system:
rarely - dyskinesia, reactions in the form of acute liver failure and impaired liver function in patients with generalized atherosclerosis.
Laboratory indicators:
rarely - increased serum transaminase levels; thrombocytopenia, leukopenia, anemia, decreased prothrombin levels, impaired blood glucose control (hyperglycemia, hypoglycemia) in patients with pre-existing diabetes mellitus; hypercholesterolemia, glycosuria, hyperkalemia, hypertriglyceridemia, hyponatremia, increased levels of alkaline phosphatase, creatinine, urea, hyperuricemia.
Other side effects:
rarely - flu-like symptoms, fever, erectile dysfunction;
very rarely - hypoesthesia, anaphylactic reactions, manifestations of latent diabetes, exacerbation of symptoms of existing diabetes, depressed mood, asthenia, pain.
With the exception of dizziness, visual disturbances and bradycardia, none of the side effects described above are dose-dependent.
Dizziness, fainting, headache and asthenia are usually mild and occur more frequently at the beginning of treatment.
In patients with congestive heart failure, worsening of heart failure and fluid retention may occur during up-titration of carvedilol.
Heart failure as an adverse reaction was very commonly observed in patients treated with placebo (14.5%) and carvedilol (15.4%), and in patients with left ventricular dysfunction after acute myocardial infarction.
Reversible deterioration of renal function has been observed during carvedilol therapy in patients with chronic heart failure with low blood pressure, ischemic heart disease, diffuse vascular diseases and/or underlying renal failure.
Because these events were observed in a population of uncertain size, it is not always possible to reliably estimate their frequency and establish a causal relationship to carvedilol use.
Beta-adrenergic receptor blockers may cause the manifestation of latent diabetes, exacerbation of diabetes, and suppression of blood glucose regulation.
Carvedilol can cause urinary incontinence in women, which disappears after stopping the drug.
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 30 °C.
Keep out of reach of children.
Packaging
12.5 mg tablets: 7 tablets in a blister, 4 blisters in a cardboard box; 10 tablets in a blister, 3 blisters in a cardboard box.
25 mg tablets: 7 tablets in a blister, 4 blisters in a cardboard box; 14 tablets
