3.125 mg tablets: round, slightly biconvex, white tablets with a bevel;
6.25 mg tablets: oval, slightly biconvex, white tablets, scored on one side and marked “S2” on the other.
Pharmacotherapeutic group
Blockers of a- and b-adrenergic receptors.
ATX code C07A G02.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Carvedilol is a non-selective β-blocker with vasodilator effects. It also has antioxidant and antiproliferative properties.
Pharmacodynamic effects
The active ingredient, carvedilol, is a racemate; the enantiomers differ in their effects and metabolism. The S(–) enantiomer has blocking activity against α1- and β-adrenoceptors, while the R(+) enantiomer has blocking activity only against α1-adrenoceptors. Due to cardioselective blockade of β-adrenoceptors, the drug reduces blood pressure, heart rate, and cardiac output. Carvedilol reduces pressure in the pulmonary arteries and in the right atrium. Due to blockade of α1-adrenoceptors, it causes peripheral vasodilation and reduces their resistance. Due to these effects, carvedilol relaxes the heart muscle and prevents the development of angina attacks. In patients with heart failure, carvedilol helps to increase left ventricular blood output and improves symptoms of the disease. Similar effects have been observed in patients with left ventricular dysfunction. Carvedilol does not have the effect of a true sympathomimetic, but, like propranolol, has membrane-stabilizing properties. Plasma renin activity is reduced, and fluid retention is a rare occurrence.
Certain properties of traditional β-blockers do not appear to be inherent in some vasodilator β-blockers, such as carvedilol.
Clinical efficacy and safety.
Clinical studies have shown that the balance of vasodilation and β-blockade provided by carvedilol causes the following effects.
Hypertension. The effect on blood pressure and heart rate is evident 1–2 hours after taking the drug.
In hypertensive patients with normal renal function, carvedilol reduces renal vascular resistance. There are no significant changes in glomerular filtration, renal plasma flow, or electrolyte excretion.
Carvedilol has been shown to maintain stroke volume and reduce total peripheral resistance without compromising the blood supply to individual organs and vascular beds, such as the kidneys, skeletal muscles, forearms, legs, skin, brain, or carotid artery. The incidence of cold extremities and early fatigue during physical activity is reduced.
Hypertensive patients with renal failure. Several open-label studies have shown that carvedilol is effective in patients with renal hypertension. The same applies to patients with chronic renal failure, patients on hemodialysis or after kidney transplantation. Carvedilol causes a gradual decrease in blood pressure on both dialysis and non-dialysis days, and the blood pressure-lowering effects are comparable to those observed in patients with normal renal function.
Stable angina. In patients with stable angina, carvedilol has demonstrated anti-ischemic (improved total exercise time, time to 1 mm ST-segment depression, and time to angina) and antianginal properties that were maintained during long-term treatment. Acute hemodynamic studies have demonstrated that carvedilol significantly reduces myocardial oxygen demand and sympathetic overactivity, and reduces myocardial preload (pulmonary artery pressure and pulmonary wedge pressure) and afterload (total peripheral resistance), with subsequent improvement in left ventricular systolic and diastolic function without significant changes in cardiac output.
Carvedilol has no adverse effect on metabolic risk factors for coronary heart disease. It does not affect normal serum lipid levels, and in hypertensive patients with dyslipidemia, a beneficial effect on serum lipids has been observed after 6 months of oral therapy.
Two studies compared carvedilol 25 mg twice daily with other antianginal drugs with proven efficacy in patients with chronic stable angina pectoris. The selected dosing regimens were widely used in clinical practice. Both trials were double-blind, parallel-group designs. The primary objective was to determine total exercise time (TET).
Report No.
Control (dose)
Number of patients carvedilol/comparator
Duration of treatment
060
Verapamil (120 mg 3 times a day
126/122
12 weeks
061
Isosorbide dinitrate (40 mg twice daily)
93/94
12 weeks
The results of both studies clearly demonstrated that there was no significant difference in VTE at trough levels after 12 weeks of therapy. However, the hazard ratios derived from the Cox proportional hazards model showed a trend in favor of carvedilol, indicating that on average carvedilol was 114% more effective than verapamil (90% CI [confidence interval]: 85–152%) and 134% more effective than isosorbide dinitrate (90% CI: 96–185%). This also applied to time to angina and ST-segment depression. The increase in VTE was about 50 seconds in all groups; the improvements in time to angina and ST-segment depression were about 30 seconds, which is clinically significant.
In study 060, 48-hour Holter monitoring demonstrated a reduction in the number and duration of ST-segment depressions (silent myocardial ischemia) in both treatment groups. Carvedilol also reduced premature atrial and ventricular contractions, couplings, and conduction.
Chronic heart failure. Carvedilol significantly reduces mortality and the need for hospitalization and improves symptoms and left ventricular function in patients with ischemic or non-ischemic chronic heart failure. The effect of carvedilol is dose-dependent.
Patients with chronic heart failure and renal failure. Carvedilol reduces morbidity and mortality in dialysis patients with dilated cardiomyopathy, as well as all-cause mortality, cardiovascular mortality, and mortality from heart failure or the need for first hospitalization in heart failure patients with mild to moderate chronic kidney disease not requiring dialysis. A meta-analysis of placebo-controlled clinical trials involving a large number of patients (> 4000) with mild to moderate chronic kidney disease supports the treatment of patients with left ventricular dysfunction, with or without symptomatic heart failure, with carvedilol to reduce the risk of death and heart failure-related events.
Pediatric Patients. The safety and efficacy of carvedilol in children and adolescents have not been established due to the limited number and size of studies. The available studies have focused on the treatment of pediatric heart failure, which differs from adult disease in characteristics and etiology. Due to the small number of participants compared to studies in adults and the lack of an optimal dosing regimen for children and adolescents, the available data are insufficient to establish the pediatric safety profile of carvedilol.
Pharmacokinetics
Absorption.
After oral administration of a 25 mg capsule to healthy subjects, carvedilol is rapidly absorbed with a maximum plasma concentration of 21 mg/l, which is reached after approximately 1.5 hours (tmax). The Cmax values are linearly dependent on the dose. After oral administration, carvedilol undergoes extensive first-pass metabolism, resulting in an absolute bioavailability of approximately 25% in healthy male subjects. Carvedilol is a racemate and the S-(-)-enantiomer appears to be metabolized more rapidly than the R-(+)-enantiomer, showing an absolute oral bioavailability of 15% compared to 31% for the R-(+)-enantiomer. The maximum plasma concentration of R-carvedilol is approximately 2-fold higher than that of S-carvedilol.
In vitro studies have shown that carvedilol is a substrate for the efflux transporter P-glycoprotein. The role of P-glycoprotein in the distribution of carvedilol has also been confirmed in vivo in healthy subjects.
Food does not affect bioavailability, residence time, or peak serum concentration, although the time to peak plasma concentration is delayed.
Distribution.
Carvedilol is highly lipophilic, plasma protein binding is about 95%. The volume of distribution ranges from 1.5 to 2 L/kg and is increased in patients with cirrhosis.
Biotransformation.
In humans, carvedilol is extensively metabolized in the liver by oxidation and conjugation to various metabolites, which are mainly excreted in the bile. Enterohepatic circulation of the parent compound has been demonstrated in animals.
Demethylation and hydroxylation on the phenolic ring form three metabolites with beta-adrenergic blocking activity.
In preclinical studies, the 4'-hydroxyphenol metabolite is approximately 13 times more potent as a beta-blocker than carvedilol. The three active metabolites have weak vasodilatory activity compared with carvedilol. In humans, the concentrations of the three active metabolites are approximately 10 times lower than those of the parent compound. Two of the hydroxycarbazole metabolites of carvedilol are extremely potent antioxidants, with 30–80 times greater activity than carvedilol in this regard.
Pharmacokinetic studies in humans have shown that the oxidative metabolism of carvedilol is stereoselective. In vitro studies have shown that various cytochrome P450 isoenzymes may be involved in the oxidation and hydroxylation processes, including CYP2D6, CYP3A4, CYP2E1, CYP2C9, and CYP1A2.
Studies in healthy volunteers and patients have shown that the R-enantiomer is predominantly metabolized by CYP2D6. The S-enantiomer is predominantly metabolized by CYP2D6 and CYP2C9.
Results from clinical pharmacokinetic studies in humans have shown that CYP2D6 plays an important role in the metabolism of R- and S-carvedilol. As a result, plasma concentrations of R- and S-carvedilol are increased in CYP2D6 poor metabolizers. The importance of CYP2D6 genotype in the pharmacokinetics of R- and S-carvedilol has been confirmed in population pharmacokinetic studies, while other studies have not confirmed this observation. It was concluded that CYP2D6 genetic polymorphisms may be of limited clinical significance.
Elimination.
After a single oral dose of 50 mg carvedilol, approximately 60% is excreted in the bile and in the feces as metabolites within 11 days. After a single oral dose, only about 16% is excreted in the urine as carvedilol or its metabolites. Urinary excretion of unchanged drug is less than 2%. After intravenous infusion of 12.5 mg in healthy volunteers, plasma clearance of carvedilol reaches approximately 600 ml/min and the half-life is approximately 2.5 hours. The half-life from a 50 mg capsule observed in the same subjects was 6.5 hours, which is indeed consistent with the half-life from the capsule. After oral administration, the total clearance of S-carvedilol is approximately twice that of R-carvedilol.
Special patient groups.
Elderly: Age has no statistically significant effect on the pharmacokinetics of carvedilol in patients with hypertension.
Pediatric patients: Studies in pediatric patients have shown that weight-adjusted clearance is significantly higher in children compared to adults.
Hepatic impairment: In a study in patients with liver cirrhosis, the bioavailability of carvedilol was four times higher, the peak plasma concentration was five times higher, and the volume of distribution was three times higher than in healthy volunteers.
Renal impairment: Since carvedilol is primarily excreted in the feces, significant accumulation in patients with renal impairment is unlikely.
In patients with arterial hypertension and renal insufficiency, the area under the concentration-time curve, half-life, and maximum plasma concentration are not significantly altered. Renal excretion of unchanged drug is reduced in patients with renal insufficiency; however, changes in pharmacokinetic parameters are modest.
Carvedilol is not removed by dialysis because it does not cross the dialysis membrane, probably due to its high level of plasma protein binding.
Heart failure: In a study of 24 Japanese patients with heart failure, the clearance of R- and S-carvedilol was significantly lower than previously estimated in healthy volunteers. These results suggest that the pharmacokinetics of R- and S-carvedilol are significantly altered in heart failure in Japanese patients.
Preclinical safety data.
No special hazard for humans was identified based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.
Impairment of Fertility: When high doses of carvedilol were administered to pregnant rats (≥ 200 mg/kg - at least 100 times the maximum daily human dose), adverse effects on pregnancy and fertility (poor mating, fewer corpora lutea, and fewer implants) were observed.
Teratogenicity: Animal studies do not indicate a teratogenic effect of carvedilol.
Embryotoxicity (increased post-implantation mortality) was observed, but no malformations were observed in rats and rabbits at doses of 200 mg/kg and 75 mg/kg, respectively (38-100 times the maximum daily human dose). The relevance of these findings to humans is unknown. In addition, animal studies have shown that carvedilol crosses the placental barrier, so the possible effects of alpha and beta blockade on the fetus and newborn should also be borne in mind (see section "Use during pregnancy and lactation").
Therefore, effects in non-clinical studies were observed only at exposures considerably in excess of the maximum human exposure, indicating little relevance to clinical use (see section 4.6).
Indication
– Essential hypertension. Coriolus® can be used alone or in combination with other antihypertensive drugs (especially thiazide diuretics);
– chronic stable angina;
– chronic stable heart failure (as an adjunct to standard therapy with diuretics, digoxin or ACE inhibitors), to prevent disease progression in patients with heart failure class II-III according to the NYHA (New York Heart Association) classification.
Contraindication
– Hypersensitivity to carvedilol or to any of the ingredients of the drug.
– Decompensated heart failure – NYHA class IV heart failure that requires intravenous inotropic agents.
– Unstable heart failure.
– Atrioventricular block of the II-III degree (if a permanent pacemaker is not installed).
– Concomitant intravenous administration of verapamil, diltiazem or other antiarrhythmics (especially class I antiarrhythmics).
– Severe hypotension (systolic blood pressure < 85 mm Hg).
– Pulmonary hypertension.
– Pulmonary heart.
– History of bronchial asthma or bronchospasm.
– Clinically pronounced liver failure.
– Concomitant use of MAO inhibitors (except MAO-B inhibitors).
– Metabolic acidosis.
– Pheochromocytoma.
– Prinzmetal's angina.
– Obstructive respiratory diseases.
– Galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
– Pregnancy and breastfeeding.
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 of up to 20% has been shown 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 starting, adjusting or discontinuing carvedilol. Carvedilol did not affect intravenous 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 co-administered with carvedilol. In addition, the bioavailability of carvedilol may be altered by inducers or inhibitors of P-glycoprotein.
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 significant increases 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 and tacrolimus: 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 appears to increase the exposure of oral ciclosporin by approximately 10-20%. In an attempt to maintain therapeutic levels of ciclosporin, an average reduction of the ciclosporin dose by 10-20% was required. The mechanism of interaction is unknown, but inhibition of intestinal P-glycoprotein by carvedilol may be involved. Due to the large interindividual 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.
In addition, there is evidence that CYP3A4 is involved in the metabolism of carvedilol. Since tacrolimus is a substrate of P-glycoprotein and CYP3A4, carvedilol may also affect its pharmacokinetics through these interaction mechanisms.
Inhibitors and inducers of CYP2D6 and CYP2C9 may stereoselectively alter the systemic and/or presystemic metabolism of carvedilol, resulting in increased or decreased plasma concentrations of R- and S-carvedilol. Some examples of such drug effects observed in patients or healthy subjects are given below.
Antiarrhythmic drugs.
Isolated cases of conduction disturbances (rarely with haemodynamic compromise) have been observed when carvedilol and diltiazem have been administered concomitantly. For other drugs with β-blocking properties, ECG and blood pressure monitoring are recommended when carvedilol is administered orally with calcium channel blockers such as verapamil or diltiazem. These drugs should not be administered intravenously.
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.
Alcohol: Alcohol consumption has an acute hypotensive effect that may potentiate the blood pressure lowering effect of carvedilol. Since carvedilol is soluble in ethanol, the presence of alcohol may affect the rate and/or extent of intestinal absorption of carvedilol. In addition, carvedilol is partially metabolized by CYP2E1, an enzyme known to be induced and inhibited by alcohol.
Grapefruit juice: A single dose of 300 ml of grapefruit juice resulted in a 1.2-fold increase in carvedilol AUC compared to water. Although the clinical significance is unclear, patients should avoid concomitant grapefruit juice, at least until a stable dose-response relationship has been established.
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.
Non-dihydropyridine calcium channel blockers or other antiarrhythmics.
In combination with carvedilol, the risk of AV conduction disturbances may increase (see "Special instructions"). Isolated cases of conduction disturbances (rarely with hemodynamic disturbances) have been observed with the simultaneous use of carvedilol with diltiazem. As with other drugs with β-blocking properties, if carvedilol is to be administered orally with non-dihydropyridine calcium channel blockers such as verapamil or diltiazem, amiodarone or other antiarrhythmics, it is recommended to monitor ECG and blood pressure.
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.
Nonsteroidal anti-inflammatory drugs (NSAIDs), estrogens, and corticosteroids.
Concomitant use of NSAIDs, estrogens or 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.
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.
Digoxin.
Concomitant use of β-blockers and digoxin may lead to additive prolongation of atrioventricular conduction time.
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 treatment with Coriolum® (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. Carvedilol treatment should not be discontinued abruptly, especially in patients with ischemic heart disease. The dose should be reduced gradually (over a period of 2 weeks).
Chronic heart failure.
In most cases, carvedilol should be prescribed in addition to diuretics, 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.
Left ventricular dysfunction after acute myocardial infarction.
Before treatment with carvedilol, the patient should be clinically stable and have been taking an ACE inhibitor for at least 48 hours prior to carvedilol administration. The dose of the ACE inhibitor should be stable for at least 24 hours.
Diabetes.
Caution should be exercised when using carvedilol in patients with diabetes mellitus, as this may be associated with worsening of blood glucose control, or early signs of acute hypoglycemia may be masked or attenuated. Alternatives to beta-blockers are generally preferable in insulin-dependent patients. Therefore, regular monitoring of blood glucose levels is necessary in diabetics when carvedilol is initiated or up-titrated, and hypoglycemic therapy adjusted accordingly (see Interactions with other medicinal products and other forms of interaction).
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.
Bradycardia.
In case of bradycardia (heart rate less than 55 beats/min), the dose of carvedilol should be reduced.
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.
Patients with a history of psoriasis associated with beta-blocker therapy should be prescribed carvedilol only after consideration of the benefit/risk ratio.
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).
Concurrent use of debrisoquine.
Patients with poor metabolism of debrisoquine require caution at the beginning of treatment.
Pheochromocytoma.
In patients with pheochromocytoma, an alpha-blocker should be used before any beta-blocker. Although carvedilol has both alpha- and beta-blocking pharmacological activity, there is no experience with the use of carvedilol in this condition. Therefore, caution should be exercised when prescribing carvedilol to patients suspected of having pheochromocytoma.
Hypersensitivity reactions.
Patients with a history of serious hypersensitivity reactions and those undergoing desensitization should
Specifications
Characteristics
Active ingredient
Carvedilol
Adults
Can
ATC code
C MEDICINES AFFECTING THE CARDIOVASCULAR SYSTEM; C07 BETA-ADRENORECEPTOR BLOCKERS; C07A BETA-ADRENORECEPTOR BLOCKERS; C07A G Combined alpha- and beta-adrenoreceptor blockers; C07A G02 Carvedilol
Country of manufacture
Slovenia
Diabetics
With caution
Dosage
6,25 мг
Drivers
It is impossible.
For allergies
With caution
For children
It is impossible.
Form
Tablets
Method of application
Inside, solid
Nursing
It is impossible.
Pregnant
It is impossible.
Primary packaging
blister
Producer
KRKA
Quantity per package
28 pcs
Trade name
Coriolus
Vacation conditions
By prescription
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