Carvedilol

Package leaflet (information for patients)

Tradename
Carvedilol

Dosage form
Tablets 6.25 mg.

Description
Round, flat, beveled to the edge white tablets with an imprint in the form of the brand name "V" on one side.

Structure
Active ingredient: Carvedilol 6.25 mg.
Excipients: microcrystalline cellulose 102, calcium stearate, aerosil ® 200 (hydrophilic pyrogenic silicon dioxide).

Pharmacotherapeutic group
Alpha and beta blockers.

Pharmacological properties
Carvedilol has a combined non-selective β 1 -, β2 - and α1-adrenergic blocking effect. The drug does not have its own sympathomimetic activity, it has membrane stabilizing properties. Due to the blockade of β- adrenergic receptors of the heart can decrease blood pressure, cardiac output, and slows the heart rate. Carvedilol suppresses the renin- angiotensin - aldosterone system by blocking the β- adrenergic receptors of the kidneys, causing a decrease in plasma renin activity. By blocking α- adrenergic receptors, the drug can cause peripheral vasodilation, thereby reducing systemic vascular resistance. Combination of β- blockadeadrenergic receptors and vasodilation has the following effects: in patients with arterial hypertension - lowering blood pressure; in patients with coronary artery disease - anti - ischemic and antianginal action; in patients with left ventricular dysfunction and circulatory insufficiency - favorably affects hemodynamic parameters, increases the ejection fraction of the left ventricle and reduces its size.
Pharmacokinetics
Carvedilol is rapidly absorbed from the gastrointestinal tract. Possesses high lipophilicity. Cmax in the blood is reached after 1-1.5 hours. T1 / 2 is 6-10 hours. It binds to blood plasma proteins by 95-99%. The bioavailability of the drug is 24-28%. Food intake does not affect bioavailability. It is metabolized in the liver with the formation of a number of active metabolites - 60-75% of the adsorbed drug is metabolized during the first "passage" through the liver. Metabolites have a pronounced antioxidant and adrenergic blocking effect. The elimination of the drug from the body occurs through the gastrointestinal tract.
In case of impaired renal function, the pharmacokinetic parameters of carve dilol do not change significantly.
In patients with impaired liver function, the systemic bioavailability of carvedilol increases due to a decrease in metabolism during the first "pass" through the liver. Carvedilol is contraindicated in severely impaired liver function.
Carvedilol crosses the placental barrier, excreted in the chest

Indications for use
Essential hypertension (mild to moderate) as well as chronic angina pectoris for the prevention of seizures.
Treatment of stable symptomatic mild, moderate and severe chronic insufficiency (class II - IV according to the classification of the New York Heart Association (NYHA)) of ischemic or cardiomyopathic genesis in addition to standard therapy (diuretics, digoxin, ACE inhibitors).

Method of administration and dosage
Inside, with a sufficient amount of liquid. The dose is selected individually.
It is not necessary to take with meals, but patients with heart failure should take the capsules with food in order to slow absorption and reduce the frequency of orthostatic reactions.
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.
Elderly patients
Initial dose: 12.5 mg once daily. In some patients, this dose is sufficient to control blood pressure. In case of insufficient effectiveness, the dose can be gradually increased at intervals of at least 2 weeks up to a maximum dose of 50 mg per day.
Chronic angina
The starting dose is 12.5 mg twice daily for the first two days. Then a dose of 25 mg is recommended 2 times a day. In case of insufficient exposure, the dose can be gradually increased at intervals of at least 2 weeks, bringing to the highest daily dose of 100 mg, divided into 2 doses.
Elderly patients
As a rule, the dose of 25 mg 2 times a day should not be exceeded.
Chronic heart failure: the dose is selected individually, during dose titration, careful monitoring of the patient is required. In patients receiving digitalis drugs, diuretics and ACE inhibitors, their doses should be stabilized before starting treatment with carvedilol. The recommended dose for starting therapy is 3.125 mg 2 times a day for 2 weeks. With good tolerance, the dose is increased with an interval of at least 2 weeks to 6.25 mg 2 times a day, then to 12.5 - 25 mg 2 times a day (if the body weight is less than the maximum dose is 25 mg 2 times a day, with a mass of more - 50 mg 2 times a day). The dose should be increased to the maximum dose that is well tolerated by the patient. Before each dose increase, the physician should evaluate the renal function of these patients and check for increased heart failure or symptoms of vasodilation. Short-term exacerbation of heart failure, vasodilation and fluid retention can be eliminated by adjusting the dose of a diuretic or ACE inhibitor, as well as changing or short-term discontinuation of carvedilol therapy.
If the treatment is interrupted for more than 1 week, then its use is started with a lower dose, and then increased according to the recommendations. If the treatment is interrupted for more than 2 weeks, then its use begins with a dose of 3.125 mg 2 times a day, followed by the selection of doses according to the recommendations.
Treatment should be started with low doses, gradually increasing to an adequate clinical dose. When skipping a dose, the drug should be used as soon as possible, however, if the time for taking the next dose is approaching, then only take it, without doubling it. The drug should be withdrawn gradually over 1-2 weeks (especially in patients with angina pectoris).
If the drug has not been taken for more than 2 weeks, treatment must be resumed starting with the lowest doses.
Patients with chronic heart failure and impaired renal function
The required dose should be determined individually for each patient. On the basis of the pharmacokinetic parameters of carvedilol in patients with heart failure, as well as moderate to severe renal failure, no dose adjustment of carvedilol is required (see the Pharmacokinetics section).
Patients with impaired liver function
Carvedilol is contraindicated in patients with clinical manifestations of hepatic insufficiency (see sections Pharmacokinetics, Contraindications).
Elderly patients
Elderly patients may be quite susceptible to the effects of carvedilol and should be monitored more closely. As with other beta-blockers, withdrawal of carvedilol is gradual, especially in patients with coronary artery disease.
Children
The safety and effectiveness of carvedilol in children and adolescents under the age of 18 has not been established.

Side effects
Generalized Security Profile
The frequency of side effects does not depend on the dose, with the exception of vertigo or dizziness, visual impairment, bradycardia.
List of side effects
The risk of adverse reactions associated with carvedilol is similar for all indications.
Exceptions are presented at the end of this section.
Side effects, depending on the frequency, are divided into the following groups:
Very frequent (≥1 / 10);
Frequent (≥1 / 100 to <1/10);
Uncommon (≥1 / 1000 to <1/100);
Rare: (≥1 / 10,000 to <1/1000);
Very rare: (<1/10000);
The frequency is unknown (cannot be estimated from the available data).
Within each group, the side effects of the drug are presented in decreasing order of importance.
Infections and invasions
frequent: bronchitis, pneumonia, upper respiratory tract infections, urinary tract infections.
Blood and lymphatic system disorders
frequent: anemia;
rare: thrombocytopenia;
very rare: leukopenia.
Immune system disorders
very rare: hypersensitivity (allergic reactions), severe skin reactions (eg, erythema, Stevens- Johnson syndrome, toxic epidermal necrolysis).
Metabolic and nutritional disorders
frequent: weight gain, hypercholesterolemia, impaired blood glucose control (hyperglycemia, hypoglycemia) in patients with diabetes mellitus;
infrequent: hypertriglyceridemia, hypokalemia.
Nervous system disorders
very frequent: dizziness, headache;
frequent: fainting, light-headedness;
infrequent: paresthesia, hypokinesia, increased sweating.
Mental disorders
frequent: depression, depressed mood;
infrequent: insomnia, nightmares, hallucinations, confusion;
very rare: psychosis, impaired concentration, pathological thinking, emotional lability.
Violations of the organ of vision
frequent: blurred vision, decreased tearing (dry eyes), eye irritation.
Hearing disorders and labyrinth disorders
infrequent: tinnitus.
Heart disorders
very common: heart failure;
frequent: bradycardia, edema, fluid retention, fluid retention;
infrequent: atrioventricular block, angina pectoris, tachycardia.
Vascular disorders
very common: arterial hypotension;
frequent: orthostatic hypotension, impaired peripheral circulation (cold extremities, disease of peripheral blood vessels, intermittent claudication, Raynaud's syndrome).
Respiratory, Chest and Mediastinal Disorders
frequent: shortness of breath, pulmonary edema, asthma (in predisposed patients);
rare: nasal congestion.
Gastrointestinal disorders
frequent: nausea, diarrhea, vomiting, dyspepsia, abdominal pain;
infrequent: constipation;
rare: dry mouth.
Liver and biliary tract disorders
rare: an increase in the content of bilirubin in the blood;
very rare: increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT).
Skin and subcutaneous tissue disorders
infrequent: skin reactions (allergic exanthema, dermatitis, urticaria, itching, exacerbation of psoriatic eruptions, a reaction similar to lichen planus), alopecia.
Musculoskeletal and connective tissue disorders
frequent: pain in the limbs.
Kidney and urinary tract disorders
frequent: acute renal failure and impaired renal function in patients with diffuse peripheral vascular disease and / or impaired renal function, frequent urination;
very rare: involuntary urination in women.
Reproductive system and breast disorders
infrequent: erectile dysfunction.
Complications of a general nature and reactions at the injection site
very frequent: asthenia (including fatigue);
frequent: pain.
The following potentially important events were reported for ≤0.1% of patients: complete AV block, bundle branch block, myocardial ischemia, cerebrovascular accidents, seizures, migraine, neuralgia, paresis, anaphylactoid reaction, alopecia, exfoliative dermatitis, amnesia, GI bleeding, bronchospasm, pulmonary edema, hearing loss, repressive alkalosis, increased AMK, decreased HDL cholesterol, pancytopenia and the appearance of atypical lymphocytes.
According to post-marketing studies, due to the beta-blocking properties of carvedilol, the appearance of latent diabetes mellitus or an aggravation of overt diabetes, inhibition of blood glucose regulation is not excluded. Monitor for the occasional occurrence of hypoglycemia.
Post-marketing research
Metabolism, metabolic disorders
Based on beta- blocking properties, it is possible that latent diabetes mellitus may occur or overt diabetes may worsen, or blood sugar regulation may be inhibited (see "Precautions"). Monitor for incidental hypoglycemia.
Dysfunction of the skin and subcutaneous adipose tissue
Alopecia.
Severe adverse skin reactions such as toxic epidermal necrolysis and Steven Johnson syndrome (see PRECAUTIONS).
Kidney and urinary tract disorders
There have been reports of isolated cases of urinary incontinence in women, which resolved after drug withdrawal.
Description of selected adverse reactions
Dizziness, fainting, headache, and asthenia are usually mild to moderate and most likely at the start of treatment.
In patients with chronic heart failure, increased symptoms and fluid retention may occur when the dose of carvedilol is increased.
Heart failure is a very common adverse reaction for both placebo (14.5%) and carvedilol (15.4%) patients with left ventricular dysfunction after acute myocardial infarction.
During treatment with carvedilol, a reversible deterioration in renal function has been observed in chronic heart failure in patients with low blood pressure, coronary artery disease and diffuse peripheral vascular disease and / or previous renal failure.
If you experience the listed adverse reactions or reactions not listed in the package insert, you should consult a doctor.

Contraindication
hypersensitivity to carvedilol or any excipient;
chronic heart failure in the stage of decompensation II-IV class according to the classification of the New York Heart Association (NYHA) in patients who need intravenous administration of inotropic agents;
chronic obstructive respiratory disease;
bronchial asthma (2 deaths with status asthmaticus were reported after taking a single dose);
allergic rhinitis;
laryngeal edema;
pulmonary heart;
sick sinus syndrome (including sinoauricular block);
atrioventricular (AV) block II and III degree;
severe arterial hypotension (systolic blood pressure <85 mm Hg).
severe bradycardia (less than 50 beats / min at rest);
cardiogenic shock;
myocardial infarction with complications;
clinical manifestations of liver failure;
metabolic acidosis;
simultaneous use of MAO inhibitors (with the exception of MAO-B inhibitors);
slow metabolizers of debrisoquine and mephenytoin ;
pregnancy and breastfeeding;
age up to 18 years;
intolerance to fructose or galactose, Lapp lactase deficiency, malabsorption of glucose-galactose or sucrose-isomaltose.

Overdose
Symptoms: severe hypotension, bradycardia, respiratory failure (in incl. Bronchospasm), heart failure, in severe cases - cardiogenic shock, conduction disorders, up to a cardiac arrest; violation of consciousness, up to coma; Generators alizovannye cramps.
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 put him on his back with slightly raised legs and a lowered head, the patient without knowledge should be laid on his side.
Beta- adrenergic 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 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 to 2 mg. To maintain heart failure: glucagon - 1-10 mg IV quickly in 30 seconds, after which a continuous infusion is performed at the rate of 2-5 mg / hour.
If the peripheral vasodilator effect predominates (warm extremities, in addition to significant hypotension), it is necessary to prescribe norepinephrine in repeated doses of 5-10 μg or as an infusion - 5 μg / min.
To stop bronchospasm, beta- adrenomimetics (in the form of an aerosol I or IV) or aminophylline IV are prescribed.
If seizures develop, slow administration of diazepam or clonazepam is recommended.
In severe cases of intoxication, when the symptoms of shock dominate, antidote treatment should be continued until the patient's condition stabilizes, taking into account T1 / 2 carvedilol (6-10 hours).

Precautions
Due to lack of data, Carvedilol should not be used:
in children;
with unstable or secondary hypertension;
with unstable angina pectoris;
with complete interventricular block;
at the end stage of peripheral arterial blood supply disorders, since in these patients beta- adrenergic receptor blockers cause symptoms of arterial insufficiency or may worsen them;
with a fresh myocardial infarction;
with a tendency to lower blood pressure when changing position (orthostatic disorders);
while being treated with certain medications that lower blood pressure (alpha1 receptor antagonists).
Termination of therapy
Patients with coronary artery disease who are being treated with carvedilol should be aware of the inadmissibility of abrupt discontinuation of therapy. After abrupt withdrawal of beta-blockers in patients with angina pectoris, cases of progression of angina pectoris, myocardial infarction and ventricular arrhythmias were recorded. The last two complications can occur both after an exacerbation of angina pectoris, and against the background of remission. As with other beta-blockers, when carvedilol is planned to be discontinued, the patient should be carefully evaluated and recommended to minimize physical activity. If possible, you should stop taking carvedilol within 1 to 2 weeks. In the event of an increase in the manifestations of angina pectoris or the development of acute coronary insufficiency, it is recommended to resume taking carvedilol, at least temporarily. Since coronary artery disease is common and can be latent, it is recommended to avoid abrupt withdrawal of carvedilol, even in patients receiving it only for the treatment of hypertension or heart failure.
Bradycardia
Carvedilol can cause bradycardia. If the heart rate drops below 55 beats per minute, the dose of carvedilol should be reduced.
Hypotension
9.7% of patients with heart failure who received carvedilol developed hypotension and 3.4% experienced syncope, compared with 3.6% and 2.5% of patients receiving placebo, respectively. The risk of these effects was highest during the first 30 days of treatment, which corresponds to the titration phase. Patients with decompensated heart failure, impaired electrolyte balance, low blood pressure and / or in old age should be under close medical supervision for 2 hours after taking the first dose or after taking the first increased dose due to the risk of a sudden drop in blood pressure and fainting. The risk of these complications can be reduced by prescribing the drug in small initial doses and taking it with meals. In patients concurrently taking calcium channel blockers (verapamil or diltiazem) and other antiarrhythmic drugs, careful monitoring of the electrocardiogram and blood pressure is necessary.
Chronic heart failure
With increasing doses of carvedilol, there may be an increase in symptoms of heart failure or fluid retention. In these cases, it is recommended to increase the dose of diuretics without increasing the dose of carvedilol until a stable state is achieved. Sometimes it may be necessary to reduce the dose of carvedilol or to temporarily stop taking it. Such episodes do not preclude successful titration of carvedilol doses.
In patients with heart failure, if their baseline SBP is less than 100 mm Hg. Art. or there are concomitant diseases - coronary heart disease, peripheral vascular disease or impaired renal function, the condition of the urinary system should be checked more often, because treatment may affect kidney function (usually temporarily). If suppression of renal function is observed, the dose of the drug should be reduced or treatment should be discontinued.
Pheochromocytoma
For pheochromocytoma, it is recommended to start using an α-blocker before starting any β-blocker. Although carvedilol has both alpha- and beta-blocking pharmacological properties, there is no data on its use in this case. It is recommended to prescribe carvedilol with caution to patients who have a suspicion of this disease.
Angina Prince of Metal (variant angina)
Non-selective beta-blockers can cause chest pain in patients with Prinzmetal angina. There is no clinical experience with carvedilol in these patients, although it is possible that, due to the a-blocking action, carvedilol will be able to prevent such symptoms. Despite this, it is recommended to use carvedilol with caution in patients with suspected Prinzmetal angina.
Zab Olevanov peripheral vascular
Carvedilol is recommended to be taken with caution in patients with peripheral vascular disease, as β-blockers can cause arterial insufficiency or worsen its symptoms.
Raynaud 's syndrome
Carvedilol is recommended to be taken with caution in patients suffering from peripheral blood flow disorders, as the drug can worsen the symptoms of the disease.
Hypersensitivity reaction
With beta-blocker therapy in patients with a severe hypersensitivity reaction or in those undergoing a course of desensitization, there is a risk of increased sensitivity to allergens and an increase in the severity of anaphylactic reactions. Care should be taken in these cases.
Severe unwanted skin reactions (SCAR)
In very rare cases, severe adverse skin reactions such as toxic epidermal necrolysis (TEN) and Steven-Johnson syndrome have been reported during treatment with carvedilol (see “Side Effects: Post-Market Experience”). Carvedilol should no longer be prescribed to patients who have experienced severe skin reactions (possibly caused by carvedilol).
Psoriasis
Patients with psoriasis (including those with a family history) should receive carvedilol only after a careful assessment of the risks and benefits.
Diabetes
It is recommended to prescribe carvedilol with caution to patients with diabetes mellitus because of the possible masking or weakening of early signs of acute hypoglycemia. In these patients with heart failure, carvedilol may be associated with impaired blood glucose control.
Blood glucose should be monitored regularly, including to detect cases of increased blood glucose, latent diabetes mellitus (see section "Contraindications"),
Thyrotoxicosis
β- blockers can mask the symptoms of thyrotoxicosis, for example, tachycardia. Abrupt withdrawal of drugs of this class may worsen the symptoms of hyperthyroidism or cause a thyrotoxic crisis.
Non-allergic bronchospasm
Patients with a tendency to bronchospastic reactions (eg, chronic bronchitis, emphysema) should not be prescribed beta-blockers. Carvedilol can be prescribed with caution at the lowest effective dose only in cases where the effect of other antihypertensive drugs has not been obtained. In patients with a predisposition to bronchospastic reactions, shortness of breath may occur due to an increase in airway resistance. At the beginning of treatment or when the dose is increased, such patients should be carefully monitored, reducing the dose when the initial signs of bronchospasm appear.
Contact lenses
Patients who wear contact lenses should be aware of the possibility of reducing tear separation.
Intraoperative syn core atopic iris (IFIS)
Intraoperative atonic iris syndrome is observed during cataract surgery in some patients treated with alpha-1 blockers (carvedilol is an alpha / beta blocker). This variant of narrow pupil syndrome is characterized by a combination of atonic iris that deforms during flushing during surgery, progressive constriction of the pupil during surgery despite preoperative dilation using standard mydriatic agents, and possible iris prolapse during phacoemulsification. The ophthalmologist should be prepared for possible changes in the technique of the operation, for example, the use of hooks for the iris, expansion rings or viscoelastic substances. Discontinuation of alpha-1 blocker therapy prior to cataract surgery is not advisable.
Anesthesia and general surgery
Due to the synergistic negative inotropic effects of carvedilol and general anesthetics with negative inotropic effects, close monitoring of vital signs during surgery is recommended.
Liver damage
Cases of liver dysfunction have been reported during controlled clinical trials in patients with arterial hypertension and chronic heart failure who took carvedilol, which was confirmed by renewed exposure. It was found that liver damage was reversible and manifested itself after short and / or long-term treatment with minor clinical symptoms. No deaths due to liver dysfunction have been reported. When the first symptoms / signs of liver dysfunction appear (such as itching, dark urine, persistently decreased appetite, jaundice, pressing pain in the right upper quadrant of the abdomen, or unexplained flu-like symptoms), laboratory tests should be performed. If laboratory tests confirm liver damage or jaundice, carvedilol should be discontinued and never given again.
Interaction with other medicinal products
In patients with chronic heart failure who are receiving treatment with cardiac glycosides, diuretics and / or ACE inhibitors, carvedilol should be prescribed with caution (see the section "Interactions with other medicinal products"). This medicinal product contains lactose, therefore patients with rare hereditary intolerance to lactose, glucose-galactose, malabsorption syndrome or sucrose isomaltase deficiency should not take this remedy.

Interaction with other medicinal products
While taking the drug Carvedilol with other drugs, the following interactions should be considered:
Farm akokineticheskie interaction:
Carvedilol is both a substrate and an inhibitor of glycoprotein R. As a result, when taken simultaneously with drugs transported by glycoprotein P, the bioavailability of the latter may increase. Furthermore, the bioavailability of carvedilol may vary under the influence of inducers or inhibitors of glycoprotein P. inhibitors as inductors, CYP2D6, CYP1A2 and CYP2C9 can stereoselectively modify the system and / or presystemic metabolism of carvedilol, which leads to an increase or decrease of the concentrations of R and S stereoisomers of carvedilol in blood plasma (see " Pharmacokinetics " and "Metabolism"). Some examples of such interactions observed in patients or healthy volunteers are listed below, but this list is not complete.
Digoxin : With combination therapy with the drug carvedilol and digoxin, an increase in the concentration of digoxin may occur. Patient environments GUSTs Carvedilol can cause clinically significant increase in maximum concentration of digoxin in plasma (60%). AUC digitoxin slightly increased (+ 13%). It is recommended to control the concentration of digoxin and digitoxin when starting and ending treatment with the drug Carvedilol, as well as when selecting its dose (see "Precautions").
Cyclosporine : Two studies in patients who underwent a kidney and heart transplant and received oral cyclosporine showed an increase in the plasma concentration of cyclosporine after starting treatment with carvedilol. It turned out that carvedilol increases the absorption of cyclosporin when taken orally by inhibiting the activity of glycoprotein P in the intestine. When trying to maintain the concentration of cyclosporine in the therapeutic range, it was necessary to reduce the dose of cyclosporine by 10-20%. Due to the pronounced individual fluctuations in the concentration of cyclosporine, it is recommended to carefully monitor its concentration after starting carvedilol therapy and to adjust the daily dose of cyclosponrin accordingly (see "Precautions").
Rifampicin : In a study involving 12 healthy volunteers, rifampicin reduced plasma carvedilol concentrations, most likely by inducing glycoprotein P, which led to a decrease in carvedilol absorption and a decrease in its antihypertensive effect.
Amiodarone : In patients with heart failure, amiodarone decreased the clearance of the S stereoisomer of carvedilol, possibly due to inhibition of CYP2C9. The mean concentration of the R stereoisomer of carvedilol in blood plasma did not change. Consequently, due to the increasing concentration of S stereoisomer carvedilol, can increase the risk baa Such adrenoceptor blocking action.
Fluoxetine : In a randomized crossover study in 10 patients with heart failure, concomitant administration of fluoxetine, the strongest inhibitor of CYP2D6, resulted in a stereoselective inhibition of carvedilol metabolism with a 77% increase in the mean AUC0-12 for the R (+) enantiomer. However, there were no differences in side effects, blood pressure or heart rate between the two groups.
Phar macodynamic interactions
Oral insulin or hypoglycemic agents: The effectiveness of insulin or oral hypoglycemic agents may be enhanced. Symptoms of hypoglycemia may be masked or subside (especially tachycardia). Therefore, in diabetics, blood sugar should be monitored regularly (see "Precautions").
Digoxin : The combined use of beta-blockers and digoxin may additionally slow down atrioventricular conduction (AV) (see PRECAUTIONS).
Verapamil, diltiazem, amiodarone or other antiarrhythmics: Like other beta-blockers, oral calcium antagonists such as verapamil and diltiazem, amiodarone and other antiarrhythmic drugs should be taken with extreme caution, since there is a risk of atrioventricular conduction disturbance due to simultaneous administration. Calcium antagonists and antiarrhythmics should not be administered intravenously during treatment with the drug Carvedilol.
Drugs that reduce the content of catecholamines: Patients taking simultaneously drugs with beta- adrenergic blocking properties and drugs that reduce the content of catecholamines of monoamine oxidase (MAO)) should be closely monitored for the risk of hypotension and / or severe bradycardia.
Like other beta-blockers, the drug Carvedilol can enhance the pressure-lowering effect of drugs that have a pressure-lowering effect in their profile of exposure or secondary exposure.
Nifedipine : Concomitant use of nifedipinan and the drug Carvedilol can lead to severe pressure drop.
Calcium channel blockers (see "PRECAUTIONS"). With the simultaneous appointment of carvedilol and diltiazem, there have been isolated cases of conduction disorders (rarely - with violations of hemodynamic parameters). As with other drugs with beta- adrenergic blocking properties, when carvedilol is taken orally with calcium channel blockers such as verapamil or diltiazem, it is recommended to monitor the ECG and blood pressure.
Clonidine : Concomitant administration of clonidine and drugs with beta- adrenergic blocking properties may enhance the antihypertensive and bradycardic effect. If you plan to discontinue combination therapy with a drug with beta- adrenergic blocking properties and clonidine, the beta-blocker should be canceled first. Clonidine can be gradually withdrawn a few days after treatment with the drug Carvedilol has been completed (see PRECAUTIONS).
Simultaneous administration of the medicinal agent Carvedilol and cardiac glycosides can slow pre- cardio-gastric conduction.
Inhibitors of oxidative metabolism (for example, cimetidine) increase the plasma concentration of the drug Carvedilol (AUC of carvedilol increases by 30%).
Anesthetics: It is recommended to closely monitor vital signs during anesthesia due to the synergistic negative inotropic effect (see “Precautions”).
NSAIDs: Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and beta-blockers can lead to increased blood pressure and decreased blood pressure control.
Beta-agonists of bronchodilators : non - cardioselective beta-blockers interfere with the bronchodilator effect of bronchodilators. Careful observation of patients is recommended (see “PRECAUTIONS ”).
Anesthesia and major surgery
If treatment with the drug Carvedilol should be continued during the perioperative period, special care is recommended when using anesthetics that suppress myocardial function, such as ether, cyclopropane and trichlorethylene. See Overdose for information on the treatment of bradycardia and hypotension.

Pregnancy and elbowing
The drug is contraindicated for use during pregnancy and lactation.

Influence on the ability to drive vehicles and work with mechanisms
Does not affect.

Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C, out of the reach of children.

Shelf life
3 years. Do not use after the expiration date printed on the package.

Vacation conditions
On prescription.

Packaging
Carvedilol 6.25 mg Tablets. There are 30 tablets in a blister. 2 blisters are packed in a cardboard box together with an enclosed leaflet.