Composition, form of production and packaging
Tablets are yellow, with patches, with a risk for division on one side and with engraving of the number "6" - on the other.
1 tab.
carvedilol 6.25 mg
Auxiliary substances: sucrose - 13.285 mg, povidone 30 - 0.638 mg, lactose monohydrate 200 - 90.193 mg, silicon dioxide colloid - 0.531 mg, croscarmellose sodium - 2.444 mg, magnesium stearate - 1.594 mg, iron oxide yellow - 0.065 mg.
15 pcs. - blisters (1) - packs of cardboard.
15 pcs. - blisters (2) - packs of cardboard.
Tablets are brownish-yellow in color, with patches, with a risk for division on one side and with engraving of the number "12" - on the other.
1 tab.
carvedilol 12.5 mg
Auxiliary substances: sucrose - 12.5 mg, povidone 30 - 0.6 mg, lactose monohydrate 200 - 84.865 mg, silicon dioxide colloid - 0.5 mg, croscarmellose sodium - 2.3 mg, magnesium stearate - 1.5 mg, iron oxide yellow - 0.23 mg, iron oxide red - 0.005 mg.
15 pcs. - blisters (1) - packs of cardboard.
15 pcs. - blisters (2) - packs of cardboard.
The tablets are brownish-yellow in color, with splotches, with the risk for division on one side and with the engraving of the number "25" - on the other.
1 tab.
carvedilol 25 mg
Auxiliary substances: sucrose - 25 mg, povidone 30-1.2 mg, lactose monohydrate 200-169.73 mg, silicon colloidal dioxide 1 mg, croscarmellose sodium 4.6 mg, magnesium stearate 3 mg, iron oxide yellow 0.46 mg, iron oxide red 0.01 mg.
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Beta 1 -, beta 2 -adrenergic blocker. Alpha 1- adrenoblocker. Has vasodilating, antianginal and antiarrhythmic action. Carvedilol is a racemic mixture of R (+) and S (-) stereoisomers, each of which has the same alpha-adrenergic blocking properties. The beta-adrenergic blocking effect of carvedilol is non-selective and is due to the levorotatory S (-) stereoisomer.
The drug does not have its own sympathomimetic activity, it has membrane-stabilizing properties.
The vasodilating effect is associated mainly with blockade? 1- adrenoreceptors. Thanks to vasodilation reduces OPSS.
Efficiency
In patients with arterial hypertension, a decrease in blood pressure is not accompanied by an increase in OPSS, peripheral blood flow (in contrast to beta-blockers) does not decrease. Carvedilol suppresses RAAS by blocking the? -adrenoceptors of the kidneys, causing a decrease in plasma renin activity. The heart rate decreases slightly.
In patients with IHD has an antianginal effect. Reduces pre- and postnagruzku on the heart. It has no pronounced effect on the lipid metabolism and the content of potassium, sodium and magnesium ions in the blood plasma. When the drug is used, the ratio of HDL / LDL remains normal.
In patients with impaired left ventricular function and / or heart failure, the hemodynamic parameters favorably influence and improve the ejection fraction and the size of the left ventricle.
Carvedilol lowers the mortality rate and reduces the frequency of hospitalizations, reduces symptoms and improves left ventricular function in patients with chronic heart failure of ischemic and non-ischemic origin.
The effects of carvedilol are dose-dependent.
PHARMACOKINETICS
Suction
Carvedilol is rapidly absorbed from the digestive tract. Has high lipophilicity. C max in blood plasma is reached after about 1 hour. Bioavailability of the drug is 25%.Eating does not affect bioavailability.
Distribution
Carvedilol has a high lipophilicity. It binds to blood plasma proteins by 98-99%. V d is about 2 l / kg and increases in patients with cirrhosis. The enterohepatic circulation of the starting material in animals was demonstrated.
Metabolism
Carvedilol undergoes biotransformation in the liver by oxidation and conjugation to form a number of metabolites. 60-75% of the absorbed drug is metabolized by the "first pass" through the liver. The existence of intestinal-hepatic circulation of the starting material is shown.
The metabolism of carvedilol as a result of oxidation is stereoselective. R-stereoisomer is metabolized mainly by CYP2D6 and CYP1A2, and the S-stereoisomer is mainly by CYP2D9 and to a lesser extent by CYP2D6. Other isoenzymes P450 involved in the metabolism of carvedilol include CYP3A4, CYP2E1 and CYP2C19.The C max R-stereoisomer in plasma is about 2 times greater than that of the S-stereoisomer.
R-stereoisomer is metabolized, mainly by hydroxylation. In slow metabolizers of CYP2D6, an increase in the plasma concentration of carvedilol, primarily R-stereoisomer, is possible, which is reflected in an increase in alpha-adrenergic blocking activity of carvedilol.
As a result of demethylation and hydroxylation of the phenolic ring, 3 metabolites are formed (their concentrations are 10 times lower than the concentration of carvedilol) with beta-adrenoblocking activity (in the 4'-hydroxyphenol metabolite it is approximately 13 times stronger than in carvedilol itself). 3 active metabolites have less pronounced vasodilating properties than carvedilol. 2 hydroxycarbazole metabolite carvedilol are extremely powerful antioxidants, and their activity in this respect is 30-80 times greater than that of carvedilol.
Excretion
T 1/2 carvedilol is about 6 hours, plasma clearance is about 500-700 ml / min. Excretion occurs mainly through the intestine, the main way of excretion is with bile. A small part of the dose is excreted by the kidneys in the form of various metabolites.
Carvedilol penetrates the placental barrier.
Pharmacokinetics in specific patient groups
With prolonged therapy with carvedilol, the intensity of renal blood flow is maintained, the glomerular filtration rate does not change.
In patients with hypertension and moderate (KK 20-30 ml / min) or severe (KC <20 ml / min) renal failure, the carvedilol concentration in the blood plasma was approximately 40-55% higher than in patients with normal renal function. However, the data obtained are highly variable. Taking into account the fact that the excretion of carvedilol occurs mainly through the intestine, a significant increase in its concentration in the blood plasma of patients with impaired renal function is unlikely.
Existing data on pharmacokinetics in patients with varying degrees of renal dysfunction suggest that patients with moderate to severe renal insufficiency do not need to adjust doses of carvedilol.
In patients with cirrhosis of the liver, the systemic bioavailability of the drug is increased by 80% due to a decrease in the expression of metabolism during the "first passage" through the liver. Consequently, carvedilol is contraindicated in patients with a clinically manifested impairment of liver function.
In a study in 24 patients with heart failure, the clearance of R and S stereoisomers of carvedilol was significantly lower compared to the previously observed clearance in healthy volunteers. These results indicate that the pharmacokinetics of R and S stereoisomers of carvedilol in heart failure significantly change.
Age does not have a statistically significant effect on the pharmacokinetics of carvedilol in patients with arterial hypertension. According to clinical studies, the tolerability of carvedilol in patients with hypertension or ischemic heart disease of the elderly and senile does not differ from that in patients of a younger age.
In patients with type 2 diabetes and hypertension, carvedilol does not affect the fasting blood glucose concentration after fasting, the glycosylated hemoglobin (HbA1) content in the blood, or the dose of hypoglycemic agents. In clinical studies, it has been shown that in patients with type 2 diabetes mellitus carvedilol does not cause a decrease in glucose tolerance. In patients with hypertension who had insulin resistance (syndrome X), but without concomitant diabetes mellitus, carvedilol improves insulin sensitivity. Similar results were obtained in patients with arterial hypertension and type 2 diabetes mellitus.
INDICATIONS
- arterial hypertension;
- IHD: stable angina;
- chronic heart failure (as part of combination therapy).
DOSING MODE
The drug is taken orally, regardless of food intake, with a sufficient amount of liquid.
Arterial hypertension
The initial dose is 12.5 mg 1 time / day in the first 2 days of treatment. Then - 25 mg 1 time / day. Possible a gradual increase in dose with an interval of at least 2 weeks.
If the hypotensive effect is inadequate after 2 weeks of therapy, the dose can be increased 2 times. The maximum recommended daily dose of the drug is 50 mg 1 time / day (you can divide the dose into 2 divided doses).
IHD: Stable angina
The initial dose is 12.5 mg 2 times / day in the first 2 days of treatment. Then - 25 mg 2 times / day. If the antianginal effect is inadequate after 2 weeks of therapy, the dose may be increased 2-fold. The maximum recommended daily dose of the drug is 100 mg / day, divided into 2 divided doses.
In elderly patients, the recommended initial dose for the first 2 days of treatment is 12.5 mg 2 times / day. Then the treatment is continued at the maximum recommended daily dose of 25 mg 2 times / day.
Safety and efficacy in children and adolescents under the age of 18 years have not been established.
Chronic heart failure
The dose should be selected individually, under careful medical supervision.
Carvedilol can be used as a supplement to standard therapy, but it can also be used in patients with intolerance to ACE inhibitors or in patients who do not receive digitalis, hydralazine, or nitrate preparations. Doses of digoxin, diuretics and ACE inhibitors should be selected prior to treatment with carvedilol.
The recommended initial dose is 3.125 mg (1/2 tablets of Carvedilol Zenitiva 6.25 mg with a risk) 2 times / day for 2 weeks. With good tolerance, the dose is increased at intervals of at least 2 weeks to 6.25 mg 2 times / day, then to 12.5 mg 2 times / day, then to 25 mg 2 times / day. The dose should be increased to the maximum, which is well tolerated by the patient.
The recommended maximum dose is 25 mg 2 times / day for all patients with chronic heart failure of severe degree, and also for patients with chronic heart failure of mild and moderate severity with a body weight of <85 kg.
In patients with chronic heart failure of mild and moderate severity with a body weight> 85 kg, the recommended maximum dose is 50 mg 2 times / day.
At the beginning of treatment or with increasing doses, transiently increased symptoms of heart failure, especially in patients with severe chronic heart failure and / or receiving large doses of diuretics. As a rule, it is not necessary to cancel treatment, however, the dose of the drug should not be increased. After starting the application or increasing the dose of carvedilol, the patient / physician should be monitored by a doctor / cardiologist. Before each dose increase, a check should be performed to identify possible increased symptoms of heart failure or excessive vasodilation (including determination of renal function, body weight, blood pressure, heart rate and heart rate). With the progression of symptoms of heart failure or fluid retention, the dose of diuretics should be increased; In such a situation, the dose of carvedilol should not be increased until the patient's condition stabilizes. If bradycardia occurs or if the AV-conduction time is prolonged, first of all it is necessary to control the dose of digoxin. In some cases, it may be necessary to reduce the dose of carvedilol or to temporarily discontinue treatment. However, even in such cases, it is often possible to successfully continue titrating the dose of carvedilol.
During the titration of the dose, regular monitoring of renal function, platelet counts and glycemia should be performed (in the presence of type 1 or type 2 diabetes).After the titration of the dose, the monitoring frequency can be reduced.
Older patients may be more sensitive to the action of carvedilol, so their condition should be watched especially carefully.
Safety and efficacy in children and adolescents under the age of 18 years have not been established.
Carvedilol should not be used in patients with severe impairment of liver function . Patients with moderate-level hepatic insufficiency may need a dose adjustment.
In patients with renal insufficiency, the dose of carvedilol should be selected individually, however, based on pharmacokinetic parameters, dose adjustment is generally not required.
Discontinuation of treatment
Carvedilol treatment should not be stopped suddenly, especially in patients with IHD. Treatment should be discontinued gradually, within 7-10 days, for example, reducing the daily dose of the drug twice every 3 days.
SIDE EFFECT
This section presents the adverse reactions reported with carvedilol, divided into groups according to the MedDRA terminology and the following frequency categories according to the WHO classification: very frequent (> 1/10), frequent (> 1/100 to <1 / 10), infrequent (from> 1/1000 to <1/100), rare from> 1/10 000 to <1/1000), very rare (from <1/10 000, including individual reports).
From the immune system: very rare - hypersensitivity.
On the part of the hematopoiesis system: frequent - anemia; rare - thrombocytopenia; very rare - leukopenia.
From the nervous system: very frequent - dizziness, headache; infrequent - pre-fainting condition, fainting, paresthesia.
From the side of the organ of vision: frequent - impaired vision, reduced tearing (dry eyes), eye irritation.
From the cardiovascular system: very frequent - heart failure in the period of increasing the dose, a pronounced decrease in blood pressure; frequent - bradycardia, edema, hypervolemia, fluid retention, orthostatic hypotension, peripheral circulatory disorders (cold extremities, peripheral vascular disease, exacerbation of intermittent claudication syndrome and Raynaud's syndrome); infrequent - AV-blockade II-III degree, angina.
On the part of the respiratory system: frequent - shortness of breath, pulmonary edema, asthma in predisposed patients, bronchitis, pneumonia, upper respiratory tract infections; rare - nasal congestion.
On the part of the digestive system: frequent - nausea, diarrhea, vomiting, dyspepsia, abdominal pain; infrequent - constipation, dry mouth.
From the liver and bile ducts: very rare - increased activity of ALT, AST and GGT.
From the skin and subcutaneous tissues: infrequent - skin reactions (for example, allergic exanthema, dermatitis, urticaria, pruritus, psoriasis-like and lichen-like skin lesions, alopecia); very rare - erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
From the musculoskeletal system: frequent - pain in the limbs.
On the part of the urinary system: frequent - urinary tract infections, urination disorders, renal failure and renal dysfunction in patients with diffuse vasculitis and / or renal dysfunction; very rarely - urinary incontinence in women (reversible after drug withdrawal).
From the genitals and the breast: infrequent - erectile dysfunction.
From the side of metabolism and nutrition: frequent - hypercholesterolemia, hyperglycemia or hypoglycemia in patients with diabetes mellitus.
General disorders: very frequent - asthenia, fatigue; frequent - an increase in body weight.
Dizziness, fainting, headache and asthenia are usually mild in the beginning of therapy with Carvedilol Zentiva.
When applying the drug in patients with chronic heart failure and low blood pressure (systolic blood pressure <100 mm Hg), CHD and diffuse vessel changes and / or kidney failure, reversible renal dysfunction was noted.
Presence of beta-adrenoblocking properties in the preparation does not exclude the possibility of manifestation of latent diabetes mellitus, decompensation of already existing diabetes mellitus or oppression of the contrinular system.
CONTRAINDICATIONS
- acute and chronic heart failure in the stage of decompensation (IV functional class according to the NYHA classification), requiring in / in the introduction of inotropic agents;
- clinically significant violations of liver function;
- AV blockade of II-III degree (except for patients with an artificial pacemaker);
- pronounced bradycardia (heart rate <50 beats / min);
- SSSU (including sinoatrial blockade);
- severe arterial hypotension (systolic blood pressure <85 mm Hg);
- cardiogenic shock;
- bronchospasm and bronchial asthma (in the anamnesis);
- age under 18 years (efficiency and safety not established);
- Pregnancy;
- intolerance to fructose, lactose, lactase deficiency, sucrose / isomaltase, glucose-galactose malabsorption (the preparation contains lactose and sucrose);
- hypersensitivity to carvedilol or other components of the drug.
Caution should be given to the drug in COPD, Prinzmetal angina, thyrotoxicosis, peripheral vascular occlusive diseases, pheochromocytoma, psoriasis, renal insufficiency, first degree AV blockade, extensive surgical interventions and general anesthesia, diabetes mellitus, hypoglycemia, depression, myasthenia gravis.
PREGNANCY AND LACTATION
Data from animal studies are insufficient to determine the effect on pregnancy, embryo / fetal development, childbirth, or postnatal development. A potential risk to a person is not known.
Beta-adrenoblockers reduce placental blood flow, which can lead to intrauterine fetal death and premature birth. In addition, the fetus and newborn can develop unwanted reactions (in particular, hypoglycemia and bradycardia, complications from the heart and lungs).
A sufficient experience of the drug Carvedilol Zentiva in pregnant women is not available. The drug is contraindicated for use in pregnancy, except when the intended benefit to the mother exceeds the potential risk to the fetus.
Data on the isolation of carvedilol with breast milk are not available, so if Carvedilol Zentiva is needed during lactation, then breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
Precautions should be used drug in renal failure. In patients with renal insufficiency, the dose of carvedilol should be individualized, however, based on the pharmacokinetic parameters, dose adjustment is usually not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Carvedilol should not be used in patients with severe hepatic impairment . In patients with hepatic insufficiency of moderate severity may require dose adjustment.
APPLICATION FOR CHILDREN
Do not use this medication in children and adolescents under the age of 18 years (effectiveness and safety have been established).
APPLICATION IN ELDERLY PATIENTS
In elderly patients with coronary artery disease the recommended starting dose for the first 2 days of treatment is 12.5 mg of 2 times / day. Treatment is then continued to the maximum recommended daily dose of 25 mg of 2 times / day.
Elderly patients may be more sensitive to the effects of carvedilol, so their condition should be monitored especially carefully.
SPECIAL INSTRUCTIONS
Patients with chronic heart failure during the selection of a dose of the drug carvedilol can Zentiva marked increase in symptoms of chronic heart failure or fluid retention. If you experience these symptoms you need to increase the dose of diuretics or increase the dose of the drug Carvedilol Zentiva until stabilization of hemodynamic parameters. Sometimes it is necessary to reduce the dose of the drug Carvedilol Zentiva or, in rare cases, temporarily stop the drug. Such episodes do not preclude further correct selection of the dose.
Carvedilol Zenitva with care is used in combination with cardiac glycosides (possibly excessive deceleration AV-conduction).
In applying the drug carvedilol Zentiva in patients with chronic heart failure and low blood pressure (systolic blood pressure <100 mmHg. V.), Ischemic heart disease and diffuse vascular changes and / or renal insufficiency noted reversible renal impairment. Dose is adjusted depending on renal function.
Patients with COPD (including with bronchospastic syndrome) not receiving oral or inhaled antiasthmatics, Carvedilol Zenitva drug should be used only if the possible benefits of its use outweigh the potential risks.
In the presence of predisposition to bronchospastic syndrome while taking the drug carvedilol Zentiva due to an increase of airway resistance may develop shortness of breath. At the beginning of the reception, and by increasing the dose of the drug Carvedilol Zentiva must carefully monitor the condition of these patients, reducing the dose of the drug with the appearance of initial symptoms of bronchospasm.
Precautions Carvedilol Zentiva prescribed to patients with diabetes mellitus, because the drug may mask or reduce the symptoms of hypoglycemia (especially tachycardia). In patients with chronic heart failure and diabetes drug application may be accompanied by fluctuations in blood glucose.
Care must be taken when using the drug carvedilol Zenitva in patients with peripheral vascular disease (including Raynaud's syndrome) as beta-blockers may enhance arterial insufficiency symptoms.
As with other beta-blockers, Zentiva drug carvedilol can reduce the severity of symptoms of hyperthyroidism.
Surgery under general anesthesia, due to the potential gain of negative effects of the drug carvedilol Zentiva and means for general anesthesia Precautions should be prescribed to patients undergoing.
Zentiva drug carvedilol can cause bradycardia, with heart rate <55 bpm. / Min dose should be reduced.
Care must be taken when using the drug carvedilol Zentiva in patients with severe hypersensitivity reactions history or undergoing desensitization rate as beta blockers may increase the sensitivity to allergens and severity of anaphylactic reactions.
Patients with a history of instructions of the occurrence or exacerbation of psoriasis when applying beta-blockers Zentiva Carvedilol should be prescribed only after careful evaluation ratios possible risks and benefits.
Patients concurrently taking calcium channel blockers slow (e.g., verapamil or diltiazem), and other antiarrhythmics, must regularly monitor ECG and arterial blood pressure.
Patients with pheochromocytoma before the use of any beta-blocker, you must assign an alpha-blocker. Although drug carvedilol Zentiva has both beta and alpha adrenoceptor blocking properties and experience of their use in such patients have, however with caution should be used in patients with suspected pheochromocytoma.
Non-selective beta-blockers may provoke the appearance of pain in patients with angina Prinzmetal. Experience with the drug Carvedilol Zentiva have no such patients. Despite the fact that the alpha-adrenoceptor blocking properties of carvedilol Zentiva drug may prevent such symptoms, to prescribe a drug in such cases should be cautious.
Patients who use contact lenses, you should remember about the possibility of reducing the amount of tear fluid.
Treatment with Carvedilol Zentiva held long. Therapy should not be stopped abruptly, you must gradually reduce the dose at weekly intervals. This is particularly important in patients with CAD.
When the need for surgery using general anesthesia should warn the anesthesiologist prior to therapy with carvedilol Zentiva.
The treatment should exclude alcohol.
Caution is advised to use the drug in patients with depression, metabolic acidosis, and myasthenia gravis (myasthenia gravis).
Carvedilol Zentiva contains sucrose. Patients with rare hereditary diseases associated with galactose intolerance, malabsorption of glucose-galactose and sucrase-isomaltase insufficiency should not take the drug.
Carvedilol Zentiva contains lactose. Patients with a rare hereditary diseases associated with galactose intolerance, lactase deficiency or lapp-galactose malabsorption of glucose should not take the drug.
Impact on the ability to drive vehicles and manage mechanisms
Special studies of the effect of the drug on the ability to drive vehicles and operating machinery has not been. Due to the possibility of side reactions such as dizziness and fatigue, ability to drive vehicles and operating mechanisms could be compromised. Especially it should be considered early in the treatment, after a dose increase when changing drugs as well as alcohol use.
OVERDOSE
Symptoms: marked decrease in blood pressure (accompanied by dizziness or syncope), bradycardia, dyspnea (due to bronchoconstriction) rvota. In severe cases respiratory failure, mental confusion, generalized convulsions, cardiac failure, cardiac conduction disturbances, cardiogenic shock, cardiac arrest.
Treatment:symptomatic therapy. It is necessary to monitor and maintain vital body functions, if necessary - in the intensive care unit. If bradycardia is expedient in / use m-anticholinergics (atropine of 0.5-2 mg) to maintain cardiovascular activity; glucagon to 1-10 mg / bolus, followed by 2-5 mg per hour as a continuous infusion. If the clinical picture is dominated by overdose marked reduction of blood pressure, is introduced sympathomimetics (norepinephrine (noradrenaline), epinephrine (adrenaline), dobutamine) in different doses, depending on the body weight and response to treatment, under continuous control indicators circulation. When resistance to treatment is shown bradycardia pacemaker application.When bronchospasm beta-adrenergic agonist is administered as an aerosol (at inefficiency - in / in) or aminophylline / in. In convulsions in / slow administered diazepam or clonazepam. Because of severe overdose with symptoms of shock, possibly lengthening T1/2 carvedilol and excretion of the drug from the depot, it is necessary to continue maintenance therapy for quite a long time.
DRUG INTERACTION
Pharmacokinetic interaction
Since carvedilol is both a substrate and inhibitor of P-glycoprotein by its simultaneous use with drugs that transported glycoprotein F, the latter can increase bioavailability. Moreover, carvedilol bioavailability may change under the influence of inducers or inhibitors of glycoprotein P.
inhibitors and inducers of CYP2D6 and CYP2C9 stereoselectively can modify the system and / or presystemic metabolism of carvedilol, resulting in an increase or decrease of the concentrations of R and S stereoisomers carvedilol plasma. Some examples of such interactions observed in patients or healthy volunteers, are listed below, but this list is not complete.
With simultaneous use of carvedilol and digoxin digoxin concentrations increased by approximately 15%. At the start of carvedilol treatment, the selection of the dose or withdrawal of the drug, it is recommended regular monitoring of digoxin plasma concentration.
In two studies with the use of carvedilol in patients undergoing kidney transplantation and heart and receiving cyclosporine orally, there was an increase of cyclosporine concentrations in blood plasma. It was found that by inhibiting the activity of P-glycoprotein in the gut, carvedilol increases the absorption of cyclosporine when administered orally. To maintain the concentration of cyclosporine in the therapeutic range, the dose of cyclosporin required reduction in average by 10-20%. Due to severe vibrations careful monitoring the individual concentration recommended concentration of cyclosporine after initiation of therapy of carvedilol and, if required, corresponding correction daily dose cyclosporine. The on / in the introduction of cyclosporin any interaction with carvedilol is expected.
In a study involving 12 healthy volunteers rifampicin reduced the plasma concentration of carvedilol, likely through induction of P-glycoprotein, resulting in decreased absorption of carvedilol in the gut and reduce its antihypertensive action.
In patients with heart failure, amiodarone decreased the clearance of S stereoisomer carvedilol inhibiting CYP2C9. The average concentration of R stereoisomer carvedilol was not changed. Consequently, due to the increase in the concentration of carvedilol S stereoisomer possible risk of increased beta-adrenoceptor blocking action.
In a randomized study with cross-over design in 10 patients with heart failure, the simultaneous use of fluoxetine (CYP2D6 inhibitor) led to inhibition of the metabolism of carvedilol stereoselective - to increase the average AUC for the R (+) by 77%. However, the difference in the side effects, the magnitude of blood pressure or heart rate between the two groups was observed.
Pharmacodynamic interaction
Drugs with a beta-adrenoceptor blocking properties may enhance the hypoglycemic effect of insulin or hypoglycemic agents for oral administration. Symptoms of hypoglycemia, particularly tachycardia, may be masked or weaken. Patients receiving insulin or hypoglycemic agents for oral administration, it is recommended the regular control of blood glucose.
Patients receiving both drugs with beta-adrenoceptor blocking properties and drugs that reduce catecholamine content (e.g., reserpine and MAO inhibitors) must be carefully monitored because of the risk of hypotension and / or severe bradycardia.
Combined beta-blockers and digoxin therapy may lead to an additional deceleration of AV-conduction.
The use of verapamil, diltiazem, amiodarone or other antiarrhythmic drugs simultaneously with carvedilol can increase the risk of AV-conduction disturbances.
Concomitant use of clonidine with beta-blockers may potentiate the hypotensive and bradycardic effect. If you plan to stop the combined therapy with beta-blockers and clonidine, must first cancel the beta-blocker, and in a few days you can cancel clonidine, gradually reducing the dose.
With simultaneous use of carvedilol and diltiazem noted individual cases of cardiac conduction disturbances (rarely - with hemodynamic disorders). The use of carvedilol with the slow calcium channel blockers (e.g., verapamil or diltiazem) recommended for the control of blood pressure and electrocardiogram.
Like other drugs with beta-adrenoblokiruyuschey activity, carvedilol may potentiate the effect of other simultaneously received antihypertensives (e.g., alpha-blockers) or drugs that cause hypotension as a side effect.
It should be conducted carefully monitored vital signs living organism under general anesthesia in connection with the possibility of synergistic negative inotropic action of carvedilol and means for general anesthesia.
The simultaneous use of NSAIDs and beta-blockers can lead to hypertension and reduce blood pressure control.
As a non-cardioselective beta-blockers prevent the bronchodilator effect of bronchodilators, which are stimulants? -adrenoceptor, careful observation of patients receiving these drugs.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 30 В° C. Shelf life - 2 years.
