Composition, form of production and packaging
Tablets are round, flat-cylindrical, with a facet and a risk, from white to white with a creamy shade of color, slight marble is allowed.
1 tab.
carvedilol 6.25 mg
Excipients: Ludypress LCE (lactose monohydrate - 94.7-98.3%, povidone - 3-4%) - 81.95 mg, sodium carboxymethyl starch - 0.9 mg, magnesium stearate - 0.9 mg.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
Tablets square with rounded corners, biconvex, with a crosswise notching on one side and engraving "AL1" on the other, from white to white with a creamy shade of color, slight marble is allowed.
1 tab.
carvedilol 12.5 mg
Excipients: Ludypress LCE (lactose monohydrate - 94.7-98.3%, povidone - 3-4%) - 95.3 mg, sodium carboxymethyl starch 1.1 mg, magnesium stearate 1.1 mg.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
Tablets are oval, biconcave, with partial incision on both sides and engraving "AL2" on one side, from white to white with a creamy shade of color, light marble is allowed.
1 tab.
carvedilol 25 mg
Excipients: Ludypress LCE (lactose monohydrate - 94.7-98.3%, povidone - 3-4%) - 190.6 mg, sodium carboxymethyl starch - 2.2 mg, magnesium stearate - 2.2 mg.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Carvedilol is a blocker? 1 -,? 1 , - and? 2- adrenoreceptors, has an organoprotective effect, is an antioxidant that removes free oxygen radicals, has an antiproliferative effect against smooth muscle cells of the vessel walls. Carvedilol is a racemic mixture of R (+) and S (-) stereoisomers, each of which has the same alpha-adrenergic blocking and antioxidant properties. The beta-adrenergic blocking effect of carvedilol is non-selective and is due to the levorotatory S (-) stereoisomer.
Carvedilol has no internal sympathomimetic activity and, like propranolol, has membrane-stabilizing properties. By blocking? -adrenoceptors, it reduces the activity of the renin-angiotensin-aldosterone system, decreasing the release of renin, so fluid retention (characteristic of selective alpha-blockers) occurs rarely.
Selectively blocking? 1- adrenoreceptors, carvedilol reduces OPSS.
Carvedilol does not adversely affect the lipid profile, while maintaining a normal ratio of high and low density lipoproteins (HDL / LDL).
In patients with arterial hypertension, carvedilol lowers blood pressure due to a combined blockade? 1 - and? -adrenoceptors. Decrease in blood pressure is not accompanied by a simultaneous increase in OPSS, which is observed with the use of nonselective beta-blockers. The heart rate somewhat decreases. Kidney blood flow and kidney function in patients with hypertension persist. It is shown that carvedilol does not change the shock volume of the blood and reduces the OPSS; does not impair blood supply to organs and peripheral blood flow, incl. in skeletal muscles, forearms, lower extremities, skin, brain and carotid arteries. Coldness of limbs and increased fatigue during exercise are rare. The hypotensive effect of carvedilol in hypertension persists for a long time.
In patients with coronary artery disease, carvedilol has anti-ischemic and antianginal effects (an increase in the total duration of exercise, the time until the development of ST-segment depression 1 mm in depth and the time before the onset of angina attack) that persist with prolonged therapy. Carvedilol significantly reduces myocardial oxygen demand and the activity of the sympathoadrenal system. Also reduces preload (pulmonary wedge wedge pressure and pulmonary capillary pressure) and postnagruzku (OPSS). 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
After ingestion, carvedilol is rapidly absorbed. Carvedilol is the substrate of a carrier protein that acts as a pump in the lumen of the intestine, the P. C maxglycoprotein in the blood plasma is reached after about 1 hour. The absolute bioavailability of carvedilol is approximately 25%.
Distribution
Carvedilol has a high lipophilicity. About 98-99% of carvedilol binds to blood plasma proteins. Its V d is approximately 2 l / kg. 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.
Metabolism
The metabolism of carvedilol by 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 manifested 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 the starting material) 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 of the hydroxycarbazole metabolites of 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.
Pharmacokinetics in special groups of patients
Patients with impaired renal function
With prolonged therapy with carvedilol, the intensity of renal blood flow is maintained, the glomerular filtration rate does not change.
In patients with arterial hypertension and impaired renal function, AUC, T 1/2 and C max do not change. Renal excretion of unchanged drug in patients with renal insufficiency decreases, but changes in pharmacokinetic parameters are not very pronounced.
Patients with impaired hepatic function
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 in the "first pass" through the liver. Consequently, carvedilol is contraindicated in patients with clinically manifested impairment of liver function.
Patients with heart failure
In some studies in 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.
Patients of elderly and senile age
Age does not have a statistically significant effect on the pharmacokinetics of carvedilol in patients with arterial hypertension.
Children
Data on the pharmacokinetics of the drug in patients under 18 years of age are limited.
Patients with diabetes mellitus
In patients with type 2 diabetes and arterial hypertension, carvedilol does not affect the fasting blood glucose concentration after fasting, the level of glycosylated hemoglobin (HbA 1 ), or the dose of hypoglycemic agents for oral administration. In some clinical studies, it has been shown that in patients with type 2 diabetes carvedilol does not cause a decrease in glucose tolerance. In patients with arterial hypertension who had insulin resistance (syndrome X), but without concomitant diabetes, carvedilol improves insulin sensitivity. Similar results were obtained in patients with arterial hypertension and type 2 diabetes mellitus.
INDICATIONS
- arterial hypertension: essential hypertension (in monotherapy or in combination with other antihypertensive agents, for example, slow calcium channel blockers or diuretics);
- IHD (including in patients with unstable angina and painless myocardial ischemia);
- chronic heart failure: treatment of stable and symptomatic mild, moderate and severe chronic heart failure (II-IV functional classes according to the New York Heart Association (NYHA)) ischemic or non-ischemic genesis in combination with ACE inhibitors and diuretics, with or without cardiac glycosides (standard therapy), in the absence of contraindications.
DOSING MODE
Inside, regardless of food intake, with enough liquid.
Essential hypertension
The recommended initial dose is 12.5 mg 1 time / day for the first 2 days of therapy, then 25 mg 1 time / day. If necessary, in the future, the dose can be increased at intervals of at least 2 weeks, bringing to the maximum recommended dose of 50 mg 1 time / day (or divided into 2 divided doses).
Cardiac ischemia
The recommended initial dose is 12.5 mg 2 times / day in the first 2 days, then 25 mg 2 times / day. If necessary, the dose can then be increased at intervals of at least 2 weeks, bringing to the highest daily dose of 100 mg divided into 2 doses.
Chronic heart failure
The dose is selected individually, careful monitoring of the doctor is necessary. In patients receiving cardiac glycosides, diuretics and ACE inhibitors, their doses should be adjusted before treatment with the drug Acridilol В® .
The recommended initial dose is 3.125 mg (1/2 tablets at 6.25 mg) 2 times / day for 2 weeks. With good tolerability, 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 dose, which is well tolerated by the patient. The recommended maximum dose is 25 mg 2 times / day for all patients with severe chronic heart failure and for patients with mild to moderate chronic heart failure with a body weight of less than 85 kg . In patients with mild and moderate chronic heart failure and a body weight of more than 85 kg - the recommended maximum dose is 50 mg 2 times / day.
Before each increase in the dose, the physician should examine the patient to identify a possible increase in symptoms of chronic heart failure or vasodilation. With a transient increase in the symptoms of chronic heart failure or fluid retention in the body, the dose of diuretics should be increased, although sometimes it is necessary to reduce the dose of the drug Acridilol В® or temporarily to cancel it.
Symptoms of vasodilation can be eliminated by reducing the dose of diuretics. If the symptoms persist, you can reduce the dose of an ACE inhibitor (if the patient takes it), and then, if necessary, the dose of the drug Acridilol В® . In this situation, the dose of Acrydilol В® should not be increased until symptoms of worsening chronic heart failure or hypotension improve.
If treatment with the drug Acridilol В® is interrupted for more than 1 week, then its appointment is resumed in a smaller dose, and then increased in accordance with the recommendations above. If treatment with the drug Acridilol В® is interrupted for more than 2 weeks, then its appointment should be resumed at a dose of 3.125 mg (1/2 tablets at 6.25 mg) 2 times / day, then select the dose in accordance with the recommendations above.
Dosing in special groups of patients
Existing data on pharmacokinetics in patients with varying degrees of renal dysfunction (including renal failure) suggest that patients with moderate and severe renal insufficiency do not need to adjust the dose of AcrydilolВ®.
Acrydilol is contraindicated in patients with clinical manifestations of liver dysfunction.
Data that would dictate the need for dose adjustment in elderly patients are lacking.
SIDE EFFECT
Unwanted reactions, occurring with a frequency of <10%, are regarded as very often. Unwanted reactions, occurring with a frequency of <1% to <10%, are regarded as often. Unwanted reactions, occurring with a frequency of <0.1% to <1%, are regarded as infrequent. Unwanted reactions, occurring with a frequency of <0.01% to <0.1%, are regarded as rare. Unwanted reactions occurring with a frequency of <0.01%, including individual reports, are regarded as very rare. The frequency of adverse reactions, with the exception of dizziness, visual impairment and bradycardia, does not depend on the dose of the drug.
Undesirable reactions in patients with chronic heart failure
From the side of the central nervous system: very often - dizziness, headache (usually mild and occurring more often at the beginning of treatment); asthenia (including increased fatigue), depression.
From the cardiovascular system: often - bradycardia, postural hypotension, marked decrease in blood pressure, edema (including generalized, peripheral, depending on the position of the body, swelling of the perineum, edema of the lower extremities, hypervolemia, fluid retention); infrequently - syncopal conditions (including presyncopal), AV blockade and heart failure during the period of dose increase.
From the digestive tract: often - nausea, diarrhea, vomiting.
From the hemopoietic system: rarely - thrombocytopenia; very rarely - leukopenia.
From the side of metabolism: often - weight gain, hypercholesterolemia; in patients with existing diabetes mellitus - hyperglycemia or hypoglycemia, violations of glycemic control.
Other: often - visual impairment; rarely renal failure and impaired renal function in patients with diffuse vasculitis and / or renal dysfunction.
Undesirable reactions in patients with arterial hypertension and ischemic heart disease
The nature of side effects from the cardiovascular system in the treatment of hypertension and long-term therapy of coronary heart disease is similar to that of chronic heart failure, but their frequency is somewhat less.
From the side of the central nervous system: often - dizziness, headache and general weakness, usually light and arising, in particular, at the beginning of treatment;infrequently - mood lability, sleep disturbances, paresthesia.
From the cardiovascular system: often - bradycardia, postural hypotension, syncopal conditions (infrequently), especially at the beginning of therapy; infrequent peripheral circulatory disorders (cold extremities, exacerbation of intermittent claudication syndrome and Raynaud's syndrome), AV blockade, angina (pain in the chest), development or aggravation of heart failure symptoms and peripheral edema.
From the respiratory system: often - bronchospasm and shortness of breath in predisposed patients; rarely - nasal congestion.
From the digestive tract: often - dyspeptic disorders (including nausea, abdominal pain, diarrhea); infrequently - constipation, vomiting.
From the skin: rarely - skin reactions (skin rash, dermatitis, urticaria and skin itching).
Laboratory parameters: very rarely - increased activity of hepatic transaminases (ALT, ACT and GGT), thrombocytopenia and leukopenia.
Other: often - pain in the limbs, reducing tear and eye irritation; infrequent - decreased potency, visual impairment; rarely dry mouth and urinary disorders; very rarely - exacerbation of psoriasis, sneezing, flu-like syndrome. Separate cases of allergic reactions.
CONTRAINDICATIONS
- acute and chronic heart failure in the stage of decompensation, requiring in / in the introduction of inotropic agents;
- clinically significant impairment of liver function;
- age to 18 years (efficacy and safety of the drug Acridilol В® are not established);
- AV blockade II and III degree (except for patients with an artificial pacemaker);
- pronounced bradycardia (heart rate less than 50 beats per minute);
- SSSU (including sinoatrial blockade);
- severe arterial hypotension (systolic blood pressure less than 85 mm Hg);
- cardiogenic shock;
- anamnestic indications for bronchospasm and bronchial asthma;
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
- hypersensitivity to carvedilol or any component of the drug.
With caution: with COPD, depression, myasthenia gravis, hypoglycaemia, AV blockade of I degree, thyrotoxicosis, with extensive surgical interventions and general anesthesia, prinzmetal angina, diabetes mellitus, occlusive diseases of peripheral vessels, suspected pheochromocytoma, renal insufficiency, psoriasis.
PREGNANCY AND LACTATION
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).
Animal studies have not revealed teratogenic effects of carvedilol in.
Enough experience with the drug Akridilol В® pregnant no. Carvedilol is contraindicated during pregnancy, except in cases where the potential benefits of its application for the mother outweighs the potential risk to the fetus.
In animals, carvedilol and its metabolites into breast milk. Data on the penetration of carvedilol passes into breast milk in humans are not available, therefore, if the drug is needed during lactation, breast-feeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
It is recommended to monitor renal function in patients with chronic renal failure patients.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in severe hepatic impairment.
APPLICATION FOR CHILDREN
Contraindicated under the age of 18 years (effectiveness and safety have been established).
APPLICATION IN ELDERLY PATIENTS
The data that would have dictated the need for dose adjustment in elderly patients , no.
SPECIAL INSTRUCTIONS
Chronic heart failure
Patients with chronic heart failure during the selection of the dose Akridilol В® can be marked increase in symptoms of congestive heart failure or fluid retention. In the event of such symptoms is necessary to increase the dose of diuretics and not to increase the drug dose Akridilol В® until stabilization of hemodynamic parameters.
Sometimes it is necessary to reduce the dose of the drug Akridilol В® or, in rare cases, temporarily stop the drug. Such episodes are not impede further correct selection of dose preparation Akridilol В® .
Akridilol В® with care is used in combination with cardiac glycosides (possibly excessive deceleration AV-conduction).
Renal function in chronic heart failure
When assigning Akridilol drug В® patients with chronic heart failure and low blood pressure (systolic blood pressure less than 100 mm Hg), ischemic heart disease, and diffuse vascular changes and / or renal insufficiency noted reversible renal impairment. Dose is adjusted depending on renal function.
COPD
Patients with COPD (including bronchospastic syndrome) not receiving oral or inhaled antiasthmatics, Akridilol В® administered only if the possible benefits of its use outweigh the potential risks. In the presence of the original predisposition to bronchospastic syndrome when receiving Akridilol preparation В® 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 Akridilol В® in these patients should be carefully observed, reducing the dose of the drug with the appearance of initial symptoms of bronchospasm.
Diabetes
Precautions drug prescribed to patients with diabetes because it can mask or reduce the symptoms of hypoglycemia (especially tachycardia). In patients with chronic heart failure and diabetes medication use Akridilol В® may be associated with impaired glycemic control.
Peripheral vascular disease
Caution is needed when assigning Akridilol drug В® patients with peripheral vascular disease (including Raynaud's syndrome) as beta-blockers may enhance arterial insufficiency symptoms.
Thyrotoxicosis
As with other beta-blockers, Akridilol В® may reduce the severity of symptoms of hyperthyroidism.
General anesthesia and extensive surgery
Caution is required in patients undergoing surgery under general anesthesia, because of the potential adverse effects of the drug summation AkridilolВ® and funds for general anesthesia.
Bradycardia
Akridilol В® can cause bradycardia, with heart rate less than 55 beats urezhenii. / Min dose should be reduced.
Hypersensitivity
Care should be taken when administering the drug Akridilol В® patients with a history indications of severe hypersensitivity reactions or undergoing a course desensitization as beta blockers may increase the sensitivity to allergens and severity of anaphylactic reactions.
Psoriasis
Patients with a history indications of the appearance or worsening of psoriasis when applying beta-blockers, Akridilol В® can be administered only after careful analysis of the possible risks and benefits.
Simultaneous treatment with blockers of slow calcium channels (BCCI)
in patients taking concomitant BCCI type verapamil or diltiazem, as well as other antiarrhythmics, should regularly monitor the ECG and blood pressure.
Pheochromocytoma
Patients with pheochromocytoma before the use of any beta-blocker, you must assign an alpha-blocker. Although Akridilol В®It has both beta and alpha-adrenoceptor blocking properties and experience of their use in such patients is not, so it should be used with caution in patients with suspected pheochromocytoma.
Prinzmetal angina
nonselective beta-blockers may provoke the appearance of pain in patients with angina Prinzmetal. Exp destination Akridilol preparation В® these patients no. Although its alpha-adrenoceptor blocking properties may prevent such symptoms, prescribe carvedilol in such cases should be cautious.
Contact lenses
Patients who use contact lenses should bear in mind the possibility of reducing the amount of tear fluid.
Withdrawal
Treatment with Akridilol В®It held for a long time. It should not be stopped abruptly, you must gradually reduce the dose at weekly intervals. This is particularly important in patients with CHD.
In the case of the need for surgery using general anesthesia is necessary to warn the anesthetist prior to therapy with Akridilol В® .
During treatment excludes alcohol.
Impact on the ability to drive vehicles and manage mechanisms
During the period of treatment must be careful when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions.
OVERDOSE
Symptoms: marked reduction of blood pressure, bradycardia, heart failure, cardiogenic shock, cardiac arrest; possible respiratory failure, bronchospasm, vomiting, confusion, and generalized convulsions.
Treatment: in addition to the general measures necessary to carry out monitoring and correction of vital signs, if necessary - in the intensive care unit. You can use the following measures:
- put the patient on the back (with raised legs);
- with bradycardia - atropine of 0.5-2 mg / in;
- to maintain cardiovascular activity - glucagon to 1-10 mg / bolus, followed by 2-5 mg per hour as a continuous infusion;
. - sympathomimetics (dobutamine, isoprenaline, orciprenaline or epinephrine (adrenaline) at different doses, depending on the body weight, and response to treatment
if the clinical picture overdose dominates hypotension administered norepinephrine (noradrenaline), it is administered in continuous control indicators circulation . when refractory to treatment shown bradycardia pacemaker application bronchospasm when beta-adrenergic agonist is administered as an aerosol (at inefficiency - in / in). aminophylline or I / at p. Roads in / slow administered diazepam or clonazepam.
Because of severe overdose with symptoms of shock, possibly lengthening the half-life of carvedilol and excretion of the drug from the depot, it is necessary to continue maintenance therapy for quite a long time. The duration of maintenance / detoxification therapy depends on the degree of severity of overdose, it must continue to stabilize the clinical condition of the patient.
DRUG INTERACTION
Pharmacokinetic interaction
Since carvedilol is both a substrate and inhibitor of P-glycoprotein by its simultaneous administration with drugs 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.
Digoxin
When simultaneous administration 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.
cyclosporine
In two studies in the appointment of carvedilol in patients who have had a kidney transplant and heart and receiving cyclosporine orally, was an increase in the concentration of cyclosporine. 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. In the case of intravenous administration of cyclosporin, any interaction with carvedilol is expected.
rifampicin
In a study of 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.
Amiodarone
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 increasing concentration of S stereoisomer carvedilol possible risk of increased beta-adrenoceptor blocking action.
fluoxetine
In a randomized crossover design study in patients with heart failure, the simultaneous reception of fluoxetine (CYP2D6 inhibitor) led to inhibition of the metabolism of carvedilol stereoselective - to increase the average AUC for the index 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 of
insulin or hypoglycemic agents for oral administration
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 content.
Drugs that reduce the content of catecholamines
Patients receiving means simultaneously with the beta-adrenoceptor blocking properties and means for reducing the content of catecholamines (e.g., reserpine and MAO inhibitors) must be carefully monitored because of the risk of hypotension and / or severe bradycardia.
Digoxin
Combination therapies with a beta-adrenoceptor blocking properties and digoxin may lead to an additional deceleration of atrioventricular conduction. Verapamil, diltiazem, amiodarone or other antiarrhythmic drugs concomitantly with carvedilol can increase the risk of AV-conduction disturbances.
Clonidine
Co-administration of clonidine with agents with beta-adrenoceptor blocking properties may potentiate the antihypertensive effect and bradikarditichesky. If you plan to stop drug combination therapy with a beta-adrenoceptor blocking properties and clonidine, must first cancel the beta-blocker, and in a few days you can cancel clonidine, gradually reducing the dose.
Calcium channel blockers slow (BCCI)
When concomitant administration of carvedilol and diltiazem observed isolated cases of conduction disturbance (rarely - violations of hemodynamic parameters). As is the case with other drugs with beta-adrenoceptor blocking properties, the appointment of carvedilol with BCCI type verapamil or diltiazem is recommended to be under the control of ECG and blood pressure.
Antihypertensives
Like other drugs with beta-adrenoblokiruyuschey activity, carvedilol may potentiate other concomitant antihypertensive agents (e.g., alpha 1 adrenoblokatorov) or drugs that cause hypotension as a side effect.
General anesthetics
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.
NSAIDs
Joint NSAID and beta-blockers can lead to increased blood pressure and reduce blood pressure control.
Bronchodilators (agonists? Adrenoceptor)
As a non-cardioselective beta-blockers prevent bronholitiruyuschemu effect of bronchodilators, which are stimulants? -adrenoceptor, careful monitoring of patients receiving these drugs.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The preparation should be stored in a dry place, protected from light, reach of children at a temperature not higher than 25 В° C. Shelf life - 3 years.
