Corioli tab. of 12.5 mg No. 28

Pharmacological properties

Pharmacodynamics. karvedilol — a non-selective blocker of β-adrenoceptors with vazodilatiruyushchy action. it also has antioxidant and anti-proliferative properties.

Active ingredient karvedilol is a racemate; enantiomer differ in effects and metabolism. S (–) - an enantiomer has the activity directed to blocking α to ₁ — and β-adrenoceptors whereas R (+)-enantiomer shows only the activity directed to blocking α to ₁ - adrenoceptors. Thanks to cardionon-selective blockade of β-adrenoceptors karvedilol lowers the arterial blood pressure, ChSS and warm emission. Karvedilol reduces pressure in a pulmonary artery and the right auricle. By blockade α ₁ - adrenoceptors causes a peripheral vazodilatation and reduces OPSS. Thanks to these effects the load of a cardiac muscle decreases and development of stenocardia is prevented. At patients with heart failure it leads to increase in fraction of emission from a left ventricle and to reduction of expressiveness of symptoms of a disease. Similar effects noted at patients with dysfunction of a left ventricle. Karvedilol does not show internal sympathomimetic activity and, as well as propranolol, has membrane stabilizing properties. The activity of renin in blood plasma decreases, and the liquid delay in an organism occurs seldom. Influence on the ABP and ChSS is most significant in 1–2 h after administration of drug.

At patients with AG against the background of normal function of kidneys karvedilol is reduced by renal vascular resistance. At the same time there are no significant changes of glomerular filtration, a renal blood-groove and excretion of electrolytes. Thanks to maintenance of a peripheral blood-groove seldom note the pokholodeniye of extremities characteristic of treatment by blockers of β-adrenoceptors. Karvedilol, as a rule, does not influence the level of lipoproteins in blood plasma.

Pharmacokinetics. Karvedilol after oral administration quickly and almost is completely soaked up. Almost completely contacts proteins of blood plasma. The volume of distribution is about 2 l/kg. Concentration in blood plasma is proportional to the entered dose.

Only about 30% of the entered karvedilol are bioavailable because of considerable presistemny metabolism (mainly thanks to enzymes of a liver of CYP 2D6 and CYP 2C9). Three active metabolites with ability to block β-adrenoceptors are formed; one of them (4 ’-hydroxyphenyl derivative) is by 13 times more powerful, than karvedilol, concerning blockade of β-receptors.

In comparison with karvediloly the active metabolites have weak vazodilatatorny effect. Stereoselection metabolism; therefore level R (+) the karvedilola in blood plasma by 2–3 times exceeds level S (–) of a karvedilol. Levels of active metabolites in blood plasma there is about 10 times below than the level of karvedilol. The t _½ very much differs: 5–9 h for R (+) a karvedilola and 7–11 h for S (–) a karvedilol. At elderly people note increase in level of a karvedilol approximately for 50%. At patients with cirrhosis the bioavailability of a karvedilol increases by 4 times, and the C _max in blood plasma by 5 times exceeds the corresponding sizes at healthy people.

At patients with an abnormal liver function the bioavailability increases to 80% in view of reduction of metabolic disintegration of the first passing. As karvedilol improbably significant accumulation of medicament is allocated mainly with a stake, at patients with a renal failure.

Meal slows down medicament absorption speed, but it does not affect its bioavailability.

Indication

Corioli of 3.125 and 6.25 mg

Essential arterial hypertension. Corioli it is possible to apply separately or in a combination with other antihypertensive medicaments (especially with thiazide diuretics).

Chronic stable stenocardia.

Chronic stable heart failure (in addition to standard therapy by diuretics, digoxin or APF inhibitors), for prevention of progressing of a disease at patients with heart failure of the II-III class on classification of NYHA.

Corioli of 12.5 and 25 mg

• Essential arterial hypertension.
• Chronic stable stenocardia.
• Chronic heart failure of moderate and heavy degree as additional therapy.

Use

For delay of absorption and prevention of orthostatic effects of Corioli should be accepted after a meal.

Dose should be selected individually. Treatment should be begun with low doses which should be raised to achievement of optimum clinical effect gradually. After reception of the first dose and after each increase in a dose it is recommended to measure the ABP in a standing position in 1 h after introduction for an exception of possible hypotension.

Drug treatment of Corioli should be stopped gradually by decrease in doses during 1–2 weeks

If treatment stops more than on 2 weeks, then it should be restored from purpose of a low dose.

Essential arterial hypertension. The initial dose of Koriol makes 12.5 mg in the morning after a breakfast or on 6.25 mg 2 times a day (in the morning and in the evening). After 2 days of treatment the dose should be raised to 25 mg in the morning (1 tablet on 25 mg) or to 12.5 mg 2 times a day. In 14 days of treatment the dose can be raised to 25 mg 2 times again a day.

Maximum dose of Koriol for treatment of hypertensia makes 25 mg 2 times a day. The recommended initial dose of Koriol for treatment of AG at patients with heart failure makes 3.125 mg 2 times a day.

Chronic stable stenocardia. The initial dose of Koriol makes 12.5 mg 2 times a day after a meal. In 2 days of treatment it is necessary to raise a dose to 25 mg 2 times a day.

Maximum dose of Koriol for treatment of chronic stenocardia makes 25 mg 2 times a day. The recommended initial dose of Koriol for treatment of stenocardia at patients with heart failure makes 3.125 mg 2 times a day.

Chronic heart failure. Corioli recommend for treatment stable poorly, moderate or heavy chronic heart failure as supportive application at use of standard drugs, such as diuretics, APF inhibitors or medicaments of a digitalis. Corioli patients who do not transfer APF inhibitors can also accept. The patient can appoint Corioli only after equilibration of doses of diuretic, APF inhibitor and cardiac glycosides (if it is appointed). The dose is selected individually. For the first 2–3 h after the first reception or after increase in a dose the careful medical observation is necessary for control of tolerance of drug. If at the patient note decrease in ChSS 55 ud. / min., that Koriol's dose needs to be lowered. If there are symptoms of arterial hypotension, then at first it is necessary to consider the possibility of a dose decline of diuretic or APF inhibitor; and if these measures are insufficient, then to lower Koriol's dose.

In an initiation of treatment Koriol or after increase in a dose tranzitorny strengthening of heart failure can arise. In that case it is necessary to raise a diuretic dose. Sometimes it is necessary to lower temporarily Koriol's dose or even to cancel. After stabilization of a clinical state it is possible to resume treatment by Koriol or to raise his dose.

Initial dose makes 3.125 * mg 2 times a day. If the patient well transfers this dose, then it can be raised gradually (in each 2 weeks) to achievement of an optimum dose. The following doses make 6.25 mg 2 times a day, then — 12.5 mg 2 times a day and 25 mg 2 times a day. The patient should accept the maximum tolerable dose. The maximum recommended dose for patients with body weight to 85 kg makes 25 mg 2 times a day. For patients with the body weight of 85 kg — up to 50 mg 2 times a day.

Patients of advanced age. There is no need to change a dose.

Children. Drug is not recommended to use at children.

Patients with a liver failure. Corioli is not recommended to apply at patients with a heavy liver failure.

Patients with a renal failure. For patients with systolic arterial blood pressure of 100 mm Hg. special changes of a dose are not required (see. Special INSTRUCTIONS).

* In need of use of a dose of 3.125 mg to appoint other medicaments of a karvedilol in the corresponding dosage form and a dosage.

Contraindication

Hypersensitivity to active ingredient or any of medicament excipients;

• dekompensirovanny heart failure — heart failure of the IV class on classification of NYHA which demands introduction of inotropic means;
• blockade of II and III degree (except cases when the constant pacemaker is established);
• accompanying administration of verapamil, diltiazem or other antiarrhytmic means (especially antiarrhytmic means of class I);
• profound bradycardia (ChSS 50 ud. / mines);
• profound arterial hypotension (systolic arterial blood pressure of 85 mm Hg.);
• cardiogenic shock;
• sick sinus syndrome (including sinuatrial blockade);
• noncompensated heart failure demanding introduction positive isotropic and/or diuretics;
• pulmonary heart, pulmonary hypertensia;
• OH or obstructive respiratory diseases which are followed by a bronchospasm;
• a pheochromocytoma (except for cases when it is properly controlled at use of blockers of α-adrenoceptors);
• Printsmetal's stenocardia;
• profound abnormal liver functions;
• simultaneous use of MAO inhibitors (except for MAO-B inhibitors);
• intolerance of a galactose, insufficiency of Lappa lactase or glyukozo-galaktozny malabsorption;
• metabolic acidosis;
• period of pregnancy and feeding by a breast, children's age.

Frequency of side reactions is estimated by

thus: very often (10%), it is frequent (1%, 10%), infrequently (0.1%, 1%), is rare (0.01%, 1%), very seldom, including separate cases (0.01%).

from the system of blood and lymphatic system: often — anemia; seldom — thrombocytopenia; very seldom — a leukopenia, decrease in level of a prothrombin.

from the immune system: very seldom — hypersensitivity (allergic reaction), anaphylactic reactions.

Disturbance of metabolism and digestion: often — increase in body weight, a hypercholesterolemia, disturbance of control of glucose in blood (hyperglycemia, a hypoglycemia) at patients with already existing diabetes, are possible manifestations of latent diabetes, symptoms of the existing diabetes can amplify during therapy, a hyperpotassemia, a gipertriglitseridemiya, a hyponatremia, increase in the SF level, creatinine, urea.

Mental disturbances: often — a depression, depressive mood; infrequently — sleep disorders.

from nervous system: very often — dizziness, a headache; infrequently — a state before a loss of consciousness, a loss of consciousness, paresthesias.

from an organ of sight: often — a disorder of vision, decrease in a slezootdeleniye (xerophthalmus), irritation of eyes.

from a cardiovascular system: very often — heart failure, hypotension; often — bradycardia, hypostasis (including generalized, peripheral, dependent hypostasis and hypostasis of genitals and legs), a hypervolemia, glut liquid, orthostatic hypotension, disturbances of circulation of peripheral blood (cold extremities, a disease of peripheral vessels, aggravation of a syndrome of Sharko and Reynaud's phenomenon); infrequently — blockade, stenocardia, arterial hypertension, heartbeat.

Respiratory, thoracic and mediastinal disturbances: often — short wind, a fluid lungs, asthma at sensitive patients; seldom — congestion of a nose.

from a digestive tract: often — nausea, diarrhea, vomiting, dyspepsia, an abdominal pain; infrequently — a constipation; seldom — dryness in a mouth, periodontitis, a melena.

from a liver and biliary tract: very seldom — increase in ALT, AST and gammaglyutamiltransferaza (GGT).

from skin and hypodermic fabrics: infrequently — skin reactions (for example an allergic dieback, dermatitis, the increased sweating, urticaria, an itching, similar psoriatic and red flat depriving of damage of skin), an alopecia, deterioration in a course of psoriasis, the increased sweating.

from the musculoskeletal device and connective tissue: often — extremity pain; seldom — an arthralgia, spasms.

from kidneys and urinary tract: often — a renal failure and a renal failure at patients with a diffusion disease of vessels and/or the main renal failure, urination disturbances; very seldom — incontinence of urine at women, a hamaturia, an albuminuria, a glucosuria, a hyperuricemia.

from a reproductive system and mammary glands: infrequently — disturbance of erectile function.

General disturbances: very often — an asthenia (fatigue); often — pain, grippopodobny symptoms, fervescence; dizziness, a loss of consciousness, a headache and an asthenia usually easy and probably develop in an initiation of treatment.

At patients with heart failure with developments of stagnation the deterioration in heart failure and a delay of liquid can appear at increase in a dose of a karvedilol by titration.

About heart failure was often reported as about a by-effect as at the patients accepting placebo and at the patients accepting karvedilol (14.5 and 15.4% respectively, at patients with dysfunction of a left ventricle after an acute myocardial infarction).

Reversible deterioration in function of kidneys was observed by

during therapy of a karvedilol at patients with chronic heart failure with the low ABP, an ischemic heart disease and a diffusion disease of vessels and/or the main renal failure.

As a class blockers of β-adrenoceptors can strengthen manifestations of latent diabetes, deterioration in a course of the profound diabetes and to suppress regulation of level of glucose in blood.

Karvedilol can cause incontinence of urine in women, disappears after the termination of administration of drug.

Special instructions

Arterial hypotension. medicament is not recommended to be used at patients with lowered arterial blood pressure.

Orthostatic hypotension. Especially in an initiation of treatment the orthostatic hypotension with dizziness and vertigo, sometimes also with a faint can arise Koriol and at increase in a dose. Patients with heart failure, elderly people and also patients who accept other antihypertensives or diuretics are exposed to the greatest risk. These effects can be prevented use of a low initial dose of Koriol, careful increase in a maintenance dose and administration of medicament after a meal. Patients should tell about measures for prevention of orthostatic hypotension (care when rising, at appearance of dizziness the patient has to sit down or lay down).

treatment Termination. At the sharp termination of treatment by Koriol (as well as the increased sweating, tachycardia, short wind and strengthening of stenocardia can arise other blockers of β-adrenoceptors). Those patients with stenocardia who can have a heart attack are exposed to the greatest risk. The dose needs to be reduced gradually during 1–2 weeks

If treatment was suspended more than on 2 weeks, its updating should be carried out, since the lowest dose.

Chronic heart failure. In most cases patients with chronic heart failure karvedilol need to appoint in addition to therapy diuretics, APF inhibitors, foxgloves and/or vazodilatator. The initiation of treatment should be carried out in a hospital under observation of the doctor. Therapy can be begun only if when performing the standard basic therapy the condition of the patient is stable during not less than 4 weeks. Patients with heavy heart failure, deficiency of salts or dehydration, to elderly people with the AD low main level during about 2 h after reception of the first dose or after increase in a dose need constant observation as development of arterial hypotension is possible. Arterial hypotension which resulted from excessive vasodilatation at first treat a dose decline of diuretics and if symptoms do not disappear, then it is possible to lower a dose of any APF inhibitor. In an initiation of treatment or at increase in a dose of medicament can worsen a course of heart failure or arise a liquid delay. In that case it is necessary to raise a diuretic dose. However in certain cases there can be a need for a dose decline or medicament withdrawal. The dose of a karvedilol should not be raised, so far the symptoms connected with deterioration in a course of heart failure or arterial hypotension owing to excessive vasodilatation will not be controllable.

with care the patient with chronic heart failure taking the foxglove medicaments as this combination increases AV conductivity.

Karvedilol can become the cause of bradycardia. If ChSS makes 55 ud. / mines there are also symptoms connected with bradycardia, the dose of medicament needs to be lowered.

a karvedilol, with care patients should appoint it with heart block of the I degree.

Renal failure. At patients with heart failure and the low ABP (systolic 100 mm Hg.), the ischemic heart disease or system atherosclerosis and/or against the background of a renal failure at treatment of a karvedilol observed deterioration in function of kidneys which had reversible character. At patients with heart failure with such risk factors it is necessary to control function of kidneys during titration of a dose of a karvedilol. If considerable deterioration in function of kidneys is observed, a dose of a karvedilol it is necessary to lower or stop treatment.

Diabetes and hyperthyroidism. Blockers of β-adrenoceptors slow down ChSS and therefore can mask a hypoglycemia at patients with diabetes and a thyrotoxicosis at patients with a disease of a thyroid gland. Patients to heart failure against the background of diabetes can have a decrease or increase in level of glucose in blood.

Antiarrhytmic means. At simultaneous use of a karvedilol with blockers of calcium channels, such as verapamil and diltiazem or other antiarrhytmic drugs, especially Amiodaronum, it is necessary to control indicators of the ABP and the ECG therefore it is necessary to avoid their simultaneous in/in uses.

Thyrotoxicosis. Karvedilol, as well as other medicaments with the β-blocking action, can mask thyrotoxicosis symptoms.

General anesthesia. Blockers of β-adrenoceptors reduce risk of developing of arrhythmia during anesthesia, but, besides, risk of developing arterial hypotension therefore it is necessary to apply some anesthetics with care can increase.

Abnormal liver function. Karvedilol seldom or never can cause deterioration in function of a liver. At suspicion it is necessary to check function of a liver for clinical deterioration. In case of a liver failure the patient should stop Koriol's reception. As a rule, after the termination of treatment there is a normalization of function of a liver.

HOBL. Blockers of β-adrenoceptors can strengthen bronchial obstruction; therefore patients with HOBL are not recommended to use these drugs. In exceptional cases Corioli patients can appoint with a mild disease of lungs at inefficiency of other drugs; however at the same time it is necessary to carry out careful observation. It is important that these patients accepted Koriol minimal effective dose. At emergence of signs of obstruction of airways the treatment by Koriol needs to be stopped at once.

Disease of peripheral vessels and Reynaud's syndrome. Karvedilol with care to apply at patients with diseases of peripheral vessels and Reynaud's syndrome as blockers of β-adrenoceptors can increase expressiveness of symptoms of a disease.

Psoriasis. With care to appoint sick psoriasis as it can strengthen skin reactions.

Printsmetal's Stenocardia. Not selective blockers of β-adrenoceptors can cause a stethalgia in patients with Printsmetal's stenocardia (α ₁ - the adrenoceptor blocking effect of a karvedilol can prevent it, but there is no sufficient clinical experience of use of a karvedilol in Printsmetal's stenocardia).

Pheochromocytoma. Patients with a pheochromocytoma can accept blockers β-adrenoceptors, only if they initially already began to accept blockers of α-adrenoceptors.

Reaction of hypersensitivity. Patients with heavy reactions of hypersensitivity in the anamnesis and that who undergoes desensitization need to appoint with care karvedilol as blockers of β-adrenoceptors can increase reactivity when carrying out tests for an allergy, enhance sensitivity to allergens and weight of anaphylactic reactions.

Contact lenses: those who carry contact lenses should be warned about a possibility of reduction of a slezootdeleniye.

therefore it is not recommended to be applied at such patients.

Information on medicament excipients. Sucrose and lactose are a part of drug. This medicament should not be taken to patients with the following disturbances: intolerance of fructose, deficiency of lactase, galactosemia, syndrome of disturbance of absorption of glucose galactose or deficiency of invertase-isomaltase.

to Patients is not recommended to take alcoholic beverages as alcohol can enhance effects of a karvedilol during treatment.

As medicament contains sucrose, it should be considered sick diabetes.

Period of pregnancy and feeding by a breast. For a karvedilol not enough clinical data on influence during pregnancy are obtained. Results of experiments on animals are insufficient for impact assessment during pregnancy on fetation and on the child after the birth. The potential risk for the person remains to unknown.

Blockers of β-adrenoceptors have negative pharmacological impact on a fruit. They can cause hypotension, bradycardia and a hypoglycemia in a fruit.

Corioli it is contraindicated during pregnancy.

As probability that karvedilol gets into breast milk, throughout treatment by Koriol do not recommend feeding of the child a breast exists.

Children. Safety and efficiency of use of Koriol for children are not established therefore prescribing of medicament is contraindicated to children.

Interaction

Some antiarrhytmic, narcotic, antihypertensives, medicaments for treatment of stenocardia, other blockers of β-adrenoceptors (for example in the form of eye drops), the medicaments reducing the level of catecholamines (for example Mao's inhibitors, reserpine) and cardiac glycosides can enhance effects of a karvedilol. therefore the dose of these medicaments and a koriol should be selected with care.

Pharmacokinetic interactions

Digoksin. Concentration of digoxin increase approximately by 15% at simultaneous administration of digoxin and a karvedilol. As digoxin, and karvedilol slow down AV conductivity. Recommend the increased monitoring of levels of digoxin at the beginning, at dose adjustment or the termination of reception of a karvedilol.

Insulin or oral hypoglycemic means. Drugs with the β-blocking properties can enhance effect of insulin and oral hypoglycemic means concerning decrease in level of glucose in blood. Manifestations of a hypoglycemia can be disguised or weakened (especially tachycardia). Therefore for patients who accept insulin or oral hypoglycemic means, recommend regular monitoring of level of glucose in blood.

Inductors or inhibitors of the R-glycoprotein, CYP 2D6, CYP 2D9. Karvedilol is R-glycoprotein inhibitor therefore the bioavailability of medicines which are transported by the R-glycoprotein can increase at simultaneous use with karvediloly.

Inhibitors, as well as inductors CYP 2D6 and CYP 2D9, can stereoselektivno change system or presistemny metabolism of a karvedilol, raising or reducing concentration of R- and S-karvedilola in blood plasma.

Fluoxetine. In researches of patients with heart failure the simultaneous use of fluoxetine as powerful CYP inhibitor 2D6 led to stereoselection inhibition of metabolism of a karvedilol with increase in level R (+) an enantiomer of AUC for 77%.

β-agonists of bronchodilators. Not cardioselective blockers of β-adenoretseptor counteract effects of β-agonists of bronchodilators therefore such patients need careful observation.

Stimulators and inhibitors of metabolism in a liver. Rifampicin reduces concentration of a karvedilol in blood plasma approximately by 70%. Cimetidinum increases AUC approximately by 30%, but does not cause changes of the C _max . Special attention can be necessary for those who accept stimulators of oxidases of the mixed function, for example, rifampicin as levels of a karvedilol in blood plasma can be reduced, or inhibitors of oxidases of the mixed function, for example, Cimetidinum as levels in blood plasma can be increased. However, considering rather low influence of Cimetidinum on levels of a karvedilol, the probability of any clinically important interaction is minimum.

Drugs reducing the level of catecholamines: patients who take the medicaments with the β-blocking properties and medicament which can reduce catecholamines (for example reserpine and MAO inhibitors), it is necessary to observe carefully regarding manifestations of hypotension and/or heavy bradycardia.

Cyclosporine: moderate increase in average minimum concentration of cyclosporine after an initiation of treatment of the karvediloly 21 patient with transplantation of a kidney with chronic vascular rejection was observed. Approximately at 30% of patients the dose of cyclosporine needed to be lowered for the purpose of maintenance of concentration of cyclosporine in the therapeutic range, at the same time others did not need correction. On average at these patients the dose of cyclosporine was reduced approximately by 20%. In view of broad intraspecific variability of need of dose adjustment, it is recommended to control carefully concentration of cyclosporine after the beginning of therapy karvediloly if necessary to carry out cyclosporine dose adjustment.

Antiarrhytmic drugs. Separate cases of disturbance of conductivity (seldom with hemodynamic disturbance) were observed when karvedilol and diltiazem was entered in parallel. As well as with the β-blocking properties if karvedilol it is appointed orally with blockers of calcium channels of type of verapamil or diltiazem, the ECG and monitoring of the ABP is recommended to carry out other drugs. It is not necessary to administer these medicaments in / century. It is necessary to carry out careful monitoring of a condition of the patient at simultaneous use of a karvedilol and Amiodaronum (orally) or antiarrhytmic medicaments I of a class. Soon after an initiation of treatment by blockers of β-adrenoceptors it was reported about development of bradycardia, cardiac arrest, fibrillation of ventricles in patients which at the same time accepted Amiodaronum. There is a risk of developing heart failure in case of carrying out accompanying in/in therapy by antiarrhytmic medicaments of the classes Ia or Ic.

Other antihypertensive medicines. As well as other medicaments with the β-blocking properties, in case of need simultaneous use of a karvedilol with blockers of calcium channels of type of verapamil or diltiazem recommend to carry out the ECG and monitoring of the ABP. As well as with the β-blocking action, karvedilol the effect of other at the same time used hypotensive medicaments can strengthen other medicaments (for example antagonists of α-adrenoceptors) that can lead to hypotension as a part of a profile of side effects.

Pharmakodinamichesky interactions

Klonidin: the accompanying reception of a clonidine with medicaments with the β-blocking properties can strengthen decrease in the ABP and ChSS. At completion of the accompanying treatment by medicaments with the β-blocking properties and a clonidine the first should stop intake of the β-blocking drug. Then, in several days, it is possible to stop therapy by a clonidine by a gradual dose decline.

Digidropiridin. At simultaneous use of dihydropyridines and a karvedilola it is necessary to provide careful observation of the patient as it was reported about cases of development of heart failure and heavy arterial hypotension.

Nitrates. Strengthen hypotensive action.

NPVP, estrogen and corticosteroids. The antihypertensive effect of a karvedilol is weakened at simultaneous use with medicaments which detain liquid and sodium in an organism.

Sympathomimetics, α-mimetik and β-mimetik. At simultaneous use there is a risk of development of AG and the profound bradycardia.

Ergotamine. At simultaneous use the vasoconstriction amplifies.

Muscle relaxants. At a combination of a karvedilol with muscle relaxants the neuromuscular blockade amplifies.

Derivative xanthine. It is necessary to apply with care with xanthine derivatives (Aminophyllinum, theophylline) because of reduction of expressiveness of β-adrenoceptor blocking action.

Anesthetics: it is necessary to observe extra care during anesthesia in view of synergy negative inotropic and hypertensive effects of a karvedilol and anesthetics.

Overdose

Symptoms: significant decrease hell, bradycardia, heart failure, cardiogenic shock, cardiac arrest; breath disturbances, a bronchospasm, vomiting, confusion of consciousness and generalized spasms are possible.

Treatment: except actions of the general character, it is necessary to carry out monitoring and correction of the vital indicators, if necessary — in the conditions of intensive care unit.

Patient on a back.

in the presence of the profound bradycardia — in/in administration of atropine in a dose of 0.5-2 mg.

For maintenance of cardiovascular activity — a glucagon in/in struyno on 1–10 mg, and then in the form of long infusion on 2–5 mg/h.

Sympathomimetics (Dobutaminum, izoprenalin, ortsiprenalin or epinephrine) in various doses, depending on body weight and therapeutic effectiveness.

In need of administration of medicaments with positive isotropic action to appoint FED inhibitors. If in a clinical picture of overdose the arterial hypotension dominates, to enter Norepinephrinum; to appoint it in the conditions of continuous monitoring of indicators of blood circulation.

In bradycardia, resistant to treatment, showed use of an artificial pacemaker.

At a bronchospasm to enter β-adrenomimetik in the form of aerosol (at inefficiency — in / c) or Aminophyllinum in / century. In spasms in/in slowly to enter diazepam or clonazepam. As at heavy overdose with symptomatology of shock the lengthening of T _½ medicament from depot is possible, it is necessary to continue maintenance therapy rather long time. Duration of the supporting disintoxication therapy depends on weight of overdose, it should be continued before stabilization of a condition of the patient.

Karvedilol cannot be removed by means of dialysis.

in case of heavy overdose when the patient is in a condition of cardiogenic shock, long enough as removal or redistribution of a karvedilol can take place more slowly, than usually.

Storage conditions

At a temperature not above 30 °C.