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Dosage form: & nbsppills
Composition:

1 tablet contains:

active substance: carvedilol 3.125 mg;

Excipients: lactose monohydrate 75.375 mg, sucrose 5,000 mg, povidone 2,000 mg, crospovidone 3,000 mg, silicon dioxide colloid, anhydrous 0.500 mg, magnesium stearate 1,000 mg.

Description:

Round, slightly biconvex tablets white or almost white, with a bevel.

Pharmacotherapeutic group:Alpha- and beta-blocker
Pharmacodynamics:

Carvedilol - blocker of alpha1, beta1, beta2-adrenoreceptors, has an organoprotective effect. Has antiproliferative properties in respect of smooth muscle cells of the walls of blood vessels, is a racemic mixture R(+) and S(-) stereoisomers, each of which has the same alpha-adrenergic blocking properties. Due to cardioselective blocking of adrenergic receptors, due to S(-) stereoisomer, carvedilol reduces blood pressure (BP), reduces heart rate (heart rate) and cardiac output, reduces pressure in the pulmonary arteries and in the right atrium. Due to the blockade of alpha-adrenergic receptors, it causes peripheral vasodilation and reduces peripheral vascular resistance (PSS).Reduces the stress on the heart muscle and prevents the development of angina pectoris. In patients with chronic heart failure (CHF) increases the fraction of the left ventricular ejection (LV) and reduces the severity of the symptoms of the disease. Similar effects were noted in patients with LV dysfunction.

Carvedilol does not have intrinsic sympathomimetic activity, and just like propranolol, has the property of stabilizing membranes. The activity of the renin-angiotensin-aldosterone system (RAAS) decreases, decreasing the release of renin, so fluid retention (characteristic of selective alpha-blockers) develops rarely. The effect on blood pressure and heart rate is most pronounced 1-2 hours after taking the drug.

Carvedilol does not adversely affect the lipid profile, maintaining a normal ratio of high and low density lipoproteins (HDL / LDL).

In patients with arterial hypertension (AH) and kidney disease carvedilol reduces the resistance of renal vessels, while there is no significant change in the rate of glomerular filtration, renal plasma flow, or excretion of electrolytes.Peripheral blood flow is maintained, so the coldness of the hands and feet, often noted when taking beta-blockers, develops rarely.
Pharmacokinetics:

Carvedilol is rapidly absorbed after oral administration.

The maximum concentration of carvedilol in blood plasma (CmAch) is achieved after 1 hour. Absolute bioavailability of carvedilol is about 25%.

Distribution

Carvedilol has a high lipophilicity. Approximately 98-99% of it binds to blood plasma proteins. The volume of distribution is approximately 2 l / kg.

Metabolism

Carvedilol undergoes biotransformation in the liver by oxidation and conjugation to form a number of metabolites. Metabolized by the "first pass" through the liver.

The metabolism of carvedilol by oxidation is stereoselective. R(+) isomer is metabolized mainly by isoenzymes CYP2D6 and CYP1A2, a S(-) isomer mainly by CYP2D9 and, to a lesser extent, with the help of CYP2D6. Other cytochrome P450 isoenzymes involved in the metabolism of carvedilol include CYP3A4, CYP2E1, CYP2C19.

As a result of demethylation and hydroxylation of the phenolic ring, 3 metabolites are formed which have less pronounced vasodilating properties than carvedilol.

Excretion

The half-life (T1 / 2) is about 6 hours, the plasma clearance is about 500-700 ml / min. Displayed carvedilol mainly with bile through the intestine and partly kidneys in the form of metabolites.

The patient's age does not have a statistically significant effect on the pharmacokinetics of carvedilol.

In patients with cirrhosis of the liver, the bioavailability of carvedilol is increased by 80% due to a decrease in the expression of metabolism during the "first passage" through the liver.

Indications:

- Arterial hypertension (monotherapy or combination with other antihypertensive agents);

- angina pectoris;

- chronic heart failure.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- bronchial asthma or bronchospasm (in the anamnesis);

- acute and chronic heart failure in the stage of decompensation, requiring intravenous injection of inotropic agents;

- cardiogenic shock;

- severe bradycardia (less than 50 beats per minute at rest), sinus node weakness syndrome (including sinoauric block), atrioventricular block II-III degree (except for cases with an established pacemaker);

- severe hepatic failure, metabolic acidosis;

- Patients receiving / in verapamil or diltiazem therapy, because of the possibility of developing severe bradycardia (less than 40 beats / min) and arterial hypotension;

- severe arterial hypotension (systolic blood pressure less than 85 mm Hg);

- sugarase / isomaltase deficiency, lactase deficiency, fructose intolerance, lactose intolerance, glucose-galactose malabsorption syndrome;

- lactation period;

- age to 18 years (safety and efficacy not established).

Carefully:

Chronic obstructive pulmonary disease (COPD), angina Prinzmetal, AV blockade degree I, diabetes mellitus, hypoglycemia, hyperthyroidism, occlusive peripheral vascular disease, pheochromocytoma, depression, myasthenia gravis, psoriasis, extensive surgery, holding a total benzocaine, renal failure, pheochromocytoma suspected pregnancy.

Pregnancy and lactation:

Data on the use of Coriol® during pregnancy are limited.

The potential risk to humans is unknown.

Beta-blockers reduce placental blood flow, have an adverse impact on the development of the embryo, may cause hypotension, bradycardia and hypoglycaemia in the fetus.

Coriol® should not be used during pregnancy, unless absolutely necessary, if the potential benefit to the mother justifies the risk to the fetus. Because the carvedilol is secreted into breast milk, during treatment with Coriol®, breastfeeding should be discontinued.

Dosing and Administration:

Inside, after eating, washed down with water.

The dose of the drug is selected individually. Treatment should begin with low doses, which gradually increase to achieve the optimal clinical effect. After the first reception of Coriol® preparation and after each dose increase, in order to exclude possible arterial hypotension, it is recommended to measure BP after 1 hour after taking the drug.

Therapy with Coriol® should be stopped gradually, reducing the dose within 1-2 weeks.

If after the cessation of therapy more than 2 weeks have elapsed, it is recommended to resume taking the drug again, starting with a low dose.

Arterial hypertension

For the treatment of hypertension, it is necessary to apply the preparation Coriol® in other dosages: 6.25 mg, 12.5 mg or 25 mg.

The initial dose is 12.5 mg (4 tablets) in the morning, after breakfast, or at 6.25 mg (2 tablets) 2 times a day (morning and evening).

After 7-14 days of treatment (sometimes after 2 days) the dose of the drug should be increased to 25 mg in the morning or up to 12.5 mg twice a day. After 14 days the dose of the drug can again be increased to 25 mg twice a day.

The maximum daily dose is 25 mg twice a day (50 mg).

Angina pectoris

For the therapy of angina pectoris, Coriol ® in other dosages: 6.25 mg, 12.5 mg or 25 mg.

The initial dose is 12.5 mg twice a day.

After 7-14 days of treatment (if necessary after 2 days) the dose of the drug should be increased to 25 mg twice a day.

The maximum daily dose is 25 mg twice a day (50 mg).

Chronic heart failure (CHF)

The initial dose is 3,125 mg twice a day. If this dose is well tolerated, it can be gradually increased (at an interval of 2 weeks).

The next dose is 6.25 mg (2 tablets) 2 times a day.

Then, if you need to increase the dose, use Coriol® in other dosages.

The next dose is 12.5 mg twice a day and, finally, 25 mg twice a day.

The maximum dose is 25 mg twice a day (50 mg).

In patients weighing more than 85 kg, the dose can be gently increased to 50 mg twice a day.

If treatment with Coriol® is interrupted for more than 1 week, then its use is resumed at a lower dose, and then increased in accordance with the above recommendations.If treatment with Coriol® is interrupted for more than 2 weeks, then it should be resumed at a dose of 3.125 mg twice a day, then picking up the dose in accordance with the recommendations above.

Symptoms of vasodilation can be eliminated by reducing the dose of diuretics. If symptoms persist, you can reduce the dose of an ACE inhibitor (if the patient takes it), and then, if necessary, the dose of Coriol®. The dose of Coriol® should not be increased until symptoms of worsening heart failure or hypotension are stabilized.

Specials groups patients

Elderly patients

Elderly patients do not need dose adjustment.

Patients with impaired hepatic function

Coriol is not recommended for patients with severe hepatic insufficiency.

Patients with impaired renal function

Existing data on pharmacokinetics in patients with varying degrees of renal dysfunction (including renal failure) suggest that with moderate and severe renal failure, Coriol® dosage adjustment is not required.

Side effects:

Classification of the incidence of adverse events (WHO): very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including individual reports.

The frequency of some unwanted effects, such as dizziness, arterial hypotension, bradycardia and visual disturbances, is proportional to the size of the dose. These effects usually develop with increasing dose and bowl - in patients with CHF and are usually unstable in nature. The most frequent of undesirable effects of carvedilol is dizziness, with ortostatic hypotension or without it, which develops at about 6% patients.

With the development of serious adverse effects, drug treatment should be discontinued.

On the part of the hematopoiesis and lymphatic system

- rarely: thrombocytopenia;

- very rarely: leukopenia.

From the nervous system

- often: dizziness, headache (especially at the beginning of treatment or when changing doses), general weakness;

- rarely: sleep disturbances, mood changes / thinking, paresthesia, myasthenia gravis, loss of consciousness.

From the sense organs

- often: decrease in secretion of tears (pay attention when using contact lenses);

- very rarely: visual disturbances, eye irritation.

From the side of the cardiovascular system

- very often: orthostatic hypotension;

- often: aetiology;

- rarely: worsening of the clinical picture of heart failure (especially with increasing doses), coldness of hands and feet, lowering blood pressure, fainting;

- Very rarely: disturbances of cardiac conduction, palpitation, aggravation of angina pectoris, occlusive disorders of peripheral circulation, "intermittent" lameness, peripheral edema.

From the respiratory system

- rarely: shortness of breath, bronchospasm (in predisposed patients), nasal congestion.

From the digestive system

- often: nausea, abdominal pain (up to 2%), mild diarrhea, dryness of the oral mucosa;

- rarely: decreased appetite, vomiting, flatulence, constipation;

- very rarely: dry mouth, increased activity of "liver" transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (ACT), gamma-glutamyltransferase).

From the skin

- very rarely: exacerbation of psoriasis, alopecia, exfoliative dermatitis.

From the side of the musculoskeletal system

- rarely: pain in the muscles, bones, spine.

From the urinary system

- rarely: urination disorders;

- very rarely: severe renal dysfunction, edema.

Laboratory indicators

- rare: increased concentration of triglycerides and cholesterol;

From the side of metabolism

- often: weight gain, hypercholesterolemia; in patients with already existing diabetes - hyperglycemia or hypoglycemia.

Other

- often: general weakness;

- infrequently: reactions of increased sensitivity (skin itching, rash, urticaria), decreased potency;

- rarely: peripheral edema;

- very rarely: flushes of blood to the skin of the face, sneezing, flu-like syndrome.

Overdose:

Symptoms: a marked decrease in blood pressure (systolic blood pressure of 80 mm Hg and below), bradycardia (less than 50 beats / min), impaired breathing (including bronchospasm), heart failure, cardiogenic shock, cardiac arrest, generalized seizure, bronchospasm , vomiting, confusion.

Treatment: it is necessary to monitor and correct vital signs, if necessary - in the intensive care unit.

Put the patient on his back (with raised legs), with severe bradycardia - atropine 0.5-2 mg IV; with severe arterial hypotension - norepinephrine (noradrenaline); if necessary - glucagon 1-10 mg in / in struino, then at 205 mg / h in the form of a long infusion; sympathomimetics in doses, depending on body weight.

Interaction:

Patients are not advised to take alcohol during treatment with carvedilol. ethanol can potentiate the undesirable effects of carvedilol. Some antiarrhythmic, narcotic, antihypertensive drugs, agents for the treatment of angina pectoris, other beta-blockers (for example, in the form of eye drops), drugs depleting the supplies of catecholamines (eg, monoamine oxidase inhibitors, reserpine) and cardiac glycosides can potentiate the effects of carvedilol, in connection with which the above drugs carvedilol must be taken with caution.

Simultaneous therapy digoxin can lead to an increase in the concentration of digoxin in the blood plasma (about 15%).

Simultaneous administration of clonidine with beta-adrenoblocking properties can potentiate an antihypertensive and bradycardic effect. If you plan to stop the combination therapy with a drug with beta-adrenergic blocking properties and clonidine, you should first cancel the beta-blocker,and after a few days cancel clonidine, gradually reducing its dose.

Carvedilol can increase plasma concentrations cyclosporine, therefore at the beginning of therapy with carvedilol and when changing its dose, it is recommended to check the concentration of cyclosporine.

Carvedilol enhances action insulin and sulfonylurea derivatives (simultaneously masking or reducing the severity of symptoms of hypoglycemia, reducing the decomposition of liver glycogen to glucose), hypotensive drugs (ACE inhibitors, thiazide diuretics, vasodilators).

Simultaneous reception of carvedilol with aantiarrhythmic drugsand, incl. with diltiazem and amiodarone, may increase the risk of violation of atrioventricular conduction.

With the simultaneous use of carvedilol and diltiazem There were isolated cases of conduction disorders (rarely - with violations of hemodynamics). As with other drugs with beta-adrenergic blocking properties, the appointment of carvedilol along with blockers of "slow" calcium ropes such as verapamil or diltiazem is recommended to be performed under the control of ECG and AD.

It is necessary to carefully monitor the main indicators of vital activity of the body during general anesthesia in connection with the possibility of a synergistic negative inotropic action of carvedilol and general anesthetic agents. Phenobarbital, rifampicin accelerate metabolism and reduce the concentration of carvedilol in blood plasma.

Inhibitors of microsomal oxidation (cimetidine), Diuretics and ACE inhibitors intensify the hypotensive effect of carvedilol.

Since cardioselective beta-blockers interfere with the bronchodilating effect of bronchodilators, which are stimulators of beta-adrenergic receptors, it is necessary to monitor patients receiving these medications.

Special instructions:

The drug Coriol® is recommended for the treatment of CHF, as an adjunct to standard diuretic therapy, ACE inhibitors or cardiac glycosides only after choosing a dose of a diuretic. It can also be used in patients who do not tolerate ACE inhibitors.

Arterial hypotension: the drug is not recommended for patients with low blood pressure.

Orthostatic hypotension: sometimes, especially at the beginning of therapy with Coriol® or after increasing its dose, orthostatic hypotension and dizziness may develop, sometimes with syncope, especially in patients with heart failure, elderly patients and taking other hypotensive drugs or diuretics simultaneously. These effects can be prevented by prescribing an initial low dose of Coriol® and gradually increasing to a maintenance dose, as well as taking the drug after a meal. Patients should explain how orthostatic hypotension can be avoided (to gently rise from the "lying" or "sitting" position, and when dizziness develops, one must sit or lie down).

Heart failure: patients with mild or moderate heart failure may take Coriol® only if their condition is successfully controlled by drugs of the cardiac glycoside group and / or diuretics. If the course of heart failure worsens during treatment, it is necessary to increase the dose of the diuretic, and the dose of Coriol® should be reduced or temporarily discontinued (see section "Method of administration and dose").

Diabetes mellitus and thyrotoxicosis: beta-adrenoblockers reduce heart rate and therefore can mask symptoms of hypoglycemia in patients with diabetes mellitus, as well as manifestations of thyrotoxicosis in patients with thyroid disease. In patients with heart failure, the concentration of glucose in the blood can increase or decrease.

General anesthesia: when conducting general anesthesia, patients taking beta-blockers should use narcotic analgesics with minimal inotropic effect, or preliminary (gradually) abolish the beta-blocker.

Dysfunction of the liver: in some cases carvedilol can cause violations of the liver. With the development of liver failure, the use of Coriol® should be discontinued. As a rule, after the withdrawal of the drug, the function of the liver is normalized.

COPD: beta-adrenoblockers can aggravate bronchial obstruction, so patients with COPD usually do not use them. In exceptional cases, patients with a mild course of the disease may take Coriol® with ineffectiveness of other drugs, but such patients need careful medical supervision.It is important that patients take the lowest effective doses of Coriol®. If signs of airway obstruction appear, immediately stop using Coriol®.

Beta-adrenoblockers can worsen the clinical picture peripheral arteriopathy, psoriasis and anaphylactic reactions and strengthen the body's response to allergoproob.

Beta-adrenoblockers can provoke the appearance of pain in patients with stenocardia prinzmetala.

Patients from pheochromocytoma can accept beta-blockers only after treatment with alpha-blockers has been started.

Discontinuation of therapy: with a sharp discontinuation of therapy with Coriol® (as well as other beta-blockers), sweating, tachycardia, dyspnea and worsening of the course of angina may develop. The most vulnerable to the occurrence of these reactions are patients with angina pectoris, in whom myocardial infarction may develop. If you cancel the drug Coriol® dose is reduced gradually, within 1-2 weeks.

If after the cessation of therapy more than 2 weeks have elapsed, it is recommended to resume taking the drug again, starting from low doses.

It is not recommended to take Coriol® medication for patients younger than 18 years of age. effectiveness and safety of carvedilol in this group of patients is not established.

Coriol® contains sucrose and lactose. The drug should not be taken to patients with a deficiency of sugar / isomaltase, lactase deficiency, fructose intolerance, lactose intolerance, glucose-galactose malabsorption syndrome.

Effect on the ability to drive transp. cf. and fur:Given the potential side effects of Coriol®, caution should be exercised when driving vehicles and practicing potentially hazardous activities requiring increased attention and speed of psychomotor reactions.
Form release / dosage:

Tablets 3,125 mg.

Packaging:10 tablets per blister.
For 3 blisters are placed in a pack of cardboard along with instructions for use.
Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription
Registration number:LS-001308
Date of registration:13.12.2010
Date of cancellation:2018-02-06
The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO
Manufacturer: & nbsp
KRKA, d.d. Slovenia
Representation: & nbspKRKA KRKA Slovenia
Information update date: & nbsp06.02.2018
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