Carvedilol - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 89.51 mg / 77.06 mg, microcrystalline cellulose 63 mg / 63 mg, povidone 5.4 mg / tablet 12.5 mg), povidone (KZO) (5.4 mg for a 25 mg tablet), crospovidone 7.2 mg / 7.2 mg, silicon dioxide colloid 0.72 mg / 0.72 mg, magnesium stearate 1.62 mg / 1.62 mg, quinoline yellow (0.05 mg for the tablet 12.5 mg).

Description:

Tablets with a dosage of 12.5 mg: round, slightly biconcave, with a risk on one side, yellowish in color.

Tablets with a dosage of 25 mg: round, slightly biconcave, with a risk on one side, white or almost white.

Pharmacotherapeutic group:Alpha- and beta-blocker

ATX: & nbsp

C.07.A.G.02 Carvedilol

Pharmacodynamics:

Carvedilol - blocker of alpha1, beta1 and beta2-adrenoreceptors. Provides vasodilating, antianginal and antiarrhythmic action. Carvedilol is a racemic mixture R(+) and S(-) stereoisomers, each of which has the same α-adrenoblocking and antioxidant properties. Beta-adrenoblokiruyuschee action carvedilol is non-selective and is due to levorotatory S(-) stereoisomer.

Carvedilol does not have its own sympathomimetic activity, it has membrane-stabilizing properties.

The vasodilating effect is mainly due to the blockade of alpha 1-adrenergic receptors. Due to vasodilation, the overall peripheral vascular resistance (OPSS) decreases. The combination of vasodilation and blockade of beta-adrenoreceptors leads to the following effects: in patients with arterial hypertension, a decrease in blood pressure (BP) is not accompanied by an increase in OPSS, peripheral blood flow (in contrast to beta-blockers) does not decrease. The heart rate (heart rate) decreases slightly. In patients with ischemic heart disease, it 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.

In patients with impaired left ventricular function and / or heart failure, the hemodynamic parameters favorably affect and improve the ejection fraction and the size of the left ventricle. It has an antioxidant effect, eliminating free oxygen radicals.

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:Carvedilol is rapidly absorbed from the gastrointestinal tract when ingested. Has high lipophilicity. The maximum concentration in the blood is achieved through 1 hour.

The half-life is 6-10 hours. It binds to blood plasma proteins by 95-99%. Bioavailability of the preparation 24-28%. Absolute bioavailability of carvedilol is about 25%: 30% for Rand 15% for S-form. Whenem food does not affect bioavailability.

Carvedilol is metabolized predominantly in the liver by oxidation and conjugation to form a number of metabolites. Metabolized by "primary passage" through the liver. The metabolism of carvedilol by oxidation is stereoselective. R(+) The isomer is metabolized mainly by isoenzymes CYP2D6 and CYP1A2, a S(-) isomer mainly by isoenzyme CYP2D9 and, to a lesser extent, by means of an isoenzyme CYP2D6. Other isoenzymes of cytochrome P450 involved in the metabolism of carvedilol include isoenzymes 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.

The half-life is 6-10 hours. Metabolites have a pronounced antioxidant and adrenoblocking effect. Displayed carvedilol, mainly with bile through the intestine and in part with kidneys in the form of metabolites.

When the renal function is impaired, the pharmacokinetic parameters of carvedilol do not change significantly.

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 in the "primary passage" through the liver. With serious violations of liver function carvedilol is contraindicated.

Carvedilol penetrates the placental barrier, excreted in breast milk.

Carvedilol is almost never removed from the blood plasma during hemodialysis.

Indications:

- Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs, for example, blockers of "slow" calcium channels or diuretics);

- chronic heart failure (as part of combination therapy);

- ischemic heart disease (including in patients with unstable angina and painless myocardial ischemia).

Contraindications:

Hypersensitivity to carvedilol or other components of the drug, acute and chronic heart failure in the stage of decompensation, requiring intravenous inotropic drugs, clinically expressed hepatic impairment, atrioventricular blockade II-III (except for patients with an artificial pacemaker), severe bradycardia (less than 50 beats / min), sinus node weakness syndrome (including sinoauric blockade), severe arterial hypotension (systolic blood pressure less than 85 mmHg), cardiogenic shock, severe forms of bronchial asthma or bronchospasm (in the anamnesis), pheochromocytoma (without simultaneous use of alpha-adrenoblockers), terminal stage of occlusive diseases of peripheral vessels, age up to 18 years (efficacy and safety not confined are inserted). Lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

Carefully:

Angina pectoris, thyrotoxicosis,occlusive diseases of peripheral vessels, suspected pheochromocytoma, chronic obstructive pulmonary disease, psoriasis, renal failure, atrioventricular blockade of the 1st degree, extensive surgical interventions and general anesthesia, diabetes mellitus, hypoglycemia, depression, myasthenia gravis.

Pregnancy and lactation:

Data on the use of the drug Carvedilol during pregnancy are limited. Beta-adrenoblockers reduce placental blood flow, have adverse effects on the development of the embryo, can cause arterial hypotension, bradycardia and hypoglycemia in the fetus. Sufficient experience in the use of the drug Carvedilol in pregnant women there. A drug Carvedilol is contraindicated for use during pregnancy, except in cases of extreme necessity, if the potential benefit to the mother justifies the risk to the fetus.

In animals carvedilol and its metabolites penetrate into breast milk. Data on the isolation of carvedilol in human milk are not available, so if taking the drug is necessary during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, regardless of food intake.

Arterial hypertension

The recommended initial dose is 6.25 - 12.5 mg (1/2 tablets of 12.5 mg - 1 tablet) once a day for the first two days of treatment, then 25 mg once a day. If the antihypertensive effect is inadequate after 2 weeks of therapy, the dose can be increased 2-fold. The maximum recommended daily dose of the drug is 50 mg once a day (possibly divided into 2 receptions).

Cardiac ischemia

The recommended initial dose is 12.5 mg twice a day for the first two days of treatment. Then 25 mg twice a 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 per day, divided into 2 receptions.

Chronic heart failure

The dose is selected individually, under the careful supervision of the doctor. In patients receiving cardiac glycosides, diuretics and ACE inhibitors, their doses should be adjusted before treatment with the drug Carvedilol.

The recommended initial dose is 3.125 mg (the drug may be used carvedilol in another dosage form: tablets of 6.25 mg with a risk) 2 times a day for 2 weeks. With good tolerance, the dose is increased at intervals of at least 2 weeks to 6.25 mg (1/2 tablets of 12.5 mg) twice a day, then to 12.5 mg twice a day, then to 25 mg 2 times per day. The recommended maximum dose is 25 mg twice a 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 to moderate chronic heart failure and a body weight of more than 85 kg, 50 mg twice a day.

Before every increase in the dose, a doctor's examination is necessary to detect a possible increase in the 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 it is sometimes necessary to reduce the dose of the drug Carvedilol or temporarily 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 Carvedilol. In this situation, the dose of the drug Carvedilol Do not increase until symptoms of worsening chronic heart failure or arterial hypotension improve.

If drug therapy is interrupted for more than 1 week, then its use is resumed at a lower dose, and then increased in accordance with the recommendations given above. If the drug treatment Carvedilol interrupt for more than 2 weeks, then his appointment should be resumed at a dose of 3,125 mg (possibly the drug carvedilol in another dosage form: tablets of 6.25 mg with a risk) 2 times a day, then select the dose in accordance with the above recommendations,

In patients with moderate to severe degree of renal failure, dose adjustment of Carvedilol is not required.

Carvedilol is contraindicated in patients with clinical manifestations of liver dysfunction.

Side effects:

The frequency of undesired reactions is estimated as follows: "very often" (> 1/10), "often" (> 1/100, <1/10), "infrequently" (> 1/1000, <1/100), " rarely "(> 1/10 000, <1/1000)," very rarely "(<1/10 000).

Undesirable reactions in patients with chronic heart failure

From the central nervous system: very often - dizziness, headache (usually not strong and arising at the beginning of treatment), asthenia, fatigue, depression.

From the side of the cardiovascular system: often - bradycardia, orthostatic 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 - syncope (including presyncopal), atrioventricular block and heart failure during the period of dose increase.

From the side of the digestive tract: often - nausea, diarrhea, vomiting.

On the part of the hematopoiesis 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 - kidney failure and impaired renal function patients with diffuse vasculitis and / or renal dysfunction.

Undesirable reactions in patients with arterial hypertension and coronary heart disease

From the central nervous system: often - dizziness, headache (usually not strong and arising at the beginning of treatment), weakness, increased fatigue; infrequently - mood lability, sleep disturbances, paresthesia.

From the side of the cardiovascular system: often - bradycardia, orthostatic hypotension, syncopal conditions (infrequently), especially at the beginning of therapy; infrequent peripheral circulatory disorders (cold extremities, exacerbation of the intermittent claudication syndrome and Raynaud's syndrome), atrioventricular block, angina pectoris, development or progression of symptoms of heart failure and peripheral edema.

From the respiratory system: often - bronchospasm and shortness of breath in predisposed patients; rarely - nasal congestion.

From the side of the digestive tract: often - nausea, diarrhea, abdominal pain; infrequently - constipation, vomiting.

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

On the part of the hematopoiesis system: very rarely - thrombocyte singing, leukopenia.

From the side of metabolism: weight gain, violation of carbohydrate metabolism.

From the skin: infrequently - skin reactions (skin rash, dermatitis, urticaria and skin itching).

Other: often - pain in the limbs, reducing tear and eye irritation; infrequent - decreased potency, visual impairment; rarely - dryness of the oral mucosa and urination disorders; very rarely - exacerbation of psoriasis, sneezing, flu-like syndrome; individual cases of allergic reactions.

Also, the presence of beta-adrenoblocking properties in the drug does not exclude the possibility of manifestation of latent diabetes mellitus, decompensation of existing diabetes mellitus or suppression of the contrinsular system, alopecia, rare incontinence in women reversible after drug withdrawal.

Overdose:

Symptoms: marked decrease in blood pressure, bradycardia, heart failure, cardiogenic shock, cardiac arrest; possible respiratory disorders, bronchospasm, vomiting, confusion and generalized convulsions.

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

You can use the following activities:

a) put the patient on his back (with raised legs);

b) with pronounced bradycardia - atropine 0.5-2 mg intravenously;

c) for the maintenance of cardiovascular activity - glucagon 1-10 mg intravenously struino, then 2-5 mg per hour in the form of a long infusion;

d) sympathomimetics (dobutamine, epinephrine (epinephrine)) in different doses, depending on body weight and response to ongoing therapy.

If the clinical picture of an overdose is dominated by hypotension, norepinephrine (noradrenaline); he is appointed in conditions of continuous monitoring of blood circulation parameters.

In the case of bradycardia resistant to treatment, the use of an artificial pacemaker is indicated.

When bronhospazme enter beta-adrenomimetiki in the form of an aerosol (if ineffectiveness - intravenously) or aminophylline intravenously.

When convulsions are intravenously slowly injected diazepam.

Since a severe overdose with symptoms of shock may prolong the half-life of carvedilol and remove the drug from the depot, it is necessary to continue supporting therapy for a long time.

Interaction:

Carvedilol can potentiate the effect of other concurrently taken antihypertensive drugs or drugs that have an antihypertensive effect (nitrates).

With the combined use of carvedilol and diltiazem, amiodarone and other antiarrhythmics impairment of conduction of cardiac impulses and violations of hemodynamic parameters may develop.

With the simultaneous administration of carvedilol and digoxin the concentration of the latter increases and the time of atrioventricular conduction may increase.

Carvedilol may potentiate the action insulin and hypoglycemic agents for oral administration, while the symptoms of hypoglycemia (especially tachycardia) can be masked, so in patients with diabetes it is recommended that the blood glucose concentration be monitored regularly.

Inhibitors of microsomal oxidation (cimetidine) amplify, and inductors (phenobarbital, rifampicin) weaken the antihypertensive effect of carvedilol.

Drugs that reduce the content of catecholamines (reserpine, monoamine oxidase inhibitors), increase the risk of developing arterial hypotension and severe bradycardia.

With simultaneous application cyclosporine the concentration of the latter increases (a correction of the daily dose of cyclosporine is recommended).

Simultaneous appointment clonidine can potentiate antihypertensive and heart rhythm-reducing effects of carvedilol.

General anesthetics increase the negative inotropic and antihypertensive effect of carvedilol.

Simultaneous application non-steroidal anti-inflammatory drugs (NSAIDs) and beta-blockers can lead to increased blood pressure and lower blood pressure control.

Bronchodilators (beta-adrenergic agonists) - since noncardioselective beta-blockers interfere with the bronchodilating effect of bronchodilators, which are stimulators of beta-adrenergic receptors, regular monitoring of patients receiving these drugs is necessary.

Special instructions:

Therapy should be carried out for a long time and should not abruptly stop, especially in patients with coronary heart disease, since this can lead to a worsening of the course of the underlying disease.If necessary, the dose reduction should be gradual, within 1-2 weeks.

At the beginning of therapy with Carvedilol or with an increase in the dose of the drug in patients, especially the elderly, there may be an excessive decrease in blood pressure, especially during the transition from the prone position to the standing position. A dose adjustment is necessary. In patients with chronic heart failure, the choice of a dose may increase the symptoms of chronic heart failure, the appearance of edema. In this case, do not increase the dose of carvedilol, recommended the appointment of large doses of diuretics until the patient's condition is stabilized.

Sometimes it is necessary to reduce the dose of the drug Carvedilol or, in rare cases, temporarily discontinue the drug. Such episodes do not prevent further correct selection of the dose of the drug Carvedilol.

Carvedilol should be used with caution at the same time as cardiac glycosides (risk of slowing atrioventricular conduction).

It is recommended to monitor the electrocardiograms and blood pressure continuously while prescribing Carvedilol and blockers"slow" calcium channels, derivatives of phenylalkylamine (verapamil) and benzodiazepine (diltiazem), and also with antiarrhythmic agents.

Non-selective beta-blockers can provoke the appearance of pain in patients with Prinzmetal angina, use the drug with caution.

Patients with COPD (including bronchospastic syndrome) who do not receive oral or inhaled antiasthmatics, Carvedilol appoint only if the possible benefits of its use exceed the potential risk.

If there is an initial predisposition to bronchospastic syndrome when taking the drug Carvedilol As a result of increasing airway resistance, dyspnea may develop. At the beginning of therapy and with an increase in the dose of the drug Carvedilol such patients should be observed, reducing the dose of the drug with the appearance of initial signs of bronchospasm.

It is recommended to monitor kidney function in patients with chronic renal failure, arterial hypotension and chronic heart failure.In the case of a surgical procedure using general anesthesia, it is necessary to warn the anesthesia doctor about the previous therapy with the drug Carvedilol.

With caution, the drug is prescribed to patients with diabetes, because it can mask or relieve the symptoms of hypoglycemia (especially tachycardia). In patients with CHF and diabetes mellitus, the drug Carvedilol can be accompanied by violations of glycemic control.

Caution is necessary when using the drug Carvedilol in patients with peripheral vascular disease (including Raynaud's syndrome), since beta-blockers may increase the symptoms of arterial insufficiency.

Like other beta-blockers, Carvedilol can reduce the severity of symptoms of thyrotoxicosis.

Care should be taken when prescribing the drug Carvedilol patients with anamnestic indications of severe hypersensitivity reactions or undergoing desensitization, since beta-blockers can increase sensitivity to allergens and the severity of anaphylactic reactions. During the treatment period, avoid drinking alcohol.

Patients with pheochromocytoma prior to therapy should be assigned alpha-blockers.

Patients with anamnestic indications for the development or exacerbation of psoriasis during the use of beta-blockers, Carvedilol It can be appointed only after a careful analysis of the possible benefits and risks.

Patients wearing contact lenses should note that the drug may cause a decrease in tearing.

Effect on the ability to drive transp. cf. and fur:

Care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, due to the possible development of dizziness.

Form release / dosage:

Tablets 12.5 mg, 25 mg.

Packaging:

10 tablets per blister.

For 3 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001959

Date of registration:26.12.2011

The owner of the registration certificate:REPLEK FARM Skopje, OOOREPLEK FARM Skopje, OOO Macedonia

Manufacturer: & nbsp

REPLEKPHARM, AD Macedonia

Representation: & nbspREPLECK FARM LTD SCOPJEREPLECK FARM LTD SCOPJERussia

Information update date: & nbsp15.07.2013

Illustrated instructions

Instructions

Carvedilol (Carvedilol)