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

Pharmacodynamics:Carvedilol blocks alpha₁-, beta₁- and beta₂-adrenoreceptors, has antiarrhythmic, antianginal and vasodilating effect. As a result of the blockade of alpha₁adrenoreceptors, the drug causes an expansion of peripheral vessels, reducing the overall peripheral resistance of the vessels. Blocking beta₁-adrenoceptors, moderately reduces atrioventricular conduction, the frequency and strength of heartbeats, without causing a sharp bradycardia. When blocking beta₂-adrenoreceptors may increase the tone of the bronchi, some vessels, as well as tonus and peristalsis of the intestine. In patients with heart failure, the drug increases the fraction of the ejection of the left ventricle. The effect on the heart rate and blood pressure is most pronounced 1-2 hours after taking the drug. Carvedilol does not have its own sympathomimetic effect.

Pharmacokinetics:Bioavailability is 25-35%. V_d - 1,5 ± 0,3 l / kg (increases with cirrhosis of the liver). The connection with plasma proteins is 98%.Biotransformation in the liver (CYP2D6, 2C9, 3A4) - 100%. A pronounced effect of the first passage through the liver with the formation of active metabolites is characteristic. The half-life is 7-10 hours. Clearance - 8,7 ± 1,7 ml / min (decreases with cirrhosis of the liver). Elimination with feces and kidneys (less than 2%). It is not removed during hemodialysis.

Indications:Arterial hypertension, angina pectoris (stable and secondary prophylaxis of ischemic heart disease), chronic heart failure (against a background of selected therapy with digitalis preparations, diuretics and ACE inhibitors).

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

IX.I10-I15.I15 Secondary Hypertension

IX.I20-I25.I20 Angina pectoris [angina pectoris]

IX.I30-I52.I50.0 Congestive heart failure

Contraindications:Hypersensitivity, atrioventricular blockade of II-III degrees, hepatic insufficiency, severe bradycardia, sinus node weakness syndrome, cardiogenic shock, bronchial asthma, arterial hypotension (systolic pressure less than 85 mmHg), age under 18 years (safety and efficacy not studied).

Carefully:Low fraction of the left ventricle according to echocardiographybronchospastic syndrome, chronic bronchitis, emphysema, prinzmetal angina, diabetes mellitus, hypoglycemia, thyrotoxicosis, peripheral vascular occlusive diseases, pheochromocytoma, depression, myasthenia gravis, psoriasis, renal failure, decompensated chronic heart failure (NYHA functional class IV), pregnancy, lactation.

Pregnancy and lactation:Controlled studies of the use of carvedilol in pregnant women have not been carried out, and therefore the prescription of this category of patients is possible only in cases when the benefit to the mother exceeds the potential risk for the fetus. Not recommended breastfeeding during treatment with carvedilol.

Dosing and Administration:The drug is taken inwards.

With arterial hypertension - in a dose of 12.5 mg once a day for the first 2 days, then 25 mg once a day with a possible gradual increase in the dose with an interval of not less than 2 weeks.

For angina pectoris, 12.5 mg once a day for the first 2 days, then 25 mg twice a day (the maximum dose is 100 mg divided into 2 divided doses).

In chronic heart failure - on start with a dose of 3.125 mg 2 times a day for 2 weeks, then 6.25 mg 2 times a day, then to 12.5-25 mg 2 times a day (with body weight less than 85 kg the maximum dose is 25 mg 2 times a day, with a mass of more than 85 kg - 50 mg 2 times a day). If treatment is interrupted for more than 2 weeks, the reception is resumed with a dose of 3.125 mg 2 times a day; in the future, the dose is increased.

Side effects:From the cardiovascular system: orthostatic hypotension, occlusive disorders of peripheral circulation, progression of heart failure, atrioventricular block, bradycardia, syncopal conditions (including presyncopal ones), stenocardia, "intermittent" lameness.

Allergic reactions: skin allergic reactions (exanthema, hives, itching, rashes), exacerbation of psoriatic eruptions.

From the digestive system: abdominal pain, dry mouth, nausea, diarrhea or constipation, vomiting, increased activity of "liver" transaminases.

On the part of the respiratory system: dyspnea (in predisposed patients), bronchospasm, sneezing, nasal congestion.

From the hematopoiesis: thrombocytopenia, and leukopenia.

From the endocrine system: hypo- or hyperglycemia, hypercholesterolemia.

From the side of the central nervous system: headache, dizziness, depression, parasthesia.

From the genitourinary system: severe violations of kidney function, edema, rarely - decreased potency.

Other: pain in the extremities, reduced tearing (important for patients wearing contact lenses), muscle weakness (often at the beginning of treatment), weight gain.

Overdose:Symptoms: bradycardia, lowering of arterial pressure, dizziness (fainting), arrhythmias, difficulty breathing, cyanosis of fingers or palms, convulsions.

Treatment: with severe bradycardia - intravenous atropine (1-2 mg dose), epinephrine, at low efficiency - pacemaker (temporarily); with ventricular extrasystole - lidocaine (preparations IA class do not apply); with arterial hypotension and in the absence of signs of pulmonary edema - intravenous injection of plasma-substituting solutions, with inefficiency - epinephrine, dopamine, dobutamine; glucagon (has a pronounced positive inotropic and not so significant chronotropican action independent of beta-adrenergic receptors); bronchospasm - inhalation or parenteral administration of beta₂adrenomimetics and / or theophylline.

Interaction:Drugs with hypotensive effect - deepening of hypotension.

Preparations with beta-adrenoblocking properties - increased hypoglycemic action of insulin and oral hypoglycemic drugs. Regular monitoring of glucose levels is required when combined.

Cardiac glycosides, diuretics and / or ACE inhibitors - AV delay is possible.

Increases the content of digoxin in the blood serum.

General anesthetics increase the negative inotropic and hypotensive effects of carvedilol.

Phenobarbital, rifampicin and other agents that inhibit microsomal enzymes, accelerate metabolism and reduce plasma concentration.

Caution should be used with antiarrhythmic drugs and calcium channel blockers, especially with diltiazem and verapamil (incompatible with intravenous administration of calcium antagonists).

Special instructions:It is necessary to constantly monitor the parameters of peripheral blood,glucose concentrations (in individuals with diabetes mellitus), heart, kidney, functional liver function, blood pressure, ECG, and heart rate (with intravenous administration).

Treatment with the drug should not abruptly cease, especially in patients with angina. Dose reduction should be gradual within 1-2 weeks.

It is not recommended to drive at the beginning of therapy and with an increase in the dose of the drug. It is necessary to refrain from other activities associated with the need for high concentration of attention and rapid psychomotor reactions.

Instructions

Carvedilol (Carvedilolum)