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

Excipients: iron oxide red 25.0 μg, lactose monohydrate 65.1 mg, cellulose microcrystalline 21.25 mg, crospovidone 5.0 mg, povidone K30 4.0 mg, silicon dioxide colloid 0.5 mg, magnesium stearate 1.0 mg.

Tablets of 6.25 mg:

active substance: carvedilol 6.25 mg;

Excipients: iron oxide yellow 0.20 mg, lactose monohydrate 61.8 mg, cellulose microcrystalline 21.25 mg, crospovidone 5.0 mg, povidone K30 4.0 mg, silicon dioxide colloid 0.5 mg, magnesium stearate 1.0 mg.

Tablets of 12.5 mg:

active substance: carvedilol 12.5 mg;

Excipients: iron oxide red 95.0 μg, iron oxide yellow 155 μg, lactose monohydrate 55.5 mg, cellulose microcrystalline 21.25 mg, crospovidone 5.0 mg, povidone K30 4.0 mg, silicon dioxide colloid 0.5 mg, magnesium stearate 1.0 mg.

Tablets of 25 mg:

active substance: carvedilol 25 mg;

Excipients: lactose monohydrate 111.5 mg, cellulose microcrystalline 42.5 mg, crospovidone 10.0 mg, povidone K30 8.0 mg, silicon dioxide colloid 1.0 mg, magnesium stearate 2.0 mg.

50 mg tablets:

active substance: carvedilol 50 mg;

Excipients: lactose monohydrate 223.0 mg, microcrystalline cellulose 85.0 mg, crospovidone 20.0 mg, povidone K30 16.0 mg, silicon dioxide colloid 2.0 mg, magnesium stearate 4.0 mg.

Description:

Tablets of 3.125 mg:

Tablets are light pink in color, round, biconvex, with risk from both sides and on the sides and applying "C1" on one side.

Tablets of 6.25 mg:

Tablets are yellow, round, biconvex, with risk from both sides and on the sides and applying "C2" on one side.

Tablets of 12.5 mg:

The tablets are pinkish-beige, round, biconvex, with a risk on both sides and on the sides and applying "SZ" on one side.

Tablets of 25 mg:

Tablets are white or almost white, round, biconvex, with a risk on both sides and on the sides and applying "C4" on one side.

50 mg tablets:

Tablets are white or almost white, round, biconvex, with a risk on both sides and on the sides and applying "C5" on one side.

Pharmacotherapeutic group:Alpha- and beta-blocker

ATX: & nbsp

C.07.A.G.02 Carvedilol

Pharmacodynamics:

Has combined non-selective beta-blocking, alpha1-blocking and antioxidant effect. The vasodilating effect is mainly related to the blockade of alpha-1 receptors.Due to vasodilation reduces the overall peripheral vascular resistance. Does not have an internal sympathomimetic activity and, like propranolol, has a membrane-stabilizing effect.

A powerful antioxidant, eliminates free oxygen radicals. The combination of vasodilators and beta-blockers has the following effect:

The combination of vasodilating action and beta-adrenoblocking properties of carvedilol leads to the fact that in patients with arterial hypertension, a decrease in blood pressure is not accompanied by a simultaneous increase in the total peripheral resistance, which is noted when taking beta-blockers. Slightly decreases the heart rate, kidney blood flow and kidney function persist. As the peripheral blood flow is preserved, cold extremities are very rare, unlike patients who are treated with beta-blockers.

The antihypertensive effect develops rapidly - 2-3 hours after a single dose and lasts for 24 hours. With prolonged treatment, the maximum effect is observed after 3-4 weeks.

In patients with ischemic heart disease carvedilol has anti-ischemic and antianginal action. Reduces pre- and afterload on the heart. It has no pronounced effect on the lipid metabolism and the content of potassium, sodium and magnesium ions in the plasma.

In patients with impaired left ventricular function and / or circulatory failure carvedilol has a beneficial effect on hemodynamic parameters: increases the function of ejection of the left ventricle and reduces its size.

Carvedilol has a beneficial effect on the hemodynamics of the heart and the fraction of the left ventricular ejection both in dilated cardiomyopathy and in the ischemic form of heart failure. With heart failure, the end-systolic and end-diastolic volume decreases, as well as peripheral and pulmonary vascular resistance. The ejection fraction and cardiac index do not change with normal heart function.

In the case of a violation of the function of the left ventricle, alpha 1-adrenoblocking action of carvedilol leads to an expansion of arterial and, to a lesser extent, venous vessels.It was found that with an additional appointment against the background of cardiac glycosides, angiotensin-converting enzyme inhibitors and diuretics carvedilol reduces the death rate, slows the progression of the disease and improves the overall condition of the patient regardless of the severity of the disease. The effect of carvedilol is more pronounced in patients with tachycardia (heart rate more than 82 beats / min) and low ejection fraction (less than 23%).

During treatment with carvedilol, the ratio of HDL / LDL cholesterol does not change.

Pharmacokinetics:

Absorption of carvedilol is fast and high. The maximum concentration in the blood plasma is reached 1 hour after taking the drug. Concentration in plasma is proportional to the dose taken. The bioavailability is about 30%. Simultaneous food intake slows the absorption of the drug, but does not affect the amount of bioavailability.

Binding to plasma proteins is about 98-99%. The volume of distribution is about 2 liters / kg and increases (by 80%) in case of liver dysfunction (due to a decrease in the effect of the first passage through the liver).

Metabolized mainly in the liver due to intensive connection with glucuronic acid. By demethylation and hydroxylation of the phenyl ring, three active metabolites are formed with pronounced antioxidant and adrenoblocking properties.

The half-life of carvedilol is 6-10 hours, the plasma clearance is about 590 ml / min. It is excreted mainly with bile and a small part - through the kidneys.

It penetrates through the placental barrier and is excreted in breast milk.

Carvedilol is practically not excreted in hemodialysis.

With cirrhosis of the liver, the bioavailability of carvedilol is 4 times higher, and the maximum concentration in the blood plasma is 5 times higher than normal.

It should be borne in mind that in elderly patients carvedilol concentration in the blood plasma is 50% higher than at a young age.

Indications:

Arterial hypertension in the form of monotherapy or with simultaneous use with other antihypertensive drugs, for example blockers of "slow" calcium channels or diuretics).

Ischemic heart disease (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 in combination with angiotensin-converting enzyme (ACE) inhibitors and diuretics, with or without cardiac glycosides, in the absence of contraindications).

Contraindications:

Hypersensitivity to the drug and other components of the drug.

Acute and chronic heart failure in the stage of decompensation, requiring intravenous inotropic drugs.

Syndrome of weakness of the sinus node, including sinoauric block.

Atrioventricular (AV) blockade II-III st, except for patients with an artificial pacemaker.

Pronounced bradycardia (heart rate less than 50 beats per minute).

Severe arterial hypotension (systolic blood pressure less than 85 mm Hg).

Cardiogenic shock, collapse.

Bronchospasm and bronchial asthma (in the anamnesis).

Severe liver dysfunction.

Metabolic acidosis.

An untreated pheochromocytoma (without simultaneous use of alpha-blockers).

Tsevere violations of peripheral arterial blood circulation.

Xobstructive pulmonary disease with bronchial obstruction.

FROMConcurrent intravenous therapy with verapamil and diltiazem.

Pregnancy.

Lactation period.

Age to 18 years (effectiveness and safety not established).

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Carefully:

With caution should be used in patients with diabetes mellitus, hypoglycemia, thyrotoxicosis, pheochromocytoma (with simultaneous use of alpha-blockers, see "Special instructions"), peripheral vascular occlusive diseases, grade I atrioventricular block, chronic heart failure with reduced myocardial contractility, psoriasis, impaired renal function, depression, myasthenia gravis, planning extensive surgical intervention with general anesthesia, weighed down with allergic anamnesis (see "Special instructions"), in the treatment of alpha-adrenergic blockers and alpha-adrenomimetics, with simultaneous use with cardiac glycosides, diuretics and / or monoamine oxidase (MAO) inhibitors, slow calcium channel blockersverapamil, diltiazem).

Pregnancy and lactation:

Controlled clinical trials in pregnant women taking carvedilol, was not carried out. Beta-adrenoblockers reduce placental blood flow, which can lead to intrauterine fetal death or premature birth. In addition, the fetus and newborns may develop hypoglycemia, bradycardia, and the risk of complications from the heart and lungs increases. A drug Carvedilol Sandoz® is contraindicated in pregnancy, except when the benefit to the mother exceeds the potential risk to the fetus. Studies in animals have not revealed teratogenicity.

It is not known whether the Carvedilol Sandoz® in breast milk, so nursing mothers are not recommended to take the drug Carvedilol Sandoz® during lactation or for the period of treatment should be discontinued breast-feeding.

Dosing and Administration:

Carvedilol Sandoz® is taken orally with a sufficient amount of liquid.

Carvedilol is excreted mainly through the gastrointestinal tract, so if there is a violation of the kidney function, cumulation of the drug is not observed.

Arterial hypertension

The initial dose is 12.5 mg / day once (morning after breakfast) for the first 2 days, then 25 mg once a day. If necessary, after 14 days, the dose may be increased. The maximum dose is 50 mg per day once or in 2 divided doses (morning and evening).

In elderly patients, in a number of cases, a dose of 12.5 mg can be effective.

Angina pectoris

The initial dose is 12.5 mg twice a day for the first 2 days, then 25 mg twice (morning and evening) per day. If necessary, after 7-14 days, the daily dose can be increased to a maximum of 100 mg / day divided into 2 doses.

In elderly people, the maximum daily dose is 50 mg divided into 2 divided doses.

Chronic heart failure

The dose is selected individually, conducting careful monitoring. It is necessary to observe the patient's condition within the first 2-3 hours after the first intake or after the first increased dose. The dose and administration of other medicines, such as digoxin, diuretics and ACE inhibitors should be fixed before the drug is prescribed Carvedilol Sandoz®.

Carvedilol Sandoz® should be taken with meals (to reduce the risk of orthostatic hypotension).

The recommended starting dose is 3,125 mg twice daily for 14 days.With good tolerability of the drug and the need to increase dosage, the drug is prescribed in a dose of 6.25 mg twice a day, then up to 25 mg twice a day. Patients are prescribed the maximum tolerated dose. The maximum recommended dose is 25 mg twice a day for patients weighing up to 85 kg and 50 mg twice a day for patients with a body weight of more than 85 kg.

At the beginning of treatment and before each dose increase, the patient's condition should be monitored, since a deterioration in the course of heart failure is possible.

A fluid retention may develop, and in connection with the presence of a vasodilator effect - arterial hypotension and lethargy. When fluid is delayed, the dose of diuretics should be increased, in addition, a temporary reduction in the dose of the drug may be required Carvedilol Sandoz®. Sometimes a temporary suspension of treatment is required.

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, < 1/10000, rarely (> 1/10000, <1/1000) and very rarely (<1/10000), the frequency is unknown - it was not possible to establish the frequency of occurrence according to available data.

Infectious and parasitic diseases

often: bronchitis, pneumonia, upper respiratory tract infections, urinary tract infections.

On the part of the blood and lymphatic system

often: anemia;

rarely: thrombocytopenia;

Very rarely: leukopenia.

From the immune system

very rarely: allergic reactions.

From the side of metabolism and nutrition

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

From the nervous system

very often: dizziness, headache (usually mild and occurring more often at the beginning of treatment);

often: depression, mood lability, syncopal conditions;

infrequently: loss of consciousness, sleep disturbances, paresthesia.

From the side of the organ of vision

often: impaired vision, reduced tearing, eye irritation.

From the side of the cardiovascular system

very often: development or (AD);

often: bradycardia, orthostatic hypotension, edema (including generalized, peripheral, body-dependent, perineal edema, edema of the lower limbs, hypervolemia, fluid retention), peripheral circulation disorders (cold extremities, exacerbation of intermittent claudication syndrome, Raynaud's syndrome );

infrequently: atrioventricular block, angina, chest pain.

On the part of the respiratory system, organs of the chest and mediastinum

often: dyspnea, pulmonary edema, bronchospasm (in predisposed patients);

rarely: nasal congestion.

From the gastrointestinal tract

often: dyspeptic disorders (including nausea, diarrhea, vomiting, abdominal pain);

infrequently: constipation; rarely: dryness of the oral mucosa;

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

From the side of the kidneys and urinary tract

often: violation of urination, renal failure (especially in patients with diffuse occlusive vascular disease);

very rarely: urinary incontinence women.

From the genitals and breast

infrequently: erectile dysfunction.

FROMabout the side of the musculoskeletal and connective tissue

often: pain in the limbs.

From the skin and subcutaneous tissues

infrequently: reactions (urticaria, dermatitis, itching, skin rash, appearance of skin lesions like psoriasis and red flat lichen), alopecia;

very rarely: toxic epidermal necrolysis (Lyell's syndrome), polymorphic erythema, incl. malignant exudative erythema (Stevens-Johnson syndrome).

General disorders and disorders at the site of administration

very often: asthenia (including increased fatigue), general weakness;

frequency is unknown: sneezing, flu-like syndrome.

Overdose:

Symptoms: vomiting, impaired consciousness, marked decrease in blood pressure (systolic pressure <80 mmHg), severe bradycardia (less than 50 beats per minute), impaired respiratory function (bronchospasm, etc.), generalized convulsions, development or worsening of cardiac symptoms insufficiency, cardiogenic shock, cardiac arrest.

Overdosing requires intense treatment. The patient should be in a position with raised legs (Trendelenburg position).

Antidote beta-adrenergic blocking action is orciprenaline or isoprenaline 0.5-1 mg intravenously and / or glucagon in a dose of 1-5 mg (maximum dose of 10 mg). Severe hypotension is treated with parenteral fluid administration and repeated administration of epinephrine at a dose of 5-10 mg (or its intravenous infusion at a rate of 5 μg / min).

With severe bradycardia, intravenously atropine in a dose of 0.5-2 mg. If the peripheral vasodilator action predominates (warm limbs, in addition to significant arterial hypotension), norepinephrine should be given in repeated doses of 5-10 μg or as an infusion of 5 μg / min.

For relief of bronchospasm, beta-blockers (in the form of an aerosol or intravenously) or aminophylline intravenously. If seizures develop, slow diazepam or clonazepam is recommended.

In case of severe intoxication, when symptoms of shock predominate, symptomatic therapy should continue until the patient's condition stabilizes, taking into account the half-life of carvedilol 6-10 hours.

In the conditions of resuscitation, to monitor the indicators of vital organs.

Interaction:

Pharmacokinetic interaction

Carvedilol is a substrate, as well as an inhibitor of the P-glycoprotein, so the bioavailability of drugs that bind to the P-glycoprotein can be increased by simultaneous application with carvedilol. In addition, the bioavailability of carvedilol can be altered by simultaneous use with inducers or P-glycoprotein inhibitors.Inhibitors and inducers of the isoenzyme CYP2D6 and CYP2C9 can selectively alter the systemic and / or systemic metabolism of carvedilol, which leads to an increase or decrease in the plasma concentration of R (+) and S (-) stereoisomers of carvedilol.

Digoxin

The concentration of digoxin is increased by approximately 15% with simultaneous application with carvedilol. Since both drugs slow the AV conduction, it is recommended to monitor the concentration of digoxin in the blood plasma at the start / stop treatment and when correcting the dose of carvedilol.

Rifampicin

Rifampicin reduces the plasma concentration of carvedilol by approximately 70%, probably due to the induction of P-glycoprotein, which leads to a decrease in carvedilol absorption in the intestine.

Cyclosporin

In some studies, when cyclosporine was administered orally, its plasma concentration increased after treatment with carvedilol. It is recommended to carefully monitor the plasma concentration of cyclosporine after the initiation of carvedilol therapy, since its fluctuations are possible within a wide range. If necessary, the question of correcting the dose of cyclosporine should be addressed.

Amiodarone

In patients with heart failure amiodarone reduces the clearance of the S (-) stereoisomer of carvedilol, probably by inhibiting the isoenzyme CYP2C9. The mean plasma concentrations of the R (+) stereoisomer of carvedilol did not change. Therefore, there is a potential risk of increased AV blockade of beta-adrenergic receptors caused by an increase in the plasma concentration of the carvedilol stereoisomer S (-).

Fluoxetine

Simultaneous use of fluoxetine, a strong inhibitor of the isoenzyme CYP2D6, led to a stereoselective inhibition of carvedilol metabolism with an average 77% increase in the plasma concentration of the R (+) stereoisomer carvedilol. However, the clinical significance of this is unknown.

Pharmacodynamic interaction

Insulin or hypoglycemic agents for oral administration

Carvedilol increases the action of insulin and hypoglycemic agents for oral administration (simultaneously masking or relaxing the symptoms of hypoglycemia, reducing the decomposition of liver glycogen to glucose). Patients taking insulin or hypoglycemic agents inside should regularly monitor the concentration of glucose in the blood plasma.

Cataracts depleting resources of catecholamines (reserpine, monoamine oxidase inhibitors) can cause severe bradycardia and arterial hypotension.

When combined with antiarrhythmics (especially I class) and nondihydropyridine blockers of "slow" calcium channels (verapamil, diltiazem) increases the risk of AV conduction disorders, and increases the risk of severe arterial hypotension and heart failure (ECG and blood pressure monitoring recommended). Intravenous administration of these drugs against the background of taking carvedilol is contraindicated.

Clonidine

Simultaneous use of clonidine with beta-blockers can reduce blood pressure and heart rate. In the case of simultaneous administration of clonidine and beta-blocker, in order to avoid the development of a "withdrawal syndrome", the beta-blocker should first be canceled. Then, clonidine therapy can also be discontinued after a few days with a gradual dose reduction. Other antihypertensive drugs Microsomal oxidation inhibitors (cimetidine), diuretics (including thiazide), vasodilators and angiotensin-converting enzyme (ACE) inhibitors increase the antihypertensive effect of carvedilol and can lead to a sharp drop in blood pressure.

General anesthetics increase negative inotropic and hypotensive effects.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Simultaneous use of NSAIDs and beta-blockers can lead to an increase in blood pressure.

Beta-adrenomimetics (bronchodilators)

Cardioselective beta-blockers reduce the bronchodilation effect of beta-adrenomimetics, therefore careful monitoring of patients is recommended.

Special instructions:

Patients with chronic heart failure perhaps exacerbation of cardiac symptoms insufficiency or delay fluid in the body during titration dose of carvedilol. If there are such symptoms, it is recommended to increase the dose diuretics and suspend increasing the dose of carvedilol up to stabilization of the patient's condition. Sometimes it may be necessary reduce the dose of carvedilol or, in rare cases, its temporary cancel. Such episodes do not exclude the possibility of a subsequent successful titration dose carvedilol.

Reversible impaired renal function was observed with drug therapy Carvedilol Sandoz® patients with chronic heart failure and low blood pressure figures (systolic blood pressure <100 mm Hg. ), ischemic heart disease and diffuse vascular damage and / or renal insufficiency.

Left ventricular dysfunction after acute myocardial infarction

Prior to the use of the drug, the patient should be clinically stable and take ACE inhibitors for at least 48 hours, and the dose of an ACE inhibitor should be stable for at least the last 24 hours.

Carvedilol Sandoz should be used with caution in patients with chronic obstructive pulmonary disease (COPD) with a bronchospastic component that do not receive bronchodilators (inside or inhalation), and only if the potential benefit exceeds the potential risk.

Patients with predisposition to bronchospasm on the background of taking the drug Carvedilol Sandoz®, as a result of a possible increase in airway resistance, respiratory distress syndrome may occur. Patients should be carefully observed at the beginning of therapy and during titration of the dose of the drug. The dose of the drug should be reduced when there is bronchospasm during treatment.

Care should be taken when using the drug in patients with diabetes mellitus, since the early signs and symptoms of acute hypoglycemia can be masked or weakened. The use of the drug in patients with chronic heart failure with diabetes mellitus may be accompanied by a worsening control of blood glucose concentration.

A drug Carvedilol Sandoz® should be used with caution in patients with diseases of peripheral vessels (for example, Raynaud's syndrome), since beta-blockers can provoke or aggravate the symptoms of arterial insufficiency.

Carvedilol may mask symptoms thyrotoxicosis.

Carvedilol can cause bradycardia. If the patient's heart rate drops less than 55 beats per minute, the dose of carvedilol should be reduced or canceled.

Care should be taken when using the drug Carvedilol Sandoz® in patients with severe reactions increased sensitivity in the history and during the course of desensitizing therapy, since beta-adrenoblockers can increase sensitivity to allergens and weight the symptoms of anaphylactic reactions.

Patients with psoriasis in the history, connected with application of beta-adrenoblockers, it is necessary to accept a preparation Carvedilol Sandoz® only after considering the risk / benefit ratio.

It is necessary to carefully monitor the ECG and blood pressure in patients with concomitant therapy with nondihydropyridine blockers of "slow" calcium channels (for example, verapamil, diltiazem) or other antiarrhythmic drugs.

In patients with pheochromocytoma alpha-adrenoblocker should be assigned before adherence to beta-blocker therapy (initiation of carvedilol therapy). Although carvedilol is both an alpha and beta-adrenoblocker, there is no experience of its use in such patients. Therefore, care should be taken when using the drug in patients with suspected pheochromocytoma.

The use of nonselective beta-blockers can provoke chest pain in patients with Prinzmetal angina. No experience The clinical use of carvedilol in these patients, although the alpha-adrenoblocking property of the drug can prevent these symptoms.

Patients using contact lenses, should be warned that the drug reduces tearing.

During the treatment period, alcohol.

Abolition of the drug should be done gradually (within 1-2 weeks) in order to avoid the development of the "withdrawal" syndrome, especially in patients with coronary heart disease.

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

During the period of drug treatment Carvedilol Sandoz® should be careful (risk of dizziness, headache, visual impairment) when driving vehicles and performing other potentially hazardous activities, requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets of 3,125, 6,25, 12,5, 25 and 50 mg.

Packaging:

For 10 tablets in PVC / aluminum foil blisters.

By 1, 2, 3,4 or 5 blisters together with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep medicinal product out of the reach of children.

Shelf life:

3 years. .

Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006859/08

Date of registration:22.08.2008

The owner of the registration certificate:HEXAL AG HEXAL AG Germany

Manufacturer: & nbsp

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp12.11.2014

Illustrated instructions

Instructions

Carvedilol Sandoz® (Carvedilol Sandoz®)