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

3.125 mg: dactive substance: carvedilol 3.125 mg; Excipients: lactose monohydrate 71.125 mg, sucrose (category of Pharma) 5 mg, ferric oxide iron yellow 0.75 mg; povidone (K30) 1 mg, crospovidone XL-10,3 mg, magnesium stearate 1 mg, silicon dioxide colloid 1 mg;

6.25 mg: active substance: carvedilol 6.25 mg; Excipients: lactose monohydrate 68.75 mg, sucrose (category of Pharma) 5 mg, povidone (K30) 1 mg, crospovidone XL-10,3 mg, magnesium stearate 1 mg, silicon dioxide colloid 1 mg;

12.5 mg: active substance: carvedilol 12.5 mg; Excipients: lactose monohydrate 62.43 mg, sucrose (category Pharma) 5 mg, ferric oxide red oxide 0.07 mg, povidone (K30) 1 mg, crospovidone XL-10,3 mg, magnesium stearate 1 mg, silicon dioxide colloid 1 mg;

25 mg: active substance: carvedilol 25 mg; Excipients: lactose monohydrate 125 mg, sucrose (category Pharma) 10 mg, povidone (K30) 2 mg, crospovidone XL-10,6 mg, magnesium stearate 2 mg, silicon dioxide colloid 2 mg.

Description:

3.125 mg: Round, flat-cylindrical tablets of light yellow color with impregnations, with a facet and a risk on one side. Light marble is allowed.

6.25 mg: Round, flat-cylindrical tablets of white or almost white color, with a facet and a risk on one side. Light marble is allowed.

12.5 mg: Round, flat-cylindrical tablets from light pink to brownish-brown color, with impregnations, with a facet and a risk on one side. Light marble is allowed.

25 mg: Round, flat cylindrical tablets of white or almost white color, with a facet and a risk on one side. Light marble is allowed.

Pharmacotherapeutic group:Alpha- and beta-blocker

ATX: & nbsp

C.07.A.G.02 Carvedilol

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 alpha1-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 attacks. In patients with chronic heart failure (CHF) increases the fraction of the ejection of the left ventricle and reduces the severity of the symptoms of the disease. Similar effects were observed in patients with left ventricular 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 to 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).

Patients with hypertension 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 the blood plasma (Cmach) is reached after 1 hour. Absolute bioavailability of carvedilol is about 25%: 30% for Rand 15% for S-form.

Carvedilol has a high lipophilicity. Approximately 98-99% of it binds to blood plasma proteins. The volume of distribution is approximately 2 l / kg and increases in patients with cirrhosis due to a decrease in the effect of "first passage" through the liver.

Carvedilol is metabolized predominantly 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 isoenzyme CYP2D9 and, to a lesser extent, with the help of 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.

Half-life (T1 / 2) is about 6 hours, 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.

Carvedilol penetrates the placental barrier and into breast milk. Carvedilol almost not removed from the blood plasma during hemodialysis.

Indications:

- Arterial hypertension (in monotherapy or in combination with other antihypertensive

means, for example, blockers of "slow" calcium channels);

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

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

Contraindications:

Hypersensitivity to carvedilol or other components of the drug; chronic obstructive pulmonary disease (COPD); bronchial asthma or bronchospasm (in the anamnesis); chronic heart failure IV functional class by classification NYHA, acute and chronic heart failure (CHF) in the stage of decompensation, requiring intravenous injection of inotropes; angina of Prinzmetal; cardiogenic shock; pronounced bradycardia (less than 50 beats per minute at rest), sinus node weakness syndrome (including sinoauric block), atrioventricular (AV) blockade II-III degree (except for patients with an artificial pacemaker); terminal stage of occlusive diseases of peripheral vessels; clinically significant impairment of liver function, metabolic acidosis; patients receiving intravenous therapy with verapamil or diltiazem, 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.item); fructose intolerance and glucose / galactose absorption disorder or sugarase / isomaltase deficiency; the period of breastfeeding; age under 18 years (safety and efficacy not established), pheochromocytoma (without simultaneous use of alpha-blockers).

Carefully:

AV blockade of I degree, angina of princemetal, diabetes mellitus, hypoglycemia, thyrotoxicosis, peripheral vascular occlusive diseases, pheochromocytoma (with simultaneous use of alpha-blockers), depression, myasthenia gravis, psoriasis, extensive surgical interventions, general anesthesia, kidney failure, pregnancy.

Pregnancy and lactation:

Data on the use of the drug Rekardium during pregnancy are limited. 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.

The drug Rekardium should not be used during pregnancy, except in cases of extreme necessity, if the potential benefit for the mother justifies the risk to the fetus.

Because the carvedilol is excreted in breast milk, during treatment with the drug Rekardium 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, gradually increasing to achieve the optimal clinical effect. After the first reception of the drug Rekardium and after each dose increase, to exclude possible arterial hypotension, it is recommended to measure BP after 1 hour after taking the drug.

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

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

Arterial hypertension

The initial dose is 12.5 mg once a day in the morning during the first 2 days, then 25 mg once a day. In the future, if necessary, the dose can be increased at intervals of not less than 2 weeks, bringing to a maximum daily dose of 50 mg per day (divided into 2 doses).

Cardiac ischemia

The initial dose is 12.5 mg 2 times a day for the first 2 days, then 25 mg twice (morning and evening) daily.

Chronic heart failure

The dose is selected individually, careful monitoring of the doctor is necessary. It is necessary to observe the patient's condition within the first 2-3 hours after the first intake of the drug or after the first dose increase. The dose and use of other agents, such as digoxin, diuretics and angiotensin-converting enzyme (ACE) inhibitors, should be adjusted before starting therapy with Rekardium. Patients should take tablets during meals (to reduce the risk of orthostatic hypotension).

The recommended initial dose is 3,125 mg 2 times a day. If this dose is well tolerated, it can be gradually (with an interval of 2 weeks) increased to 6.25 mg 2 times a day, then to 12.5 mg 2 times a day, then to 25 mg 2 times a day. Patients take the maximum tolerated dose. The maximum recommended dose for patients weighing up to 85 kg is 25 mg twice a day and for patients with a body weight of more than 85 kg, 50 mg twice a day.

Patients with chronic heart failure with a view to preventing orthostatic hypotension are advised to take the drug while eating.

Before each dose increase, the physician should examine the patient to identify a possible increase in the symptoms of the course 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 sometimes a reduction in the dose of Rekardium or a temporary withdrawal is necessary. The dose of the drug Rekardium should not be increased until the symptoms of increased heart failure or arterial hypotension stabilize.

If Rekardium treatment 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 treatment with the drug Rekardium was suspended for more than 2 weeks, then the therapy should be resumed at a dose of 3.125 mg 2 times a day, then selecting the dose in accordance with the recommendations above.

Elderly patients

Correction of the dose is not required.

Patients with impaired renal function

Existing data on the pharmacokinetics in patients with varying degrees of renal dysfunction (including renal failure) suggest that with moderate and severe renal failure, dose adjustment of the drug Rekardium is not required.

Side effects:

The incidence of adverse events developing with carvedilol is classified according to the recommendations of the World Health Organization: very often - at least 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 incidence of some side effects, such as dizziness, marked decrease in blood pressure, bradycardia and visual disturbances, is dose-dependent. These effects are more common in patients with heart failure. The most common of the side effects of carvedilol is dizziness with orostatic hypotension or without it, which develops in about 6% of patients.

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

From the hemopoietic system and lymphatic system:rarely - thrombocytopenia; very rarely - leukopenia.

From the nervous system: very often - dizziness, headache (especially at the beginning of treatment); rarely - sleep disorders, mood changes / thinking, paresthesia, myasthenia gravis, loss of consciousness.

From the sense organs: often - reduced tear and eye irritation (pay attention when using contact lenses); very rarely - visual disturbances,eye irritation.

From the side of the cardiovascular system: very often - orthostatic hypotension; often bradycardia; rarely - deterioration of the course of heart failure (especially with increasing doses), coldness of the hands and feet, lowering blood pressure, fainting; rarely - conduction disorders, palpitations, exacerbation 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%), diarrhea, dryness of the oral mucosa; rarely - decreased appetite, vomiting, flatulence, constipation; very rarely - dryness of the oral mucosa, increased activity of "hepatic" 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 muscles, bones, spine.

From the urinary system: rarely - urination disorders; very rarely - severe renal dysfunction.

From the side of metabolism: often - weight gain, hypercholesterolemia, in patients with already existing diabetes - hyperglycemia or hypoglycemia; rarely - an increase in the concentration of triglycerides.

Other: often - general weakness; infrequently - reactions of hypersensitivity (skin itching, rashes, urticaria), decreased potency; very rarely - flushes of blood to the skin of the face, sneezing, flu-like syndrome.

Rare cases of urinary incontinence in women, reversible after drug withdrawal, are registered.

Overdose:

Symptoms: a marked decrease in blood pressure (systolic BP 80 mmHg or less), severe bradycardia (less than 50 beats / min), impaired breathing (including bronchospasm), heart failure, cardiogenic shock, cardiac arrest, generalized convulsions , vomiting, confusion.

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

During the first hours after an overdose, you should induce vomiting and rinse the stomach.Put the patient on his back (with raised legs), with severe bradycardia - atropine 0,5-2 mg intravenously, in the case of bradycardia resistant to therapy, the operation of setting an artificial pacemaker is shown; with a pronounced decrease in blood pressure - norepinephrine (noradrenaline); at bronhospazme apply beta-adrenomimetiki for inhalation (with ineffectiveness - intravenously) or aminophylline intravenously.

When convulsions are intravenously slowly injected diazepam or clonazepam.

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. The duration of maintenance therapy depends on the severity of the overdose, it should continue until the patient's clinical condition is stabilized.

Interaction:

Patients should not drink alcohol during treatment with Rekardium. ethanol can potentiate the side effects of carvedilol.

With the simultaneous administration of carvedilol and digoxin the concentration of digoxin in the blood plasma increases by approximately 16% and the time can increase AV conductivity.At the beginning of carvedilol therapy, it is recommended that the concentration of digoxin in the blood plasma be monitored regularly when choosing its dose or abolishing the drug. Rekardium can potentiate the action of insulin and hypoglycemic agents for oral administration, including derivatives of sulfonylureas, and the symptoms of hypoglycemia (especially tachycardia) can be masked, therefore, in patients with diabetes it is recommended that the blood glucose concentration be monitored regularly. Carvedilol enhances the effect of antihypertensive agents (ACE inhibitors, thiazide diuretics, vasodilators).

Simultaneous application with drugs that reduce the content of catecholamines (reserpine, monoamine oxidase inhibitors), increases the risk of a marked decrease in blood pressure and severe bradycardia.

When applying carvedilol in patients who underwent kidney transplantation who developed chronic vascular rejection of the transplant, there was a moderate increase in the mean minimum concentrations of cyclosporine. To maintain the concentration of cyclosporine in the therapeutic range, approximately 30% of patients had to reduce the dose of cyclosporine (on average by 20%), the rest of the patients did not need dose adjustment.In connection with the expressed individual fluctuations of the required daily dose of cyclosporine, careful monitoring of the concentration of cyclosporine in the blood plasma is recommended after the initiation of carvedilol therapy and, if necessary, appropriate correction of the daily dose of cyclosporine.

Simultaneous application of carvedilol with blockers of "slow" calcium channels (derivatives of the dihydropyridine series) can lead to severe heart failure and severe arterial hypotension.

Sympathomimetics with alpha and beta-adrenomimetic effects, with simultaneous use with carvedilol increases the risk of hypertension and severe bradycardia.

Verapamil, diltiazem and other antiarrhythmics (propranolol, amiodarone) with simultaneous application with carvedilol may increase the risk of impairment AV conductivity.

With the simultaneous use of carvedilol and diltiazem Some cases of conduction disturbances were noted (rarely - with violations of hemodynamic parameters). As in the case of other drugs with beta-adrenoblocking properties,The use of carvedilol along with blockers of "slow" calcium channels such as verapamil and diltiazem is recommended to be performed under the control of ECG and blood pressure.

Simultaneous application with clonidine can potentiate the antihypertensive and negative chromotropic effects of carvedilol.

Inhibitors of microsomal oxidation (cimetidine, ketoconazole, fluoxetine, haloperidol, verapamil, erythromycin) amplify, and inductors (barbiturates, rifampicin) weaken the hypotensive effect of carvedilol.

Nitrates and beta-blockers (eg, in the form of eye drops) can potentiate the antihypertensive effect of carvedilol.

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

Ergotamine enhances vasoconstriction with simultaneous application with carvedilol. Nonsteroidal anti-inflammatory drugs reduce the antihypertensive effect of carvedilol.

Special instructions:

The drug Recallium is recommended for the treatment of CHF, as an addition to the standard therapy of CHF: diuretics, ACE inhibitors or cardiac glycosides, only after choosing a dose of a diuretic.It can also be used in patients with intolerance to ACE inhibitors.

At the beginning of Rekardium therapy or after increasing its dose, orthostatic hypotension and dizziness may sometimes 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 applying the initial low dose of the drug to Recardium and gradually increasing to a maintenance dose, as well as taking the drug during meals. Patients need to explain how to avoid orthostatic hypotension (gently rise from the "lying" or "sitting" position, with dizziness you need to sit down or lie down).

Patients with CHF can take the drug Rekardium only if their condition is successfully controlled by drugs of the group of cardiac glycosides and / or diuretics. If during the treatment the course of CHF worsens, it is necessary to increase the dose of the diuretic, and the dose of the drug Rekardium should be reduced or temporarily discontinued (see Application and dosage section).

Beta-blockers can mask symptoms of hypoglycemia in patients with diabetes mellitus, as well as manifestations of thyrotoxicosis in patients with thyroid disease, reducing the manifestations of tachycardia. In patients with CHF, blood glucose concentration may increase or decrease.

When conducting general anesthesia, patients taking beta-blockers should use narcotic analgesics with minimal inotropic action, or preliminary (gradually!) To cancel the beta-blocker.

In some cases carvedilol can cause violations of the liver. With the development of liver failure, the use of the drug Rekardium must be discontinued. As a rule, after the withdrawal of the drug, the liver function is normalized. Beta-adrenoblockers in COPD can aggravate bronchial obstruction, so patients with COPD should not use them.

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

Beta-adrenoblockers can provoke the appearance of pain in patients with Prinzmetal angina.

Patients with pheochromocytoma can take beta-blockers only after therapy with alpha-blockers has been started.

With a sharp cessation of therapy with the drug Rekardium (as well as other beta-blockers), there may be increased sweating, tachycardia, dyspnea and worsening of the course of angina. The most vulnerable to the occurrence of these reactions are patients with angina pectoris, in whom myocardial infarction may develop. With the withdrawal of the drug Rekardium dose reduced gradually, within 1-2 weeks.

If after the cessation of therapy more than 2 weeks have passed, resumption of the drug is recommended from low doses.

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

If the number of cardiac contractions decreases to 50 beats / min, the drug should be discarded.

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 3,125 mg, 6.25 mg, 12.5 mg, 25 mg.

Packaging:

Tablets 3,125 mg, 6.25 mg, 12.5 mg: 15 tablets per blister of aluminum foil. 2 blisters with instructions for use in a cardboard box.

Tablets 25 mg: 10 tablets in a blister of aluminum foil. 3 blisters with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-001343

Date of registration:09.12.2011

The owner of the registration certificate:Torrent Pharmaceuticals Co., Ltd.Torrent Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

TORRENT PHARMACEUTICALS, Ltd. India

Representation: & nbspTORRENT PHARMACEUTICALS LTD. TORRENT PHARMACEUTICALS LTD. India

Information update date: & nbsp09.12.2011

Illustrated instructions

Instructions

Rekardium (Recardium)