Composition, form of production and packaging
Tablets are round, biconcave, white or almost white in color.
1 tab.
carvedilol 12.5 mg
Excipients: microcrystalline cellulose, lactose monohydrate, hydroxypropylcellulose, corn starch, talc, silicon dioxide colloid, magnesium stearate.
14 pcs. - blisters (2) - packs of cardboard.
15 pcs. - blisters (2) - packs of cardboard.
Tablets are white or almost white, round, biconvex, with engraving "CA25" on one side.
1 tab.
carvedilol 25 mg
Excipients: microcrystalline cellulose 224 mg, lactose monohydrate 134.16 mg, low-substituted giprolose 36.36 mg, corn starch 50.88 mg, talc 2.4 mg, silicon dioxide colloid 2.72 mg, magnesium stearate 4.48 mg.
28 pcs. - blisters (1) - packs of cardboard.
30 pcs. - blisters (1) - packs of cardboard.
Tablets are white or almost white, round, biconvex, with engraved "CA3" on one side.
1 tab.
carvedilol 3.125 mg
Excipients: microcrystalline cellulose 28 mg, lactose monohydrate 16.77 mg, low-substituted giprolose 4.545 mg, corn starch 6.36 mg, talc 300 Ојg, silicon dioxide colloid 340 mg, magnesium stearate 560 Ојg.
14 pcs. - blisters (2) - packs of cardboard.
15 pcs. - blisters (2) - packs of cardboard.
Tablets are white or almost white, round, biconvex, with engraving "CA6" on one side.
1 tab.
carvedilol 6.25 mg
Excipients: microcrystalline cellulose 56 mg, lactose monohydrate 33.54 mg, low-substituted giprolose 9.09 mg, corn starch 12.72 mg, talc 600 Ојg, silicon dioxide colloid 680 Ојg, magnesium stearate 1.12 mg.
14 pcs. - blisters (2) - packs of cardboard.
15 pcs. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Carvedilol - blocker alpha 1 -, beta 1 -, beta 2 -adrenoreceptors, has an organoprotective effect. It has antiproliferative properties in relation to smooth muscle cells of the vessel walls, is a racemic mixture of R (+) and S (-) stereoisomers, each of which has the same alpha-adrenergic blocking properties. Due to cardioselective blocking of adrenergic receptors due to the S (-) stereoisomer, carvedilol lowers blood pressure, reduces heart rate and cardiac output, reduces pressure in the pulmonary arteries and in the right atrium. Due to the blockade of alpha 1- adrenoreceptors, 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, like propranolol, it 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 and kidney disease, carvedilol reduces the resistance of renal vessels, with this there is no significant change in the glomerular filtration rate of renal plasmotox or electrolyte excretion. 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. C max carvedilol in blood plasma is achieved after 1 hour. Absolute bioavailability of carvedilol is about 25%: 30% for R-form and 15% for S-form.
Carvedilol has a high lipophilicity. Approximately 98-99% binds to blood plasma proteins. V d 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. The R (+) isomer is metabolized mainly by the CYP2D6 and CYP1A2 isoenzymes, and the S (-) isomer is mainly by the CYP2D9 isoenzyme and, to a lesser extent, by the CYP2D6 isoenzyme. 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.
T 1/2 is about 6 hours, plasma clearance is about 500-700 ml / min. Carvedilol is excreted, mainly with bile through the intestine and in part with 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 is almost never removed from the blood plasma during hemodialysis.
INDICATIONS
- arterial hypertension (in monotherapy or in combination with other antihypertensive drugs);
- Ischemic heart disease: prevention of attacks of stable angina pectoris;
- chronic cardiac insufficiency II and III of the functional class according to the NYHA classification (as part of a combination therapy with diuretics, digoxin or ACE inhibitors).
DOSING MODE
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 administration of the drug Carvedilol-Teva 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 Carvedilol-Teva should be stopped gradually, reducing the dose within 1-2 weeks.
If, after discontinuing therapy, more than 2 weeks have elapsed, it is recommended to resume taking the medication, again starting at a low dose.
Arterial hypertension
The initial dose is 12.5 mg 1 time / day in the morning for the first 2 days, then 25 mg 1 time / day. In the future, if necessary, the dose can be increased at intervals of at least 2 weeks, bringing to a maximum daily dose of 50 mg (divided into 2 divided doses).
Ischemic heart disease: prevention of attacks of stable angina
The initial dose is 12.5 mg 2 times / day for the first 2 days, then 25 mg 2 times (morning and evening) / day.
Chronic heart failure of II and III functional class according to NYHA classification
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 administration of the drug or after the first dose increase. The dose and use of other agents, such as digoxin, diuretics and ACE inhibitors, should be adjusted before therapy with Carvedilol-Teva. Patients should take tablets during meals (to reduce the risk of orthostatic hypotension). The recommended initial dose is 3.125 mg 2 times / day. If this dose is well tolerated, it can be gradually (at intervals of 2 weeks) increased to 6.25 mg 2 times / day, then to 12.5 mg 2 times / day, then to 25 mg 2 times / day. Patients take the maximum tolerated dose. The maximum recommended dose for patients weighing up to 85 kg is 25 mg 2 times / 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 Carvedilol-Teva or a temporary withdrawal is necessary. The dose of Carvedilol-Teva should not be increased until the symptoms of worsening heart failure or arterial hypotension stabilize. If treatment with Carvedilol-Teva 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 Carvedilol-Teva has been suspended for more than 2 weeks, then the therapy should be resumed at a dose of 3.125 mg 2 times / day, then picking up the dose in accordance with the recommendations above.
Elderly patients: dose adjustment is not required.
Patients with impaired renal function
Existing data on pharmacokinetics in patients with varying degrees of renal dysfunction (including kidney failure) suggest that with moderate and severe renal failure, dose adjustment of Carvedilol-Teva is not required.
SIDE EFFECT
The incidence of side effects 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 senses: often - reduced tear and eye irritation (pay attention when using contact lenses); very rarely - visual disturbances, eye irritation.
From 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 disturbance, palpitation, aggravation of angina pectoris, occlusive disorders of peripheral circulation, intermittent claudication, peripheral edema.
On the part of 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 (ALT, ACT, GGT).
From the skin: very rarely - exacerbation of psoriasis, alopecia, exfoliative dermatitis.
From 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.
CONTRAINDICATIONS
- chronic obstructive pulmonary disease (COPD);
- bronchial asthma or bronchospasm (in the anamnesis);
- chronic heart failure IV functional class according to NYHA classification, acute and chronic heart failure (CHF) in the stage of decompensation, requiring in / in the introduction of inotropic agents; angina of Prinzmetal;
- cardiogenic shock;
- marked bradycardia (less than 50 beats / min at rest), sinus node weakness syndrome (including sinoauric blockade), 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 IV 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);
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
- the period of breastfeeding;
- age under 18 years (safety and efficacy not established);
- pheochromocytoma (without simultaneous use of alpha-blockers);
- hypersensitivity to carvedilol or other components of the drug.
With caution :
- AV blockade of the 1st degree;
- diabetes;
- hypoglycemia;
- thyrotoxicosis;
- occlusive diseases of peripheral vessels;
- 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 Carvedilol-Teva 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. Carvedilol-Teva should not be used during pregnancy, unless absolutely necessary, if the potential benefit to the mother justifies the risk to the fetus.
Because carvedilol is excreted in breast milk, breast-feeding should be discontinued during Carvedilol-Teva therapy.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated:
- clinically significant impairment of liver function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Existing data on pharmacokinetics in patients with varying degrees of renal dysfunction (including kidney failure) suggest that with moderate and severe renal failure, dose adjustment of Carvedilol-Teva is not required.
APPLICATION FOR CHILDREN
Carvedilol-Teva is not recommended for patients under the age of 18 years . effectiveness and safety of the drug Karvedilol-Teva in this group of patients is not established.
APPLICATION IN ELDERLY PATIENTS
Elderly patients: dose adjustment is not required.
SPECIAL INSTRUCTIONS
Carvedilol-Teva is recommended for the treatment of CHF, as an adjunct 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 therapy with Carvedilol-Teva 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 an initial low dose of Carvedilol-Teva and gradually increasing to a maintenance dose, as well as taking the drug during meals. Patients need to explain how orthostatic hypotension can be avoided (gently getting out of the "lying" or "sitting" position, with dizziness developing it is necessary to sit or lie down).
Patients with CHF can take Carvedilol-Teva only if their condition is successfully controlled by drugs of the group of cardiac glycosides and / or diuretics. If the course of treatment worsens during CHF, it is necessary to increase the dose of diuretic, and the dose of Carvedilol-Teva drug to reduce or temporarily stop its use.
Alpha- and beta-adrenoblockers 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 alpha and beta adrenoblockers should use narcotic analgesics with minimal inotropic action, or preliminary (gradually!) Cancel the alpha and beta adrenoblocker.
In some cases, carvedilol can cause liver dysfunction. With the development of hepatic insufficiency, the use of Carvedilol-Teva should be stopped. As a rule, after the withdrawal of the drug, the liver function is normalized.
Alpha- and beta-adrenoblockers in COPD can aggravate bronchial obstruction, so patients with COPD should not use them.
Alfa-and beta-adrenoblockers can worsen the clinical picture of peripheral arteriopathy, psoriasis and anaphylactic reactions and strengthen the body's response to allergic tests.
Alpha- and beta-blockers may provoke the appearance of pain in patients with angina Prinzmetal.
Patients with pheochromocytoma may take alpha-and beta-blockers only after it started an alpha-blocker therapy.
In sharp termination of therapy with carvedilol-Teva (and other alpha- and beta-blockers), can develop increased sweating, tachycardia, dyspnea, and worsening of angina. Most are at risk for these reactions, patients with angina who can develop myocardial infarction. To remove the drug Carvedilol-Teva reduce the dose gradually over 1-2 weeks.
If more than 2 weeks after discontinuation of therapy, it is recommended to renew the drug at low doses.
Patients wearing contact lenses should take into account that the drug may cause a reduction in tearing.
In the case of deceleration of heart rate to 50 bpm. / Min medication should be discontinued.
Use in Pediatrics
The drug carvedilol, Teva is recommended not to accept patients under the age of 18 years , as efficacy and safety of carvedilol-Teva in this group of patients has not been established.
Impact on the ability to drive vehicles and manage mechanisms
Caution should be exercised when driving and occupations potentially hazardous activities, due to the fact that the possibility of side effects that can affect the concentration of attention and quickness of psychomotor reactions.
OVERDOSE
Symptoms: marked decrease in blood pressure (systolic blood pressure of 80 mmHg or less), bradycardia (less than 50 beats / min.), Impaired lung function (including bronchospasm), heart failure, cardiogenic shock, cardiac arrest, generalized convulsions, vomiting, confusion.
Treatment: it is necessary to carry out monitoring and correction of vital body functions, if necessary - in the intensive care unit.
During the first hours after the overdose, induce vomiting and stomach wash. Put the patient on his back (with raised feet) with bradycardia - atropine 0.5-2 mg / in at resistant to therapy bradycardia shows the operation setting artificial cardiac pacemaker; In marked decrease in blood pressure - norepinephrine (noradrenaline); with bronchospasm used beta-agonists for inhalation (for inefficiency in / in) or aminophylline / in.
In convulsions in / slow administered diazepam or clonazepam.
Because of severe overdose with symptoms of shock, possibly lengthening the half-life of carvedilol and excretion of carvedilol from the depot, it is necessary to continue maintenance therapy for quite a long time.
Length of maintenance treatment depends on the severity of overdose, it must continue to stabilize the patient's clinical condition.
DRUG INTERACTION
During treatment with carvedilol-Teva patients is not recommended to drink alcohol, because Ethanol can potentiate the side effects of carvedilol.
When simultaneous administration of carvedilol and digoxin digoxin concentration in the blood plasma increased by approximately 16% and can be increased while AV-conduction. At the start of carvedilol treatment, the selection of the dose or withdrawal of the drug is recommended regular monitoring of digoxin plasma concentration.
Carvedilol may potentiate the action of insulin and hypoglycemic agents for oral administration, including sulfonylureas, with symptoms of hypoglycemia (especially tachycardia) may be masked, so diabetic patients recommended the regular control of blood glucose concentration.
Carvedilol enhances the effect of antihypertensive agents (ACE inhibitor, thiazide diuretics, vasodilators).
The simultaneous use of drugs to lower content of catecholamines (reserpine, MAO inhibitors) that increases the risk of significant decrease in blood pressure and bradycardia.
In applying carvedilol in patients undergoing kidney transplantation, who developed a chronic vascular graft rejection, it was observed a moderate increase in average minimum concentration of cyclosporine. To maintain the concentration of cyclosporine in the therapeutic range, approximately 30% of patients had to reduce the dose of cyclosporin (on average 20%), the rest of the patients the dose correction is not required. Due to the pronounced individual variations required daily dose of cyclosporin recommended careful monitoring of cyclosporin plasma concentrations after initiation of therapy of carvedilol and, if required, corresponding correction daily dose cyclosporine.
The simultaneous use of carvedilol with calcium channel blockers slow (dihydropyridine derivatives) may lead to severe heart failure and severe arterial hypotension, Sympathomimetics having alpha and beta adrenomimeticheskim effects, while the use of carvedilol is increased risk of hypertension and severe bradycardia.
Verapamil, diltiazem and other antiarrhythmic agents (propranolol, amiodarone), while the use of carvedilol may increase the risk of disturbances AV-conduction.
With simultaneous use of carvedilol and diltiazem, marked individual cases conduction disturbances (rarely - with hemodynamic disorders). As in the case of other drugs with beta-adrenoceptor blocking properties, the use of carvedilol with calcium channel blockers slow type verapamil and diltiazem recommended under the control of ECG and blood pressure.
The simultaneous use of clonidine may potentiate antigipertenzivnty hromotropny and negative effects of carvedilol.
Inhibitors of microsomal oxidation (cimetidine, ketoconazole, fluoxetine, haloperidol, verapamil, erythromycin) increase, and inductors (barbiturates, rifampicin) weaken the antihypertensive effect of carvedilol.
Nitrates and beta-blockers (e.g., in the form of eye drops) may potentiate the antihypertensive effect of carvedilol.
General anesthetics enhance the negative inotropic and hypotensive effect of carvedilol.
Ergotamine vasoconstriction increases while the use of carvedilol.
Nonsteroidal anti-inflammatory drugs reduce the antihypertensive effect of carvedilol.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
At temperatures above 25 В° C. Keep out of the reach of children. Shelf life - 3 years.
