Composition, form of production and packaging
Tablets of light yellow color, round, flat, with a facet, with a risk on one side and with engraving "E341" - on the other; odorless or almost odorless.
1 tab.
carvedilol 6.25 mg
[PRING] lactose monohydrate - 50 mg, crospovidone - 15 mg, sucrose - 12.5 mg, silicon dioxide colloid - 6 mg, povidone K-25 -2 mg, magnesium stearate - 2 mg, dye quinoline yellow (C.I.47005 E .E.S.104) - 0.003 mg.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
20 pcs. - bottles of dark glass (1) - packs of cardboard.
30 pcs. - bottles of dark glass (1) - packs of cardboard.
Tablets of light orange color (possible blotches of a darker color), round, flat, with a facet, with a risk on one side and with engraving "E342" - on the other; odorless or almost odorless.
1 tab.
carvedilol 12.5 mg
[PRING] lactose monohydrate - 50 mg, crospovidone - sucrose - 12.5 mg, silicon dioxide colloid - 6 mg, povidone K-25 - 2 mg, magnesium stearate - 2 mg, dye sunset yellow sunset (CI15985 EEC.110 ) - 0.006 mg.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
20 pcs. - bottles of dark glass (1) - packs of cardboard.
30 pcs. - bottles of dark glass (1) - packs of cardboard.
Tablets white or almost white, round, flat, with a facet, with a risk on one side and with engraving "E343" - on the other; odorless or almost odorless.
1 tab.
carvedilol 25 mg
[PRING] lactose monohydrate - 50 mg, crospovidone - 15 mg, sucrose - 12.5 mg, silicon dioxide colloid - 6 mg, povidone K-25 -2 mg, magnesium stearate - 2 mg.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
20 pcs. - bottles of dark glass (1) - packs of cardboard.
30 pcs. - bottles of dark glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
Alpha 1 - and beta 1 -, beta 2 -adrenergic blocker. The drug is an indiscriminate beta-adrenoblocker with a vasodilating action (due to blockade of? 1- adrenoreceptors), and also has antioxidant activity. The active substance of Talliton is a mixture of racemates of two enantiomers of carvedilol.
Carvedilol reduces OPSS, depresses the renin-angiotensin-aldosterone system. Reduces the activity of renin in the blood plasma, so when it is used, there is almost no delay in the fluid in the body.
Carvedilol, being a competitive blocker of? -adrenoceptors, has a negative chrono, batmo- and inotropic effect. The drug slows the conductivity in the AV node.Carvedilol does not have intrinsic sympathomimetic activity, it has a membrane-stabilizing effect.
The combination of vasodilating and beta-adrenergic blocking properties of carvedilol is manifested by the following clinical effects.
The purpose of the drug is not accompanied by an increase in OPSS (as in cases with the use of other beta-blockers). Carvedilol slightly reduces heart rate, however, kidney perfusion and their function remain unchanged. Since OPSS also does not change, the sensation of cold extremities with carvedilol is rare (unlike the use of beta-blockers without vasodilating activity).
Antihypertensive effect develops in 2-3 hours after a single application and lasts for 24 hours. With prolonged treatment, the maximum effect is observed after 3-4 weeks.
With IHD, carvedilol has an antianginal effect that persists with prolonged treatment. Studies of hemodynamics have shown that carvedilol reduces pre- and postnagruzku on the heart.
The favorable effect of carvedilol on the hemodynamics of the heart, the fraction of the ejection of the left ventricle is observed both in dilated cardiomyopathy and in the ischemic form of heart failure. With heart failure, carvedilol reduces the end-systolic and end-diastolic volume, 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. In clinical studies, it was found that, with an additional appointment against the background of cardiac glycosides, ACE inhibitors and diuretics, carvedilol reduces mortality, slows the progression of the disease and improves the overall condition of the patient regardless of the severity of the disease.
During treatment with carvedilol, the ratio of Xc-HDL / Xc-LDL does not change.
PHARMACOKINETICS
Suction
After ingestion, carvedilol is rapidly absorbed from the digestive tract. It is metabolized by the "first pass" through the liver. Bioavailability is about 25%. C max isachieved after 1 hour after ingestion.
Pharmacokinetics of carvedilol is linear (concentration in the blood plasma is proportional to the dose taken). Concomitant food intake does not affect the bioavailability of carvedilol and the C max value in blood plasma, however it can increase the time to reach C max .
Distribution
Carvedilol is a lipophilic compound. Binding to plasma proteins is 98-99%. The apparent V d is approximately 2 l / kg.
Carvedilol and its metabolites can penetrate the placental barrier, and also excrete with breast milk.
Metabolism
Cavedilol is metabolized primarily in the liver, primarily due to the formation of glucuronides. Demethylation and hydroxylation of the phenyl ring leads to the formation of 3 metabolites with beta-adrenergic blocking activity; 4-hydroxy metabolite as a beta-blocker is 13 times more active than carvedilol. At the same time, active metabolites have weaker vasodilating properties, and 2 hydroxycarbazole metabolites are stronger antioxidants compared to the parent compound.
Excretion
The average T 1/2 carvedilol is 6-10 hours. Blood plasma clearance is 590 ml / min. Carvedilol is excreted mainly with bile.
Pharmacokinetics in special clinical cases
The concentration of carvedilol in blood plasma in elderly patients is 50% greater than in young patients.
Carvedilol is excreted mainly through the gastrointestinal tract, so if there is a violation of kidney function, there is no cumulation of the drug.
With cirrhosis of the liver, the apparent V d increases significantly, the bioavailability of carvedilol is 4 times greater than normal, C max is 5 times greater than normal.
Carvedilol is practically not removed from the blood during hemodialysis.
INDICATIONS
- Essential hypertension (in the form of monotherapy or in combination with diuretics);
- stable angina pectoris;
- Chronic heart failure (IIHA and III functional class according to NYHA classification) in combination with diuretics, digoxin or ACE inhibitors.
DOSING MODE
With essential hypertension, the initial dose of the drug is 12.5 mg 1 time / day for 2 days (1 tablet at 12.5 mg in the morning or 1 tablet 6.25 mg 2 times / day in the morning and in the evening). The recommended maintenance dose is 25 mg (1 tab to 25 mg in the morning or 1 tablet 12.5 mg 2 times / day in the morning and evening).
If the effect is insufficient, but not earlier than 14 days of treatment, the dose can be increased to the maximum - 50 mg / day (25 mg 2 times / day morning and evening).
The maximum single dose is 25 mg, the maximum daily dose is 50 mg.
With chronic stable angina, the recommended initial dose is 12.5 mg 2 times / day (morning and evening) for the first 2 days. The recommended maintenance dose is 25 mg 2 times / day (morning and evening).
With insufficient effect, but not earlier than 14 days of treatment, the dose can be increased to the maximum - 50 mg 2 times / day (morning and evening).
In chronic heart failure, the dose should be selected individually, during the increase in the dose should be monitored. It is necessary to observe the patient's condition within 2-3 hours after the first intake or after the first increased dose. Additional application of Tallitone requires a stable clinical state. Doses and administration of other drugs (such as digoxin, diuretics or ACE inhibitors) should be documented before Tallitona is taken. Patients should take pills during meals (to reduce the risk of orthostatic hypotension).
The recommended initial dose is 3.125 mg 2 times / day for 14 days (1/2 tablets at 6.25 mg in the morning and in the evening). If the treatment is well tolerated and there is a clinical need, the dose can be increased to 6.25 mg 2 times / day (1 table 6.25 mg in the morning and in the evening). Perhaps a subsequent increase in the dose to 12.5 mg 2 times / day (1 tablet, 12.5 mg in the morning and in the evening), then to 25 mg 2 times / day (1 tablet, 25 mg in the morning and in the evening).Patients are prescribed the maximum tolerated dose. The maximum dose for patients weighing up to 85 kg is 25 mg 2 times / day (morning and evening) and 50 mg 2 times / day (morning and evening) for patients with a body weight of more than 85 kg .
At the beginning of treatment and until each dose is increased, the condition of the patients should be monitored. possibly worsening of the course of heart failure. A fluid retention may develop, and in connection with vasodilator action - arterial hypotension and lethargy. If fluid is delayed, the dose of diuretics should be increased, in addition, a reduction in the dose of Tallitone may be required. In some cases, treatment with Talliton should be interrupted.
Tablets should be taken whole, squeezed with a sufficient amount of liquid.
SIDE EFFECT
In recommended doses, the drug is usually well tolerated, but in some cases, the following side effects may occur.
From the central nervous system and peripheral nervous system: headache, syncope, dizziness, fatigue; rarely - depressed mood, sleep disturbance, paresthesia.
On the part of the cardiovascular system: orthostatic hypotension, bradycardia, marked decrease in blood pressure, attacks of angina pectoris; rarely - violations of peripheral circulation (cold extremities), intermittent claudication, Raynaud's syndrome, peripheral edema, AV blockade, progression of heart failure.
On the part of the respiratory organs: dyspnea, bronchospasm; rarely - nasal congestion.
On the part of the digestive system: dry mouth, nausea, diarrhea, abdominal pain; rarely - constipation, vomiting, increased activity of hepatic transaminases.
Dermatological reactions: allergic exanthema, hives, itching, exacerbation of psoriatic rashes, in isolated cases - anaphylactic reactions.
On the part of the hematopoiesis system: leukopenia, thrombocytopenia.
Other: rarely - pain in the limbs, reduced tear fluid production, eye irritation, urination disorder, renal dysfunction, flu-like syndrome. Possible manifestations of latent current diabetes mellitus or an increase in its symptoms.
CONTRAINDICATIONS
- heart failure in the stage of decompensation;
- conduction disorders (SSSU, sinoatrial blockade, AV blockade of II and III degree), except for patients with an artificial pacemaker;
- pronounced bradycardia (heart rate less than 50 beats per minute);
- arterial hypotension (systolic blood pressure less than 85 mm Hg);
- cardiogenic shock;
- bronchial asthma;
severe hepatic impairment;
metabolic acidosis;
- simultaneous IV application of verapamil, diltiazem or other antiarrhythmic drugs (especially class I);
- Pregnancy;
- lactation period (breastfeeding);
- children and adolescence under 18;
- Hypersensitivity to the components of the drug.
Caution should be prescribed for chronic obstructive pulmonary diseases, prinzmetal angina, diabetes, hypoglycemia, thyrotoxicosis, pheochromocytoma (only stabilized by the use of alpha-blockers), occlusive peripheral vascular disease, grade I AV block, unstable angina, psoriasis, renal dysfunction , depression, myasthenia gravis, with simultaneous use of MAO inhibitors, treatment with alpha 1- adrenoblockers or alpha 2 -adrenomimetics.
PREGNANCY AND LACTATION
Talliton В® should not be administered during pregnancy due to lack of sufficient clinical data. If it is necessary to use the drug during lactation, breastfeeding should be stopped.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution should apply the drug for violations of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The use of the drug is contraindicated in severe violations of liver function.
APPLICATION FOR CHILDREN
Contraindication: children and adolescence under 18 years.
SPECIAL INSTRUCTIONS
Patients with severe heart failure (more than the third functional class according to the NYHA classification), with an impaired electrolyte balance, a lower blood pressure level (less than 100 mm Hg), or elderly patients should be under medical supervision for 2 hours after the first dose or after taking the first increased dose due to the risk of sudden fall in BP, orthostatic hypotension and syncopal conditions. The risk of developing these complications can be reduced by using the drug in small initial doses or by taking it at meals.
The dose of the drug should be reduced if the patient has a bradycardia (heart rate less than 55 beats per minute).
Caution should be given to TallitonВ® for patients receiving cardiac glycosides, diuretics and / or ACE inhibitors for heart failure.
In patients with heart failure with initial systolic blood pressure less than 100 mm Hg. or in the presence of concomitant diseases (coronary heart disease, peripheral vascular lesions, renal dysfunction), the urinary system should be checked more frequently. The use of Talliton may temporarily affect kidney function. If oppression of kidney function is noted, the dose of Talliton should be reduced or treatment should be discontinued.
In patients with Prinzmetal angina, indiscriminate beta-blockers can cause chest pain (although alpha 1- adrenergic blocking effect can prevent this action). When prescribing the drug with unstable angina, as well as with AV blockade I degree, you need to monitor the patient's condition and ECG.
Carvedilol can mask symptoms of hypoglycemia. Therefore, the use of Tallitone in patients with diabetes requires special attention and more frequent measurement of blood glucose.
Carvedilol can mask symptoms of increased thyroid function. With a sudden reversal of Tallitona, probably an increase in thyrotoxicosis and possibly the development of a crisis.
The use of Tallitone in patients with established pheochromocytoma should not begin before the appropriate therapeutic blockade of alpha-adrenergic receptors.
The use of Talliton in patients with psoriasis requires an assessment of the benefit-risk ratio, Carvedilol may exacerbate the manifestations of the disease or provoke the appearance of symptoms.
Each Tallitone tablet contains 50 mg of lactose, which should be taken into account when the drug is prescribed for lactase deficiency, galactosemia, glucose / galactose absorption disorder.
Each tablet of Talliton contains 12.5 mg of sucrose, which should be taken into account in diabetes mellitus, hereditary fructose intolerance, impaired glucose / galactose uptake, or with a deficiency of sucrose / isomaltase.
Treatment should be stopped gradually, reducing the dose.
Patients using contact lenses should be warned that carvedilol reduces the production of tear fluid.
Impact on the ability to drive vehicles and manage mechanisms
At the beginning of treatment with Talliton, patients may experience dizziness, fatigue. In this case, they should refrain from driving vehicles and practicing potentially dangerous activities that require increased attention and speed of psychomotor reactions. In the future, the determination of the safe dose is carried out individually.
OVERDOSE
Symptoms: severe arterial hypotension, bradycardia, heart failure, cardiogenic shock, cardiac arrest.
Treatment: in the first hours - gastric lavage, artificial vomiting. The patient should be in a position with raised lower limbs. Antidote beta-adrenoblokiruyuschey action is orciprenaline or isoprenaline (iv in a dose of 0.5-1 mg) or glucagon in a dose of 1-5 mg (the maximum dose is 10 mg).
In severe hypotension, parenteral fluid administration and repeated administration of epinephrine (adrenaline) at a dose of 5-10 Ојg or as an IV infusion at a rate of 5 Ојg / min are indicated.
For the treatment of bradycardia, atropine is administered iv at a dose of 0.5-2 mg. To maintain cardiac activity, glucagon iv is used at a dose of 1-10 mg quickly, for 30 seconds, then - a constant infusion at a rate of 2-5 mg / h.
If peripheral vasodilator action predominates (warm extremities, hypotension), norepinephrine (norepinephrine) should be prescribed in repeated doses of 5-10 Ојg or as an infusion of 5 Ојg / min.
To stop bronchospasm, beta-adrenomimetics (in the form of an aerosol or IV) or aminophylline IV are prescribed.
When developing seizures, slow administration of diazepam or clonazepam is recommended.
In severe cases of intoxication, when shock symptoms dominate, antidote treatment should continue until the patient's condition stabilizes, taking into account T 1/2carvedilol (6-10 h).
DRUG INTERACTION
With the simultaneous use of Talliton with drugs depleting the supplies of catecholamines (reserpine, MAO inhibitors), severe bradycardia and arterial hypotension are noted.
With the simultaneous use of Talliton with calcium channel blockers (verapamil, diltiazem) and antiarrhythmics (especially class I), marked arterial hypotension and heart failure are noted. In / in the introduction of such combinations is contraindicated.
At simultaneous application with Talliton alpha- and beta-agonists may develop hypertension, marked reflex bradycardia and asystole, as well as a decrease in beta-adrenoceptor blocking action of carvedilol.
With simultaneous use of carvedilol with clonidine marked decrease mutual intensification of blood pressure and heart rate. With simultaneous application removal should be gradual, starting from carvedilol again several days may be gradually discontinued reception clonidine.
When applied simultaneously with digoxin Talliton slows AV-conduction.
With simultaneous application Talliton with insulin and hypoglycemic agents for oral administration there is a growing hypotensive action and masking the symptoms of hypoglycemia.
With simultaneous application Talliton with nitrates and antihypertensive agents (clonidine, guanethidine, alpha-methyldopa, guanfacine) noted increased hypotensive effect and decrease in heart rate.
With simultaneous application Talliton with means for anesthesia has increased, inotropic and hypotensive actions.
With simultaneous application Talliton with means affecting the CNS (hypnotics, tranquilizers, tricyclic antidepressants, ethanol), there is mutual enhancing effects.
With simultaneous use of NSAIDs Talliton marked decrease in the hypotensive action due to decreased production of prostaglandins.
With simultaneous use of Talliton with ergotamine should consider the vasoconstrictor effect of the latter.
When applied simultaneously with Talliton xanthine derivatives (aminophylline, theophylline) marked decrease in beta-adrenoceptor blocking action.
Because Carvedilol undergoes oxidative metabolism, its pharmacokinetics may change when the induction or inhibition of isoenzymes of cytochrome P450.
When applied simultaneously with rifampicin Talliton marked decrease in serum concentration of carvedilol is 70%.
When applied simultaneously with barbiturates Talliton marked reduction actions of carvedilol.
When applied simultaneously with cimetidine Talliton carvedilol is increased bioavailability of 30%.
With simultaneous application Talliton with digoxin increased digoxin concentration in the blood plasma.
When applied simultaneously with inhibitors Talliton isoenzyme CYP2D6 (quinidine, fluoxetine, paroxetine, propafenone) optionally increasing the concentration of R (+) enantiomer of carvedilol.
When applied simultaneously with cyclosporin Talliton carvedilol delays the metabolism of cyclosporin.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be protected from light and moisture at a temperature of from 15 В° to 25 В° C. Shelf-life of the drug in blister packs - 3 years in bottles - 5 years.
