Talliton: instructions for using the medicine, structure, Contraindications
Active material: Karvedilol
When ATH: C07AG02
CCF: Beta1-,beta2-adrenoblokator. Alpha1-adrenoblokator
ICD-10 codes (testimony): I10, i20, I50.0
When CSF: 01.01.01.01.02
Manufacturer: EGIS PHARMACEUTICALS Plc (Hungary)
Talliton: dosage form, composition and packaging
Pills pale yellow, round, flat, chamfered, with Valium on one side and with an engraving “E341” – another; odorless or almost odorless.
| 1 tab. | |
| karvedilol | 6.25 mg |
Excipients: lactose monohydrate, sucrose, Colloidal anhydrous silica, povidone K-25, krospovydon, magnesium stearate, ariavit quinoline yellow (S.I.47005 E.E.S.104).
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.
20 PC. – vials of dark glass (1) – packs cardboard.
30 PC. – vials of dark glass (1) – packs cardboard.
Pills pale orange (possible blotches of darker color), round, flat, bevelled on both sides, with Valium on one side and with an engraving “E342” – another; odorless or almost odorless.
| 1 tab. | |
| karvedilol | 12.5 mg |
Excipients: lactose monohydrate, sucrose, Colloidal anhydrous silica, povidone K-25, krospovydon, magnesium stearate, ariavit Sunset yellow (C.I.15895 E.E.S.110).
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.
20 PC. – vials of dark glass (1) – packs cardboard.
30 PC. – vials of dark glass (1) – packs cardboard.
Pills white, round, flat, bevelled on both sides, with Valium on one side and with an engraving “E343” – another; odorless or almost odorless.
| 1 tab. | |
| karvedilol | 25 mg |
Excipients: lactose monohydrate, sucrose, Colloidal anhydrous silica, povidone K-25, krospovydon, magnesium stearate.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.
20 PC. – vials of dark glass (1) – packs cardboard.
30 PC. – vials of dark glass (1) – packs cardboard.
Talliton: pharmachologic effect
Alpha1– and beta1-, beta2-adrenoblokator. The drug is a non-selective beta-blocker with vasodilating action (by blocking α1-adrenoreceptorov), and also possesses antioxidant activity. Talliton active substance is a mixture of two enantiomers of racemic carvedilol.
Carvedilol reduces round, ugnetaet renin-angiotensin-alydosteronovuyu sistemu. Reduces the activity of renin in blood plasma, therefore, when applied practically not observed water retention.
Karvedilol, Being competitive β-adrenergic blocker, It has a negative chrono, ʙatmo- and inotropic effect. The drug slows conduction in AV-node. Carvedilol has no intrinsic sympathomimetic activity, It has a membrane-stabilizing effect.
The set vasodilator and beta-adrenoceptor blocking properties of carvedilol manifests the following clinical effects.
The appointment of the drug is not accompanied by an increase in systemic vascular resistance (as in the case with other beta-blockers). Carvedilol significantly reduces the heart rate, However, renal perfusion and function remain unchanged. As well as PR does not change, the feeling of cold extremities when using carvedilol is rare (in contrast to the use of beta-blockers without vasodilating activity).
The antihypertensive effect develops in 2-3 h after a single application and lasts for 24 no. In long-term treatment of the maximum effect observed after 3-4 of the week.
In CHD carvedilol has antianginal, which is stored in the long-term treatment. Studies have shown hemodynamic, Carvedilol reduces pre- and afterload on the heart.
The beneficial effect of carvedilol on hemodynamics of the heart, Left ventricular ejection fraction was observed as in dilated cardiomyopathy, and in the form of ischemic heart disease. In heart failure, carvedilol reduces end-systolic and end-diastolic volume, as well as peripheral and pulmonary vascular resistance. Ejection fraction and cardiac index in the normal function of the heart do not change.
In the case of left ventricular dysfunction alpha1-adrenoceptor blocking effect of carvedilol leads to arterial and expansion, less, veins. In clinical studies it has been found, that the supplemental taken against the background of cardiac glycosides, ACE inhibitors and diuretics, carvedilol reduces mortality, It slows the progression of the disease and improves the general condition of the patient regardless of the severity of the disease.
During treatment with carvedilol ratio of HDL-C / LDL-C is not changed.
Talliton: pharmacokinetics
Absorption
After oral administration, carvedilol is rapidly absorbed from the gastrointestinal tract. Metabolized in the “first pass” through the liver. Bioavailability is about 25%. Cmax achieved through 1 hours after oral administration.
Pharmacokinetics carvedilol is linear (plasma concentration is proportional to the dose). Concomitant food has no effect on the bioavailability and carvedilol value Cmax plasma, but can increase the time to reach Cmax.
Distribution
Carvedilol is lipophilic compound. Plasma protein binding - 98-99%. In Кажущийсяd approximately 2 l / kg.
Carvedilol and its metabolites can cross the placental barrier, and are excreted in breast milk.
Metabolism
Kavedilol metabolized primarily in the liver, primarily due to the formation of glucuronides. Demethylation and hydroxylation of the phenyl ring results in the formation 3 metabolites with beta activity adrenoblokiruyuschey; 4-hydroxy metabolite of beta-blocker in 13 times more active carvedilol. At the same time, active metabolites possess weaker vasodilator properties, and 2 gidroksikarbazolovyh metabolite is more potent antioxidants as compared to the parent compound.
Deduction
Average T1/2 karvedilola - 6-10 no. The clearance of plasma - 590 ml / min. Carvedilol is derived mainly from the bile.
Pharmacokinetics in special clinical situations
The concentration of carvedilol plasma levels in elderly patients 50% better, than young.
Carvedilol is derived mainly through the digestive tract, therefore, renal impairment is not observed drug accumulation.
In cirrhosis apparent Vd significantly increased, bioavailability carvedilol 4 times, than normal, Cmax – in 5 times more, than normal.
Carvedilol substantially not removed from the blood during dialysis.
Talliton: testimony
- essential hypertension (alone or in combination with a diuretic);
- stable angina;
- congestive heart failure (II and III functional class NYHA classification) in combination with a diuretic, digoxin or ACE inhibitors.
Talliton: dosing regimen
At essential hypertension the initial dose is 12.5 mg 1 times / day for 2 days (1 tab. by 12.5 mg in the morning or 1 tab. 6.25 mg 2 times / day, morning and evening). The recommended maintenance dose – 25 mg (1 tab. by 25 mg in the morning or 1 tab. 12.5 mg 2 times / day, morning and evening).
With little effect, but not earlier 14 days of treatment, dose can be increased up to the maximum - 50 mg / day (by 25 mg 2 times / day, morning and evening).
The maximum single dose - 25 mg, The maximum daily dose - 50 mg.
At chronic stable angina The recommended starting dose – by 12.5 mg 2 times / day (in the morning and in the evening) during 2 first days. The recommended maintenance dose - 25 mg 2 times / day (in the morning and in the evening).
With little effect, but not earlier 14 days of treatment, dose can be increased to a maximum - for 50 mg 2 times / day (in the morning and in the evening).
At chronic heart failure the dose should be adjusted individually, while increasing the dose should be monitoring. Should the patient's condition during the 2-3 hours after the first dose, or increased after the first dose. Additional application Talliton requires a stable clinical condition. Doses and administration of other drugs (such as digoxin, diuretics or ACE inhibitors) You must be fixed before you start taking Talliton. Patients should take the tablets during meals (to reduce the risk of orthostatic hypotension).
The recommended starting dose is 3.125 mg 2 times / day for 14 days (1/2 tab. by 6.25 mg in the morning and evening). If the treatment is well tolerated and has a clinical need, the dose can be increased to 6.25 mg 2 times / day (by 1 tab. 6.25 mg in the morning and evening). Perhaps subsequent increase in dose to 12.5 mg 2 times / day (by 1 tab. 12.5 mg in the morning and evening), then to 25 mg 2 times / day (by 1 tab. 25 mg in the morning and evening). Patients received the maximum tolerated dose. The maximum dose for patients weighing up to 85 kg - By 25 mg 2 times / day (in the morning and in the evening) and 50 mg 2 times / day (in the morning and in the evening) – to patients weighing more 85 kg.
At the beginning of treatment, and to increase the dose of each state of the patients should be monitored, tk. possibly worsening heart failure. It may develop fluid retention, but due to the vasodilator effect - hypotension and lethargy. When fluid retention should increase the dose of diuretics, Besides, may require dose reduction Talliton. In some cases, the treatment should be interrupted Talliton.
Tablets should be taken as a whole, drinking plenty of fluids.
Talliton: side effects
At recommended doses, the drug is generally well tolerated, but in some cases may cause the following side effects.
From the central and peripheral nervous system: headache, syncope, dizziness, fatigue; rarely - depressed mood, sleep disturbance, paresthesia.
Cardio-vascular system: orthostatic hypotension, bradycardia, marked reduction in blood pressure, angina; rarely - peripheral circulatory disorders (cold extremities), intermittent claudication, Raynaud's syndrome, peripheral edema, AV блокада, progression of heart failure.
On the part of the respiratory system: breathlessness, bronchospasm; seldom - nasal congestion.
From the digestive system: dry mouth, nausea, diarrhea, stomach ache; rarely - constipation, vomiting, increase in liver transaminases.
Dermatological reactions: an allergic rash, hives, itch, worsening of psoriatic lesions, in rare cases - anaphylactic reactions.
From the hematopoietic system: leukopenia, thrombocytopenia.
Other: rarely - a pain in the extremities, decrease in production of tear fluid, eye irritation, dysuria, impairment of renal function, flu-like symptoms. Possible manifestations of latent diabetes mellitus, or the current strengthening of its symptoms.
Talliton: Contraindications
- heart failure decompensation;
- conduction disorders (SSS, sinoatrialynaya blockade, AV-blockade II and III degrees), except in patients with an artificial pacemaker;
- vыrazhennaya bradycardia (HR less 50 u. / min);
- hypotension (systolic blood pressure less than 85 mm Hg. Art.);
- cardiogenic shock;
- bronchial asthma;
- severe liver;
- metabolic acidosis;
- simultaneous i / v use of verapamil, diltiazem or other antiarrhythmics (especially class I);
- pregnancy;
- lactation (breast-feeding);
- childhood and adolescence up 18 years;
- hypersensitivity to the drug.
FROM caution It should be prescribed the drug for chronic obstructive pulmonary disease, Prinzmetal angina, diabetes, gipoglikemii, thyrotoxicosis, pheochromocytoma (Only stabilized using alpha-blockers), occlusive peripheral vascular disease, AV-blockade I degree, unstable angina, psoriaze, renal impairment, depression, myasthenia, while the use of MAO inhibitors, alpha treatment1-blockers or alpha2-adrenomimetikami.
Talliton: Pregnancy and lactation
Talliton® should not be administered during pregnancy because of the lack of sufficient clinical data. If necessary, use during lactation should stop breastfeeding.
Talliton: Special instructions
Patients with severe heart failure (more functional class III NYHA classification), to electrolyte imbalance, with reduced blood pressure (less 100 mmHg.) or elderly patients should be under medical supervision for 2 hours after the first dose or after the first dose increased due to the risk of a sudden drop in blood pressure, orthostatic hypotension and syncope. The risk of these complications can be reduced by applying the drug in the small initial doses or by receiving it with meals.
The dose should be reduced, if the patient is marked bradycardia (HR less 55 u. / min).
Precautions should be prescribed Talliton® sick, receiving cardiac glycosides, diuretics and / or ACE inhibitors in heart failure.
In patients with heart failure at baseline systolic blood pressure less than 100 mmHg. or in the presence of concomitant diseases (CHD, peripheral vascular disease, renal dysfunction) should frequently check the condition of the urinary system, tk. Talliton application may temporarily affect renal function. If there is oppression of renal function, Talliton the dose should be reduced or the treatment should be discontinued.
In patients with angina Prinzmetal indiscriminate beta-blockers can cause chest pain (Although alpha1-adrenoceptor blocking effect can prevent this action). In appointing the drug in unstable angina, as well as AV-blockade of I degree is necessary to monitor the patient and ECG.
Carvedilol may mask the symptoms of hypoglycemia. Therefore, the use Talliton diabetic patients requires special attention and more frequent measurement of blood glucose.
Carvedilol may mask the symptoms of increased thyroid function. With the sudden cancellation Talliton likely to strengthen and hyperthyroidism may develop crisis.
Application Talliton in patients with pheochromocytoma should not be set to start up the respective therapeutic blockade of the alpha-adrenergic.
Application Talliton in patients with psoriasis requires an assessment of benefit-risk ratio, tk. Carvedilol can enhance the symptoms of the disease or trigger symptoms.
Each tablet contains Talliton 50 Lactose mg, which should be considered when administering the drug with insufficient lactase, galaktozemii, malabsorption syndrome glucose / galactose.
Each tablet contains Talliton 12.5 Sucrose mg, which should be considered for patients with diabetes, hereditary fructose intolerance, malabsorption of glucose / galactose or deficit sucrase / isomaltase.
Treatment should be stopped gradually, reducing the dose.
Patients, using contact lenses, should notify, Carvedilol reduces production of the tear fluid.
Effects on ability to drive vehicles and management mechanisms
Early treatment Talliton patients may experience dizziness,, fatigue. In this case, they should refrain from driving vehicles and Occupation potentially hazardous activities, require increased attention and psychomotor speed reactions. In the future, the definition of the safe dose is individually.
Talliton: overdose
Symptoms: severe hypotension, bradycardia, heart failure, cardiogenic shock, cardiac arrest.
Treatment: in the early hours – gastric lavage, artificial vomiting. The patient should be in a position with raised lower limbs. Antidote beta-adrenoceptor blocking action is orciprenaline or isoprenaline (I / dose 0.5-1 mg) or glucagon doze 1-5 mg (the maximum dose - 10 mg).
If severe hypotension shown parenteral administration of fluids and re-introduction of epinephrine (adrenaline) dose 5-10 ug or in / in infusion of 5 mcg / min.
For the treatment of bradycardia atropine administered in / dose 0.5-2 mg. To maintain cardiac glucagon used / in a dose of 1-10 mg fast, for 30 sec, then – continuous infusion rate of 2-5 mg / h.
If the predominant peripheral vasodilator effect (warm extremities, gipotenziya) you must assign norepinephrine (noradrenaline) in repeated doses 5-10 ug or as an infusion 5 mcg / min.
For relief of bronchospasm prescribe beta-agonists (in an aerosol or /) or aminophylline in /.
With the development of convulsions is recommended to slow introduction of diazepam or clonazepam.
In severe cases of intoxication, when dominated by symptoms of shock, Treatment should continue antidotes, It is to stabilize the patient's condition, given T1/2 karvedilola (6-10 no).
Talliton: drug interaction
In an application with drugs Talliton, deplete catecholamines (reserpine, MAO inhibitors), observed severe bradycardia and hypotension.
In an application Talliton with calcium channel blockers (verapamil, diltiazem) and antiarrhythmics (especially class I) It notes the development of severe arterial hypotension and heart failure. In / in the introduction of such combinations is contraindicated.
In an application with alpha Talliton- 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 strengthening mutual reduction of blood pressure and heart rate. In an application removal should be gradual, starting from carvedilol, then a few days could be phased receiving clonidine.
In an application Talliton with digoxin slows AV-conduction.
In an application Talliton insulin and hypoglycemic agents for oral administration there is a growing hypotensive action and masking of symptoms of hypoglycaemia.
In an application Talliton with nitrates and antihypertensives (klonidin, guanethidine, alpha-methyldopa, guanfaцin) noted increased hypotensive effect and decrease in heart rate.
In an application with Talliton anesthetics there is a growing inotropic and hypotensive action.
In an application with the means Talliton, affecting the CNS (hypnotics, trankvilizatorы, tricyclic antidepressants, ethanol), says mutual reinforcement effects.
In an application with NSAIDs Talliton marked decrease in the hypotensive action due to decreased production of prostaglandins.
In an application Talliton with ergotamine should take into account the effect of the last vasoconstrictor.
In an application Talliton with xanthine derivatives (aminofillinы, theophylline) marked decrease of beta-adrenoceptor blocking action.
Unnecessarily. Carvedilol undergoes oxidative metabolism, it may change in the pharmacokinetics of induction or inhibition of cytochrome P450 isoenzymes.
In an application with rifampicin Talliton marked decrease in the concentration of carvedilol in the blood serum 70%.
In an application with barbiturates Talliton a decline of carvedilol action.
In an application with cimetidine Talliton increases the bioavailability of carvedilol on 30%.
In an application Talliton with digoxin increases the concentration of digoxin in the blood plasma.
In an application with inhibitors Talliton isozyme CYP2D6 (quinidine, fluoxetine, paroxetine, propafenone) may increase the concentration of R(+) enantiomera karvedilola.
At simultaneous application with cyclosporine Talliton carvedilol inhibits metabolism of cyclosporine.
Talliton: terms of dispensing from pharmacies
The drug is released under the prescription.
Talliton: terms and conditions of storage
The drug should be stored away from light and moisture at a temperature of 15 ° to 25 ° C. Shelf-life of the drug in a blister - 3 year, in vial – 5 years.
