Composition, form of production and packaging
Tablets are yellow, round, biconcave, with a risk on both sides and on the sides and with the inscription "C2" on one side.
carvedilol 6.25 mg
Excipients: iron oxide yellow, lactose monohydrate, microcrystalline cellulose, crospovidone, povidone K30, silicon dioxide colloid, magnesium stearate.
10 pieces. - blisters (3) - packs of cardboard.
The tablets are pinkish-beige, round, biconvex, with a risk on both sides and on the sides and with the inscription "C3" on one side.
carvedilol 12.5 mg
Excipients: iron oxide red, iron oxide yellow, lactose monohydrate, microcrystalline cellulose, crospovidone, povidone K30, silicon dioxide colloid, magnesium stearate.
10 pieces. - blisters (3) - packs of cardboard.
Tablets are white or almost white, round, biconcave, with a risk on both sides and on the sides and with the inscription "C4" on one side.
carvedilol 25 mg
Excipients: lactose monohydrate, microcrystalline cellulose, crospovidone, povidone K30, silicon dioxide colloid, magnesium stearate.
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
Beta 1 -, beta 2 -adrenergic blocker. Alpha 1- adrenoblocker. Has combined non-selective beta-adrenoblocking, alpha 1- adrenoblocking and antioxidant effect. The vasodilating effect is associated mainly with blockade? 1- adrenoreceptors. Thanks to vasodilation reduces OPSS. Does not have an internal sympathomimetic activity and, like propranolol, has a membrane-stabilizing effect.
Eliminates free oxygen radicals.
The combination of vasodilating action and beta-adrenergic blocking 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 OPSS, which is noted when taking beta-blockers. Slightly decreases heart rate, renal blood flow and kidney function are preserved. 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. For prolonged treatment, the maximum effect is observed after 3-4 weeks.
In patients with ischemic heart disease, carvedilol has anti-ischemic and antianginal effects. 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: it increases the function of the left ventricular ejection 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, ACE inhibitors and diuretics, carvedilol reduces the mortality 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 per minute) and low ejection fraction (less than 23%).
During treatment with carvedilol, the ratio of Xc-HDL / LDL does not change.
Absorption of carvedilol is fast and high. C max in blood plasma is achieved after 1 hour after taking the drug. Concentration in plasma is proportional to the dose taken. Bioavailability is about 30%. Simultaneous food intake slows the absorption of the drug, but does not affect the bioavailability.
Binding to plasma proteins is about 98-99%. V d - about 2 l / kg.
It penetrates through the placental barrier and is excreted in breast milk.
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.
T 1/2 carvedilol is 6-10 hours, plasma clearance is about 590 ml / min. It is excreted mainly with bile and a small part - through the kidneys.
Carvedilol is practically not excreted in hemodialysis.
Pharmacokinetics in special clinical cases
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.
V d increases (by 80%) in the case of a violation of the liver (by reducing the effect of the first passage through the liver).
It should be borne in mind that in elderly patients carvedilol concentration in the blood plasma is 50% higher than at a young age.
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 in the form of mono- or combination therapy (in combination with thiazide diuretics);
- stable angina pectoris;
- Chronic heart failure in combination with diuretics, digoxin or ACE inhibitors.
Carvedilol Sandoz В® is taken orally with a sufficient amount of liquid.
The initial dose is 12.5 mg 1 time / day (in the morning after breakfast) for the first 2 days, then for 25 mg 1 time / day. If necessary, after 14 days, the dose may be increased. The maximum dose is 50 mg / day in 1 or 2 doses (morning and evening).
In elderly patients, in some cases, a dose of 12.5 mg can be effective.
The initial dose is 12.5 mg 2 times / day for the first 2 days, then 25 mg twice a day (morning and evening). 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 patients, 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 drugs such as digoxin, diuretics and ACE inhibitors should be documented prior to the prescription of Carvedilol Sandoz В® .
Carvedilol Sandoz В® should be taken with meals (to reduce the risk of orthostatic hypotension).
The recommended initial dose is 3.125 mg 2 times / day 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 2 times / day, then - up to 25 mg 2 times / day. Patients are prescribed the maximum tolerated dose. The maximum recommended dose is 25 mg 2 times / day for patients with a body weight of up to 85 kg and 50 mg 2 times / 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. possibly worsening of the course of heart failure. A fluid retention may develop, and in connection with the presence of a vasodilator effect - arterial hypotension and lethargy. If fluid is delayed, the dose of diuretics should be increased, and a temporary dose reduction of Carvedilol Sandoz В® may be required. Sometimes a temporary cessation of treatment is required.
In recommended doses, Carvedilol Sandoz В® is well tolerated, but in some cases, side effects are possible.
On the part of the digestive system: nausea, dry mouth, abdominal pain, diarrhea or constipation, vomiting, increased activity of hepatic transaminases.
From the side of the central nervous system: headache, dizziness, fatigue, loss of consciousness, muscle weakness (usually at the beginning of treatment), sleep disturbance, depression, paresthesia.
From the senses: a decrease in tearing.
On the part of the genitourinary system: violations of the function of the kidneys, swelling.
From the hematopoiesis: leukopenia, thrombocytopenia.
From the cardiovascular system: bradycardia, otrostatic hypotension, stenocardia, AV blockade, progression of circulatory failure (cold extremities), progression of heart failure.
Allergic reactions: urticaria, itching, rashes, the appearance and / or exacerbation of psoriasis, sneezing, nasal congestion, bronchospasm, dyspnea (in predisposed patients); very rarely anaphylactoid reactions.
Other: rarely aggravation of the syndrome of intermittent claudication, Raynaud's syndrome, pain in the limbs, urination disorder, flu-like syndrome, weight gain.
As with the use of other alpha-blockers, latent diabetes mellitus may develop or its symptomatology may increase.
- chronic heart failure in the stage of decompensation;
- AV blockade II and III degree, except for patients with an artificial pacemaker;
- pronounced bradycardia (heart rate less than 50 beats per minute);
- cardiogenic shock, collapse;
- bronchial asthma;
severe hepatic impairment;
- joint intravenous administration of verapamil, diltiazem or other antiarrhythmic drugs (especially class I);
- the period of lactation (breastfeeding);
- age under 18 years (efficiency and safety not established);
- Hypersensitivity to the components of the drug.
With caution and under control, the drug should be prescribed for diabetes mellitus, hypoglycemia, thyrotoxicosis, pheochromocytoma (only stabilized by the appointment of alpha-blockers), peripheral vascular occlusive diseases, grade I AV block, chronic obstructive pulmonary disease, prinzmetal angina, psoriasis, renal dysfunction , depression, myasthenia gravis, in the treatment of alpha-adrenergic blockers and alpha-adrenomimetics, with simultaneous use with digitalis preparations, diuretics and / or inhibitor MAO, as well as elderly patients.
PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy.
If you need the drug Carvedilol Sandoz В® during lactation, breastfeeding should be abolished.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution and under control, the drug should be prescribed for violations of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in severe violations of liver function.
APPLICATION FOR CHILDREN
Contraindicated: age under 18 years (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
With caution and under control, the drug should be prescribed to elderly patients.
If the heart rate drops to 55 bpm, the drug should be discontinued.
In patients with allergies or undergoing a course of desensitization, taking carvedilol may increase allergensensitivity.
Patients who use contact lenses should be warned that the drug reduces tearing.
At the end of the course of treatment with Carvedilol Sandoz В® concomitantly with clonidine, first gradually reduce the dosage of clonidine and then first abolish clonidine and then carvedilol.
During the treatment, exclude alcohol.
With the progression of circulatory insufficiency against the background of treatment, it is recommended to increase the dose of diuretics, with renal failure to adjust the dose in accordance with the indicators of the functional state of the kidneys.
If surgical intervention with general anesthesia is necessary, an anesthesiologist should be warned of previous therapy with carvedilol.
It should be borne in mind that the drug can mask the symptoms of thyrotoxicosis and hypoglycemia, so it is recommended that regular monitoring of blood glucose levels be carried out and, if necessary, adjusting the doses.
The drug should be withdrawn gradually (within 1-2 weeks) in order to avoid the development of withdrawal syndrome, especially in patients with IHD.
Impact on the ability to drive vehicles and manage mechanisms
Caution should be given to patients whose work requires a rapid psychomotor reaction (management of vehicles, work with equipment).
Symptoms: marked decrease in blood pressure (systolic pressure 80 mm Hg and below), pronounced bradycardia (less than 50 beats per minute), respiratory disorders (bronchospasm), chronic circulatory failure, cardiogenic shock, cardiac arrest.
Treatment: During the first 2 hours, induce vomiting and rinse the stomach. Overdosing requires intensive treatment. The patient should be in a position with raised legs (in the Trendelenburg position). Antidote beta-adrenoblokiruyuschey action is orciprenaline or isoprenaline at a dose of 0.5-1 mg iv 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 (adrenaline) at a dose of 5-10 mg (or its IV infusion at a rate of 5 Ојg / min).
With excessive bradycardia, intravenous atropine is given in a dose of 0.5-2 mg. To maintain cardiac activity in / in quickly (within 30 seconds) inject glucagon, followed by a constant infusion at a rate of 2-5 mg / h. If the peripheral vasodilator action predominates (warm limbs, in addition to a significant arterial hypotension), norepinephrine should be given in repeated doses of 5-10 Ојg or as an infusion of 5 Ојg / min.
To stop bronchospasm, beta-blockers are prescribed (in the form of an aerosol or IV) or aminophylline IV.
If seizures develop, slow diazepam or clonazepam is recommended.
In severe cases of intoxication, when symptoms of shock predominate, treatment with antidotes should continue until the patient's condition stabilizes, taking into account T 1/2 carvedilol 6-10 hours.
In the conditions of resuscitation, to monitor the indicators of vital organs.
With the simultaneous use of the drug Carvedilol Sandoz В® with funds depleting supplies of catecholamines (reserpine, MAO inhibitors), severe bradycardia and arterial hypotension can develop.
Simultaneous administration with carvedilol of ACE inhibitors, thiazide diuretics, and vasodilators prescribed simultaneously may lead to a sharp drop in blood pressure.
Carvedilol enhances the action of insulin and sulfonylurea derivatives (simultaneously masking or reducing the severity of hypoglycemia symptoms, reducing the digestion of liver glycogen to glucose). At simultaneous appointment with insulin or hypoglycemic preparations of oral application, it is necessary to control the level of glucose in the blood.
When used simultaneously with inhibitors of the isoenzyme CYP2D6 (quinidine, fluoxetine, propafenone), an increase in the concentration of the R (+) enantiomer of carvedilol is possible.
The combined use of carvedilol with antiarrhythmics (especially I class) and slow calcium channel blockers (verapamil, diltiazem) can cause severe arterial hypotension and heart failure. In / in the administration of these drugs, together with the use of carvedilol is contraindicated.
Carvedilol increases the concentration of digoxin, which requires monitoring of its concentration, simultaneous administration with cardiac glycosides can lead to AV blockade.
General anesthetics increase the negative inotropic and hypotensive effect of carvedilol.
Phenobarbital and rifampicin accelerate metabolism and reduce the concentration of carvedilol in the plasma.
Inhibitors of microsomal oxidation (cimetidine), diuretics and ACE inhibitors increase the concentration and intensify the hypotensive effect of carvedilol.
Carvedilol delays the metabolism of cyclosporine.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 3 years.