carvedilol 25 mg;
colloidal silicon dioxide;
Carvedilol - alpha and beta adrenergic blocking, hypotensive, antioxidant, antianginal.
Has a combined non-selective beta-blocking, alpha 1 -blocking and antioxidant effects. The vasodilating effect is mainly associated with the blockade of alpha 1 receptors. Due to vasodilation, it reduces TPVR. It has no intrinsic sympathomimetic activity and, like propranolol, has a membrane stabilizing effect.
Powerful antioxidant, eliminates free oxygen radicals. The combination of the vasodilating action and beta-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 observed when taking beta-blockers. Heart rate decreases slightly, renal blood flow and renal function are preserved. Since peripheral blood flow is maintained, coldness of the extremities is very rare, in contrast to patients who are treated with beta-blockers.
The antihypertensive effect develops rapidly - 2-3 hours after a single dose and lasts for 24 hours. With 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. Does not have a pronounced effect on lipid metabolism and the content of potassium, sodium and magnesium ions in plasma. In patients with impaired left ventricular function and / or circulatory failure, the alpha 1 -adrenoceptor blocking effect of carvedilol leads to dilation of arterial and, to a lesser extent, venous vessels; carvedilol has a beneficial effect on hemodynamic parameters: it increases the ejection function of the left ventricle and reduces its size.
Carvedilol has a beneficial effect on heart hemodynamics and left ventricular ejection fraction in both dilated cardiomyopathy and ischemic heart failure. In heart failure, end-systolic and end-diastolic volume decreases, as well as peripheral and pulmonary vascular resistance. The ejection fraction and cardiac index do not change during normal heart function.
It was found that with additional prescription against the background of cardiac glycosides, ACE inhibitors and diuretics, carvedilol reduces the mortality rate, slows down the progression of the disease and improves the general 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 bpm) and low ejection fraction (less than 23%).
During treatment with carvedilol, the ratio of HDL / LDL cholesterol does not change.
The absorption of carvedilol is fast and high. T max is 1 hour after taking the drug. Plasma concentration is proportional to the dose taken. The bioavailability is about 30%. Simultaneous food intake slows down the absorption of the drug, but does not affect the value of bioavailability.
Plasma protein binding is about 98–99%. V d - about 2 l / kg and increases (by 80%) in case of liver dysfunction (due to a decrease in the effect of the first passage through the liver). It is metabolized mainly in the liver due to intensive connection with glucuronic acid. By demethylation and hydroxylation of the phenyl ring, three active metabolites with pronounced antioxidant and adrenergic blocking properties are formed. T 1/2 of carvedilol is 6–10 hours, plasma clearance is about 590 ml / min. It is excreted mainly in the bile and a small part through the kidneys.
Penetrates the placental barrier and is excreted in breast milk.
Carvedilol is practically not excreted during hemodialysis. In liver cirrhosis, the bioavailability of carvedilol is 4 times higher, and C max in blood plasma is 5 times higher than normal. Carvedilol is excreted mainly through the gastrointestinal tract, therefore, in case of impaired renal function, accumulation of the drug is not observed.
It should be borne in mind that in elderly patients, the concentration of carvedilol in blood plasma is 50% higher than in younger patients.
- arterial hypertension in the form of mono- or combined therapy (in combination with thiazide diuretics);
- stable angina pectoris;
- chronic heart failure in combination with diuretics, digoxin, or ACE inhibitors.
Application during pregnancy and lactation
The drug is contraindicated in pregnancy.
If you need to use the drug Carvedilol Sandoz during lactation, you should stop breastfeeding.
- hypersensitivity to carvedilol and other components of the drug;
- chronic heart failure in the stage of decompensation;
- sick sinus syndrome;
- AV block II-III degree, with the exception of patients with an artificial pacemaker;
- severe bradycardia (heart rate less than 50 beats / min);
- cardiogenic shock, collapse;
- bronchial asthma;
- severe liver dysfunction;
- metabolic acidosis;
- lactation period;
- age up to 18 years (efficacy and safety have not been established);
- joint intravenous administration of verapamil, diltiazem or other antiarrhythmics (especially class I antiarrhythmics).
With care and control:
- pheochromocytoma (only stabilized by the appointment of alpha-blockers);
- peripheral vascular occlusive disease;
- AV blockade I degree;
- Prinzmetal's angina;
- impaired renal function;
- myasthenia gravis;
- treatment with alpha-blockers and alpha-adrenergic agonists;
- simultaneous use with digitalis drugs, diuretics and / or MAO inhibitors ;
- elderly age.
In recommended doses, Carvedilol is well tolerated, but side effects are possible in some cases.
From the digestive system: nausea, dry mouth, abdominal pain, diarrhea or constipation, vomiting, increased activity of hepatic transaminases.
From the nervous system: headache, dizziness, fatigue, loss of consciousness, muscle weakness (usually at the beginning of treatment), sleep disturbance, depression, paresthesia.
From the senses: reduction of lacrimation.
From the genitourinary system: renal dysfunction, edema, urinary disorders.
From the side of hematopoiesis: leukopenia, thrombocytopenia.
Allergic reactions: urticaria, itching, rash, appearance and / or exacerbation of psoriasis, sneezing, nasal congestion, bronchospasm, shortness of breath (in predisposed patients), very rarely - anaphylactoid reaction.
From the CVS: bradycardia, orthostatic hypotension, angina pectoris, AV blockade, progression of circulatory failure (cold extremities), progression of heart failure, exacerbation of intermittent claudication syndrome, Raynaud's syndrome.
Endocrine Disorders: Weight gain.
Others: pain in the limbs, flu-like symptoms.
As with the use of other drugs that block alpha-adrenergic receptors, latent current diabetes mellitus may appear or its symptoms may increase.
Catecholamine depletion drugs (reserpine, MAO inhibitors) can cause severe bradycardia and arterial hypotension. Concomitant administration with carvedilol of ACE inhibitors, thiazide diuretics, vasodilators, administered simultaneously, can lead to a sharp drop in blood pressure.
Enhances the action of insulin and sulfonylurea derivatives (while masking or weakening the severity of symptoms of hypoglycemia, reducing the breakdown of liver glycogen to glucose).
When administered simultaneously with insulin or oral hypoglycemic drugs, blood glucose should be monitored. Inhibitors of the CYP2D6 isoenzyme (quinidine, fluoxetine, propafenone) can increase the concentration of the R (+) - enantiomer of carvedilol.
Combined use with antiarrhythmic drugs (especially class I) and BMCC (verapamil, diltiazem) can provoke severe arterial hypotension and heart failure. Intravenous administration of these drugs together with carvedilol is contraindicated.
Increases the concentration of digoxin, which requires monitoring of its concentration, because simultaneous administration with cardiac glycosides can lead to AV block.
General anesthetics enhance the negative inotropic and hypotensive effects. Phenobarbital and rifampicin accelerate the metabolism and reduce the plasma concentration of carvedilol. Inhibitors of microsomal oxidation (cimetidine), diuretics and ACE inhibitors increase the concentration and enhance the hypotensive effect of carvedilol. Carvedilol inhibits the metabolism of cyclosporine.
How to take, course of administration and dosage
Carvedilol is taken orally, after meals, with a small amount of liquid. The dose is selected individually. Arterial hypertension: the recommended dose in the first 7-14 days is 12.5 mg / day in the morning after breakfast or divided into 2 doses of 6.25 mg, then 25 mg / day once in the morning or divided into 2 doses of 12.5 mg ...
After 14 days, the dose can be increased again. A Stable angina pectoris: the initial dose is 12.5 mg 2 times a day, after 7-14 days, under the supervision of a doctor, the dose can be increased to 25 mg 2 times a day. After 14 days, with insufficient efficacy and good tolerability of the drug, the dose can be further increased. The total daily dose should not exceed 100 mg (50 mg 2 times a day), over the age of 70 - 50 mg / day (25 mg 2 times a day).
When skipping the next dose, Carvedilol should be taken as soon as possible, however, if the time for taking the next dose is approaching, then take only it, without doubling. If it is necessary to cancel Carvedilol, Obolensk dose reduction should be done gradually over 1-2 weeks.
Symptoms: a marked decrease in blood pressure (SBP 80 mm Hg and below), severe bradycardia (less than 50 beats / min), impaired respiratory function (bronchospasm, etc.), chronic circulatory failure, cardiogenic shock, cardiac arrest.
Treatment: during the first two hours induce vomiting and wash out the stomach. Overdose requires intensive treatment, control of vital functions is necessary. The patient should be in a position with raised legs, i.e. in the Trendelenburg position. Beta-blocking antidotes are orciprenaline or isoprenaline 0.5–1 mg IV and / or glucagon at a dose of 1–5 mg (maximum dose 10 mg). Severe hypotension is treated with parenteral fluid and repeated administration of 5–10 mg epinephrine (or an IV infusion at 5 mcg / min).
With excessive bradycardia, intravenous atropine is prescribed at a dose of 0.5–2 mg. To maintain cardiac activity: intravenously, glucagon is administered rapidly (within 30 s), followed by a continuous infusion at the rate of 2–5 mg / h. If the peripheral vasodilator effect predominates (warm extremities, in addition to significant arterial hypotension), it is necessary to prescribe norepinephrine at 5-10 mcg in the form of intravenous infusion - 5 mcg / min.
To relieve bronchospasm, beta-adrenomimetics (in the form of an aerosol or IV) or aminophylline IV are prescribed. If seizures develop, slow administration of diazepam or clonazepam is recommended. In severe cases of intoxication, when the symptoms of shock dominate, treatment should be continued until the patient's condition stabilizes, taking into account the T1 / 2 of carvedilol, which is 6-10 hours.
If the heart rate drops to 55 beats / min, the drug should be discontinued. In people with allergies or desensitization, taking carvedilol may increase allergic sensitivity.
Contact lens wearers should be warned that the drug reduces tear production. Upon completion of the course of treatment with Carvedilol, Sandoz, simultaneously with clonidine, first gradually reduce the dosage of clonidine and then first cancel clonidine, and then carvedilol.
If you need to use Carvedilol Sandoz during lactation, you should stop breastfeeding. During the period of treatment, it is necessary to exclude alcohol intake.
With the progression of circulatory failure during treatment, it is recommended to increase the dose of diuretics, in case of renal failure, adjust the dose taking into account the indicators of the functional state of the kidneys.
If surgery is necessary using general anesthesia, the anesthesiologist should be warned about prior carvedilol therapy. It should be borne in mind that the drug can mask the symptoms of thyrotoxicosis and hypoglycemia, therefore it is recommended to regularly monitor blood glucose levels and, if necessary, adjust doses.