KRKA #Circulatory_system #Hypertension #HEALTH_CARE
Pharmacological properties
Pharmacodynamics. Carvedilol is a non-selective β-adrenergic receptor blocker with a vasodilating effect. it also has antioxidant and antiproliferative properties.
The active ingredient carvedilol is a racemate; enantiomers differ in effects and metabolism. The S (-) - enantiomer has an activity aimed at blocking α1 - and β-adrenergic receptors, while the R (+) - enantiomer exhibits only activity aimed at blocking α1-adrenergic receptors. Due to the cardio-selective blockade of β-adrenergic receptors, carvedilol reduces blood pressure, heart rate and cardiac output. Carvedilol reduces pressure in the pulmonary artery and right atrium. By blocking α1-adrenergic receptors, it causes peripheral vasodilation and reduces the systemic vascular resistance. Thanks to these effects, the load on the heart muscle is reduced and the development of angina pectoris is prevented. In patients with heart failure, this leads to an increase in the ejection fraction from the left ventricle and a decrease in the severity of symptoms of the disease. Similar effects were noted in patients with left ventricular dysfunction. Carvedilol does not show internal sympathomimetic activity and, like propranolol, has membrane stabilizing properties. Plasma renin activity decreases, and fluid retention in the body is rare. The effect on blood pressure and heart rate is most pronounced 1-2 hours after taking the preparation.
In hypertensive patients with normal renal function, carvedilol decreases renal vascular resistance. In this case, there are no significant changes in glomerular filtration, renal blood flow and excretion of electrolytes. Due to the maintenance of peripheral blood flow, cold extremities are rarely noted, which is characteristic of treatment with β-adrenergic receptor blockers. Carvedilol generally does not affect plasma lipoprotein levels.
Pharmacokinetics. Carvedilol is rapidly and almost completely absorbed after oral administration. Almost completely binds to blood plasma proteins. The volume of distribution is about 2 l / kg. Plasma concentration is proportional to the administered dose.
Only about 30% of the administered carvedilol is bioavailable due to significant first pass metabolism (mainly due to the liver enzymes CYP 2D6 and CYP 2C9). Three active metabolites are formed with the ability to block β-adrenergic receptors; one of them (4'-hydroxyphenyl derivative) is 13 times more potent than carvedilol for β-receptor blockade.
In comparison with carvedilol, active metabolites have a weak vasodilatory effect. Stereoselective metabolism; therefore, the level of R (+) carvedilol in blood plasma is 2-3 times higher than the level of S (-) carvedilol. Plasma levels of active metabolites are approximately 10 times lower than carvedilol levels. T1 / 2 is very different: 5-9 hours for R (+) carvedilol and 7-11 hours for S (-) carvedilol. In the elderly, an increase in carvedilol levels of approximately 50% is noted. In patients with liver cirrhosis, the bioavailability of carvedilol is increased by 4 times, and Cmax in blood plasma is 5 times higher than the corresponding values in healthy people.
In patients with impaired liver function, bioavailability increases to 80% due to a decrease in the metabolic breakdown of the first pass. Since carvedilol is excreted mainly in the feces, significant accumulation of the preparation is unlikely in patients with impaired renal function.
Food intake slows down the rate of absorption of the preparation, but this does not affect its bioavailability.
Indications
Coriol 3.125 and 6.25 mg
Essential arterial hypertension. Coriol can be used alone or in combination with other antihypertensive preparations (especially thiazide diuretics).
Chronic stable angina pectoris.
Chronic stable heart failure (in addition to standard therapy with diuretics, digoxin, or ACE inhibitors) to prevent disease progression in patients with NYHA class II – III heart failure.
Coriol 12.5 and 25 mg
Essential arterial hypertension.
Chronic stable angina pectoris.
Moderate to severe chronic heart failure as adjunctive therapy.
Application
To slow down absorption and prevent orthostatic effects, Coriol should be taken after meals.
The dose should be selected individually. Treatment should be started with low doses, which should be gradually increased until optimal clinical response is achieved. After taking the first dose and after each dose increase, it is recommended to measure blood pressure in a standing position 1 hour after administration to exclude possible hypotension.
Treatment with Coriol should be discontinued gradually by reducing doses over 1–2 weeks.
If treatment is suspended for more than 2 weeks, then it should be reinstated with a low dose.
Essential arterial hypertension. The initial dose of Coriol is 12.5 mg in the morning after breakfast or 6.25 mg 2 times a day (morning and evening). After 2 days of treatment, the dose should be increased to 25 mg in the morning (1 tablet of 25 mg) or to 12.5 mg 2 times a day. After 14 days of treatment, the dose can be increased again to 25 mg 2 times a day.
The maximum dose of Coriol for the treatment of hypertension is 25 mg 2 times a day. The recommended starting dose of Coriol for the treatment of hypertension in patients with heart failure is 3.125 mg 2 times a day.
Chronic stable angina pectoris. The initial dose of Coriol is 12.5 mg 2 times a day after meals. After 2 days of treatment, the dose should be increased to 25 mg 2 times a day.
The maximum dose of Coriol for the treatment of chronic angina pectoris is 25 mg 2 times a day. The recommended starting dose of Coriol for the treatment of angina pectoris in patients with heart failure is 3.125 mg 2 times a day.
Chronic heart failure. Coriol is recommended for the treatment of stable mild, moderate or severe chronic heart failure as an adjunct to standard preparations such as diuretics, ACE inhibitors or digitalis preparations. Coriol can also be taken by patients who cannot tolerate ACE inhibitors. The patient can be prescribed Coriol only after balancing the doses of a diuretic, an ACE inhibitor and cardiac glycosides (if prescribed). The dose is selected individually. During the first 2-3 hours after the first dose or after increasing the dose, close medical supervision is necessary to control the tolerability of the preparation. If the patient has a decrease in heart rate of 55 beats / min, then the Coriol dose must be reduced. If symptoms of arterial hypotension occur, then you must first consider reducing the dose of a diuretic or an ACE inhibitor; and if these measures are insufficient, then reduce the Coriol dose.
At the beginning of treatment with Coriol or after increasing the dose, a transient increase in heart failure may occur. In this case, it is necessary to increase the dose of the diuretic. Sometimes it is necessary to temporarily reduce the dose of Coriol or even to cancel it. After stabilization of the clinical condition, Coriol treatment can be resumed or its dose increased.
The initial dose is 3.125 * mg 2 times a day. If the patient tolerates this dose well, then it can be gradually increased (every 2 weeks) until the optimal dose is reached. The following doses are 6.25 mg 2 times a day, then 12.5 mg 2 times a day and 25 mg 2 times a day. The patient should take the maximum tolerated dose. The maximum recommended dose for patients weighing up to 85 kg is 25 mg 2 times a day. For patients weighing 85 kg - up to 50 mg 2 times a day.
Elderly patients. There is no need to change the dose.
Children. The preparation is not recommended for use in children.
Patients with hepatic impairment. Coriol is not recommended for use in patients with severe hepatic impairment.
Patients with renal impairment. For patients with systolic blood pressure of 100 mm Hg. Art. no special dose changes are required (see SPECIAL INSTRUCTIONS).
* If it is necessary to use a dose of 3.125 mg, prescribe other carvedilol preparations in the appropriate dosage form and dosage.
Contraindications
- Hypersensitivity to the active substance or any of the excipients of the preparation;
- decompensated heart failure - NYHA class IV heart failure, which requires the introduction of inotropic preparations;
- blockade of II and III degrees (except when a permanent pacemaker is installed);
- concomitant administration of verapamil, diltiazem, or other antiarrhythmics (especially class I antiarrhythmics);
- severe bradycardia (heart rate 50 beats / min);
- severe arterial hypotension (systolic blood pressure 85 mm Hg. Art.);
- cardiogenic shock;
- sick sinus syndrome (including sinus blockade);
- uncompensated heart failure, requiring the administration of positive isotropic and / or diuretics;
- cor pulmonale, pulmonary hypertension;
- BA or obstructive airway disease accompanied by bronchospasm;
- pheochromocytoma (except when it is properly controlled with the use of blockers of α-adrenergic receptors);
- Prinzmetal's angina;
- severe liver dysfunction;
- simultaneous use of MAO inhibitors (with the exception of MAO-B inhibitors);
- intolerance to galactose, Lapp lactase deficiency or glucose-galactose malabsorption;
- metabolic acidosis;
- the period of pregnancy and lactation, children's age.
Side effects
The frequency of adverse reactions is estimated as follows: very often (10%), often (1%, 10%), infrequently (0.1%, 1%), rarely (0.01%, 1%), very rarely, including some cases (0.01%).
On the part of the blood and lymphatic system: often - anemia; rarely, thrombocytopenia; very rarely - leukopenia, a decrease in the level of prothrombin.
From the immune system: very rarely - hypersensitivity (allergic reaction), anaphylactic reactions.
Metabolic and digestive disorders: often - weight gain, hypercholesterolemia, impaired blood glucose control (hyperglycemia, hypoglycemia) in patients with pre-existing diabetes mellitus, latent diabetes manifestations are possible, symptoms of existing diabetes may increase during therapy, hyperkalemia, hypertriglyceridemia, hyponatremia , an increase in the level of alkaline phosphatase, creatinine, urea.
Mental disorders: often - depression, depressed mood; infrequently - sleep disorders.
From the nervous system: very often - dizziness, headache; infrequently - a state before loss of consciousness, loss of consciousness, paresthesia.
From the side of the organ of vision: often - visual impairment, decreased tearing (dry eyes), eye irritation.
From the side of the cardiovascular system: very often - heart failure, hypotension; often - bradycardia, edema (including generalized, peripheral, dependent edema and edema of the genitals and legs), hypervolemia, fluid overload, orthostatic hypotension, peripheral blood circulation disorders (cold extremities, peripheral vascular disease, exacerbation of Charcot's syndrome and Raynaud's phenomenon); infrequently - blockade, angina pectoris, arterial hypertension, palpitations.
Respiratory, thoracic and mediastinal disorders: often - shortness of breath, pulmonary edema, asthma in sensitive patients; rarely - nasal congestion.
From the digestive tract: often - nausea, diarrhea, vomiting, dyspepsia, abdominal pain; infrequently - constipation; rarely - dry mouth, periodontitis, melena.
From the liver and biliary tract: very rarely - an increase in ALT (ALT), AST (AST) and gamma glutamyl transferase (GGT).
On the part of the skin and subcutaneous tissues: infrequently - skin reactions (for example, allergic exanthema, dermatitis, increased sweating, urticaria, itching, skin lesions similar to psoriasis and lichen planus), alopecia, worsening of the course of psoriasis, increased sweating.
On the part of the musculoskeletal system and connective tissue: often - pain in the limbs; rarely - arthralgia, convulsions.
On the part of the kidneys and urinary tract: often - renal failure and impaired renal function in patients with diffuse vascular disease and / or underlying renal failure, urinary disorders; very rarely - urinary incontinence in women, hematuria, albuminuria, glucosuria, hyperuricemia.
From the reproductive system and mammary glands: infrequently - erectile dysfunction.
General disorders: very often - asthenia (fatigue); often - pain, flu-like symptoms, fever; dizziness, loss of consciousness, headache, and asthenia are usually mild and likely to appear early in treatment.
In patients with congestive heart failure, worsening heart failure and fluid retention may occur when the dose of carvedilol is increased by titration.
Heart failure was frequently reported as an adverse event in both placebo and carvedilol patients (14.5% and 15.4%, respectively, in patients with left ventricular dysfunction after acute myocardial infarction).
Reversible deterioration of renal function has been observed during therapy with carvedilol in patients with chronic heart failure with low blood pressure, coronary artery disease and diffuse vascular disease and / or underlying renal failure.
As a class, β-adrenergic receptor blockers can increase the manifestations of latent diabetes mellitus, worsen the course of severe diabetes mellitus and suppress the regulation of blood glucose levels.
Carvedilol can cause urinary incontinence in women and disappears when the preparation is discontinued.
Special instructions
Arterial hypotension. the preparation is not recommended for use in patients with low blood pressure.
Orthostatic hypotension. Especially at the beginning of treatment with Coriol and with increasing doses, orthostatic hypotension with dizziness and vertigo, sometimes also with fainting, may occur. Patients with heart failure, the elderly, and those taking other antihypertensive preparations or diuretics are at greatest risk. These effects can be prevented by using a low starting dose of Coriol, carefully increasing the maintenance dose, and taking the preparation after meals. Patients should be told about measures to prevent orthostatic hypotension (caution when standing up, if dizziness occurs, the patient should sit or lie down).
Termination of treatment. With an abrupt cessation of treatment with Coriol (as well as with other β-adrenergic receptor blockers), increased sweating, tachycardia, shortness of breath and increased angina pectoris may occur. Patients with angina pectoris who may have a heart attack are at greatest risk. The dose should be reduced gradually over 1–2 weeks.
If treatment has been suspended for more than 2 weeks, it should be renewed starting with the lowest dose.
Chronic heart failure. In most cases, patients with chronic heart failure should be prescribed carvedilol in addition to therapy with diuretics, ACE inhibitors, digitalis and / or vasodilators. The beginning of treatment should be carried out in a hospital under the supervision of a physician. Therapy can be started only if, during the generally accepted basic therapy, the patient's condition is stable for at least 4 weeks. Patients with severe heart failure, salt deficiency or dehydration, elderly people with a low basal blood pressure for about 2 hours after taking the first dose or after increasing the dose need constant monitoring, since arterial hypotension may develop. Arterial hypotension, which has arisen as a result of excessive vasodilation, is first treated with a decrease in the dose of diuretics, and if the symptoms persist, then the dose of any ACE inhibitor can be reduced. At the beginning of treatment or with an increase in the dose of the preparation, the course of heart failure may worsen or fluid retention may occur. In this case, it is necessary to increase the dose of the diuretic. However, in some cases, it may be necessary to reduce the dose or discontinue the preparation. The dose of carvedilol should not be increased until symptoms associated with worsening heart failure or hypotension due to excessive vasodilation are controlled.
Carvedilol should be used with caution in patients with chronic heart failure taking digitalis preparations, as this combination increases AV conduction.
Carvedilol can cause bradycardia. If the heart rate is 55 beats / min and symptoms associated with bradycardia occur, the dose of the preparation must be reduced.
Since carvedilol has a negative dromotropic effect, it should be used with caution in patients with grade I heart block.
Impaired renal function. In patients with heart failure and low blood pressure (systolic 100 mm Hg), ischemic heart disease or systemic atherosclerosis and / or against the background of renal failure during treatment with carvedilol, deterioration of renal function was observed, which was reversible. In patients with heart failure with these risk factors, it is necessary to monitor renal function during dose titration of carvedilol. If there is a significant deterioration in renal function, the dose of carvedilol should be reduced or discontinued.
Diabetes mellitus and hyperthyroidism. Β-adrenergic receptor blockers slow heart rate and therefore can mask hypoglycemia in patients with diabetes mellitus and thyrotoxicosis in patients with thyroid disease. In patients with heart failure associated with diabetes mellitus, a decrease or increase in blood glucose levels may occur.
Antiarrhythmic preparations. With the simultaneous use of carvedilol with calcium channel blockers, such as verapamil and diltiazem or other antiarrhythmic preparations, especially amiodarone, it is necessary to monitor blood pressure and ECG, therefore, their simultaneous intravenous use should be avoided.
Thyrotoxicosis. Carvedilol, like other β-blocking preparations, can mask the symptoms of thyrotoxicosis.
General anesthesia. Β-adrenergic receptor blockers reduce the risk of arrhythmia during anesthesia, but, in addition, the risk of arterial hypotension may increase, so some anesthetics must be used with caution.
Liver dysfunction. In very rare cases, carvedilol can cause liver function impairment. If clinical deterioration is suspected, liver function should be checked. In case of liver failure, the patient should stop taking Coriol. As a rule, after stopping treatment, liver function normalizes.
COPD. Β-adrenergic receptor blockers can increase bronchial obstruction; therefore, patients with COPD are not advised to use these preparations. In exceptional cases, Coriol can be prescribed to patients with mild lung disease if other preparations are ineffective; however, this requires careful observation. It is important that these patients take the minimum effective dose of Coriol. If signs of airway obstruction appear, treatment with Coriol should be discontinued immediately.
Peripheral vascular disease and Raynaud's syndrome. Carvedilol should be used with caution in patients with peripheral vascular disease and Raynaud's syndrome, since β-adrenergic receptor blockers can increase the severity of symptoms of the disease.
Psoriasis. Prescribe with caution to patients with psoriasis, as this can intensify skin reactions.
Prinzmetal's angina. In patients with Prinzmetal angina, non-selective β-adrenergic blockers can cause chest pain (the α1-adrenergic blocking effect of carvedilol can prevent this, but there is not enough clinical experience with the use of carvedilol for Prinzmetal angina).
Pheochromocytoma. Patients with pheochromocytoma can take β-adrenergic blockers only if they have already started taking α-adrenergic blockers initially.
Hypersensitivity reactions. Patients with a history of severe hypersensitivity reactions and those who undergo desensitization should be prescribed carvedilol with caution, since β-adrenergic receptor blockers can increase the reactivity during allergy tests, increase sensitivity to allergens and the severity of anaphylactic reactions.
Contact lenses: Contact lens wearers should be warned of the possibility of reducing tear production.
The safety and efficacy of Coriol in patients under the age of 18 has not been studied, therefore it is not recommended for use in such patients.
Information about the excipients of the preparation. The preparation contains sucrose and lactose. This preparation should not be taken by patients with the following disorders: fructose intolerance, lactase deficiency, galactosemia, glucose-galactose absorption disorder or sucrase-isomaltase deficiency.
Patients are not advised to consume alcoholic beverages during treatment, as alcohol can enhance the effects of carvedilol.
Since the preparation contains sucrose, this should be taken into account in patients with diabetes mellitus.
During pregnancy and breastfeeding. For carvedilol, there is insufficient clinical data on the effect during pregnancy. The results of animal experiments are insufficient to assess the effect during pregnancy on the development of the fetus and on the baby after birth. The potential risk to humans remains unknown.
Β-adrenergic receptor blockers have a negative pharmacological effect on the fetus. They can cause hypotension, bradycardia, and hypoglycemia in the fetus.
Coriol is contraindicated during pregnancy.
Since there is a possibility that carvedilol passes into breast milk, breastfeeding is not recommended during Coriol treatment.
Children. The safety and efficacy of Coriol in children has not been established, therefore, the appointment of the preparation to children is contraindicated.
Interactions
Certain antiarrhythmic, narcotic, antihypertensive preparations, preparations for the treatment of angina pectoris, other β-adrenergic receptor blockers (for example, in the form of eye drops), preparations that lower the level of catecholamines (for example, MAO inhibitors, reserpine), and cardiac glycosides can enhance the effects of carvedilol. therefore, the dose of these preparations and Coriol should be chosen with caution.
Pharmacokinetic interactions
Digoxin. Digoxin concentrations are increased by approximately 15% with the simultaneous administration of digoxin and carvedilol. Digoxin and carvedilol both inhibit AV conduction. Increased monitoring of digoxin levels at the start, dose adjustment, or discontinuation of carvedilol is recommended.
Insulin or oral hypoglycemic agents. Preparations with β-blocking properties can enhance the effect of insulin and oral hypoglycemic agents in lowering blood glucose levels. The manifestations of hypoglycemia can be masked or weakened (especially tachycardia). Therefore, regular monitoring of blood glucose levels is recommended for patients taking insulin or oral hypoglycemic agents.
Inductors or inhibitors of P-glycoprotein, CYP 2D6, CYP 2D9. Carvedilol is an inhibitor of P-glycoprotein, therefore, the bioavailability of preparations that are transported by P-glycoprotein may increase when used simultaneously with carvedilol.
Inhibitors, like inducers of CYP 2D6 and CYP 2D9, can stereoselectively change the systemic or first-pass metabolism of carvedilol, increasing or decreasing the concentration of R- and S-carvedilol in blood plasma.
Fluoxetine. In studies of patients with heart failure, the simultaneous use of fluoxetine as a potent inhibitor of CYP 2D6 led to stereoselective inhibition of carvedilol metabolism with an increase in the R (+) enantiomer AUC level by 77%.
β-Agonists of bronchodilators. Non-cardioselective β-adenoreceptor blockers counteract the effects of β-agonists of bronchodilators, therefore such patients require careful monitoring.
Stimulants and inhibitors of liver metabolism. Rifampicin reduces the plasma concentration of carvedilol by approximately 70%. Cimetidine increases AUC by approximately 30%, but does not cause changes in Cmax. Increased attention may be needed for those taking mixed function oxidase stimulants, such as rifampicin, as plasma carvedilol levels may be reduced, or mixed function oxidase inhibitors, such as cimetidine, as plasma levels may be elevated. However, given the relatively low effect of cimetidine on carvedilol levels, the likelihood of any clinically important interaction is minimal.
Preparations that lower catecholamines: Patients who are taking preparations with β-blocking properties and a preparation that can lower catecholamines (such as reserpine and MAO inhibitors) should be closely monitored for signs of hypotension and / or severe bradycardia.
Cyclosporine: There was a moderate increase in mean trough cyclosporine concentrations after starting carvedilol treatment in 21 kidney transplant patients with chronic vascular rejection. In approximately 30% of patients, the dose of cyclosporine needed to be reduced in order to maintain the concentration of cyclosporine in the therapeutic range, while others did not require adjustment. On average, in these patients, the dose of cyclosporine was reduced by approximately 20%. Due to the wide intraspecific variability of the need for dose adjustment, it is recommended to carefully monitor the concentration of cyclosporine after starting therapy with carvedilol, in order to adjust the dose of cyclosporine if necessary.
Antiarrhythmic preparations. There have been isolated cases of conduction disturbances (rarely with hemodynamic disturbances) when carvedilol and diltiazem were administered in parallel. As with other β-blocking preparations, if carvedilol is administered orally with calcium channel blockers such as verapamil or diltiazem, ECG and blood pressure monitoring are recommended. These preparations should not be given IV. It is necessary to carefully monitor the patient's condition with the simultaneous use of carvedilol and amiodarone (oral) or class I antiarrhythmic preparations. Soon after the start of treatment with β-adrenergic receptor blockers, the development of bradycardia, cardiac arrest, and ventricular fibrillation was reported in patients who were simultaneously taking amiodarone. There is a risk of developing heart failure in case of concomitant IV therapy with class Ia or Ic antiarrhythmic preparations.
Other antihypertensive medicines. Like other preparations with β-blocking properties, if it is necessary to simultaneously use carvedilol with calcium channel blockers such as verapamil or diltiazem, ECG and blood pressure monitoring are recommended. Like other β-blocking preparations, carvedilol may enhance the effect of other antihypertensive preparations (eg, α-adrenergic receptor antagonists), which can lead to hypotension as part of the side effect profile.
Pharmacodynamic interactions
Clonidine: Concomitant use of clonidine with β-blocking preparations may increase the decrease in blood pressure and heart rate. When concomitant treatment with β-blocking preparations and clonidine is completed, the β-blocker should be discontinued first. Then, after a few days, you can discontinue clonidine therapy by gradually reducing the dose.
Dihydropyridine. With the simultaneous use of dihydropyridines and carvedilol, careful observation of the patient should be ensured, since cases of heart failure and severe arterial hypotension have been reported.
Nitrates. Enhance the hypotensive effect.
NSAIDs, estrogens and corticosteroids. The antihypertensive effect of carvedilol is weakened when used simultaneously with preparations that retain fluid and sodium in the body.
Sympathomimetics, α-mimetics and β-mimetics. With simultaneous use, there is a risk of developing hypertension and severe bradycardia.
Ergotamine. With simultaneous use, vasoconstriction is enhanced.
Muscle relaxants. When carvedilol is combined with muscle relaxants, neuromuscular blockade is enhanced.
Xanthine derivatives. It should be used with caution with xanthine derivatives (aminophylline, theophylline) due to a decrease in the severity of β-adrenergic blocking action.
Anesthetics: Special care should be taken during anesthesia due to the synergistic negative inotropic and hypertensive effects of carvedilol and anesthetics.
Overdose
Symptoms: marked decrease in blood pressure, bradycardia, heart failure, cardiogenic shock, cardiac arrest; possible breathing disorders, bronchospasm, vomiting, confusion and generalized convulsions.
Treatment: in addition to general measures, it is necessary to monitor and correct vital signs, if necessary - in the intensive care unit.
The patient should be laid on his back.
In the presence of severe bradycardia, intravenous administration of atropine in a dose of 0.5–2 mg.
To maintain cardiovascular activity - glucagon in / in a jet at a dose of 1-10 mg, and then in the form of a long-term infusion at a rate of 2-5 mg / h.
Sympathomimetics (dobutamine, isoprenaline, orciprenaline, or epinephrine) in different doses, depending on body weight and therapeutic efficacy.
If it is necessary to administer preparations with a positive isotropic effect, prescribe FED inhibitors. If arterial hypotension prevails in the clinical picture of an overdose, inject norepinephrine; prescribe it in conditions of continuous monitoring of blood circulation parameters.
For treatment-resistant bradycardia, an artificial pacemaker is indicated.
In case of bronchospasm, inject β-adrenomimetics in the form of an aerosol (if ineffective - IV) or aminophylline IV. For convulsions, IV slowly inject diazepam or clonazepam. Since in severe overdose with symptoms of shock, it is possible to lengthen the T½ of the preparation from the depot, it is necessary to continue maintenance therapy for a sufficiently long time. The duration of maintenance detoxification therapy depends on the severity of the overdose, it should be continued until the patient's condition stabilizes.
Carvedilol cannot be removed by dialysis.
In case of severe overdose, when the patient is in a state of cardiogenic shock, maintenance treatment should be carried out for a long time, since the excretion or redistribution of carvedilol may take place more slowly than usual.
Storage conditions
At a temperature not higher than 30 ° C.
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