Dilatrend

Carvedilol is a medication that indiscriminately blocks the action of β-adrenergic receptors. In addition, it selectively blocks the activity of α-receptors. It has no endogenous sympathomimetic effect. Weakens the systemic preload of the heart, selectively blocking the activity of α-adrenergic receptors.

With an indiscriminate blockade of β-adrenergic receptors, the activity of the renal RAS is inhibited (a decrease in renin activity within the plasma), as well as a decrease in the level of heart rate, blood pressure and the intensity of cardiac output. When α-receptors are blocked, the drug demonstrates peripheral vasodilation, which reduces vascular resistance. [1]

Indications Carvedilol

It is used to reduce elevated blood pressure values (in monotherapy or in combination with other antihypertensive drugs), and in addition, for chronic insufficiency of the CVS function and stable angina pectoris .

Release form

The release of the drug substance is realized in tablets with a volume of 12.5 or 25 mg; inside the cell plate - 30 such tablets.

Pharmacodynamics

The combination of blocking the activity of β-receptors and vasodilation leads to the development of such effects: [2]

• in persons with ischemic heart disease, it prevents the development of pain and myocardial ischemia;
• in people with increased blood pressure values - reduces these indicators;
• in individuals with left ventricular dysfunction or insufficient blood flow, it helps to improve hemodynamics, increase the left ventricular ejection fraction and reduce its size.

The medicine does not alter lipid metabolism. [3]

Pharmacokinetics

The bioavailability of drugs is 25%. The Cmax level for oral administration is recorded after 1 hour. The drug has a linearity with respect to blood parameters and the administered portion. Bioavailability is not related to food intake.

Carvedilol is a highly lipophilic component. About 98-99% of the substance is synthesized with protein. The half-life is in the range of 6-10 hours. Indicators of the 1st intrahepatic passage - 60-75%. The level of the distribution volume is 2 l / kg. Intraplasmic clearance is 590 ml per minute.

Intrahepatic metabolism of carvedilol is realized during glucuronization, as well as oxidation relative to the phenolic ring. During the dimethylation and hydroxylation of the aromatic ring, 3 metabolic elements with β-blocking activity are formed. In preclinical processes, it was determined that the activity of 4'-hydroxy-phenol is 13 times higher than that of carvedilol. Blood levels of metabolic components are about ten times lower than carvedilol levels. The remaining 2 metabolic elements (hydroxycarbazole) have an intense antioxidant and adrenergic blocking effect. Their antioxidant properties are 30-80 times stronger than the activity of carvedilol.

Elimination of the drug is carried out with bile (and then with feces); a small part is excreted through the kidneys.

In older people, there is an increased level of drugs (50% higher). The bioavailability of the substance in people with hepatic cirrhosis is four times higher, and the level inside the blood is five times higher than in people without this disorder.

In some patients with kidney failure (CC - below ≤20 ml per minute) and an elevated blood pressure level, an increase in the blood parameters of drugs is determined (40-55%).

Dosing and administration

Carvedilol must be taken orally, without reference to food intake. In case of insufficiency of the patient's cardiovascular function, it is necessary to use the medicine with food (in order to enhance absorption, which reduces the likelihood of developing orthostatic collapse).

People with high blood pressure.

The medication should be used 1-2 times a day. The initial portion for an adult is 12.5 mg per day during the first 1-2 days.

Maintenance serving size per day is 25 mg. If required, the dosage can be gradually increased (with a minimum of 14 days) until a maximum daily serving of 50 mg is obtained.

Elderly people first need to inject 12.5 mg of the drug 1 time per day. In some cases, this dosage can be used in the future.

In the case of an increased blood pressure, no more than 50 mg of the medication can be used per day.

Persons with a stable form of angina pectoris.

During the first 1-2 days, adults are used 25 mg of the medication (divided into 2 doses). The size of the maintenance portion per day is 50 mg (25 mg is used for 1 use). A maximum of 0.1 g of Carvedilol is allowed per day (for 2 applications).

Elderly people first take 12.5 mg 1 time per day (first 1-2 days). Later, the patient is transferred to a maintenance dose (50 mg for 2 applications). The indicated dosage is the maximum for the elderly.

Insufficiency of cardiovascular activity in a chronic form.

The medication is used as an auxiliary substance together with the use of ACE inhibitors, digitalis drugs, diuretics, and also vasodilators.

To use the medicine, the patient must be in a stable condition during the last month before switching to therapy with Cardvedilol. Among other important conditions - heart rate indicators are not higher than 50 beats per minute, and the level of systolic blood pressure is higher than 85 mm Hg.

First, 6.25 mg of drugs are used once a day. In the absence of complications from the use of the drug, the portion is allowed to gradually increase (with a minimum of 14-day break) in this mode: from 2-fold intake of 6.25 mg per day to 2-fold intake of 12.5 mg / day, and then by 2 - single use of 25 mg per day.

Persons weighing ≤85 kg can use no more than 50 mg of the drug per day (for 2 uses); people weighing ≥85 kg - 0.1 g per day (for 2 applications). In the latter case - except for situations with severe cardiovascular insufficiency. The increase in the portion should be under the close supervision of the doctor.

At the beginning of treatment, some aggravation of the symptoms of cardiovascular insufficiency is possible (especially in persons using large portions of diuretics or if the disease is severe). In this case, you do not need to cancel the medicine - just refuse to increase its portion.

During therapy, the patient's condition should be monitored by a therapist or cardiologist. Before increasing the dose of drugs, it is necessary to additionally examine the patient, determining the weight, liver function, heart rate, blood pressure and heart rate. When symptoms of decompensation or delayed excretion of fluid appear, symptomatic actions are required (increasing the portion of diuretics). The dosage of Carvedilol cannot be increased (until the patient's condition stabilizes).

In some cases, it is necessary to reduce the dose of drugs or to temporarily cancel therapy (in this case, dosage titration can be performed).

When temporarily canceling the use of a medication, you need to resume taking it with a minimum portion (1-time administration of 6.25 mg per day). The increase in dosage is done gradually, according to the above scheme.

It should be borne in mind that the use of the drug by the elderly should be carried out under the constant supervision of a doctor, since they have an increased sensitivity to carvedilol.

Cancellation of drugs is carried out by gradually reducing the dosage over a period of 1-2 weeks.

• Application for children

Carvedidol should not be prescribed in pediatrics (persons under the age of 18), since there is only limited information regarding its drug efficacy and safety in this group.

Use Carvedilol during pregnancy

Carvedilol should not be prescribed for breastfeeding or pregnant patients.

Testing with animals did not reveal the teratogenic activity of the drug, but clinical tests with the study of the safety of its administration to such patients have not been carried out enough.

The medication can reduce the level of blood circulation inside the placenta, which leads to the death of the fetus inside the womb or premature birth. In the case of using drugs, a newborn or fetus may develop hypoglycemia, bradycardia, hypothermia, lung function failure and complications of the cardiorespiratory type.

It is allowed to use the medicine during pregnancy only in situations where the likely benefits are more expected than the risks of complications for the fetus. The drug taken by a pregnant woman should be canceled 2-3 days before the expected birth. If this condition is not met, it is necessary to monitor the condition of the newborn for the first 2-3 days.

The drug is lipophilic; tests with animals have determined that a drug molecule with its metabolites can be excreted in mother's milk. Therefore, breastfeeding should be avoided during therapy.

Contraindications

Among the contraindications:

• failure of cardiovascular function in a decompensated form;
• chronic obstructive bronchopulmonary pathologies;
• cadiogenic shock or asthma;
• having stage 2-3 AV block;
• bradycardia (heart rate is ≤50 beats per minute);
• severe allergy to the active element or other components of the drug;
• SSSU (also cardiac SA-blockade);
• spontaneous angina pectoris;
• untreated pheochromocytoma;
• use together with parenteral vascular use of verapamil or diltiazem;
• severe hypotension with systolic blood pressure below 85 mm Hg;
• damage to peripheral vessels;
• glucose-galactose malabsorption, hereditary hypolactasia, and Lapp lactase deficiency.

Side effects Carvedilol

The main side effects:

• problems with hematopoietic processes: a mild form of thrombocytopenia;
• metabolic disorders: hypercholesterolemia, -glycemia or -volemia, delayed excretion of fluid and peripheral edema. Hyperglycemia is commonly seen in diabetics;
• dysfunction of the central nervous system: paresthesia, dizziness, syncope, depression, sleep disorders and headaches;
• damage to the visual organs: deterioration of lacrimation, visual disturbance and irritation in the eye area;
• symptoms associated with the urinary tract: impaired urination, peripheral edema and kidney failure;
• disorders of the gastrointestinal tract: constipation, vomiting, xerostomia, nausea, pain in the abdomen, diarrhea and an increase in transaminases;
• problems with sexual function: impotence or swelling in the genital area;
• disturbances in the work of the CVS: disorder of peripheral blood flow, bradycardia or orthostatic collapse;
• ODA function impairment: pain in the extremities;
• respiratory disorders: dryness of the nasal mucosa and dyspnea (obstruction) in persons with COPD;
• problems with the subcutaneous layer and epidermis: itching, urticaria, exanthema of an allergic nature and manifestations similar to psoriasis and LP. If the patient is sick with psoriasis, he may have a worsening of epidermal symptoms;
• others: systemic weakness;
• occasionally: AV block, angina pectoris and exacerbation of the manifestations of pathologies associated with peripheral vessels (intermittent claudication, Raynaud's disease, etc.).

The use of carvedilol can lead to the development of a latent form of diabetes mellitus or a worsening of the course of existing diabetes, and in addition to insufficient control of serum glucose levels.

In the case of titration of the drug, the contractile function of the myocardium may be weakened (occasionally).

Overdose

With carvedilol poisoning, the development of heart failure, bradycardia, vomiting, intense hypotension, bronchial spasm, respiratory disorders, cardiogenic shock and seizures, as well as cardiac arrest and loss of consciousness are possible.

During therapy, it is necessary to monitor the functioning of the body systems important for life. Persons with poisoning should be in intensive care (if required).

Supportive actions:

• to prevent a severe form of bradycardia, inject 0.5-2 mg of atropine intravenously;
• to maintain cardiovascular function - the use of glucagon (jet IV method 1-10 mg, and then IV infusion of 2-5 mg per hour).

Sympathomimetics are also used - dobutamine, isoprenaline or epinephrine. The portion size is adjusted according to the patient's weight.

In the case of a refractory form of bradycardia, in addition to taking medications, cardiac electrical stimulation is performed.

To prevent bronchial spasm, β-sympathomimetics are administered via intravenous infusion or inhalation; in addition, intravenous aminophylline can be used.

To stop seizures, diazepam must be given intravenously (at a low rate).

Hemodialysis will be ineffective because carvedilol is synthesized at a high rate with blood protein.

With a severe course of signs of intoxication, maintenance procedures are performed for a long time, since the redistribution and excretion of the drug slows down. The duration of treatment is determined by the patient's condition (it is performed until the condition stabilizes).

Interactions with other drugs

Antiarrhythmic substances and Ca antagonists.

Administration together with diltiazem, amiodarone or verapamil causes hypotension and bradycardia. In people using such combinations, it is necessary to monitor blood pressure indicators, as well as perform ECG studies.

The synergistic effect that develops when using carvedilol with Ca antagonists can lead to a disorder of cardiac AV conduction, which causes decompensation.

It is necessary to carefully monitor the condition of persons who combine the medication with antiarrhythmic substances of subtype I or with amiodarone. There is evidence of the development of bradycardia and ventricular fibrillation, as well as cardiac arrest at the initial stage of treatment with Carvedilol in people using amiodarone.

With parenteral use of antiarrhythmic drugs, cardiovascular insufficiency may occur (antiarrhythmic drugs of subtypes Ia or Ic).

There is information about the appearance of bradycardia when the drug is combined with reserpine, guanfacine, methyldopa, guanethidine, or MAOI (excluding the MAO-B substance). With such schemes of use, it is necessary to control the heart rate.

You can not enter the medication together with dihydropyridines, as this can provoke cardiovascular failure and severe hypotension.

Nitrates lead to a decrease in blood pressure in the case of a combination with drugs.

The simultaneous administration of the drug and digoxin leads to an increase in the equilibrium values of digoxin with digitoxin (by 16 and 13%). It is necessary to monitor the blood level of digoxin at the beginning of therapy and at the end of the selection of the maintenance portion.

The drug potentiates the antihypertensive activity of drugs from other pharmacological categories (barbiturates, vasodilators, phenothiazines, as well as tricyclics, alcohol and α1-terminal antagonists).

The combination of drugs and cyclosporine requires monitoring the blood values of the latter, because they can increase.

Antidiabetic substances, including insulin.

The medicine is able to neutralize the manifestations of hypoglycemia; the activity of insulin and hypoglycemic drugs can be enhanced with the use of drugs, which is why it is necessary to constantly monitor the serum glucose values in such people.

When using a combination with clonidine and the need to cancel both drugs, first stop the administration of Carvedilol, and then gradually reduce the portion of clonidine.

If anesthesia through inhalation is required, negative inotropic and antihypertensive interactions between anesthetics and medication must be considered.

The therapeutic effect of drugs is weakened in the case of a combination with substances that retain Na and fluid inside the body (corticosteroids, anti-inflammatory analgesics and estrogens).

Persons using cimetidine, erythromycin, ketoconazole with barbiturates, verapamil and fluoxetine with haloperidol or rifampicin (substances that induce or slow down the action of hemoprotein P450 enzymes) should be under the doctor's control, since the drug level may increase (or decrease (with the introduction of inhibitors) using inductors).

The combination with ergotamine leads to the development of a significant vasoconstrictor effect.

Combination with substances that lead to neuromuscular blockade causes the potentiation of neuromuscular impulses.

Use together with sympathomimetics (α- or β-adrenergic agonists) increases the likelihood of an increase in blood pressure values or the development of severe bradycardia.

Storage conditions

Carvedilol should be kept out of the reach of small children, in a dark place. Temperature readings are in the range of 15-25 ° C.

Shelf life

Carvedilol can be used within 24 months from the date of manufacture of the therapeutic substance.

Analogs

Analogues of drugs are Coriol and Acridilol with Corvazan, as well as Dilatrend.

Reviews

Carvedilol receives good reviews from medical specialists - it is considered quite effective in the treatment of heart failure, as well as in the control of AV conduction and atrial fibrillation. In addition, it receives good responses as a treatment for elevated blood pressure, which increases its medicinal value.