Pharmacological properties of the drug Coriol
Carvedilol is a cardiac drug from the group of α- and β-adrenergic receptor blockers without sympathomimetic activity. Blocks α1-, β1-, and β2-adrenergic receptors and has pronounced antioxidant activity. Due to the cardionon-selective blockade of β-adrenergic receptors, the drug reduces blood pressure, heart rate and cardiac output. The drug reduces pressure in the pulmonary arteries and in the right atrium. Due to the blockade of α1-adrenergic receptors, it causes expansion of peripheral vessels and reduces their resistance. Thanks to these effects, carvedilol lowers blood pressure, relaxes the myocardium and prevents the occurrence of angina attacks. In patients with heart failure, carvedilol increases blood ejection from the left ventricle. The drug does not have sympathomimetic properties. The therapeutic effect on blood pressure and heart rate appears 1–2 hours after taking the drug. In patients with hypertension (arterial hypertension) and normal renal function, the drug reduces renal vascular resistance without changing glomerular filtration, renal plasma flow and the excretion of electrolytes. Carvedilol does not have a significant effect on plasma lipoprotein levels.
Use of the drug Coriol
AH (arterial hypertension) The dose is selected individually. The initial dose of Coriol (the first 7–14 days of treatment) is 12.5 mg. Take in the morning after breakfast. This dose can be divided into 2 doses of 6.25 mg. Treatment is continued at a dose of 25 mg. Take 12.5 mg in the morning or divided into 2 doses per day. If necessary, the dose can be increased after 14 days. The maximum dose for the treatment of hypertension (arterial hypertension) should not exceed 2x25 mg/day. Stable angina The dose is selected individually. The initial dose of Coriol (the first 7–14 days of treatment) is 12.5 mg 2 times a day. Treatment is continued at a dose of 25 mg 2 times a day. If necessary, the dose can be increased after 14 days. The maximum dose for the treatment of angina pectoris should not exceed 2x50 mg/day. In patients over 70 years of age, the maximum daily dose is 2x25 mg. Chronic heart failure The initial dose is 3.125 mg 2 times a day. The dose is increased at intervals of 2 weeks provided that the previously prescribed dose is well tolerated. The dose titration scheme is presented in the table.
| Week of treatment | |||
1st and 2nd | 3rd and 4th | 5th and 6th | 7th and 8th |
| 3.125 mg × 2 times a day | 6.25 mg × 2 times a day | 12.5 mg × 2 times a day | 25 mg × 2 times a day |
Depending on the clinical condition of the patient, a slower titration regime is possible by increasing the daily dose of Coriol (not 2, but 1.5 times) and/or increasing the time intervals between titration stages. For each patient, the dose should be titrated to the maximum tolerated. The highest target dose is 50 mg/day under the control of blood pressure and the general condition of the patient. If the patient's body weight is 85 kg, the maximum daily dose is 2 tablets of 25 mg 2 times a day under the control of blood pressure and the general condition of the patient. Coriol can be used in combination with other drugs used for heart failure. Left ventricular dysfunction after myocardial infarction. The recommended starting dose is 6.25 mg 2 times a day. If the patient tolerates the initial dose of Coriol well, it can be increased every 3–10 days to 12.5 mg 2 times a day, and then to 25 mg 2 times a day for a while. For patients who do not tolerate the initial dose, it should be reduced over 3–10 days to a dose of 3.125 mg twice daily. If the patient tolerates this dose well, it can be gradually increased until the optimal dose tolerated by the patient is reached. The maximum recommended dose is 25 mg 2 times a day. The drug should not be stopped suddenly. If it is necessary to stop treatment with Coriol, the drug is discontinued gradually over 1–2 weeks. When resuming taking the drug (if the break in use was 2 weeks), it is necessary to start with the lowest dose. The drug is taken after meals with water.
Instructions:
Clinical and pharmacological group
01.002 (Beta1-, beta2-blocker. Alpha1-blocker)
Release form, composition and packaging
The tablets are white, round, slightly biconvex, with beveled edges.
| 1 tab. | |
| carvedilol | 3.125 mg |
Excipients: sucrose, lactose monohydrate, povidone, colloidal silicon dioxide, crospovidone, magnesium stearate.
10 pieces. - blisters (3) - cardboard packs.
The tablets are white, oval, slightly biconvex, marked “S2” on one side and scored on the other side.
| 1 tab. | |
| carvedilol | 6.25 mg |
Excipients: sucrose, lactose monohydrate, povidone, colloidal anhydrous silicon dioxide, crospovidone, magnesium stearate.
10 pieces. - blisters (3) - cardboard packs.
The tablets are white, oval, slightly biconvex, marked “S3” on one side and scored on the other side.
| 1 tab. | |
| carvedilol | 12.5 mg |
Excipients: sucrose, lactose monohydrate, povidone, colloidal anhydrous silicon dioxide, crospovidone, magnesium stearate.
10 pieces. - blisters (3) - cardboard packs.
The tablets are white, round, slightly biconvex, with beveled edges, scored on one side.
| 1 tab. | |
| carvedilol | 25 mg |
Excipients: sucrose, lactose monohydrate, povidone, colloidal anhydrous silicon dioxide, crospovidone, magnesium stearate.
10 pieces. - blisters (3) - cardboard packs.
pharmachologic effect
Alpha1-, beta1- and beta2-adrenergic blocker without intrinsic sympathomimetic activity. It has a vasodilator, antianginal and antiarrhythmic effect.
Due to the blockade of β1-adrenergic receptors of the myocardium, it moderately reduces AV conduction, reduces heart rate and cardiac output, without causing severe bradycardia. By blocking α1-adrenergic receptors, the drug causes dilation of peripheral vessels, reducing peripheral vascular resistance.
With blockade of β2-adrenergic receptors, it is possible to increase the tone of the bronchi, some vessels, as well as the tone and peristalsis of the intestine.
In patients with heart failure, the drug increases left ventricular ejection fraction.
The effect on blood pressure and heart rate is most pronounced 1-2 hours after taking the drug.
Pharmacokinetics
Suction
After oral administration, carvedilol is rapidly and almost completely absorbed from the gastrointestinal tract. Cmax is reached after 1 hour. Bioavailability is 25%. Simultaneous food intake slows down the absorption of the drug, but does not affect its bioavailability.
Distribution
Plasma protein binding is 98-99%. Vd - about 2 l/kg. Passes through the placental barrier and is excreted in breast milk.
Metabolism
Carvedilol is actively biotransformed in the liver with the formation of metabolites with a pronounced antioxidant effect.
Removal
T1/2 - 6-10 hours. Excreted with bile and feces.
Pharmacokinetics in special clinical situations
In elderly patients, plasma concentrations of carvedilol are 50% higher than in young patients.
In patients with impaired liver function, bioavailability can increase up to 80%.
Dosage
For arterial hypertension, the dose is set individually. In the first 7-14 days, the recommended dose is 12.5 mg in the morning after breakfast. The dose can be divided into 2 doses of 6.25 mg Coriol. For further treatment, the drug is prescribed at a dose of 25 mg in the morning or divided into two doses of 12.5 mg. If necessary, after 14 days the dose can be increased to a maximum daily dose of 50 mg.
For stable angina, the initial dose of Coriol is 12.5 mg 2 times a day. After 7-14 days, under the supervision of a physician, the dose of the drug can be increased to 50 mg, divided into 2 doses. After 14 days, if there is insufficient effectiveness and good tolerability, the dose of Coriol can be further increased. The total daily dose of Coriol for angina pectoris should not exceed 100 mg, divided into 2 doses.
For patients over the age of 70 years, the daily dose of Coriol should not exceed 50 mg, divided into 2 doses.
For chronic heart failure, the recommended initial dose is 3.125 mg 2 times a day. The dose is increased with caution until the optimal therapeutic effect is achieved. The maximum dose is 25 mg 2 times/day for patients weighing up to 85 kg and 50 mg 2 times/day for patients weighing more than 85 kg.
The condition of patients should be monitored at the beginning of treatment and with subsequent dose increases. If treatment is interrupted for more than 2 weeks, it is resumed with a minimum dose of 3.125 mg Coriol 2 times a day, followed by an increase in dose.
The drug is taken after meals with a small amount of liquid.
Overdose
Symptoms: arterial hypotension, accompanied by dizziness or fainting; slow heart rate; shortness of breath associated with the development of bronchospasm; heart failure, vomiting; in severe cases - cardiogenic shock, impaired consciousness up to the development of coma, generalized convulsions, conduction disturbances and cardiac arrest.
Treatment: if symptoms of arterial hypotension appear, the dose should be reduced or the drug should be temporarily discontinued.
If the patient is conscious, it is necessary to induce vomiting, place the patient on his back so that the head is lowered and the legs are slightly elevated. An unconscious patient should be placed on his side. Symptomatic therapy is indicated.
To maintain heart function and blood circulation, orciprenaline or glucagon is prescribed.
For bradycardia, atropine is prescribed and, if necessary, a pacemaker.
For bronchospasm, beta2-agonists are prescribed.
For peripheral vasodilation - norepinephrine (norepinephrine), for convulsions - diazepam.
The duration of treatment depends on the degree of intoxication. In severe cases of intoxication, the elimination time of carvedilol is prolonged. Patients should be monitored until their condition is completely stabilized.
Drug interactions
In patients receiving verapamil or diltiazem intravenously, when Coriol is prescribed, a pronounced decrease in heart rate and a significant decrease in blood pressure is possible, therefore this combination of drugs is not prescribed.
Strengthening the effect of Coriol is possible with simultaneous use with certain antiarrhythmic drugs, anesthetics, antihypertensive drugs, drugs for the treatment of angina, with other beta-blockers (for example, in the form of eye drops), with MAO inhibitors, sympatholytics (reserpine), with cardiac glycosides . Therefore, during combination therapy, doses for drugs in the listed groups should be selected with caution.
When administered simultaneously with Coriol, it is possible to increase the concentration of digoxin in the blood plasma.
Diuretics enhance the effects of Coriol.
The pharmacokinetics of carvedilol may change when administered concomitantly with inducers or inhibitors of the activity of the CYP2D6 isoenzyme (for example, cimetidine increases the concentration of carvedilol in the blood serum, and rifampicin reduces it).
When used simultaneously with ergot alkaloids, a deterioration in peripheral circulation is observed.
Carvedilol may enhance the effect of hypoglycemic drugs and mask the manifestations of hypoglycemia. Therefore, regular monitoring of blood glucose concentrations is recommended.
Use during pregnancy and lactation
The use of Coriol during pregnancy is possible only in cases where the expected benefit to the mother outweighs the possible risk to the development of the fetus.
Carvedilol is excreted in breast milk, so if it is necessary to prescribe the drug during lactation, breastfeeding should be discontinued.
Side effects
From the central nervous system and peripheral nervous system: headache, dizziness, depression, paresthesia.
From the cardiovascular system: orthostatic hypotension, bradycardia, angina attacks, peripheral circulatory disorders, intermittent claudication, AV block, syncope, progression of heart failure.
From the respiratory system: shortness of breath (in predisposed patients), bronchospasm, sneezing, nasal congestion.
From the digestive system: dry mouth, nausea, vomiting, constipation, diarrhea, abdominal pain, increased activity of liver transaminases.
From the hematopoietic system: leukopenia, thrombocytopenia.
From the genitourinary system: severe renal dysfunction, edema; rarely - decreased potency.
Allergic reactions: skin rash, exanthema, urticaria, itching, exacerbation of psoriatic rashes.
Other: pain in the limbs, decreased production of tear fluid, eye irritation, muscle weakness (more often at the beginning of treatment), weight gain, hypo- and hyperglycemia, hypercholesterolemia.
Storage conditions and periods
The drug should be stored at a temperature not exceeding 30°C. Shelf life – 2 years.
Indications
- arterial hypertension (as monotherapy or in combination with other antihypertensive drugs);
- stable angina pectoris;
- chronic heart failure (as part of combination therapy).
Contraindications
— heart failure in the stage of decompensation;
— SSSU;
- AV block of II and III degrees;
- severe bradycardia;
- arterial hypotension (systolic blood pressure less than 85 mm Hg);
- bronchial asthma;
— bronchospastic syndrome;
- liver failure;
- pregnancy;
- lactation period (breastfeeding);
— age up to 18 years;
- hypersensitivity to carvedilol and other components of the drug.
special instructions
Coriol should be prescribed with caution for chronic bronchitis, pulmonary emphysema, Prinzmetal's angina, diabetes mellitus, hypoglycemia, thyrotoxicosis, occlusive diseases of peripheral vessels, pheochromocytoma, depression, myasthenia gravis, psoriasis, and renal failure.
At the beginning of treatment and with increasing doses of Coriol, patients may experience an excessive decrease in blood pressure, especially when standing up. During therapy, dizziness and fainting are possible, especially in elderly patients, with heart failure, and also with simultaneous use of other antihypertensive drugs and diuretics.
Coriol therapy should not be abruptly stopped, especially in patients with angina pectoris (as this may cause a worsening of the condition). The dose of the drug should be reduced gradually over 1-2 weeks.
In patients with renal failure, coronary artery disease, diffuse peripheral vascular disease, low blood pressure and/or heart failure, it is recommended to monitor renal function. If renal function deteriorates, Coriol should be discontinued.
Beta-blockers can aggravate the clinical picture of peripheral angiopathy, psoriasis and anaphylactic reactions, as well as reduce the sensitivity of allergy tests.
Beta-blockers can aggravate the course of Prinzmetal's angina (provoke pain).
Because beta blockers slow the heart rate, they may mask the symptoms of hypoglycemia in patients with diabetes and thyrotoxicosis in patients with thyroid disease.
While taking Coriol, it is possible to reduce tear formation, which is important for patients wearing contact lenses.
The patient should be warned that before surgery it is necessary to inform the doctor about taking Coriol.
Caution is required when performing general anesthesia using drugs that suppress the activity of the heart muscle (for example, ether, cyclopropane, trichlorethylene). Before major surgery, gradual withdrawal of Coriol is recommended.
The drug should be prescribed with caution in cases of severe metabolic acidosis.
Patients with pheochromocytoma can be prescribed β-adrenergic blockers only after starting α-adrenergic blockers.
When canceling simultaneous therapy with Coriol and clonidine, it is initially necessary to discontinue treatment with Coriol and only after a few days discontinue clonidine.
If heart failure progresses during treatment with Coriol, it is recommended to increase the dose of the diuretic; in case of renal failure, the dose is adjusted depending on the functional state of the kidneys.
During treatment you should avoid drinking alcohol.
Use in pediatrics
The safety and effectiveness of Coriol in children have not been established.
Impact on the ability to drive vehicles and operate machinery
At the beginning of treatment with Coriol and with increasing doses, an excessive decrease in blood pressure, accompanied by dizziness, is possible. Therefore, patients are not recommended to drive and should refrain from other activities that require high concentration and rapid psychomotor reactions.
Use for renal impairment
Coriol should be prescribed with caution in case of renal failure.
Conditions for dispensing from pharmacies
The drug is available with a prescription.
Side effects of the drug Coriol
Side effects requiring dose reduction or discontinuation of treatment are rare. Dizziness, hypotension, and decreased visual acuity are possible, which are usually observed when the dose of the drug is increased, especially in patients with chronic heart failure and are temporary. From the cardiovascular system: bradycardia, orthostatic hypotension, cardiac conduction disorders, tachycardia. From the side of the central nervous system: weakness, dizziness, headache, sleep disturbances. From the gastrointestinal tract: dry mouth, lack of appetite, nausea, vomiting, diarrhea. From the respiratory system : shortness of breath, bronchospasm. From the organ of vision : blurred vision, decreased tear production (should be taken into account by patients wearing contact lenses). Rarely - dysuria, impaired potency, exanthema, thrombocytopenia, leukopenia, in patients with type I diabetes - hypoglycemia, type II - hyperglycemia.
Special instructions for the use of the drug Coriol
Treatment with Coriol is not recommended for patients with hypotension. Treatment should be used with caution in the following conditions. Orthostatic hypotension : at the beginning of treatment and with increasing doses of the drug, orthostatic hypotension and dizziness may occur. The risk of hypotension is higher in patients with heart failure and in elderly patients concomitantly taking antihypertensive drugs or diuretics. To prevent these manifestations, a lower initial dose should be prescribed and the drug should be taken after meals. Discontinuation of treatment: Treatment with β-adrenergic blockers should not be stopped suddenly. Abrupt discontinuation of the drug may cause a deterioration in the patient's condition with the development of sweating, tachycardia, shortness of breath and exacerbation of angina. The dose should be reduced gradually over 1–2 weeks. When resuming taking the drug (if the break in use was 2 weeks), it is necessary to start with the lowest dose. Heart failure: Patients with mild to moderate heart failure may take Coriol if their condition is effectively controlled by taking digitalis and/or a diuretic. Treatment with Coriol should begin with 3.125 mg, and the dose of the diuretic should be increased. Medical monitoring of the condition of patients with heart failure and severe hypotension, coronary artery disease, diffuse vascular disease and/or kidney disease, and impaired renal function is recommended. Diabetes mellitus and hyperthyroidism: β-adrenergic blockers reduce heart rate and therefore can mask the manifestations of hypoglycemia in patients with diabetes mellitus and thyrotoxicosis in patients with thyroid diseases. General anesthesia: For general anesthesia in patients treated with beta-blockers, drugs with minimal negative inotropic effects should be used or carvedilol treatment should be discontinued (gradually). COPD: in exceptional cases, the drug can be prescribed to patients with COPD with caution; treatment should be carried out in minimal therapeutic doses under the supervision of a physician. The drug should be used with caution in cases of severe metabolic acidosis, myasthenia gravis, and depression. During the treatment period, you should not drink alcohol. The safety and effectiveness of Coriol in patients under 18 years of age have not been established. It is not known whether carvedilol is safe for the fetus. β-adrenergic blockers cross the placental barrier and can cause hypotension, bradycardia and hypoglycemia in the fetus. It is not recommended to prescribe the drug to pregnant women, unless the potential benefit to the mother outweighs the possible risk to the fetus. You should not take the drug during breastfeeding. Caution should be exercised during treatment with the drug (especially at the beginning of treatment or when changing the dose) when working with machinery or when performing other activities that require concentration.
Interactions of the drug Coriol
Coriol should not be prescribed to patients receiving intravenous verapamil or diltiazem, as this may lead to the development of severe bradycardia and hypotension. Concomitant use of Coriol with digoxin can lead to an increase in plasma digoxin concentrations by approximately 15%. When used in combination with rifampicin, the concentration of carvedilol in the blood plasma may decrease, and when taken simultaneously with cimetidine, it may increase. Parallel administration of other antiarrhythmic, antihypertensive drugs, drugs for the treatment of angina pectoris, narcotic analgesics, eye drops (containing β-adrenergic receptor blockers, clonidine) can modify the effect of Coriol. Coriol may enhance the effect of hypoglycemic agents and mask the symptoms of hypoglycemia (especially tachycardia).
Pharmacokinetics
Suction
After oral administration, carvedilol is rapidly and almost completely absorbed from the gastrointestinal tract. Cmax is reached after 1 hour. Bioavailability is 25%. Simultaneous food intake slows down the absorption of the drug, but does not affect its bioavailability.
Distribution
Plasma protein binding is 98-99%. Vd - about 2 l/kg. Passes through the placental barrier and is excreted in breast milk.
Metabolism
Carvedilol is actively biotransformed in the liver with the formation of metabolites with a pronounced antioxidant effect.
Removal
T1/2 - 6-10 hours. Excreted with bile and feces.
Pharmacokinetics in special clinical situations
In elderly patients, plasma concentrations of carvedilol are 50% higher than in young patients.
In patients with impaired liver function, bioavailability can increase up to 80%.
Overdose of the drug Coriol, symptoms and treatment
Severe arterial hypotension (dizziness, collapse) and bradycardia are possible; in susceptible individuals, bronchospasm may develop; vomiting, heart failure; in severe cases - cardiogenic shock, impaired consciousness or coma, generalized convulsions, conduction disturbances and cardiac arrest. Treatment is symptomatic. Gastric lavage is performed and activated charcoal is prescribed. The use of sympathomimetics, plasma expanders, and, if necessary, electrical stimulation of the heart is indicated.
Contraindications
— heart failure in the stage of decompensation;
— SSSU;
- AV block of II and III degrees;
- severe bradycardia;
- arterial hypotension (systolic blood pressure less than 85 mm Hg);
- bronchial asthma;
— bronchospastic syndrome;
- liver failure;
- pregnancy;
- lactation period (breastfeeding);
— age up to 18 years;
- hypersensitivity to carvedilol and other components of the drug.
