Index of drugs

Arterial hypertension. Chronic stable angina. Adjunctive therapy for moderate to severe stable heart failure.

1 tabl powl. contains 6.25 mg, 12.5 mg or 25 mg carvedilol. The product contains lactose and sucrose.

Vasodilator, a non-selective β-blocker that reduces vascular peripheral resistance due to selective α-receptor blockade₁ and inhibits the renin-angiotensin system by non-selective blocking of β-receptors. It does not show intrinsic sympathomimetic activity. It has a stabilizing effect on the cell membrane. Carvedilol is a racemate of two stereoisomers: both enantiomers have an α-adrenergic blocking activity; non-selective blocking of β-adrenergic receptors₁ and β₂ it is mainly associated with the S (-) enantiomer. Antioxidant properties of carvedilol have been demonstrated. In patients with hypertension, lowering of blood pressure is not accompanied by an increase in peripheral resistance. The heart rate decreases slightly; the ejection volume remains unchanged. Blood flow through the kidneys and kidney function and peripheral blood flow remain normal. In hypertensive patients, carvedilol increases the concentration of norepinephrine in the blood. In long-term treatment of patients with angina, carvedilol showed anti-ischemic and pain-relieving effects; in addition, it reduced the initial and subsequent heart loads. In patients with left ventricular dysfunction or congestive heart failure, carvedilol positively affects haemodynamics as well as ejection fraction and left ventricular dimensions. It does not have an adverse effect on the lipid profile and on the concentration of electrolytes in the blood. The absolute oral bioavailability of carvedilol is approximately 25%. The maximum concentration in the blood occurs after 1 hour. It binds to plasma proteins in 98-99%. It is metabolized in the liver mainly by oxidation of the aromatic ring and glucuronidation. It is excreted mainly from the bile and faeces, and is largely excreted by the kidneys as metabolites. Medium T_0,5 is 6-10 hours.

Hypersensitivity to carvedilol or other ingredients. Uncomparated heart failure (NYHA grade IV), requiring the use of intravenous inotropic drugs. Chronic obstructive pulmonary disease with bronchial obstruction. Clinically significant impairment of liver function. Bronchial asthma. Atrio-ventricular block IIst. or IIIst. (without a pacemaker). Severe bradycardia (<50 / min). Cardiogenic shock. Sick node syndrome (including sinoatrial block). Severe hypotension (systolic blood pressure <85 mm Hg). Metabolic acidosis. Prinzmetal Principle. Untreated phaeochromocytoma. Severe circulatory disorders in peripheral arteries. Simultaneous intravenous use of Verapamil or diltiazem. Breastfeeding period.

In patients with chronic heart failure, carvedilol should be administered predominantly as a diuretic, angiotensin converting enzyme, digitalis, and / or vasodilator. Treatment should be started under hospital supervision (a necessary condition - stable condition of the patient for at least 4 weeks, obtained after standard treatment). If patients with congestive heart failure increase cardiac insufficiency or fluid retention while increasing Carvedilol, diuretic doses should be increased, the carvedilol dose should not be increased until stabilization is achieved. Sometimes it may be necessary to reduce the dose of carvedilol, and in rare cases, discontinuation, this does not exclude the subsequent increase in the dose. In patients with congestive heart failure and with chronic heart failure with low blood pressure (systolic blood pressure <100 mmHg), ischemic heart disease, generalized atherosclerosis and / or coexisting kidney failure, renal function should be monitored during dose escalation, treatment should be discontinued or reduce the dose if your kidney function worsens. In patients with chronic obstructive pulmonary disease with a tendency to bronchospasm, not using oral or inhaled drugs, carvedilol can be used only when the expected benefit outweighs the potential risks of the drug - patients need monitoring at the beginning of treatment and during dose escalation. Carvedilol may mask the symptoms of acute hypoglycaemia. In patients with diabetes and concomitant heart failure, the use of carvedilol may impair blood Glucose control (regular glucose control indicated). Carvedilol may mask the symptoms of hyperthyroidism. The drug should be used with caution in patients with Prinzmental angina, bradycardia (less than 55 beats / min), severe history of hypersensitivity or desensitized patients, psoriasis, peripheral vascular disease, Raynaud's syndrome, with atrioventricular block I^st., in patients with chronic heart failure treated with digitalis glycocoids, in patients treated with cimetidine and anesthetized in general. Due to limited clinical experience, carvedilol should not be used in patients with unstable or secondary hypertension, orthostatic hypotension, acute myocarditis, valvular valve obstruction or haemodynamic outflow pathways, end-stage peripheral arterial disease, co-treated with α-receptor antagonists₁ or an α receptor agonist₂. Before the use of β-blockers in patients with pheochromocytoma, initial treatment with α-blockers should be used (carvedilol has an α and β blocking activity, but there is no sufficient experience in the treatment of pheochromocytoma) - caution should be exercised. Due to the lactose and sucrose content, the preparation should not be used in patients with rare hereditary problems of galactose intolerance, fructose, Lapp lactase deficiency or impaired glucose-galactose absorption, sucrose-isomaltase. The safety and efficacy of carvedilol in children and adolescents under 18 years have not been established.

Clinical data on the safety of the drug in pregnant women are inadequate. β-blockers reduce placental perfusion, which can lead to intrauterine fetal death and premature or premature delivery. In addition, side effects (including hypoglycaemia, bradycardia, respiratory depression and hypothermia) may occur in the fetus and newborn. There is an increased risk of cardiac and pulmonary complications in the newborn in the postpartum period. It can only be used during pregnancy if the expected benefit to the mother outweighs the potential risk to the fetus and / or newborn baby. Treatment should be discontinued 2-3 days before the expected delivery. If this is not possible, the newborn should be observed for the first 2-3 days. The drug is contraindicated during breastfeeding.

Patients with heart failure. Very common: hyperglycaemia (in patients with diabetes), peripheral edema, hypervolemia, fluid retention, visual disturbances, peripheral edema, bradycardia, orthostatic hypotension; nausea, diarrhea, vomiting, swelling of genital edema. Common: mild thrombocytopenia, dizziness. Uncommon: constipation. Rare: fainting, complete atrioventricular block, worsening of heart failure, worsening of renal function.Patients with hypertension and angina. Very common: pain and dizziness, decreased watering, bradycardia, orthostatic hypotension, pain in the limbs, fatigue. Common: hypercholesterolemia, nausea, abdominal pain, diarrhea, asthmatic dyspnoea. Rare: benign thrombocytopenia, leukopenia, peripheral edema, sleep disturbances, depression, paresthesia, syncope, nasal congestion, peripheral circulatory failure, constipation, vomiting, decreased renal function, increased transaminases, skin reactions (allergic rash, urticaria, pruritus and a reaction resembling lichen planus), psoriatic lesions. Very rare: visual disturbances, eye irritation; dry mouth, difficulty in passing urine, impotence, coronary pain, atrioventricular block, exacerbation of symptoms in patients suffering from intermittent claudication or Raynaud's syndrome. β-blockers may also result in the onset and exacerbation of hidden diabetes and impaired glycemic control. Mild carbohydrate disturbances may rarely occur during treatment with carvedilol.

Orally. Adults.Arterial hypertension: the recommended starting dose is 12.5 mg once a day for the first 2 days. Then, it is recommended to continue treatment with a 25 mg dose once a day. If necessary, the dose may be increased gradually at intervals of 2 weeks or more. The recommended maximum single dose is 25 mg, the highest recommended daily dose is 50 mg. The preparation can be used alone or in combination with other antihypertensive agents, especially with thiazide diuretics. In elderly patients, the recommended starting dose is 12.5 mg once a day, which may be a sufficient dose to continue treatment. In the absence of a proper response, the dose may be increased gradually at intervals of 2 weeks or more.Chronic stable angina: the recommended starting dose is 12.5 mg 2 times a day for the first 2 days of treatment. Then, it is recommended to continue the treatment with a dose of 25 mg 2 times a day. If necessary, the dose may be increased gradually at intervals of 2 weeks or more. The recommended maximum daily dose is 100 mg a day in 2 divided doses. In elderly patients, the recommended starting dose is 12.5 mg 2 times daily for 2 days. Then it is recommended to continue the treatment with a dose of 25 mg 2 times a day, which is the highest recommended daily dose.Heart failure: the product is used in combination with diuretics, ACE inhibitors, digitalis preparations and / or vasodilators. The patient should be in a stable clinical condition (without NYHA class change, without hospitalization due to heart failure), and the basic treatment must be stable for at least 4 weeks before treatment with carvedilol. In addition, the patient should have a decreased left ventricle ejection fraction, heart rate should be higher than 50 beats / min, and systolic blood pressure higher than 85 mm Hg. The starting dose is 3.125 mg twice daily for 2 weeks. If the starting dose is well tolerated, the dose may be increased gradually at intervals of 2 weeks or more, first to 6.25 mg 2 times a day, then to 12.5 mg 2 times a day, and then up to 25 mg 2 times a day. It is recommended to increase the dose to the highest level tolerated by the patient. The highest recommended dose is 25 mg twice daily in patients with a less than 85 kg, and 50 mg twice daily for patients weighing more than 85 kg, provided that heart failure is not severe. Increasing the dose to 50 mg 2 times a day should be done carefully, with close medical observation. At the beginning of treatment or during dose escalation, transient worsening of heart failure may occur, especially in patients with severe heart failure and / or taking high doses of diuretics. This is usually not a reason to stop treatment, but the dose should not be increased. After starting treatment with carvedilol or after increasing the dose, the patient should be monitored by a doctor / physician. Before each dose increase, a patient should be examined for possible signs of worsening heart failure or excessive vasodilatation (eg kidney function, body weight, blood pressure, heart rate and rhythm). Deterioration of heart failure or fluid retention should be treated by increasing the diuretic dose and the carvedilol dose should not be increased until the patient has stabilized. In case of bradycardia or prolonged atrioventricular conduction time, the concentration of Digoxin in the blood should be monitored. In some cases, it may be necessary to reduce the carvedilol dose or temporarily discontinue treatment. Even in these cases, the treatment can often be successfully continued and the carvedilol dose gradually increased. If carvedilol is discontinued for more than 2 weeks, treatment should be resumed at 3.125 mg twice daily and the dose gradually increased as per the above recommendations. In patients with renal insufficiency, dosing must be determined individually, but pharmacokinetic data do not indicate that dosage adjustment is necessary. Patients with moderate hepatic impairment may need to adjust their dosage.
However, it is recommended that patients with heart failure take carvedilol with food to slow absorption and reduce the risk of orthostatic hypotension. The tablets should be drunk with the right amount of liquid.