Instructions for Carvedilol Sandoz tablets 25 mg No. 30
Composition
active ingredient: carvedilol;
1 tablet contains carvedilol 12.5 mg or 25 mg;
excipients:
12.5 mg tablets: lactose monohydrate, microcrystalline cellulose, crospovidone, povidone KZO. colloidal anhydrous silica, magnesium stearate, red iron oxide (E 172), yellow iron oxide (E 172).
25 mg tablets: lactose monohydrate, microcrystalline cellulose, crospovidone, povidone KZO, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
Carvedilol Sandoz, 12.5 mg tablets: dark pink, round convex tablets with a score: engraved with SZ on one side.
Carvedilol Sandoz, 25 mg tablets: round, convex tablets of white or almost white color, with a score: with engraving C4 on one side.
Pharmacotherapeutic group
Alpha and beta adrenoceptor blockers.
ATX code C07A G02.
Pharmacological properties
Pharmacodynamics
Carvedilol is an adrenergic receptor blocker with multiple effects. It blocks α1-, β1- and β2-adrenoceptors. Carvedilol has been shown to have organ-protective effects. Carvedilol is a potent antioxidant and scavengers of reactive oxygen radicals (scavenging function). Carvedilol is a racemic mixture. Both enantiomers (R |+] and S [-]) have the same α-blocking and antioxidant properties. Carvedilol has antiproliferative effects on vascular smooth muscle cells. Clinical studies measuring various markers during long-term treatment with carvedilol have shown a reduction in oxidative stress in patients.
The beta-blocking effect is not selective for β1- and β2-adrenergic receptors and is attributed to the S (-) enantiomer.
Carvedilol has no intrinsic sympathomimetic activity (SMA). Like propranolol, it has membrane-stabilizing properties. Carvedilol inhibits the renin-angiotensin-aldosterone system by beta-blockade, reducing renin release. Therefore, water retention is rare.
Carvedilol reduces peripheral vascular resistance by blocking α1-adrenoceptors. Carvedilol reduces blood pressure increases induced by phenylephrine, an α1-adrenoceptor agonist, but not those induced by angiotensin II.
Carvedilol has no adverse effects on the lipid profile. The normal ratio of high-density lipoproteins to low-density lipoproteins (HDL/LDL) is not altered.
Clinical efficacy
Arterial hypertension
Carvedilol lowers blood pressure in hypertensive patients by a combination of β-blockade and α1-mediated vasodilation. The reduction in blood pressure is not associated with the concomitant increase in total peripheral resistance seen with pure beta-blockers. Heart rate is slightly reduced. Renal perfusion and renal function are preserved. It has been found that during treatment with carvedilol, stroke volume is preserved, while total peripheral resistance is reduced. Carvedilol does not affect the blood supply to individual organs and vessels, such as the kidneys, skeletal muscles, forearms, legs, skin, brain or carotid arteries. Cold extremities and early fatigue during exercise are rarely observed. The long-term antihypertensive effects of carvedilol have been proven in several controlled double-blind studies.
Coronary heart disease
In patients with coronary heart disease, carvedilol has anti-ischemic (increased total exercise time, time to 1 mm ST-segment depression, and time to angina) and antianginal properties that are maintained during long-term therapy. Studies of acute hemodynamic effects have shown that carvedilol significantly reduces myocardial oxygen demand and sympathetic nervous system activity. In addition, preload (pulmonary artery pressure and pulmonary capillary wedge pressure) and ventricular afterload (total peripheral resistance) are reduced.
Subactive indicators
Carvedilol had no effect on health-related quality of life (the primary endpoint in one trial), as measured by a standard questionnaire. However, in most trials, significant improvements in overall well-being were observed, both by patients and by the investigator.
Kidney dysfunction
A meta-analysis of placebo-controlled clinical trials with a large number of patients (>4,000) with mild to moderate chronic renal impairment indicated a benefit of carvedilol treatment in patients with left ventricular dysfunction with or without symptomatic heart failure in terms of reducing all-cause mortality as well as the incidence of heart failure events.
Pharmacokinetics
After oral administration of 25 mg capsules to healthy subjects, carvedilol is rapidly absorbed, with a peak plasma concentration (Cmax) of 21 mg/l occurring approximately 1.5 hours (Tmax) after oral administration. There is a linear relationship between Cmax and dose. After oral administration, carvedilol undergoes extensive first-pass metabolism, resulting in an absolute bioavailability of approximately 25% in healthy subjects. Carvedilol is a racemic mixture, and the 5-(-)-enantiomers appear to be metabolised more rapidly than the R-(+)-enantiomers, resulting in an absolute oral bioavailability of 15% compared with 31% for the R-(+)-enantiomers. The peak plasma concentration of R-carvedilol is approximately twice that of S-carvedilol. In vitro studies have shown that carvedilol is a substrate for the efflux transporter P-glycoprotein. The role of P-glycoprotein in the availability of carvedilol has also been confirmed in vivo in healthy subjects.
Distribution
Carvedilol Sandoz is highly lipophilic and its plasma protein binding is approximately 95%. Its volume of distribution (VDSS) ranges from 1.5 to 2 l/kg.
Biotransformation
In all animal species studied and in humans, Carvedilol Sandoz is almost completely metabolized in the liver by oxidation and conjugation to several metabolites. Demethylation and hydroxylation on the phenolic ring lead to three active metabolites with beta-blocking activity. In animals, the metabolite 4'-hydroxyphenol has 13 times more potent beta-blocking activity than carvedilol. Compared with carvedilol, these three active metabolites have a weak vasodilating effect. The Cmax values of the active metabolites reached the following values after 1 hour: M2 3.9 ng/ml, M4 4.1 ng/ml, M5 3.3 ng/ml (approximately 20% of carvedilol, Cmax 49 ng/ml).
In addition, 2 hydroxycarbazole metabolites are very potent antioxidants, with activity 30-80 times more potent than that of carvedilol.
Pharmacokinetic studies in humans have shown that the oxidative metabolism of carvedilol is stereoselective. In vitro studies suggest that various cytochrome P450 isoenzymes, including CYP2D6, CYP3A4, CYP2E1, CYP2C9 and CYP1A2, may be involved in the oxidation and hydroxylation processes.
Studies in healthy subjects and patients have shown that the R-enantiomer is metabolized primarily by CYP2D6, and the S-enantiomer is metabolized primarily by CYP2D6 and CYP2C9.
Genetic polymorphism
Results from a clinical pharmacokinetic study in humans have shown that CYP2D6 plays an important role in the metabolism of R- and S-carvedilol. Thus, in poor CYP2D6 metabolizers, plasma concentrations of R- and S-carvedilol are increased. The importance of CYP2D6 genotype for the pharmacokinetics of R- and S-carvedilol was also supported in a population pharmacokinetic study, while other studies did not confirm this observation. This indicates that the CYP2D6 genetic polymorphism may have limited clinical significance.
Breeding
After oral administration, the elimination half-life of Carvedilol Sandoz is approximately 6-10 hours. After a single dose of 50 mg carvedilol, approximately 60% of the dose is excreted in the bile as metabolites and is excreted within 11 days in the feces. After a single oral dose, only approximately 16% is excreted in the urine as carvedilol. Less than 2% of the unchanged substance is excreted in the urine. After intravenous infusion of 12.5 mg in healthy volunteers, the plasma clearance of carvedilol is approximately 600 ml/min and the elimination half-life is approximately 2.5 hours. In all subjects, the elimination half-life of the 50 mg capsule was approximately 6.5 hours, which corresponds to the true absorption half-life of the capsule. After oral administration, the total clearance of S-carvedilol is approximately twice that of R-carvedilol.
Pharmacokinetics in special populations
Patients with renal impairment
Long-term carvedilol therapy does not affect renal perfusion autoregulation or glomerular filtration.
In hypertensive patients with renal insufficiency, no significant changes in half-life and maximum plasma concentration were observed. In patients with impaired renal function, the AUC value increases by 40-50%, and the renal excretion of the parent substance decreases. However, changes in pharmacokinetic parameters are insignificant.
Several open-label studies have shown that carvedilol is effective in patients with renal hypertension. The same applies to patients with chronic renal failure, patients on dialysis and patients who have undergone kidney transplantation. After oral administration of 10 mg of carvedilol, maximum plasma concentrations are reached after 1-5 hours on both dialysis and non-dialysis days. After 24 hours, the substance is not detected in plasma.
Carvedilol leads to a gradual decrease in blood pressure both on dialysis and non-dialysis days. The hypotensive effect is comparable to that observed in patients with normal renal function. Carvedilol is not removed by dialysis because it does not pass through the dialysis membrane, possibly due to a very high degree of binding to plasma proteins.
Knowledge gained in a comparative study in hemodialysis patients shows that carvedilol is superior to diltiazem in terms of efficacy in silent ischemia.
A pharmacokinetic study in patients with liver cirrhosis demonstrated that the area under the curve (AUC) of carvedilol in patients with impaired liver function increased 6.8-fold compared to healthy subjects.
Therefore, carvedilol is contraindicated in patients with clinically evident hepatic impairment (see also sections “Contraindications” and “Method of administration and dosage: Special instructions for dose selection”).
Patients with heart failure
In a study of 24 Japanese patients with heart failure, the clearance of R- and S-carvedilol was significantly lower than previously estimated in healthy subjects. These results indicate that heart failure has a significant effect on the pharmacokinetics of R- and S-carvedilol.
Elderly patients
The pharmacokinetics of Carvedilol Sandoz depends on the age of the patients. The concentration of carvedilol in the blood plasma of elderly patients is 50% higher than in young patients. In elderly patients, Cmax and AUC may increase. In such cases, dose adjustment is necessary.
Age had no significant effect on the pharmacokinetics of carvedilol in patients with hypertension. A study in elderly patients with hypertension did not reveal any differences in the adverse event profile compared to younger patients. A subsequent study in elderly patients with coronary artery disease did not reveal any differences in adverse event reporting compared to younger patients. Therefore, no adjustment of the starting dose is required in elderly patients.
Pediatric patients
A study in children and adolescents showed that the clearance adjusted for body weight in children and adolescents is significantly higher than in adults.
Indication
Mild to moderate essential hypertension.
Prevention of heart attacks in chronic angina.
Treatment of stable heart failure from mild to severe degree (class II-1V according to the NYHA classification) of ischemic or cardiomyopathic origin in complex therapy with standard treatment (diuretics, digoxin, ACE inhibitors).
Contraindication
Hypersensitivity to the active substance or other excipients in the composition of the drug.
Decompensated chronic heart failure NYHA class II-IV in patients requiring supportive intravenous inotropic treatment.
Chronic obstructive pulmonary disease.
Bronchial asthma (2 fatal outcomes after asthmatic status have been reported. They occurred after the use of a single dose).
Allergic rhinitis.
Swelling of the larynx.
Pulmonary heart.
Sinus node dysfunction (including sinoatrial block).
Severe hypotension (systolic blood pressure <85 mmHg).
Atrioventricular (AV) block of the II and III degree.
Severe bradycardia (less than 45-50 beats per minute at rest).
Cardiogenic shock.
Heart attack with complications.
Liver dysfunction with clinical manifestations.
Metabolic acidosis.
Concomitant use of MAO inhibitors (except MAO-B inhibitors).
Slow metabolism of debrisoquine and mefepitoin.
Breast-feeding.
Interaction with other medicinal products and other types of interactions
Pharmacokinetic interactions
Effect of carvedilol on the pharmacokinetics of other drugs
Carvedilol is both a substrate and an inhibitor of P-glycoprotein. Therefore, the bioavailability of drugs transported by P-glycoprotein may be increased when carvedilol is co-administered. In addition, the bioavailability of carvedilol may be altered by inducers or inhibitors of P-glycoprotein.
Digoxin. In some studies, an increase in digoxin exposure by 20% was observed in healthy subjects and patients with heart failure. In contrast to female patients, a more pronounced effect was found in male patients. Therefore, careful and strict monitoring of plasma digoxin concentrations is recommended when initiating and terminating carvedilol therapy. as well as when reducing the dose (see section "Special instructions for use"). Carvedilol had no effect on intravenous administration of digoxin.
Ciclosporin. Two studies in renal and cardiac transplant patients receiving oral ciclosporin showed an increase in plasma ciclosporin concentrations after initiation of carvedilol treatment. Carvedilol appears to increase the exposure of oral ciclosporin by approximately 10-20%. To maintain therapeutic levels of ciclosporin, a reduction in the ciclosporin dose of 10-20% is required. The mechanism of this interaction is unknown but may involve inhibition of intestinal P-glycoprotein. Due to the large interindividual variability, it is recommended to carefully monitor ciclosporin plasma concentrations after initiation of carvedilol therapy and adjust the ciclosporin dose accordingly.
Effect of other drugs on the pharmacokinetics of carvedilol
Rifampicin. In a study of 12 healthy volunteers, the effect of carvedilol was reduced by almost 60% when rifampicin was administered concomitantly. A reduction in the effect of carvedilol on systolic blood pressure was noted. The mechanism of this interaction is unknown but may be based on induction of intestinal P-glycoprotein by rifampicin. Beta-blocking activity should be carefully monitored in patients receiving carvedilol concomitantly with rifampicin.
Amiodarone. In patients with heart failure receiving carvedilol and amiodarone, trough concentrations of R- and S-carvedilol were reduced 2.2-fold compared with patients receiving carvedilol monotherapy. The effect on S-carvedilol is attributed to desethylamiodarone, a metabolite of amiodarone, which is a potent inhibitor of CYP2C9. An in vitro study in human liver microsomes showed that amiodarone and desethylamiodarone inhibit the oxidation of R- and S-carvedilol. In patients receiving combined treatment with carvedilol and amiodarone, monitoring of beta-blocking activity is recommended.
Fluoxetine and paroxetine. In a randomized crossover study in 10 patients with heart failure, concomitant administration of fluoxetine, a potent CYP2D6 inhibitor, resulted in stereoselective inhibition of carvedilol metabolism with a 77% increase in mean AUCo-12 of the K(+) enantiomer and a statistically significant 35% increase in AUC of the 8(-) enantiomer compared to placebo. However, there were no differences between treatment groups in adverse reactions, blood pressure, or heart rate. The effect of a single dose of paroxetine, a potent CYP2D6 inhibitor, on the pharmacokinetics of oral carvedilol was studied in 12 healthy subjects following a single oral dose. Despite a significant increase in exposure to R- and S-carvedilol, no clinical effects were observed in these healthy subjects.
Pharmacodynamic interactions
Insulin and oral hypoglycemic agents: The effects of insulin and oral hypoglycemic agents may be potentiated. Symptoms of hypoglycemia may be masked or attenuated (especially tachycardia). Regular monitoring of blood glucose is recommended in diabetic patients (see section "Special precautions").
Digoxin: The combined use of beta-blockers and digoxin may lead to additive prolongation of atrioventricular conduction time.
Verapamil, diltiazem, amiodarone and other antiarrhythmics. As with other beta-blockers, oral calcium channel blockers such as verapamil and diltiazem, amiodarone and other antiarrhythmics should be used with caution, as the risk of AV conduction disturbances may increase with combined use. Calcium channel blockers and antiarrhythmics should not be administered intravenously during treatment with Carvedilol Sandoz.
Catecholamine-Depleting Drugs: Patients taking both drugs with beta-blocking properties and drugs that deplete catecholamine levels (e.g., reserpine and monoamine oxidase inhibitors) should be closely monitored for signs of hypotension and/or severe bradycardia.
Antihypertensive drugs: As with other beta-blockers, Carvedilol Sandoz may potentiate the effects or side effects of other drugs with hypotensive action.
Nifedipine. Concomitant use of nifedipine and Carvedilon Sandoz® may result in a serious decrease in blood pressure.
Clonidine. Concomitant use of clonidine with drugs with beta-blocking properties may potentiate the effects of lowering blood pressure and heart rate. When it is necessary to discontinue concomitant treatment with drugs with beta-blocking properties and clonidine, the beta-blocker should be discontinued first. The dose of clonidine can be reduced a few days after the end of treatment with Carvedilol Sandoz.
Concomitant administration of Carvedilol Sandoz® and cardiac glycosides may prolong atrioventricular conduction time: inhibitors of oxidative metabolism (e.g. cimetidine) increase plasma levels of Carvedilol Sandoz (AUC of carvedilol increased by 30%).
Anesthetics. Due to the synergistic negative inotropic and hypotensive effects of Carvedilol Sandoz and anesthetics, careful monitoring of vital signs is recommended during anesthesia.
NSAIDs: Concomitant use of nonsteroidal anti-inflammatory drugs (I II133) may increase blood pressure and affect its control.
Beta-agonist bronchodilators. Non-cardioselective beta-blockers antagonize the bronchodilator effect of beta-agonist bronchodilators. Close monitoring of patients is recommended.
Anesthesia and major surgery
If continued use of Carvedilol Sandoz is necessary in the perioperative period, special caution should be exercised when using anesthetics that depress myocardial function, such as ether, cyclopropane, and trichloroethylene. For information on the treatment of bradycardia and hypotension, see the section "Overdose".
Application features
The drug should be used with extreme caution in the following conditions:
Childhood.
Labile or secondary hypertension.
Unstable angina.
End-stage peripheral arterial perfusion (e.g. Raynaud's syndrome), as beta-blockers may cause or exacerbate symptoms of arterial insufficiency.
Recent myocardial infarction.
A tendency for blood pressure to drop when changing position (orthostasis).
Patients who are concomitantly receiving certain antihypertensive drugs (β-receptor blockers).
Hypersensitivity
When using beta-blockers, there is a risk of increased sensitivity to allergens and the incidence of serious hypersensitivity reactions (e.g. cardiovascular dysregulation, bronchospasm, dyspnea, shock) in patients with a history of serious hypersensitivity reactions and patients undergoing desensitization therapy. Therefore, it is recommended to use the drug with caution in such cases.
Severe cutaneous reactions (SCAR)
Very rare cases of severe cutaneous adverse reactions, such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported during treatment with carvedilol (see section 4.8). Carvedilol should not be used in patients suffering from severe skin reactions that may be related to carvedilol.
Psoriasis
Patients with a history of psoriasis should be prescribed beta-blockers, including Carvedilol Sandoz, only after careful assessment of the benefit/risk ratio.
Withdrawal syndrome
In patients with arterial hypertension and concomitant ischemic heart disease who require discontinuation of Carvedilol Sandoz, the dose should be gradually reduced, which applies to all other beta-blockers.
Bradycardia
In clinical trials, 2% of patients with hypertension and 9% of patients with heart failure
bradycardia was observed in patients with heart failure. If the heart rate falls below 55 beats/min, the dose should be reduced. Hypotension was reported in 9.7% and loss of consciousness in 3.4% of patients with heart failure, compared with 3.6% and 2.5% of patients receiving placebo, respectively. The risk of such effects was highest in the first 30 days of treatment. This period corresponds to the titration phase (see section "Dosage and administration").
In elderly patients, high blood pressure may decrease after the first dose of Carvedilol Sandoz.
Hyperthyroidism
Due to its beta-blocking activity, carvedilol may mask symptoms of hyperthyroidism, such as tachycardia. Abrupt withdrawal of the drug may lead to exacerbation of hyperthyroidism and the development of a hyperthyroid crisis.
Diabetes mellitus
Particularly careful monitoring is necessary in patients with diabetes mellitus, since treatment with Carvedilol Sandoz may affect blood glucose levels. Patients with diabetes mellitus should be informed that Carvedilol Sandoz may increase insulin resistance and mask or attenuate the symptoms of hypoglycemia, especially tachycardia. Non-selective beta-blockers may exacerbate insulin-induced hypoglycemia and delay the normalization of serum glucose levels. Blood glucose levels should be checked regularly and, if necessary, the doses of insulin or oral antidiabetic agents adjusted.
In patients with heart failure and concomitant diabetes mellitus, treatment with Carvedilol Sandoz may lead to exacerbation of hyperglycemia, requiring increased hypoglycemic therapy. It is recommended to closely monitor blood glucose levels when using Carvedilol Sandoz, adjust doses or, if necessary, discontinue the drug.
In patients with arterial hypertension and concomitant diabetes mellitus not responding to insulin, carvedilol had no effect on fasting and postprandial blood glucose levels, as well as on glycosylated hemoglobin A1c. Also, no dose adjustment of antidiabetic drugs was required.
In patients with diabetes who did not require insulin, carvedilol had no statistically significant effect on the results of the glucose tolerance test. In patients with hypertension without diabetes with reduced insulin response (metabolic syndrome), carvedilol slightly improved insulin response. The same was observed in patients with hypertension and diabetes who did not require insulin.
Contact lenses
Patients who wear contact lenses should be informed of the possible reduction in tear production.
Heart failure
During the titration phase of Carvedilol Sandoz in patients with heart failure, cases of worsening of heart failure symptoms and edema have been reported. If such symptoms occur, the dose of diuretics should be increased, while the dose of Carvedilol Sandoz should remain unchanged until the patient's condition is stabilized. Temporary reduction of the dose of Carvedilol Sandoz or discontinuation of treatment may be necessary (see section "Method of administration and dosage").
Carvedilol Sandoz should be administered with caution to patients with decompensated heart failure who are already receiving digitalis (e.g. digoxin), diuretics and/or ACE inhibitors, since digitalis and Carvedilol Sandoz may slow atrioventricular conduction and Carvedilol Sandoz may increase digitalis levels (see also section “Interaction with other medicinal products and other forms of interaction”).
Reversible deterioration of renal function has been observed during treatment with carvedilol in patients with decompensated heart failure and low blood pressure (systolic blood pressure <100 mm Hg), ischemic heart disease or other vascular disorders and/or renal failure. After discontinuation of the drug, renal function returned to baseline values. During the titration phase, renal function should be monitored in patients with heart failure and risk factors. If deterioration occurs, the dose should be reduced or treatment should be discontinued.
Pheochromocytoma
Patients with pheochromocytoma should only be given Carvedilol Sandoz if there is sufficient α-receptor blockade. Although Carvedilol Sandoz combines these two pharmacological properties, there is no relevant experience to date. Therefore, Carvedilol Sandoz should be used with caution in patients with pheochromocytoma.
Prinzmetal's angina
Drugs with non-selective beta-blocking activity may precipitate chest pain in patients with Prinzmetal's angina. There is no clinical experience with carvedilol in such patients, although the alpha-blocking activity of carvedilol may prevent the development of such symptoms. However, Carvedilol Sandoz should be used with caution in patients suspected of having Prinzmetal's angina.
Chronic obstructive pulmonary disease
β-blockers may increase bronchial obstruction, so patients with chronic lung disease are not recommended to use these drugs. Carvedilol Sandoz, however, can be prescribed with caution to patients with mild lung disease if other drugs are ineffective. When prescribing Carvedilol Sandoz, caution should be used to use the lowest effective dose to reduce inhibition of endogenous and exogenous β-antagonists. Breathing difficulty may occur due to increased airway resistance.
Patients with chronic obstructive pulmonary disease were enrolled in clinical trials if they did not require oral or inhaled medications for the treatment of their disease. The recommended dose should be strictly adhered to and should be reduced as soon as bronchospasm is suspected during the titration phase (see section 4.5).
Liver dysfunction
Mild liver cell damage has occasionally been observed during treatment with carvedilol. In controlled trials in patients with hypertension, the incidence of hepatic dysfunction, a reported adverse reaction, was 1.1% (13 of 1142) in patients treated with carvedilol and 0.9% (4 of 462) in patients treated with placebo. One patient treated with carvedilol in a placebo-controlled trial was excluded due to hepatic dysfunction.
In controlled trials in patients with chronic heart failure, the incidence of liver dysfunction, a reported adverse event, was 5.0% (38 out of 765) in patients treated with carvedilol and 4.6% (20 out of 437) in patients treated with placebo.
Three patients treated with carvedilol (0.4%) and two patients treated with placebo (0.5%) were excluded from placebo-controlled studies due to liver dysfunction.
Liver damage has been shown to be reversible and occurs with minimal clinical symptoms after short and long-term therapy. No fatal outcome from liver dysfunction has been reported. Laboratory tests should be performed at the first signs/symptoms of liver dysfunction (e.g., pruritus, dark urine, persistent anorexia, jaundice, right upper quadrant tenderness, or unexplained flu-like symptoms). If the patient's laboratory values confirm the presence of liver damage or jaundice, carvedilol should be discontinued and treatment should not be resumed.
The patient should be given the following recommendations:
Do not interrupt or stop treatment with Carvedilol Sandoz without consulting your doctor.
Patients with heart failure should contact their doctor if they notice signs or symptoms of worsening heart failure (weight gain or shortness of breath);
Patients may suffer from a drop in blood pressure when standing, which can lead to dizziness and, in some cases, loss of consciousness: such patients should sit or lie down if such symptoms occur;
Patients suffering from fatigue and dizziness should not drive or perform hazardous tasks: this also applies to all patients at the beginning of treatment and during the dose titration period;
Patients should contact their doctor if they experience dizziness or fainting during the titration phase.
Carvedilol Sandoz should be taken with food;
Diabetics should inform their doctor about any changes in their blood glucose levels.
Patients who wear contact lenses should be informed of the possible reduction in tear production.
Use during pregnancy or breastfeeding
Unless absolutely necessary, carvedilol should not be used during pregnancy.
Beta-blockers reduce placental perfusion, which may lead to intrauterine fetal death, miscarriage, or premature birth. In addition, adverse effects may occur in the fetus and newborn (especially hypoglycemia and bradycardia). Newborns may be at increased risk of cardiac and pulmonary complications in the postnatal period. Animal studies have not provided evidence of teratogenicity of carvedilol.
Carvedilol is contraindicated during breast-feeding. Breast-feeding should be discontinued during treatment with carvedilol. Animal studies have shown that carvedilol and/or its metabolites are excreted in the milk of rats. It is not known whether carvedilol is excreted in human breast milk. Most β-blockers, particularly lipophilic substances, are excreted in human milk in varying amounts.
Treatment with β-blockers should be discontinued 72-48 hours before the expected date of birth. If this is not possible, newborns should be monitored for the first 48-72 hours of life.
The ability to influence the reaction speed when driving or working with other mechanisms
Such studies have not been conducted. Due to possible adverse reactions (e.g. dizziness, fatigue) during treatment with Carvedilol Sandoz, driving and operating potentially dangerous machinery should be avoided. Particular attention should be paid at the beginning of treatment, after increasing the dose, when using other medicines or when combined with alcohol.
Method of administration and doses
Essential hypertension
Adults
The initial dose is 12.5 mg once daily for the first two days. After that, treatment with a dose of 25 mg once daily is recommended. If the effect is insufficient, the daily dose can be gradually increased to 50 mg in one or two doses per day (after at least 2 weeks). The maximum dose for hypertension is 50 mg.
Elderly patients
Initial dose: 12.5 mg once daily. For some patients, this dose is sufficient to provide adequate blood pressure control. If the effect is insufficient, the daily dose may be gradually increased to a maximum of 50 mg in one or two doses per day.
Angina pectoris
The initial dose is 12.5 mg twice daily for the first two days. Thereafter, treatment with 25 mg twice daily is recommended. If the effect is insufficient, the daily dose can be gradually increased to a maximum of 100 mg in two doses (at least every 2 weeks).
Elderly patients
The dose should usually not exceed 25 mg twice daily.
Treatment of mild to severe heart failure (NYHA class 1I-IV)
The dose should be selected individually and the patient's condition should be carefully monitored during the titration phase.
The dose of digitalis, diuretics and ACE inhibitors should be stabilized before starting treatment with Carvedilol Sandoz.
The recommended starting dose is 3.125 mg twice daily for two weeks. If this dose is well tolerated, it can be gradually increased (at intervals of at least every 2 weeks) to 6.25 mg twice daily, then to 12.5 mg twice daily (2 times 1 tablet of Carvedilol Sandoz 12.5 mg) and finally to 25 mg twice daily (2 times 1 tablet of Carvedilol Sandoz 25 mg). The dose should be titrated to the highest dose that is well tolerated by the patient.
The maximum recommended dose is 25 mg twice daily in patients weighing up to 85 kg and 50 mg twice daily in patients weighing more than 85 kg.
Before increasing the dose, the physician should examine the patient for signs of worsening heart failure, vasodilation (loss of blood pressure, dizziness), or bradycardia. Transient exacerbations of heart failure or the appearance of edema should be treated with concomitant use of
