CARVEDILOL

Posology Essential hypertension:

Carvedilol may be used for the treatment of hypertension alone or in combination with other antihypertensives, especially thiazide diuretics. Once daily dosing is recommended, however the recommended maximum daily dose is 50 mg. 5 mg once daily for two days.

Thereafter, the treatment is continued at the dose 25 mg/day. If necessary, the dose may be further increased gradually to a recommended daily maximum dose of 50 mg given once a day or in divided doses at intervals of two weeks or more rarely.

Dose titration should occur at intervals of at least two weeks. 5 mg once daily, which may also be sufficient for continued treatment. However, if the therapeutic response is inadequate at this dose, the dose may be further increased gradually up to the recommended daily maximum dose of 50 mg given once a day or in divided doses at intervals of two weeks or more rarely.

Paediatric population:

Safety and efficacy in children (under 18 years) has not been established. 5 mg twice a day for the first two days. Thereafter, the recommended dosage is 25 mg twice a day. If necessary, the dose may be titrated up to 50 mg twice a day.

Dose titration should occur at intervals of at least two weeks. Elderly The recommended maximum daily dose is 50 mg given in divided doses. Special dosage instructions As with all beta-blockers, treatment should not be stopped abruptly but rather gradually reduced at weekly intervals.

This is particularly important in the case of patients with concomitant coronary heart disease. 2). 1).

Symptomatic congestive heart failure:

The dosage must be titrated to individual requirements and monitored during up-titration. For Congestive Heart Failure (CHF) patients carvedilol should be given with food to slow the rate of absorption and reduce the incidence of orthostatic effects.

For those patients receiving diuretics and/or digoxin and/or ACE inhibitors, dosing of these other drugs should be stabilised prior to initiation of Carvedilol Tablets treatment. 125 mg twice daily for two weeks. 5 mg twice daily followed by 25 mg twice daily.

It is recommended that the dose is increased to the highest level tolerated by the patient. The recommended maximum dose is 25 mg given twice daily in patients weighing less than 85 kg and 50 mg twice daily in patients weighing more than 85 kg.

In patients with mild or moderate CHF weighing more than 85 kg, the maximum recommended dose is 50 mg twice daily. Before each dose increase the patient should be evaluated by the physician for symptoms of worsening heart failure or vasodilation.

Transient worsening of heart failure, vasodilation or fluid retention may be treated with increased doses of diuretics or ACE inhibitors or by modifying or temporarily discontinuing Carvedilol Tablets treatment. Under these circumstances, the dose of Carvedilol Tablets should not be increased until symptoms of worsening heart failure or vasodilation have been stabilised.

If carvedilol treatment is discontinued for more than one week, therapy should be recommenced at a lower dose level (twice daily) and up-titrated in line with the above dosing recommendation. 125 mg twice daily and increased gradually in accordance with the above recommendation.

Elderly:

As for adults elderly patients may be more susceptible to the effects of carvedilol and should be monitored more carefully.

Paediatric population Children and adolescents (< 18 years):

There is insufficient data of the efficacy and safety of carvedilol. 1) Methods of administration The tablets do not need to be taken with a meal. However, it is recommended that heart failure patients take their carvedilol medication with food to allow the absorption to be slower and the risk of orthostatic hypotension to be reduced.

Carvedilol tablets are for oral use only. The tablets should be taken with fluid.

(a) Summary of the safety profile The frequency of adverse reactions is not dose-dependent except for dizziness, visual disturbances and bradycardia. (b) Table of adverse reactions The risk of most adverse reactions associated with carvedilol is similar for all indications.

The exceptions are described in subsection (c). g. Allergic exanthema, dermatitis, urticaria, pruritus, psoriatic and lichen planus like skin lesions), alopecia Musculoskeletal and connective tissue disorders Common Pain in extremities Common Renal failure and renal function abnormalities in patients with diffuse vascular disease and/or underlying renal insufficiency Rare Micturition disorders Renal and urinary disorders Very rare Urinary incontinence in women Reproductive system and breast disorders Uncommon Erectile dysfunction Very common Asthenia (fatigue) Oedema General disorders and administration site conditions Common Pain Description of selected adverse reactions The frequency of adverse reactions is not dose-dependent, with the exception of dizziness, abnormal vision and bradycardia.

Dizziness, syncope, headache and asthenia are usually mild and are more likely to occur at the beginning of treatment. 4). 4% respectively, in patients with left ventricular dysfunction following acute myocardial infarction). 4). The following adverse events have been identified during post-marketing use of carvedilol.

Because these events are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency and/or establish a causal relationship to medicinal product exposure: Metabolism and nutrition disorders As a class, beta-adrenergic receptor blockers may cause latent diabetes to become manifest, manifest diabetes to be aggravated, and blood glucose counter-regulation to be inhibited.

Psychiatric disorders Carvedilol may cause hallucinations. g. elderly patients or patients with pre-existing bradycardia, sinus node dysfunction or atrioventricular block). 4). Hyperhidrosis. Renal and urinary disorders Carvedilol may cause urinary incontinence in women which resolves upon discontinuation of the medication.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Chronic Congestive Heart Failure In congestive heart failure patients, worsening cardiac failure or fluid retention may occur during up-titration of Carvedilol Tablets. If such symptoms occur, diuretics should be increased and the Carvedilol Tablets dose should not be advanced until clinical stability resumes.

Occasionally, it may be necessary to lower the Carvedilol Tablets dose or, in rare cases, temporarily discontinue it. Such episodes do not preclude subsequent successful up-titration of Carvedilol Tablets. 5). . Renal function in Congestive Heart Failure Reversible deterioration of renal function has been observed during Carvedilol Tablets therapy in chronic heart failure patients with low blood pressure (systolic < 100 mm Hg), ischaemic heart disease and diffuse vascular disease and/or underlying renal insufficiency.

In CHF patients with these risk factors, renal function should be monitored during dose titration of Carvedilol Tablets. If significant worsening of renal function occurs, the carvedilol dose must be reduced or therapy must be discontinued.

Chronic obstructive pulmonary disease Carvedilol should be used with caution, in patients with chronic obstructive pulmonary disease (COPD) with a bronchospastic component who are not receiving oral or inhaled medication, and only if the potential benefit outweighs the potential risk.

In patients with a tendency to bronchospasm, respiratory distress can occur as a result of a possible increase in airway resistance. Patients should be closely monitored during initiation and up- titration of carvedilol and the dose of Carvedilol Tablets should be reduced if any evidence of bronchospasm is observed during treatment.

Diabetes Care should be taken in the administration of Carvedilol Tablets to patients with diabetes mellitus, as it may be associated with worsening control of blood glucose, or the early signs and symptoms of acute hypoglycaemia may be masked or attenuated.

Alternatives to beta-blocking agents are generally preferred in insulin- dependent patients. 5). g. Raynaud’s phenomenon) as beta- blockers can precipitate or aggravate symptoms of arterial insufficiency. Thyrotoxicosis Carvedilol Tablets may mask symptoms and signs of thyrotoxicosis.

Bradycardia Carvedilol Tablets may induce bradycardia. If the patient's pulse rate decrease in pulse rate to less than 55 beats per minute, the dosage of Carvedilol Tablets should be reduced. Hypersensitivity Care should be taken in administrating Carvedilol Tablets to patients with a history of serious hypersensitivity reactions and in those undergoing desensitisation therapy as beta-blockers may increase both the sensitivity towards allergens and the severity of hypersensitivity reactions.

Risk of Anaphylactic Reaction:

While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

8). Carvedilol Tablets should be permanently discontinued in patients who experience severe cutaneous adverse reactions possibly attributable to Carvedilol Tablets. Psoriasis Cautions should be exercised when prescribing beta-blockers to patients with history of psoriasis associated with β-blocker therapy since skin reactions may be aggravated and should take Carvedilol Tablets only after consideration of the risk-benefit ratio.

, digoxin, ciclosporin, rifampicin, anaesthetic drugs, and antiarrhythmic drug. 5). Phaeochromocytoma In patients with pheochromocytoma, an alpha-blocking agent should be initiated prior to the use of any beta-blocking agent. Although Carvedilol Tablets has both alpha- and beta-blocking pharmacological activities, there is no experience with its use in this condition.

Caution should therefore be taken in the administration of Carvedilol Tablets to patients suspected of having phaeochromocytoma. Prinzmetal's variant angina Agents with non-selective beta-blocking activity may provoke chest pain in patients with Prinzmetal's variant angina.

There is no clinical experience with carvedilol in these patients although the alpha-blocking activity of carvedilol may prevent such symptoms. Caution should, however, be taken in the administration of carvedilol to patients suspected of having Prinzmetal's variant angina.

Contact lenses Wearers of contact lenses should be advised of the possibility of reduced lacrimation. Withdrawal syndrome Although angina has not been reported on stopping treatment, carvedilol therapy must be discontinued gradually within two weeks, particularly in patients with ischaemic heart disease, as Carvedilol Tablets has beta-blocking activity.

Lactose This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

1. • Unstable/decompensated heart failure requiring intravenous inotropic support. • Clinically manifest liver dysfunction. • As with other beta-blocking agents: o History of bronchospasm or asthma. o Second or third degree atrioventricular (AV) block (unless a permanent pacemaker is in place).

o Severe bradycardia (< 50 bpm). o Cardiogenic shock. o Sick sinus syndrome (including sinoatrial blocks). o Severe hypotension (systolic blood pressure below 85 mmHg).