CARVEDILOL

Posology Symptomatic congestive heart failure The dosage must be titrated to individual requirements and monitored during up- titration. For those patients receiving diuretics and/or digoxin and/or ACE inhibitors, dosing of these other medicinal products should be stabilised prior to initiation of carvedilol treatment.

5 mg once a day for the first two days. Thereafter the recommended dosage is 25 mg once a day. Although this is an adequate dose in most patients, if necessary the dose may be titrated up to a recommended daily maximum dose of 50 mg given once a day or in divided doses.

Dose titration should occur at intervals of at least two weeks. 5 mg is recommended. This has provided satisfactory control in some cases. If the response is inadequate the dose may be titrated up to the recommended daily maximum dose of 50 mg given once a day or in divided doses.

125 mg twice a day for two weeks. 5 mg twice daily and thereafter 25 mg twice daily. Dosing should be increased to the highest level tolerated by the patient. The maximum recommended dose is 25 mg twice daily for patients with severe CHF and for patients with mild to moderate CHF weighing less than 85 kg (187 lbs).

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 treatment. Under these circumstances, the dose of carvedilol 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 up-titrated in line with the above dosing recommendation.

Elderly As for adults. Special dosage instructions As with all beta-blockers, treatment should not be stopped abruptly; it should be gradually reduced at weekly intervals, particularly in patients with concomitant coronary heart disease.

2). 1). Method of administration Carvedilol film-coated tablets are for oral use only. The tablets should be taken with fluid. 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.

(a) Summary of the safety profile The frequency of adverse reactions is not dose-dependent, with the exception of dizziness, abnormal vision and bradycardia. (b) Tabulated list of adverse reactions The risk of most adverse reactions associated with carvedilol is similar across all indications.

Exceptions are described in subsection (c). g. g. Erythema multiforme, Stevens- Johnson syndrome, Toxic epidermal necrolysis) Musculoskeletal and connective tissue disorders Common: Pain in extremities Renal and urinary disorders Common: Renal failure and renal function abnormalities in patients with diffuse vascular disease and/or underlying renal insufficiency, micturition disorders Very rare: Urinary incontinence in women Reproductive system and breast disorders Uncommon: Erectile dysfunction General disorders and administration site conditions Very common: Asthenia (fatigue) Common: Pain, Oedema (c) Description of selected adverse reactions 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). 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.

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. If such symptoms occur, diuretics should be increased and the Carvedilol dose should not be further increased until clinical stability resumes.

Occasionally it may be necessary to lower the Carvedilol dose or, in rare cases, temporarily discontinue it. Such episodes do not preclude subsequent successful up-titration of Carvedilol. 5).

Renal function in congestive heart failure:

Reversible deterioration of renal function has been observed during carvedilol therapy in chronic heart failure patients with low blood pressure (systolic BP < 100 mmHg), 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 up-titration of carvedilol and the medicinal product discontinued or dosage reduced if worsening of renal failure occurs. Left ventricular dysfunction following acute myocardial infarction Before treatment with carvedilol is initiated the patient must be clinically stable and should have received an ACE inhibitor for at least thepast 48 hours, and the dose of the ACE inhibitor should have been stable for at least the past 24 hours.

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.

However, caution should be taken in the administration of carvedilol to patients suspected of having Prinzmetal’s variant angina.

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 should be reduced if any evidence of bronchospasm is observed during treatment.

Diabetes:

Care should be taken in the administration of Carvedilol to patients with diabetes mellitus, as it may be associated with worsening control of blood glucose. Furthermore, 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 may obscure the symptoms of thyrotoxicosis.

Bradycardia:

Carvedilol may induce bradycardia. If the patient's pulse rate decreases to less than 55 beats per minute, the dosage of Carvedilol should be reduced.

Hypersensitivity:

Care should be taken in administering Carvedilol to patients with a history of serious hypersensitivity reactions and in patients 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 should be permanently discontinued in patients who experience severe cutaneous adverse reactions possibly attributable to Carvedilol.

Psoriasis:

Patients with a history of psoriasis associated with beta-blocker therapy should be given Carvedilol only after consideration of the risk-benefit ratio. g. digoxin, ciclosporin, rifampicin, anaesthetics, antiarrhythmics. 5).

Phaeochromocytoma:

In patients with phaeochromocytoma, an alpha-blocking agent should be initiated prior to the use of any beta-blocking agent. Although Carvedilol has both alpha- and beta-blocking pharmacological activities, there is no experience of the use of carvedilol in this condition.

Therefore, caution should be taken in the administration of Carvedilol to patients suspected of having phaeochromocytoma. Carvedilol contains lactose monohydrate and sucrose. Patients with rare hereditary problems of galactose intolerance, fructose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption, sucrase-isomaltase insufficiency should not take this medicine.

1. ⎯ Unstable/decompensated heart failure requiring intravenous inotropic support ⎯ Clinically manifest liver dysfunction As with other beta-blocking agents: ⎯ History of bronchospasm or asthma ⎯ 2nd and 3rd degree atrioventricular (AV) heart block, (unless a permanent pacemaker is in place) ⎯ Severe bradycardia (< 50 bpm) ⎯ Cardiogenic shock ⎯ Sick sinus syndrome (including sino-atrial block) ⎯ Severe hypotension (systolic blood pressure < 85 mmHg).