CARVEDILOL

5 mg and 25 mg 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 single dose is 25 mg and the recommended maximum daily dose is 50 mg.

5 mg once a day for the first two days. Thereafter, the treatment is continued at the dose 25 mg/day. If necessary, the dose may be further increased gradually at intervals of two weeks or more rarely. 5 mg once a day, 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 at intervals of two weeks or more rarely. 5 mg twice daily for two days. Thereafter, the treatment is continued at the dose 25 mg twice daily.

If necessary, the dose may be further increased gradually at intervals of two weeks or more rarely. The recommended maximum daily dose is 100 mg in divided doses (50mg twice daily). 5 mg twice daily for two days. Thereafter, the treatment is continued at the dose 25 mg twice daily, which is the recommended maximum daily dose.

Heart failure Treatment of moderate to severe heart failure in addition to conventional basic therapy with diuretics, ACE inhibitors, digitalis, and/or vasodilators. The patient should be clinically stable (no change in NYHA-class, no hospitalisation due to heart failure) and the basic therapy must be stabilised for at least 4 weeks prior to treatment.

3). 125 mg twice a day 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, provided that the heart failure is not severe.

A dose increase to 50 mg twice daily should be performed carefully under close medical supervision of the patient. Transient worsening of symptoms of heart failure may occur at the beginning of treatment, or due to a dose increase, especially in patients with severe heart failure and/or under high dose diuretic treatment.

This does usually not call for discontinuation of treatment, but the dose should not be increased. The patient should be monitored by a physician/cardiologist after starting carvedilol treatment or increasing the dose. g. renal function, body weight, blood pressure, heart rate and heart rhythm).

Worsening of heart failure or fluid retention is treated by increasing the dose of diuretic, and the dose of carvedilol should not be increased until the patient is stabilised. If bradycardia appears or in case of lengthening of AV conduction, the level of digoxin should first be monitored.

Occasionally it may be necessary to reduce the carvedilol dose or temporarily discontinue treatment altogether. Even in these cases, carvedilol dose titration can often be successfully continued. 125 mg twice daily and increased gradually in accordance with the above recommendation.

Renal insufficiency Dosage must be determined for each patient individually, but according to pharmacokinetic parameters there is no evidence that dose adjustment of carvedilol in patients with renal failure is necessary. Moderate hepatic dysfunction.

Dose adjustment may be required. Paediatric population (< 18 years) The safety and efficacy of carvedilol in children and adolescents aged below 18 years has not been established. Elderly Elderly patients may be more susceptible to the effects of carvedilol and should be monitored more carefully.

4). Method 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.

(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) Rare: psoriatic skin lesions, existing lesions may be aggravated.

Musculoskeletal and connective tissue disorders Very common:

Pain in limb 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 Very common: Genital oedema Uncommon: Erectile dysfunction General disorders and administration site conditions Very common: Asthenia (fatigue)*, oedema Common: Pain *These reactions occur in particular at the beginning of treatment.

4). 1in patients with heart failure 2in patients with hypertension and angina (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. Acute renal insufficiency and disturbance of renal function in patients with generalised atherosclerosis and/or impaired renal function have been rare adverse reactions.

The frequency of adverse reactions is not dose dependent, with the exception of dizziness, visual disturbance, bradycardia and aggravation of heart insufficiency. Cardiac contractility may be decreased during dose titration but this is rare.

Very rare adverse reactions include angina, AV block and exacerbation of symptoms in patients suffering from intermittent claudication or Raynaud's phenomenon. Non-selective beta-blockers in particular may also result in latent diabetes mellitus becoming manifest, manifest diabetes being aggravated and blood glucose control being disturbed.

Mild disturbances of glucose balance are possible, however not common, also during treatment with carvedilol. 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.

Warnings to be considered particularly in heart failure patients. Carvedilol should be administered principally in addition to diuretics, ACE inhibitors, digitalis and/or vasodilators. Therapy should only be initiated, if the patient is stabilized on conventional basic therapy for at least 4 weeks.

Decompensated patients have to be re-compensated. Patients with severe heart failure, salt and volume depletion, elderly or patients with low basic blood pressure should be monitored for approximately 2 hours after the first dose or after dose increase as hypotension may occur.

Hypotension due to excessive vasodilatation is initially treated by reducing the dose of the diuretic. If symptoms still persist, the dose of any ACE inhibitor may be reduced. The carvedilol dose may be further reduced or temporarily discontinued, if necessary.

The carvedilol dose should not be increased again before symptoms due to the worsening of heart failure or vasodilatation are under control. 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 advanced 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 titration of carvedilol. Carvedilol should be used with caution in combination with digitalis glycosides, as both drugs slow AV conduction. Renal function in congestive heart failure Reversible deterioration of renal function has been observed during carvedilol therapy in heart failure patients with low blood pressure (systolic < 100 mm Hg), ischaemic heart disease and generalised atherosclerosis, and/or underlying renal insufficiency.

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

5). Other warnings as regards carvedilol and beta-blockers in general. 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 the preceding 48 hours, and the dose of the ACE inhibitor should have been stable for at least the preceding 24 hours.

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 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 the early signs and symptoms of acute hypoglycaemia may be masked or attenuated. . In chronic heart failure patients with diabetes, the use of carvedilol may be associated with worsening control of blood glucose.

5). Thyrotoxicosis Carvedilol may mask the symptoms and signs 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.

Concomitant use of calcium channel blockers Careful monitoring of ECG and blood pressure is necessary in patients receiving concomitant therapy with calcium channel blockers of the verapamil or diltiazem type or other antiarrhythmic drugs.

5). 5). Contact lenses Wearers of contact lenses should be advised of the possibility of reduced lacrimation. Hypersensitivity Care should be taken in administering carvedilol 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 seriousness of anaphylactic reactions.

Psoriasis Caution should be exercised when prescribing beta-blockers to patients with psoriasis since skin reactions may be aggravated. Patients with a history of psoriasis associated with b-blocker therapy should take carvedilol only after consideration of the risk-benefit ratio.

Peripheral vascular disease Carvedilol should be used with caution in patients with peripheral vascular disease as β-blockers can precipitate or aggravate symptoms of arterial insufficiency. Raynaud's phenomenon Carvedilol should be used with caution in patients suffering from peripheral circulatory disorders (eg Raynaud's phenomenon) as there may be exacerbation of symptoms.

2 “Pharmacokinetic properties”). First degree heart block Because of its negative dromotropic action, carvedilol should be administered with caution to patients with first degree heart block. Anesthesia and major surgery […]

1. Unstable/decompensated heart failure Heart failure belonging to NYHA Class IV of the heart failure classification requiring intravenous inotropic treatment. Clinically significant hepatic dysfunction. History of bronchospasm or asthma.

Second or third degree AV block (unless a permanent pacemaker is in place). Severe bradycardia (<50 bpm). Cardiogenic shock. Sick sinus syndrome (including sinoatrial blocks). Severe hypotension (systolic blood pressure below 85 mmHg).

Metabolic acidosis. Patients with phaeochromocytoma that are not receiving alpha blockade treatment. 5).