Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

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.
Carvedilol should be used with caution in combination with digitalis glycosides, since both medicine slow AV conduction (see section 4.5).

Renal function in congestive heart failure: Reversible deterioration of renal function has been observed with 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 medicine discontinued or dosage reduced if worsening of renal failure occurs.

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. Therefore, regular monitoring of blood glucose is required in diabetics when carvedilol is initiated or up- titrated and hypoglycaemic therapy adjusted accordingly (see section 4.5).

Peripheral vascular disease and Raynaud's phenomenon: carvedilol should be used with caution in patients with peripheral vascular disease (e.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.

Severe cutaneous adverse reactions (SCARs): 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 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.

Interactions with other medicinal products: There are a number of important pharmacokinetic and pharmacodynamic interactions with other medicines (e.g., digoxin, ciclosporin, rifampicin, anaesthetics, antiarrhythmics. See section 4.5).

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.

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 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, discontinuation should be gradual (over a period of 2 weeks), particularly in patients with ischaemic heart disease, as carvedilol has beta-blocking activity.

Effects on Driving

4.7 Effects on ability to drive and use machines
No studies of the effects on ability to drive and use machines have been performed.

As for other medicines which produce changes in blood pressure, patients taking carvedilol should be warned not to drive or operate machinery if they experience dizziness or related symptoms. This applies particularly when starting, dose increasing or changing treatment and in conjunction with alcohol.