Dilatrend Special Precautions

General: 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, as both drugs slow AV conduction (see Interactions).
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.
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 (see Dosage and Administration).
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.
Prinzmetal's Variant Angina: Agents with non-selective β-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 α-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.
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, or the early signs and symptoms of acute hypoglycaemia may be masked or attenuated (see Interactions and Use in Special Population).
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 β-blockers can precipitate or aggravate symptoms of arterial insufficiency.
Thyrotoxicosis: Carvedilol, like other agents with β-blocking properties, may obscure the symptoms of thyrotoxicosis.
Pheochromocytoma: In patients with pheochromocytoma, an α-blocking agent should be initiated prior to the use of any β-blocking agent. Although carvedilol has α- and β-blocking pharmacological activities, there is no experience with its use in this condition. Caution should therefore be taken in the administration of carvedilol to patients suspected of having pheochromocytoma.
Hypersensitivity: Care should be taken in administering carvedilol to patients with a history of serious hypersensitivity reactions, and in patients undergoing desensitisation therapy, as β-blockers may increase both the sensitivity towards allergens and the severity of hypersensitivity reactions.
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 Adverse Reactions]. 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 β-blocker therapy should take 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 drugs (e.g. digoxin, cyclosporin, rifampicin, anaesthetic drugs, anti-arrhythmic drugs), see Interactions, for further details.
Contact Lenses: Wearers of contact lenses should bear in mind the possibility of reduced lacrimation.
Withdrawal Syndrome: Carvedilol treatment should not be discontinued abruptly, particularly in patients suffering from ischaemic heart disease. The withdrawal of carvedilol should be gradual (over a period of two weeks).
Paediatric Use: See Dosage and Administration.
Geriatric Use: A study in elderly hypertensive patients showed that there was no difference in the adverse event profile as compared to younger patients. Another study, which included elderly patients with coronary heart disease, showed no difference in the adverse events reported vs those reported by younger patients. Therefore, no dose adjustment of the starting dose is required in the geriatric population (see Dosage and Administration).
Renal Impairment: The autoregulatory renal blood supply is preserved and the glomerular filtration is unchanged during chronic treatment with carvedilol. In patients with moderate to severe renal insufficiency, no changes in carvedilol dosage recommendations are warranted (see Dosage and Administration).
Hepatic Impairment: Carvedilol is contraindicated in patients with clinically manifest liver dysfunction (see Contraindications). A pharmacokinetic study in cirrhotic patients has shown that exposure (AUC) to carvedilol was increased by 6.8-folds in patients with liver impairment as compared to healthy subjects.
Diabetic Patients: Beta-blockers may increase insulin resistance and mask hypoglycaemic symptoms. However, numerous studies have established that vasodilating β-blockers like carvedilol are associated with more favourable effects on glucose and lipid profiles.
Carvedilol has been shown to exhibit modest insulin-sensitizing properties and can relieve some manifestations of the metabolic syndrome.
Ability to Drive and Use Machines: No studies on the effects on the ability to drive and to use machines have been performed.
Because of individually variable reactions (e.g. dizziness, tiredness), the ability to drive, operate machinery, or work without firm support may be impaired. This applies particularly at the start of treatment, after dose increases, on changing products, and in combination with alcohol.