Adverse reactions : תופעות לוואי

4.8 Undesirable effects

(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).
The following undesirable effects have been reported (e.g., from clinical trials, post- authorisation safety studies or spontaneous reporting) to occur when carvedilol is administered:
Frequency categories are as follows:
Very common ≥1/10
Common ≥1/100 to <1/10
Uncommon ≥1/1,000 to <1/100
Rare ≥1/10,000 to <1/1,000
Very rare <1/10,000

Table 1: Adverse Reactions
System Organ Class          Adverse Reaction                                   Frequency Infections and infestations Pneumonia                                          Common Bronchitis                                         Common
Upper respiratory tract infection                  Common
Urinary tract infection                            Common
Blood and lymphatic system Anaemia                                             Common disorders                   Thrombocytopenia                                   Rare Leukopenia                                         Very rare
Immune system disorders         Hypersensitivity (allergic reactions)          Very rare Metabolism and nutrition        Weight increase                                Common disorders                       Hypercholesterolaemia                          Common Impaired blood glucose control                 Common
(hyperglycaemia, hypoglycaemia) in patients with pre-existing diabetes
Psychiatric disorders           Depression, depressed mood                     Common Sleep disorders                                Uncommon
Nervous system disorders        Dizziness                                      Very common Headache                                       Very common
Syncope, presyncope                            Common
Paraesthesia                                   Uncommon
Eye disorders                   Visual impairment                              Common Lacrimation decreased (dry eye)                Common
Eye irritation                                 Common
Cardiac disorders               Cardiac failure                                Very common Bradycardia                                      Common
Hypervolaemia (fluid overload)                   Common
Atrioventricular block                           Uncommon
Angina pectoris                                  Uncommon
Vascular disorders             Hypotension                                      Very common Orthostatic hypotension                          Common
Disturbances of peripheral circulation           Common
(cold extremities, peripheral vascular disease, exacerbation of intermittent claudication and Raynaud's phenomenon)
Hypertension                                     Common
Respiratory, thoracic and      Dyspnoea                                         Common mediastinal disorders          Pulmonary oedema                                 Common Asthma in predisposed patients                   Common
Nasal congestion, flu-like symptoms              Rare
Gastrointestinal Disorders     Nausea                                           Common Diarrhoea                                        Common
Vomiting                                         Common
Dyspepsia                                        Common
Abdominal pain                                   Common
Constipation                                     Uncommon
Dry mouth                                        Rare
Hepatobiliary disorders        Alanine aminotransferase (ALT), aspartate        Very rare aminotransferase (AST) and gamma- glutamyltransferase (GGT) increased
Skin and subcutaneous          Skin reactions (e.g., allergic exanthema,        Uncommon disorders                      dermatitis, urticaria, pruritus, psoriatic and lichen planus like skin lesions), alopecia
Musculoskeletal and            Pain in extremities                              Common connective tissue disorders
Renal and urinary disorders    Renal failure and renal function                 Common abnormalities in patients with diffuse vascular disease and/or underlying renal insufficiency
Micturition disorders                            Rare
Urinary incontinence in women                    Very rare
Reproductive system and        Erectile dysfunction                             Uncommon breast disorders
General disorders and          Asthenia (fatigue)                               Very common administration site            Oedema                                           Common conditions                     Pain                                             Common 
(c) 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.
In congestive heart failure patients, worsening cardiac failure and fluid retention may occur during up-titration of carvedilol dose (see section 4.4).

Cardiac failure was a very commonly reported adverse event in both placebo (14.5%) and carvedilol-treated (15.4%) patients, in patients with left ventricular dysfunction following acute myocardial infarction.
Reversible deterioration of renal function has been observed with carvedilol therapy in chronic heart failure patients with low blood pressure, ischaemic heart disease and diffuse vascular disease and/or underlying renal insufficiency (see section 4.4).
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 medicine 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.

Cardiac disorders
Sinus arrest may occur in predisposed patients (e.g., elderly patients or patients with pre- existing bradycardia, sinus node dysfunction or atrioventricular block).

Skin and subcutaneous tissue disorders
Severe cutaneous adverse reactions (Toxic epidermal necrolysis, Stevens-Johnson syndrome (see section 4.4).
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.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il