Adverse reactions : תופעות לוואי

4.8   Undesirable effects
Summary of the safety profile

Assessment of intrinsic factors such as gender or age on the incidence of any treatment emergent adverse reactions showed an interaction for gender (female patients) for the incidence of any adverse reactions and for serious adverse reactions.

In clinical studies, premature discontinuation due to adverse reactions occurred in 11.8% of the dronedarone-treated patients and in 7.7% in the placebo-treated group. The most common reasons for discontinuation of therapy with MULTAQ were gastrointestinal disorders (3.2% of patients versus 1.8% in the placebo group).
The most frequent adverse reactions observed with dronedarone 400 mg twice daily in the 5 studies were diarrhoea (9%), nausea (5%) and vomiting (2%), fatigue and asthenia (7%).

Tabulated list of adverse reactions

The safety profile of dronedarone 400 mg twice daily in patients with atrial fibrillation (AF) or atrial flutter (AFL) is based on 5 placebo controlled studies, in which a total of 6,285 patients were randomised (3,282 patients received dronedarone 400 mg twice daily, and 2,875 received placebo).
The mean exposure across studies was 13 months. In ATHENA study, the maximum follow-up was 30 months. Some adverse reactions were also identified during post-marketing surveillance.
Adverse reactions are presented by system organ class.
Frequencies are defined as: 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); not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1: Adverse Reactions

System organ         Very             Common               Uncommon               Rare class                Common           (1/100 to <1/10)    (1/1,000 to           (1/10,000 to (1/10)                               <1/100)                <1/1,000) Immune system                                                                     Anaphylactic disorders                                                                         reactions including angioedema
Nervous system                                             Dysgeusia              Ageusia disorders
System organ         Very            Common               Uncommon               Rare class                Common          (1/100 to <1/10)    (1/1,000 to           (1/10,000 to (1/10)                              <1/100)                <1/1,000) Cardiac              Congestive      Bradycardia (see disorders            heart failure   sections 4.3 and
(see below)     4.4)

Vascular                                                                         Vasculitis, including disorders                                                                        leukocytoclastic vasculitis
Respiratory,                                              Interstitial lung thoracic and                                              disease including mediastinal                                               pneumonitis and disorders                                                 pulmonary fibrosis (see below)
Gastrointestinal                      Diarrhoea disorders                             Vomiting
Nausea
Abdominal pains
Dyspepsia
Hepatobiliary                         Liver function                             Hepatcellular liver disorders                             test                                       injury, includinfg abnormalities                              life-threatening acute liver failure
(see section 4.4)
Skin and                              Rashes               Erythemas subcutaneous                          (including           (including tissue disorders                      generalised,         erythema and rash macular, maculo-     erythematous) papular)             Eczema
Pruritus             Photosensitivity reaction
Dermatitis allergic
Dermatitis
General                              Fatigue disorders and                        Asthenia administration site conditions

Investigations       Blood creatinine increased*

QTc Bazett prolonged #
* ≥10% five days after treatment initiation (see section 4.4)
# >450 msec in male >470 msec in female (see section 4.4)

Description of selected adverse reactions

Congestive heart failure
In the 5 placebo controlled studies, CHF occurred in the dronedarone group with rates comparable with placebo (very commonly, 11.2% versus 10.9%). This rate should be considered in the context of the underlying elevated incidence of CHF in AF patients. Cases of CHF have also been reported in post-marketing experience (frequency not known) (see section 4.4).

Interstitial lung disease including pneumonitis and pulmonary fibrosis 

In the 5 placebo controlled studies, 0.6% of patients in the dronedarone group had pulmonary events versus 0.8% of patients receiving placebo. Cases of interstitial lung disease including pneumonitis and pulmonary fibrosis have been reported in post-marketing experience (frequency not known). A number of patients had been previously exposed to amiodarone (see section 4.4).

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.
Healthcare professionals are asked to report any suspected adverse reactions to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il/