Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile

The most frequently reported adverse reactions associated with icosapent ethyl were bleeding (11.8%), peripheral oedema (7.8%), atrial fibrillation (5.8%), constipation (5.4%), musculoskeletal pain (4.3%), gout (4.3%) and rash (3.0%).

Tabulated list of adverse reactions

Adverse reactions are classified according to frequency and system organ class. Reporting frequencies for adverse reactions have been estimated from a long-term cardiovascular outcomes study in which subjects were observed for a median follow-up duration of 4.9 years. Frequency categories are defined according to the following conventions: 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) and not known (cannot be estimated from the available data).

Table 1 lists adverse reactions

Table 1 Adverse reactions
MedDRA Sytem organ class                                     Adverse reaction         Frequency Immune system disorders                                      Hypersensitivity         Uncommon Pharyngeal swelling      Not known
Metabolism and nutrition disorders                           Gout                     Common Nervous system disorders                                     Dysgeusia1               Uncommon Cardiac disorders                                            Atrial fibrillation or   Common flutter2
Vascular disorders                                           Bleeding2                Very common Gastrointestinal disorders                                   Constipation2            Common Eructation               Common
Skin and subcutaneous tissue disorders                       Rash                     Common Musculoskeletal and connective tissue disorders              Musculoskeletal pain     Common General disorders and administration site                    Peripheral oedema        Common conditions
1 Dysguesia describes the “verbatim” term: Fishy taste
2 See section Description of selected adverse reactions

Description of selected adverse reactions

Bleeding
Bleeding occurred in 11.8% of subjects receiving icosapent ethyl in a placebo-controlled cardiovascular outcomes trial compared with 9.9% in subjects receiving placebo. Serious bleeding events were reported more frequently in subjects receiving icosapent ethyl than in those receiving placebo when administered in combination with concomitant antithrombotic medication (3.4% vs. 2.6%), but occurred at the same rate (0.2%) in subjects not taking concomitant anticoagulant/antiplatelet medication (see section 4.4).

The bleeding events most frequently observed with icosapent ethyl were gastrointestinal bleeding (3.1%), contusion (2.5%), haematuria (1.9%), and epistaxis (1.5%).

Atrial fibrillation/flutter

Atrial fibrillation or atrial flutter occurred in 5.8% of subjects receiving icosapent ethyl in a placebo- controlled cardiovascular outcomes trial compared with 4.5% in subjects receiving placebo. Atrial fibrillation or atrial flutter requiring hospitalisation for 24 hours or more occurred in 3% of subjects treated with icosapent ethyl compared with 2% in subjects receiving placebo. Atrial fibrillation and atrial flutter were reported more frequently in subjects with a previous history of atrial fibrillation or atrial flutter receiving icosapent ethyl than in those receiving placebo (12.5% vs. 6.3%) (see section 4.4).


Constipation
Constipation occurred in 5.4% of subjects receiving icosapent ethyl in a placebo-controlled cardiovascular outcomes trial compared with 3.6% of subjects receiving placebo. Serious constipation was less common for icosapent ethyl (0.1%) and placebo (0.2%). The relative incidence of constipation in this study may have been confounded by a residual laxative effect for placebo, which comprised a subtherapeutic dose of light mineral oil (4 mL).

The following adverse reactions have been identified from global post-marketing use of icosapent ethyl. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish causal relationship to drug exposure: blood triglycerides increased, arthralgia, diarrhoea, abdominal discomfort, and pain in the extremities.

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