Adverse reactions : תופעות לוואי

4.8     Undesirable effects

Summary of the safety profile
The safety of andexanet alfa has been evaluated in clinical trials including 417 healthy subjects administered an FXa inhibitor, as well as in 419 patients in a Phase IIIb/IV trial (study 14-505), who had acute major bleeding and were under treatment with an FXa inhibitor (apixaban and rivaroxaban).

In clinical studies in healthy subjects who were administered a FXa inhibitor and then received andexanet alfa, the frequency of adverse reactions was similar in the andexanet alfa- treated group (16.8%) and in the placebo treated group (12.2%). The most frequently observed adverse reactions were mild or moderate infusion-related reactions comprising symptoms such as flushing, feeling hot, cough, dysgeusia, and dyspnoea occurring within a few minutes to a few hours of the infusion. Among the healthy subjects studied, women experienced more adverse reactions (mainly infusion-related reactions) than men.

In the healthy subject trials, elevations > 2 x ULN in D-dimer and prothrombin fragments F1+2 were frequently observed. These elevations were maintained between several hours to a few days following administration, but no thrombotic events were reported.

In patients with major bleedings thrombosis-markers have not been investigated since bleeding can interfere with the thrombosis marker results. Thromboses and thromboembolic events have commonly been documented.

Tabulated list of adverse reactions

Table 4 provides the list of adverse reactions in patients with major bleeds from study 14- 505 including 419 patients on apixaban and rivaroxaban with acute major bleeding treated with andexanet alfa. The adverse reactions are classified by system organ class (SOC) and frequency, using the following convention: 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); or not known (cannot be estimated from available data).

Table 4: List of adverse reactions in patients with major bleeds

System organ class     Very common ≥              Common ≥ 1/100 to        Uncommon ≥ 1/10                       < 1/10                   1/1,000 to < 1/100 Nervous system                                    Cerebrovasculr           Cerebral infarction disorders                                         accident
Transient ischaemic
Ischaemic stroke         attack
Cardiac disorders                                 Acute myocardial         Cardiac arrest infarction

Myocardial infarction
Vascular disorders                                Deep vein                Iliac artery occlusion thrombosis

Respiratory,                                      Pulmonary thoracic and                                      embolism mediastinal disorders
General disorders                                 Pyrexia and administrative site conditions
Injury, poisoning                                                          Infusion related and procedural                                                             reactiona complications a reported signs/symptoms (rigors, chills, hypertension, oxygen desaturation, agitation and confusion) were transient and mild to moderate in severity.

Description of selected adverse reactions
Based on data from 419 patients from the Phase IIIb/IV study 14-505 treated with apixaban and rivaroxaban and experiencing an acute major bleeding episode, two patients (0.5%) experienced an infusion-related reaction, neither of which was assessed as severe (1 moderate; 1 mild).

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/ and emailed to the Registration Holder’s Patient Safety Unit at: drugsafety@neopharmgroup.com