Adverse reactions : תופעות לוואי

4.8.    Undesirable Effects


Summary of the safety profile
Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the application site, bronchospasm, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) may occur in rare cases in patients treated with fibrin sealants/haemostatics. In isolated cases, these reactions have progressed to severe anaphylaxis. Such reactions may especially be seen if the preparation is applied repeatedly, or administered to patients known to be hypersensitive to constituents of the product.
Antibodies against components of fibrin sealant/haemostatic products may occur rarely.
Inadvertent intravascular injection could lead to thromboembolic event and disseminated intravascular coagulation (DIC), and there is also a risk of anaphylactic reaction (see section   4.4).
Life-threatening air or gas embolism has occurred with the use of spray devices employing pressure regulator to administer EVICEL. This event appears to be related to the use of the spray device at higher than recommended pressures and/or in close proximity to the tissue surface.

For safety with respect to transmissible agents, see Section 4.4.

Tabulated list of adverse reactions
The table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level).
Frequencies have been evaluated according to 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), not known (cannot be estimated from the available data).


MedDRA System Organ
Preferred Term          Frequency
Class
Adverse reactions in retroperitoneal or intra-abdominal surgery studies
Infections and infestations        Abdominal abscess        Common
General disorders and
Pyrexia            Common administration site conditions
Blood and lymphatic system
Coagulopathy          Common disorders
Adverse reactions in vascular surgery study
Graft infection,
Infections and infestations                                 Uncommon
Staphylococcal infection
Vascular disorders                 Haematoma            Uncommon
General disorders and
Oedema Peripheral        Uncommon administration site conditions
Investigations             Decreased haemoglobin      Uncommon
Incision site haemorrhage
Vascular graft occlusion   Uncommon
Wound              Uncommon
Injury, poisoning and
Post procedural haematoma   Uncommon procedural complications
Post-operative wound      Uncommon complication          Uncommon

Adverse reactions in neurosurgery study
Infections and infestations            Meningitis           Common
Intracranial hypotension
Common
(CSF leakage)
Common
CSF rhinorrhoea
Nervous system disorders                                    Common
Headache
Common
Hydrocephalus
Common
Subdural hygroma
Vascular disorders                 Haematoma            Common

Description of selected adverse reactions


Adverse Reaction Rates in Retroperitoneal or Intra-Abdominal Surgery Studies Among 135 patients undergoing retroperitoneal and intra-abdominal surgery (67 patients treated with EVICEL and 68 controls), no adverse events were considered to be causally related to the study treatment according to the investigator assessments. However, 3 serious adverse events (SAE) (one abdominal abscess in the EVICEL group and one abdominal and one pelvic abscess in the control group) were considered by the Sponsor to be possibly related to study treatment.
In a study in a paediatric population involving 40 patients (20 patients treated with EVICEL and 20 controls), two adverse events (pyrexia and coagulopathy) were considered possibly related to EVICEL by the investigator.


Adverse Reactions - Vascular Surgery
In a controlled study involving 147 patients undergoing vascular grafting procedures (75 treated with EVICEL and 72 controls), a total of 16 subjects were reported to have had a graft thrombosis/occlusion adverse event during the study period. The events were evenly distributed across treatment arms, with 8 each in the EVICEL and the control groups.
A non-interventional post-authorisation safety study was conducted which involved 300 patients undergoing vascular surgery during which EVICEL was used. Safety monitoring focused on the specific adverse reactions of graft patency, thrombotic events, and bleeding events. No adverse reactions were reported during the study.


Adverse Reactions – Neurosurgery
In a controlled study involving 139 patients undergoing elective neurosurgical procedures (89 treated with EVICEL and 50 controls), a total of 7 subjects treated with EVICEL experienced nine AEs that were considered to be possibly related to the study product. These included intracranial hypotension (CSF leakage), CSF rhinorrhoea, meningitis, headache, hydrocephalus, subdural hygroma and haematoma.
The incidence of CSF leakage and the incidence of Surgical Site Infections were monitored as safety endpoints in the study. At 30 days post-operatively the incidence of SSIs was similar between the two treatment groups. Post-operative CSF leakage occurred within 30 days from treatment in 4/89 (4.5%) subjects treated with EVICEL (two cases of CSF leakage with impaired wound healing and two cases of rhinorrhoea) and in 1/50 (2.0%) subjects treated with additional sutures.


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 

Additionally, you may also report to the MAH, Omrix Biopharmaceuticals Ltd. by one of the following 2 ways:
Call Omrix switchboard: 073-2588562
Email: ra-omrilpv@its.jnj.com