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 sealant/haemostatic products. 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).

For safety information 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).

Within each frequency grouping, adverse reactions are presented in order of decreasing of seriousness.

Table 1. Frequency of adverse reactions (ARs) in clinical trials with VeraSealTM: 
MedDRA system organ class
Adverse reaction                     Frequency
(SOC)
Infections and infestations         Abdominal abscess, cellulitis, liver       Uncommon abscess, peritonitis, postoperative wound infection, wound infection incision site infection, post procedural infection.
MedDRA system organ class
Adverse reaction                    Frequency
(SOC)
Neoplasms benign, malignant      Plasma cell myeloma                         Uncommon and unspecified (including cysts and polyps)
Blood and lymphatic system       Anaemia, haemorrhagic anaemia,              Uncommon disorders                        leukocytosis, leukopenia
Immune system disorders          Hypersensitivity*                           Unknown Metabolism and nutrition         Hyperglycaemia, hyperkalaemia,              Uncommon disorders                        hypocalcaemia, hypoglycaemia,
hypokalaemia, hypomagnesemia,
hyponatraemia, hypoproteinaemia
Psychiatric disorders            Anxiety, insomnia                           Uncommon Nervous system disorders         Headache, somnolence                        Uncommon Eye disorders                    Conjunctival irritation                     Uncommon Cardiac disorders                Atrial fibrillation, ventricular            Uncommon tachycardia
Vascular disorders               Deep vein thrombosis, hypertension,         Uncommon hypotension
Respiratory, thoracic and        Pulmonary embolism, dyspnoea,               Uncommon mediastinal disorders            hypoxia, pleural effusion, pleurisy, pulmonary oedema, rhonchi, wheezing
Gastrointestinal disorders       Nausea                                      Common Constipation, flatulence, ileus,            Uncommon retroperitoneal haematoma, vomiting
Skin and subcutaneous tissue     Pruritus                                    Common disorders
Ecchymosis, erythema                        Uncommon
Musculoskeletal and              Back pain, pain in extremity                Uncommon connective tissue disorders
Renal and urinary disorders      Bladder spasm, dysuria, urinary             Uncommon retention
General disorders and            Chills, hyperthermia, oedema                Uncommon administration site conditions   peripheral, pain, pyrexia, vessel puncture site haematoma
Investigations                   Parvovirus B19 test positive, activated     Uncommon partial thromboplastin time prolonged,
alanine aminotransferase increased,
aspartate aminotransferase increased,
blood bilirubin increase, blood glucose increase, international normalised ratio increased, prothrombin time prolonged,
transaminases increased, urine output decreased
Drug specific antibody present*             Unknown
Injury, poisoning and            Procedural pain                             Common procedural complications
Abdominal wound dehiscence, post            Uncommon procedural bile leak, contusion, incision site erythema, incision site pain, post procedural haemorrhage, procedural
MedDRA system organ class
Adverse reaction                      Frequency
(SOC) hypotension, vascular graft complication, vascular graft thrombosis,
wound secretion
*All these reactions are class effect. None were reported in clinical trials; thus it is not possible to establish frequencies.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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/