Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Hypersensitivity or allergic reactions (which may include but are not limited to angioedema, burning and stinging at the application site, bradycardia, bronchospasm, chills, breathing difficulties, transient erythema (“flushing”), generalized urticaria, headache, hives, hypotension, lethargy, nausea, pruritus, restlessness, paresthesia, tachycardia, tightness of the chest, tingling, vomiting, wheezing) may occur in rare cases in patients treated with fibrin sealants / hemostatics, anaphylactic reactions and anaphylactic shock have included fatal outcomes.

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 aprotinin (see section 4.4) or any other constituents of the product.

Even if repeated treatment with TISSEEL FROZEN was well tolerated, a subsequent administration of TISSEEL FROZEN or systemic administration of aprotinin may result in severe anaphylactic reactions.

Antibodies against components of the fibrin sealant / hemostatic may occur in rare cases.

Inadvertent intravascular injection may result in thromboembolic events and DIC.
Furthermore there is the risk of an anaphylactic reaction (see section 4.4).
For safety with respect to transmissible agents, see section 4.4.

The adverse reactions presented in this section were reported from clinical trials investigating the safety and efficacy of TISSEEL FROZEN and from post-marketing experience (marked with a p in the adverse event table below) with Baxter Fibrin Sealants. In the clinical trials, TISSEEL FROZEN was administered for adjunct hemostasis in cardiac, vascular, and total hip replacement surgeries and in liver and spleen surgeries. Other clinical trials included the sealing of lymphatic vessels in patients undergoing axillary lymph node dissection, sealing of colonic anastomosis and in dural sealing in the posterior fossa. As the frequencies of adverse events observed in post marketing experience cannot be calculated, whenever possible, the upper limit of the 95% confidence interval was calculated using the “rule of three” in the following manner: 3/1146 = 0.0026 or 0.26% which is “Uncommon” (where “1146” is the total number of subjects to have received TISSEEL FROZEN in the clinical trials from which data were included in the SmPC)

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)

System organ class       Preferred MedDRA Term                                 Frequency (SOC)
Infections and           Postoperative wound infection                         Common infestations
Blood and lymphatic      Fibrin degradation                                    Uncommon system disorders         products increased
Immune system            Hypersensitivity reactions* p                         Uncommon disorders                Anaphylactic reactions* p                             Uncommon Anaphylactic shock* p                                 Uncommon
Paresthesia p                                         Uncommon
Bronchospasm p                                        Uncommon
Wheezing p                                            Uncommon
Pruritus p                                            Uncommon
Erythema p                                            Uncommon
Nervous system           Sensory disturbance                                   Common disorders
Cardiac disorders        Bradycardia p                                         Uncommon Tachycardia p                                         Uncommon
Vascular disorders       Axillary vein thrombosis **                           Common Hypotension                                           Rare
Haematoma (NOS) p                                     Uncommon
Embolism arterial p                                   Uncommon
Air embolism*** p                                     Not known
Cerebral artery embolism p                            Uncommon
Cerebral infarction** p                               Uncommon
Respiratory, thoracic    Dyspnoea p                                            Uncommon and mediastinal disorders
Gastrointestinal         Nausea                                                Uncommon p disorders                Intestinal obstruction                                Uncommon Skin and subcutaneous    Rash                                                  Common tissue disorders         Urticaria p                                           Uncommon Impaired healing p                                    Uncommon
Musculoskeletal and      Pain in an extremity                                  Common connective tissue disorders
General disorders and    Pain                                                  Common administration site      Increased body temperature                            Common conditions
Flushing p                                            Uncommon
Oedema p                                              Uncommon
Injury, poisoning and    Procedural pain                                       Uncommon procedural               Seroma                                                Very common complications            Angioedema p                                          Uncommon * anaphylactic reactions and anaphylactic shock have included fatal outcomes.
** as a result of intravascular application into the superior petrosal sinus.
*** as with other fibrin sealants life-threatening/fatal air or gas embolism when using devices with pressurized air or gas occurred; this event appears to be related to an inappropriate use of the spray device (e.g. at higher than recommended pressure and in close proximity to the tissue surface).
p
Adverse events observed in post-marketing experience.

Class Reactions
Other adverse reactions associated with the fibrin sealant/hemostatic class include: manifestations of hypersensitivity include application site irritation, chest discomfort, chills, headache, lethargy, restlessness, and vomiting.

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