Adverse reactions : תופעות לוואי

4.8   Undesirable effects

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 may progress 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.

Immunogenicity:

Antibodies against components of fibrin sealant/haemostatic products may occur rarely.
However, in a clinical trial with TachoSil in hepatic surgery, in which patients were investigated for the development of antibodies, 26% of the 96 patients tested and treated with TachoSil developed antibodies to equine collagen. The equine collagen antibodies that developed in some patients after TachoSil use were not reactive with human collagen.
One patient developed antibodies to human fibrinogen.
There were no adverse events attributable to the development of human fibrinogen or equine collagen antibodies.
There is very limited clinical data available regarding re-exposure of TachoSil. Two subjects have been re-exposed in a clinical trial and have not reported any immune-mediated adverse events, however, their antibody status to collagen or fibrinogen is unknown.

Thromboembolic complications may occur if the preparation is applied intravascularly (see section 4.4) 
Some cases of product residue, that might have caused a foreign-body reaction in the form of granuloma, have been reported.

For viral safety see section 4.4.

Summary of the safety profile
The safety data of TachoSil generally reflect the type of post-operative complications related to the surgical settings in which the trials were conducted and the underlying disease of the patients.

Data from the eight controlled clinical trials conducted by the MAH has been pooled into an integrated dataset. In the integrated analyses, 997 patients were treated with TachoSil and 984 patients were treated with comparator treatment.
Due to practical reasons (comparison to standard surgical and standard haemostatic treatment), blinding was not possible in the TachoSil trials. Therefore the studies were performed as open-label studies.

Tabulated summary of adverse reactions

The following adverse reactions have been reported with TachoSil during post marketing experience. The frequency of all of the events listed below has been categorised as not known (cannot be estimated from the available data).


System organ class                                          Frequency not known Immune system disorders                                     Anaphylactic shock, Hypersensitivity Vascular disorders                                          Thrombosis Gastrointestinal disorders                                  Intestinal obstruction (in abdominal surgeries) Adhesions
General disorders and administration site conditions
Foreign-body granuloma formation


Reporting of suspected adverse reactions
Reporting of 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/