Change to section

Details of change

4.1 Therapeutic Indications

Text in blue removed and text in red added:

TachoSil is indicated in adults for supportive treatment in surgery for improvement of haemostasis, to promote tissue sealing, and for suture support in vascular surgery where standard techniques are insufficient, and for supportive sealing of the dura mater to prevent postoperative cerebrospinal leakage following neurological surgery (see section 5.1).

4.4 Special warnings and precautions for use

Text in blue removed and text in red added:

…

Do not use intravascularly. Life threatening thromboembolic complications may occur if the preparation is applied intravascularly.

Specific data have not been obtained on the use of this product in neurosurgery or in gastrointestinal anastomoses surgery.

It is not known whether recent radiation therapy affects the efficacy of Tachosil when used for dura mater sealing.

As with any protein-containing product, allergic type hypersensitivity reactions are possible. Signs of hypersensitivity reactions include hives, generalised urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis. If these symptoms occur, the administration has to be discontinued immediately.

5.1 Pharmacodynamic properties

Text in red added:

…..

However, the second study investigating tissue sealing in 299 patients (149 TachoSil, 150 standard surgical treatment) with demonstrated intraoperative air leakage showed the superiority of TachoSil compared to standard treatment.

The efficacy of TachoSil was tested in a randomised controlled study in 726 patients (362 treated with TachoSil and 364 controls) undergoing skull base surgery as an adjunct to suture for sealing the dura mater, in which the efficacy outcome was measured post-operatively as verified cerebrospinal fluid (CSF) leaks or pseudomeningocoele, or treatment failure during surgery. In this study, superiority over current practise practice (which included suture, duraplasty and fibrin and polymer sealants or combinations of these) could not be documented. The numbers of subjects experiencing an efficacy outcome event were 25 (6.9%) and 30 (8.2%) for TachoSil and current practice treated patients, respectively, providing an Odds Ratio of 0.82 (95% CI: 0.47, 1.43). However, the 95% confidence intervals for the odds ratio results indicated that TachoSil had similar efficacy to current practice. In this study two application techniques for TachoSil were evaluated: application of TachoSil over the dura and application of TachoSil on both sides of the dura. The results did not support the second method. TachoSil was found to be well tolerated and safe for use as an adjunct to dura mater closure in neurosurgery.

6.6 Special precautions for disposal and other handling

Text in red added:

…

The active side of TachoSil should be applied so that it extends 1‑2 cm beyond the margins of the wound. If more than one matrix is used they should overlap. TachoSil can be cut to the correct size and shaped if too large.

In neurosurgery, TachoSil should be applied on top of the primary dura closure.

Pre-rolled TachoSil can be used for both open surgery and in minimally invasive surgery, and it can pass through a 10 mm or larger port or trocar.

…

10. Date of revision of the text

Updated text in red:

30^th March 2016

Change to section

Details of change

4.4 Special warnings and precautions for use

Text in red removed:

Do not use intravascularly. Life threatening thromboembolic complications may occur if the preparation is unintentionally applied intravascularly.

Text in red added:

As with any protein-containing product, allergic type hypersensitivity reactions are possible. Signs of hypersensitivity reactions include hives, generalised urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis. If these symptoms occur, the administration has to be discontinued immediately.

4.8 Undesirable effects

Text in red added/removed:

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 to 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 unintentionally applied intravascularly (see section 4.4)

Frequency of undesirable effects for TachoSil based on all adverse event data from six clinical trials, two post-authorisation safety studies and spontaneous reporting.

Tabulated summary of adverse reactions

Data from the six eight controlled clinical trials conducted by the MAH has been pooled into an integrated dataset. The frequencies of occurrence in this SmPC originate from this integrated dataset. In the integrated analyses, 521 997 patients were treated with TachoSil and 511 984 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).

The following categories are used to rank the undesirable effects by frequency of occurrence: 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); and very rare (<1/10,000), not known (cannot be estimated from the available data).

*Pyrexia occurred in 6.3% of the patients treated with TachoSil and in 5.9% of the patients treated with comparator treatment.

10. Date of revision of the text

Updated:

4 February 2016

Change to section

Details of change

4.4 Special warnings and precautions for use

Added:

To prevent the development of tissue adhesions at undesired sites, ensure tissue areas outside the desired application area are adequately cleansed before administration of TachoSil (see section 6.6). Events of adhesions to gastrointestinal tissues leading to gastrointestinal obstruction have been reported with use in abdominal surgery carried out in proximity to the bowel.

4.8 Undesirable effects

Text in red added:

6.6 Special precautions for disposal and other handling

Added text in red:

Pressure is applied with moistened gloves or a moist pad. Due to the strong affinity of collagen to blood, TachoSil may also stick to surgical instruments, gloves or adjacent tissues covered with blood. This can be avoided by cleansing surgical instruments, and gloves and adjacent tissues before application. It is important to note that failure to adequately clean adjacent tissues may cause adhesions (see section 4.4). After pressing TachoSil to the wound, the glove or the pad must be removed carefully. To avoid TachoSil from being pulled loose it may be held in place at one end, e.g. with a pair of forceps.

10. Date of revision of the text

Updated:

6 January 2016

CHANGE TO SECTION

DETAILS OF CHANGE

1.         NAME OF THE MEDICINAL PRODUCT

Changed:

‘‘TachoSil medicated sponge’’

to

‘’TachoSil sealant matrix’’

3.         PHARMACEUTICAL FORM

Changed:

‘‘Medicated sponge’’

to

‘’Sealant matrix’’

‘’TachoSil is an off-white sponge sealant matrix. The active side of the sponge matrix, which is coated with fibrinogen and thrombin, is marked by a yellow colour’’.

4.2      POSOLOGY AND METHOD OF ADMINISTRATION

The quantity number of TachoSil sponges to be applied should always be oriented towards the underlying clinical need for the patient. The quantity number of TachoSil sponges to be applied is governed by the size of the wound area.

Application of TachoSil must be individualised by the treating surgeon. In clinical trials, the individual dosages have typically ranged from 1-3 spongeunits (9.5 cm x 4.8 cm); application of up to 7 sponge units has been reported. For smaller wounds, e.g. in minimally invasive surgery the smaller size sponge matrices (4.8 cm x 4.8 cm or 3.0 cm x 2.5 cm) or the pre-rolled matrix (based on a matrix of 4.8 cm x 4.8 cm) is recommended.

Method and route of administration

4.4       SPECIAL WARNINGS AND PRECAUTIONS FOR USE

For local use epilesional use only.

4.8.   UNDESIRABLE EFFECTS     

Added:

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. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

6.5     NATURE AND CONTENTS OF CONTAINER

Changed:

Each sponge sealant matrix is packed in a PET-GAG blister sealed with a coated PE foil. The blister is packed in an aluminium-bonded foil sachet with a desiccant bag included and packed in a folding carton.

Pack sizes:

Package with 1 spongematrix of 9.5 cm x 4.8 cm

Package with 2 spongematrices of 4.8 cm x 4.8 cm

Package with 1 spongematrix of 3.0 cm x 2.5 cm

Package with 5 spongematrices of 3.0 cm x 2.5 cm

Added:

Package with 1 pre-rolled matrix of 4.8 cm x 4.8 cm

6.6     SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER  HANDLING

Changed:

After removal of the conventional, flat TachoSil from the sterile package it the sponge should be pre-moistened in saline solution and then applied immediately. The yellow, active side of the sponge matrix is applied to the bleeding/leaking surface and held against it with a gentle pressure for 3-5 minutes.

Added:

After removal of the pre-rolled TachoSil from the sterile package it should be applied immediately through the trocar without pre-moistening. While unrolling the matrix the yellow, active side of the matrix is applied to the bleeding/leaking surface using e.g. a pair of cleansed forceps and held against it with a moist pad under gentle pressure for 3-5 minutes. This procedure enables an easy adhesion of TachoSil to the wound surface.

Changed:

This can be avoided by pre-moisteningcleansing surgical instruments and gloves with physiological saline solutionbefore application. After pressing TachoSil to the wound, the glove or the pad must be removed carefully. To avoid the spongeTachoSil from being pulled loose it may be held in place at one end, e.g. with a pair of forceps.

Changed:

The active side of TachoSil sponge should be applied so that it extends 1-2 cm beyond the margins of the wound. If more than one spongematrix is used they sponges should overlap. The spongeTachoSil can be cut to the correct size and shaped if too large.

Added:

Pre-rolled TachoSil can be used for both open surgery and in minimally invasive surgery, and it can pass through a 10 mm or larger port or trocar.

10.      DATE OF REVISION OF THE TEXT

Changed to:

25th September 2014