TachoSil medicated sponge

TachoSil contains per cm²:

For a full list of excipients, see section 6.1.

Medicated sponge

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

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 (see section 5.1).

Posology

The use of TachoSil is restricted to experienced surgeons.

The number of TachoSil sponges to be applied should always be oriented towards the underlying clinical need for the patient. The 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 sponges (9.5 cm x 4.8 cm); application of up to 7 sponges has been reported. For smaller wounds, e.g. in minimal invasive surgery the smaller size sponges (4.8 cm x 4.8 cm or 3.0 cm x 2.5 cm) are recommended.

Method and route of administration

For local use only. Do not use intravascularly.

See section 6.6 for more detailed instructions.

Paediatric patients

TachoSil is not recommended for use in children below age 18 years due to insufficient data on safety and efficacy.

Hypersensitivity to the active substances or to any of the excipients.

For local use only.

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

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

As with any protein 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.

In case of shock, the current medical standards for shock treatment should be observed.

Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.

The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV and for the non-enveloped virus HAV. The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia).

It is strongly recommended that every time TachoSil is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.

No formal interaction studies have been performed.

Similar to comparable products or thrombin solutions, the sealant may be denatured after exposure to solutions containing alcohol, iodine or heavy metals (e.g. antiseptic solutions). Such substances should be removed to the greatest possible extent before applying the sealant.

The safety of TachoSil for use in human pregnancy or breastfeeding has not been established in controlled clinical trials. Experimental animal studies are insufficient to assess the safety with respect to reproduction, development of the embryo or foetus, the course of gestation and peri- and postnatal development.

Therefore, TachoSil should be administered to pregnant and breastfeeding women only if clearly needed.

Not relevant.

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.

Antibodies against components of fibrin sealant/haemostatic products may occur rarely.

Thromboembolic complications may occur if the preparation is unintentionally applied intravascularly (see section 4.4).

For viral safety 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.

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.

Tabulated summary of adverse reactions

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

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.

No case of overdose has been reported.

Pharmaco-therapeutic group: Local haemostatics, ATC code: B02BC30

TachoSil contains fibrinogen and thrombin as a dried coating on the surface of a collagen sponge. In contact with physiological fluids, e.g. blood, lymph or physiological saline solution the components of the coating dissolve and partly diffuse into the wound surface. This is followed by the fibrinogen-thrombin reaction which initiates the last phase of physiological blood coagulation. Fibrinogen is converted into fibrin monomers which spontaneously polymerise to a fibrin clot, which holds the collagen sponge tightly to the wound surface. The fibrin is then cross linked by endogenous factor XIII, creating a firm, mechanically stable network with good adhesive properties and therefore provides sealing as well.

Clinical studies demonstrating haemostasis were conducted in a total of 240 patients (119 TachoSil, 121 argon beamer) undergoing partial liver resection surgery and 185 patients (92 TachoSil, 93 standard surgical treatment) undergoing surgical resection of superficial renal tumour. A further controlled study in 119 patients (62 TachoSil, 57 haemostatic fleece) demonstrated sealing, haemostasis and suture support in patients undergoing cardiovascular surgery. Tissue sealing in lung surgery was investigated in two controlled trials in patients undergoing lung surgery. The first controlled clinical trial investigating tissue sealing in lung surgery failed to document superiority over standard treatment measured by air leakage due to the inclusion of a large group of patients (53%) without air leakage. 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.

TachoSil is intended for local application only. Intravascular administration is not possible.

As a consequence, intravascular pharmacokinetic studies were not performed in man.

In animal studies TachoSil shows a progressive biodegradation. The fibrin clot is metabolised in the same way as endogenous fibrin by fibrinolysis and phagocytosis. The collagen sponge is degraded by resorptive granulation tissue. Approximately 24 weeks after application only a few remnants were present without any signs of local irritation.

Single dose toxicity studies in different species of animals have shown no signs of acute toxic effect.

Equine collagen

Human albumin

Riboflavine (E 101)

Sodium chloride

Sodium citrate (E331)

L-arginine-hydrochloride.

Not applicable.

3 years.

Once the foil sachet is opened, TachoSil must be used immediately.

Do not store above 25 °C.

Each sponge 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 sponge of 9.5 cm x 4.8 cm

Package with 2 sponges of 4.8 cm x 4.8 cm

Package with 1 sponge of 3.0 cm x 2.5 cm

Package with 5 sponges of 3.0 cm x 2.5 cm

Not all pack sizes may be marketed.

TachoSil comes ready to use in sterile packages and must be handled accordingly. Use only undamaged packages. Once the package is opened post-sterilisation is not possible. The outer aluminium foil sachet may be opened in a non-sterile operating area. The inner sterile blister must be opened in a sterile operating room area. TachoSil should be used immediately after opening the inner sterile cover.

TachoSil is used under sterile conditions. Prior to application the wound area should be cleansed, e.g. from blood, disinfectants and other fluids. After removal of TachoSil from the sterile package the sponge should be pre-moistened in saline solution and then applied immediately. The yellow, active side of the sponge is applied to the bleeding/leaking surface and held against it with a gentle pressure for 3-5 minutes. This procedure enables an easy adhesion of TachoSil to the wound surface.

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

Alternatively, e.g. in case of stronger bleeding, TachoSil may be applied without pre-moistening, while also pressing gently to the wound for 3-5 minutes.

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

Any unused product or waste material should be disposed of in accordance with local requirements.

Nycomed Austria GmbH

St. Peter Strasse 25

A-4020 Linz

Austria

EU/1/04/277/001-004

Date of first authorisation: 8 June 2004

Date of latest renewal: 8 June 2009

1^st July 2010

Detailed information on this product is available on the website of the European Medicines Agency (EMA) http://www.ema.europa.eu/