Consumer medicine information

TachoSil Medicated Sponge

Fibrinogen; Thrombin

BRAND INFORMATION

Brand name

TachoSil

Active ingredient

Fibrinogen; Thrombin

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using TachoSil Medicated Sponge.

What is in this leaflet

This leaflet answers some common questions about TachoSil. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available. You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on this medicine.

Those updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you having TachoSil against the benefits they expect it will have for you.

If you have any concerns about receiving this medicine, ask your doctor.

Keep this leaflet. You may need to read it again.

What TachoSil is used for

This medicine is used during surgery to stop local bleeding (haemostasis).

This medicine contains the two active ingredients fibrinogen and human thrombin, which are proteins normally found in the blood.

When the sponge comes into contact with fluids (such as blood, lymph or saline solution) the fibrinogen and the human thrombin are activated and form a fibrin network.

This means that the sponge sticks to the tissue surface, the blood coagulates and the tissue is sealed.

In the body, TachoSil will dissolve and disappear completely.

Ask your doctor if you have any questions about why this medicine has been recommended for you. Your doctor may have prescribed it for another reason.

There is not enough information to recommend the use of this medicine for children under the age of 18 years.

Before you receive TachoSil

When you must not have it

Do not take TachoSil if you have an allergy to:

  • any medicine containing fibrinogen or human thrombin
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

TachoSil in not intended to be given intravascularly. Intravascular application of TachoSil may result in life-threatening thromboembolic events.

If you are not sure whether you should have this medicine, talk to your doctor.

Before you start to have it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

Tell your doctor if you are below 18 years of age. There is not enough information to recommend the use of TachoSil in children below 18 years of age.

If you have not told your doctor about any of the above, tell them before you receive TachoSil.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and TachoSil may interfere with each other.

How TachoSil is given

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

The surgeon treating you will administer TachoSil during surgery.

The sponge will be placed on the internal organ to stop the bleeding.

The sponge will disappear and dissolve completely over time.

How much will be given

Your doctor will determine the number of TachoSil sponges required, which will depend on the size of the wound.

It is strongly recommended that when you are given TachoSil, the name and batch number of the product are recorded at the hospital in order to maintain a record of the batches used.

After you have received TachoSil

Things you must do

If you are going to have surgery, tell the surgeon or anaesthetist that you have received TachoSil. It may affect other medicines used during surgery.

If you become pregnant soon after receiving TachoSil, tell your doctor immediately.

Keep all of your doctor’s appointments so that your progress can be checked.

Side effects

Tell your doctor as soon as possible if you do not feel well after you have been given TachoSil.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor to answer any questions you may have.

Tell your doctor as soon as possible if you notice any of the following:

  • fever
  • changes in the way your heart beats.

These are the more common side effects of the medicine.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin
  • fever, drowsiness, chills and runny nose followed about two weeks later by a rash and joint pain
  • pain in your abdomen or bowels

These may be serious side effects and you may need urgent medical attention. Serious side effects are rare.

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

Product description and storage

Storage

TachoSil should be stored by the hospital in a place where the temperature stays below 25°C.

What it looks like

TachoSil is an off-white sponge, coloured yellow on the active side.

It is available in the following dimensions and pack sizes:

  • 1 sponge of 9.5 cm x 4.8 cm
  • 2 sponges of 4.8 cm x 4.8 cm
  • 1 sponge of 3.0 cm x 2.5 cm
  • 5 sponges of 3.0 cm x 2.5 cm

Ingredients

Each square centimetre of the sponge contains 5.5 mg fibrinogen and 2.0 IU human thrombin as the active ingredients.

TachoSil also contains:

  • collagen
  • albumin
  • riboflavine
  • sodium chloride
  • sodium citrate dihydrate
  • arginine hydrochloride.

Manufacturer and Supplier

Supplied in Australia by:

Takeda Pharmaceuticals Australia Pty Ltd
Level 39
225 George Street
Sydney NSW 2000
Australia
Telephone: 1800 012 612
www.takeda.com/en-au

Distributed in Australia by:

Baxter Healthcare Pty Ltd
1 Baxter Drive
Old Toongabbie NSW 2146
AUSTRALIA

TACHOSIL® is a registered trademark of Takeda AS.

This leaflet was prepared in December 2020

AUST R 176631

Published by MIMS February 2021

BRAND INFORMATION

Brand name

TachoSil

Active ingredient

Fibrinogen; Thrombin

Schedule

Unscheduled

 

1 Name of Medicine

Fibrinogen and human thrombin.

2 Qualitative and Quantitative Composition

Each TachoSil sponge contains approximately 5.5 mg of fibrinogen and 2.0 IU of human thrombin per cm2 as the active ingredients.
Other inactive ingredients include riboflavine, collagen, albumin, sodium chloride, sodium citrate dihydrate and arginine hydrochloride.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

TachoSil is a biodegradable, highly flexible, hygroscopic surgical medicated sponge. The active side of the sponge, which is coated with fibrinogen and human thrombin, is marked by a yellow colour.
TachoSil is available in three presentations, which differ in the size of the sponge, but not in the composition of the sponge and the coating (see Section 6.5 Nature and Contents of Container).

4 Clinical Particulars

4.1 Therapeutic Indications

TachoSil is indicated as an adjunct to haemostasis during surgery when control of bleeding by standard surgical techniques is ineffective or impractical.

4.2 Dose and Method of Administration

The use of TachoSil is restricted to experienced surgeons.
TachoSil should not be used intravascularly (see Section 4.3 Contraindications). For more information on situations where TachoSil should not be used, see Section 4.4 Special Warnings and Precautions for Use.
The number of TachoSil sponges to be applied should always be orientated towards the underlying clinical need for the patient and should be 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 to 2 sponges (9.5 cm x 4.8 cm), however application of up to 7 sponges has been reported. For smaller wounds, e.g. in minimal invasive surgery, the smaller sized sponges (4.8 cm x 4.8 cm or 3.0 cm x 2.5 cm) are recommended.
Select the appropriate TachoSil size so that it extends 1 to 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.
TachoSil comes ready to use in sterile packages and must be handled accordingly. Use only undamaged packages. Once the package is opened, re-sterilisation is not possible. The outer aluminium foil sachet may be opened in a non-sterile operating area but 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 should be used under sterile conditions. Prior to application the wound area should be cleansed, e.g. from blood, disinfectants and other fluids. It is important to note that failure to adequately clean adjacent tissues may cause adhesions, see Section 4.4 Special Warnings and Precautions for Use. The fibrinogen and thrombin proteins can be denatured by alcohol, iodine or heavy metal ions. If any of these substances have been used to clean the wound area, thoroughly irrigate the area before the application of TachoSil.
After removal of TachoSil from the sterile package the sponge may be pre-moistened in saline solution for no more than 1 minute and then applied immediately. The yellow, active side of the sponge is applied to the bleeding/ leaking surface and held against it with gentle pressure for 3 to 5 minutes. This procedure enables 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, gloves or adjacent tissues covered with blood. This can be avoided by pre-moistening surgical instruments, gloves and adjacent tissues 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 premoistening, while also pressing gently to the wound for 3 to 5 minutes.
Any unused, opened product or waste material should be disposed of in accordance with local requirements.

4.3 Contraindications

Hypersensitivity to the active ingredients or to any of the excipients.
Do not apply TachoSil intravascularly. Intravascular application of TachoSil may result in life-threatening thromboembolic events.

4.4 Special Warnings and Precautions for Use

General.

TachoSil is for topical use only. There are no data on repeated application.
Specific data have not been obtained on the use of this product in neurosurgery or in gastrointestinal anastomoses surgery.
TachoSil should not be used for the treatment of severe or brisk arterial bleeding because TachoSil has not been evaluated in this treatment.
TachoSil should not be used in procedures involving the renal pelvis or ureter because it may be a focus for calculus formation.
TachoSil should not be used in the closure of skin incisions since it may interfere with the healing of skin edges or cause wound dehiscence.
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. 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 (see Section 4.8 Adverse Effects (Undesirable Effects)).

Hypersensitivity.

Administration of TachoSil may result in allergic reactions in some patients. For patients with a known allergic diathesis or a history of hypersensitivity to protein products, a careful risk-benefit assessment should be carried out prior to administration. The risk of immunisation against proteins is increased if repeated exposure occurs within six months. If it is decided to proceed with treatment in such patients, prior administration of antihistamines should be considered.
Signs of hypersensitivity reactions include hives, generalised urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis. If these symptoms occur, the administration must be discontinued immediately. In case of shock, the current medical standards for shock treatment should be observed.

Contaminated spaces.

Do not leave TachoSil in an infected or contaminated space because it may potentiate an existing infection.

Transmissible infectious agents.

The active substances of TachoSil are derived from human plasma. When medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. Products made from human plasma may contain infectious agents which can cause disease, such as viruses and theoretically Creutzfeld-Jacob disease (CJD) agents. 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. 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 (foetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia).
It is therefore 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.
All infections thought by a clinician possibly to have been transmitted by TachoSil should be reported by the clinician or other health care provider to Takeda.
Patients should be instructed to consult their clinician if symptoms of B19 virus infection appear (fever, drowsiness, chills and runny nose followed about two weeks later by a rash and joint pain).

Paediatric use.

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

Use in the elderly.

In clinical trials, no overall differences in the safety or effectiveness of TachoSil were observed in patients over the age of 65, compared to patients 18 to 65 years of age.

Effects on laboratory tests.

Interactions with laboratory tests have not been established.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No formal interaction studies have been performed.
Similar to comparable products or thrombin solutions, TachoSil 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 application.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Studies to determine the effect of TachoSil on fertility have not been performed.
(Category B2)
The safety of TachoSil for use in human pregnancy has not been established in controlled clinical trials. Therefore, TachoSil should be administered to pregnant women only if clearly needed.
 The safety of TachoSil for use in breastfeeding has not been established in controlled clinical trials. It is not known whether this drug is excreted in human milk. Therefore, TachoSil should be administered to lactating women only if clearly needed.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials experience.

From six controlled trials, 521 patients were treated with TachoSil and 511 patients treated with comparator treatment. The only individual adverse events reported in more than 5% of patients in either treatment group were atrial fibrillation (32 patients [6.1%] in the TachoSil group and 30 patients [5.9%] in the comparator group) and pyrexia (30 patients [5.8%] in the TachoSil group and 25 patients [4.9%] in the comparator group).
A summary of all adverse events reported by at least 1% of patients and a classification of their severity is shown in Table 1. There are no notable differences in the severity of adverse events between the treatment groups and the majority of adverse events reported were mild or moderate in severity.

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, about 26% of the 96 patients tested and treated with TachoSil developed antibodies to collagen (derived from equine origin). The collagen antibodies that developed in some patients after TachoSil use were not reactive with human collagen. One patient developed antibodies to fibrinogen.
There were no adverse events attributable to the development of fibrinogen or 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.

Postmarketing experience.

Immune system disorders.

Anaphylactic shock, hypersensitivity.

Vascular disorders.

Thrombosis.

Gastrointestinal disorders.

Intestinal obstruction (in abdominal surgeries), ileus (in abdominal surgeries).

General disorders and administration site conditions.

Adhesions.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

No case of overdose has been reported.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

TachoSil contains fibrinogen and human thrombin as a dried coating on the surface of a collagen sponge. Upon contact with physiological fluids such as 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 into a fibrin clot that adheres the collagen sponge to the wound surface and achieves haemostasis. The fibrin is subsequently cross linked by endogenous factor XIII, creating a firm mechanically stable network with good adhesive properties and therefore provides sealing as well.

Clinical trials.

The haemostatic efficacy and safety of TachoSil was evaluated in four open-label, multi-centre, randomised, controlled, parallel-group trials comparing TachoSil with standard surgical treatment in three surgical applications. TachoSil was applied once only topically during surgery. The patients were mostly Caucasian and aged between 18 and 86 years of age.

Liver resection.

The data from two trials provide clinical evidence for TachoSil as an adjunct treatment of haemorrhage in patients undergoing at least segmental resection (anatomical or non-anatomical) of the liver. One hundred and twenty-one patients were randomly assigned to either TachoSil (n = 59) or argon beam coagulator treatment (n = 62) in one trial, and 119 patients were treated with either TachoSil (n = 60) or argon beam coagulator (n = 59) in the second trial. Randomisation was conducted intra-operatively if residual minor to moderate (oozing) bleeding was present after primary treatment of major venous or arterial (pulsating) bleeding had been controlled by standard surgical methods. Patient demographics and characteristics, physical condition, past and concomitant illness, concomitant medication, and laboratory tests (haematology, coagulation, liver enzymes) at baseline were similar for the two treatment groups, and the surgical procedures and primary haemostatic treatment were overall well balanced between treatment groups in the two trials.
Both trials demonstrated superiority of TachoSil as secondary haemostatic treatment. The primary efficacy endpoint, time to haemostasis, resulted in a mean (median, range) value of 3.9 (3.0, 3-20) minutes for TachoSil and 6.3 (4.0, 3-39) minutes for argon beamer treated patients, respectively in one trial (p = 0.0007), and 3.6 (3.0, 3-8) minutes versus 5.0 (3.0, 3-23) minutes for the TachoSil and the argon beam coagulator treatment group, respectively, in the second liver trial (p = 0.0018).

Kidney resection.

A trial was conducted to investigate the haemostatic efficacy of TachoSil compared to standard surgery in patients scheduled for the resection of superficial tumours on the kidney. Patient demographics and characteristics, physical condition, past and concomitant illness, concomitant medication, and laboratory tests (haematology and coagulation) at baseline, surgical procedures and primary haemostatic treatment were similar in the two treatment groups. A total of 185 subjects received trial treatment with 92 patients randomised to receive TachoSil and 93 patients to standard treatment. The primary efficacy endpoint was intra-operative time to haemostasis. The results demonstrated that TachoSil was significantly superior to standard surgery. Mean (median, range) time to haemostasis was 5.3 (3.0, 3-17) minutes for TachoSil and 9.5 (8.0, 3-27) minutes for comparator treatment, respectively (p < 0.0001).

Cardiovascular surgery.

In a cardiovascular trial comparing the efficacy and safety of TachoSil versus standard haemostatic treatment (haemostatic fleece without additional active coagulation stimulating compounds), patients with a planned elective surgery on the heart, the ascending aorta or aortic arch requiring a cardiopulmonary bypass procedure were eligible. Only patients with residual haemorrhage from the heart muscle, the pericardium, a major vessel or vascular bed requiring supportive haemostatic treatment were eligible for randomization. Patient demographics and baseline characteristics including physical condition, past and concomitant illness, concomitant medication, and laboratory tests were similar for the two treatment groups. In the intention to treat (ITT) population, 59 patients were randomised to TachoSil and 60 to standard treatment. The result of the primary efficacy endpoint, proportion of patients with haemostasis at 3 minutes, was 44/59 (75%) for TachoSil treated patients and 20/60 (33%) for standard haemostatic fleece treated patients (p < 0.0001).

5.2 Pharmacokinetic Properties

TachoSil is intended for topical application only. Intravascular administration is not possible. As a consequence, intravascular pharmacokinetic studies were not performed in humans.
In animal studies, TachoSil shows progressive biodegradation. The fibrin clot is metabolised in the same way as endogenous fibrin, i.e. by fibrinolysis. The collagen sponge is degraded by phagocytosis and ingrowth of granulation tissue. Approximately 13 weeks after application, only a few remnants were present without any signs of local irritation.

5.3 Preclinical Safety Data

Genotoxicity.

Studies to determine the genotoxicity of TachoSil have not been performed.

Carcinogenicity.

Long-term animal studies to evaluate the carcinogenic potential of TachoSil have not been performed.

6 Pharmaceutical Particulars

6.1 List of Excipients

Riboflavine, collagen, albumin, sodium chloride, sodium citrate dihydrate and arginine hydrochloride.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
Once the foil sachet is opened, TachoSil must be used immediately.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

TachoSil is an off-white sponge. The active side of the sponge, which is coated with fibrinogen and human thrombin, is marked by a yellow colour.
Three sizes are available in the following dimensions (length x width):

Standard size.

9.5 cm x 4.8 cm = 45.6 cm2, containing human thrombin 91.2 IU and fibrinogen 250.8 mg.

Midi size.

4.8 cm x 4.8 cm = 23.0 cm2, containing human thrombin 46.0 IU and fibrinogen 126.5 mg.

Mini size.

3.0 cm x 2.5 cm = 7.5 cm2, containing human thrombin 15.0 IU and fibrinogen 41.3 mg.
The composition is the same for all three presentations with each square centimetre containing 5.5 mg fibrinogen and 2.0 IU human thrombin.
Each TachoSil medicated sponge is packaged individually in a blister sealed with a HDPE foil. The blister is packed in an aluminium-bonded foil sachet, with a desiccant bag.
The following pack sizes are available:
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 presentations may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Fibrinogen is a soluble plasma glycoprotein with a molecular weight of approximately 340 kDa, and circulates in plasma as a precursor of fibrin. The native molecule is a homo-dimer, in which both subunits consist of three different polypeptide chains (Aα, Bβ, and γ). All three polypeptide chains of the subunits as well as the dimer are linked with disulfide bonds. Thrombin is a serine protease with a molecular weight of approximately 39 kDa and consists of 295 amino acids. It is formed by two peptide chains of 36 and 259 amino acids respectively, linked by disulfide bonds.

7 Medicine Schedule (Poisons Standard)

Unscheduled.

Summary Table of Changes