VeraSeal

Основна информация

  • Търговско наименование:
  • VeraSeal
  • Използвай за:
  • Хората
  • Вид на лекарството:
  • алопатични наркотици

Документи

Локализация

  • Предлага се в:
  • VeraSeal
    Европейски съюз
  • Език:
  • английски

Терапевтична информация

  • Терапевтична група:
  • Antihemorrhagics,
  • Терапевтична област:
  • Hemostasis, Surgical
  • Терапевтични показания:
  • Supportive treatment in adults where standard surgical techniques are insufficient: - for improvement of haemostasis. - as suture support in vascular surgery,

Състояние

  • Източник:
  • EMA - European Medicines Agency
  • Статус Оторизация:
  • Authorised
  • Номер на разрешението:
  • EMEA/H/C/004446
  • Дата Оторизация:
  • 09-11-2017
  • EMEA код:
  • EMEA/H/C/004446
  • Последна актуализация:
  • 01-01-2020

Доклад обществена оценка

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An agency of the European Union

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© European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged.

EMA/620652/2017

EMEA/H/C/004446

EPAR summary for the public

VeraSeal

human fibrinogen / human thrombin

This is a summary of the European public assessment report (EPAR) for VeraSeal. It explains how the

Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is

not intended to provide practical advice on how to use VeraSeal.

For practical information about using VeraSeal, patients should read the package leaflet or contact

their doctor or pharmacist.

What is VeraSeal and what is it used for?

VeraSeal is a sealant (glue) used to stop bleeding during surgery or to support stitches during surgery

on blood vessels.

VeraSeal is used when standard surgery techniques do not work well enough. It contains the active

substances human fibrinogen and human thrombin.

How is VeraSeal used?

VeraSeal should only be used by an experienced surgeon who has been trained in its use. It is

available as two prefilled syringes in a syringe holder, one containing a solution of human fibrinogen

(80 mg/ml), and the other containing a solution of human thrombin (500 international units/ml).

Before use, the syringes are attached to a device supplied with the medicine that allows their contents

to mix as they are dripped or sprayed on the wound. The amount of VeraSeal to be used depends on a

number of factors, including the type of surgery, the size of the wound and the number of applications.

How does VeraSeal work?

The active substances in VeraSeal, fibrinogen and thrombin, are substances present in human plasma

(the liquid part of the blood), which are involved in the normal blood clotting process.

VeraSeal

EMA/620652/2017

Page 2/3

When the two active substances are mixed, thrombin cuts fibrinogen up into fibrin. The fibrin then

aggregates (sticks together) and forms a fibrin clot that helps the wound to heal, preventing bleeding.

What benefits of VeraSeal have been shown in studies?

Three main studies in 614 patients found that VeraSeal is effective at stopping bleeding within 4

minutes of applying it during surgery.

In one study of blood vessel surgery, VeraSeal worked better than manual compression, with 76% of

patients having no bleeding 4 minutes after treatment with VeraSeal (83 out of 109), compared with

23% after manual compression (13 out of 57).

In a second study of organ surgery, VeraSeal was as effective as another product Surgicel: 93% of the

patients had no bleeding 4 minutes after treatment with VeraSeal (103 out of 111), while 81% of the

patients had no bleeding with Surgicel (91 out of 113).

Finally, in a third study of soft tissue surgery, VeraSeal was as effective as Surgicel: 83% of the

patients had no bleeding 4 minutes after treatment with VeraSeal (96 out of 116), compared with 78%

of the patients after treatment with Surgicel (84 out of 108).

What are the risks associated with VeraSeal?

The most common side effects with VeraSeal (which may affect up to 1 in 10 people) are nausea

(feeling sick), pruritus (itchiness) and procedural pain (pain from the surgery). Rarely, VeraSeal may

cause an allergic reaction which can be severe especially when the medicine is used repeatedly. In rare

cases, patients have developed antibodies to the proteins in VeraSeal, which could interfere with blood

clotting. Thromboembolic complications (blood clots) may occur if VeraSeal is accidentally injected into

a blood vessel. Cases of gas embolism (gas bubbles that block blood flow) have occurred when such

sealants were applied as spray.

VeraSeal must not be used intravascularly (inside blood vessels) or to treat heavy bleeding of the

arteries. VeraSeal must not be applied by spraying during endoscopy (a procedure that uses a tube for

viewing inside the body).

For the full list of all side effects and restrictions with VeraSeal, see the package leaflet.

Why is VeraSeal approved?

VeraSeal has been shown to effectively stop bleeding during surgery, which can be expected to reduce

blood loss, reduce time in the operating theatre and possibly shorten hospital stays. Although patients

could develop antibodies against the medicine, which might reduce its effectiveness, this has not been

seen in the studies.

As for all medicines obtained from blood, infections could be transmitted with the medicine; however,

the medicine is manufactured using filtration and a process to inactivate viruses that minimise this

risk. The observed side effects were as expected with major surgeries or the patient’s condition. The

European Medicines Agency therefore decided that VeraSeal’s benefits are greater than its risks and

recommended that it be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of

VeraSeal?

The company that markets VeraSeal will provide educational materials for healthcare professionals

with information on how to use the medicine safely when it is applied by spraying.

VeraSeal

EMA/620652/2017

Page 3/3

Recommendations and precautions to be followed by healthcare professionals and patients for the safe

and effective use of VeraSeal have also been included in the summary of product characteristics and

the package leaflet.

Other information about VeraSeal

The European Commission granted a marketing authorisation valid throughout the European Union for

VeraSeal on 10 November 2017.

The full EPAR for VeraSeal can be found on the Agency’s website: ema.europa.eu/Find

medicine/Human medicines/European public assessment reports. For more information about

treatment with VeraSeal, read the package leaflet (also part of the EPAR) or contact your doctor or

pharmacist.

This summary was last updated in 11-2017.

Листовка за пациента: състав, показания, Нежелани лекарствени реакции, дозиране, взаимодействия, бременност, кърмене

B. PACKAGE LEAFLET

Package leaflet: Information for the user

VeraSeal solutions for sealant

human fibrinogen/human thrombin

This medicine is subject to additional monitoring. This will allow quick identification of new

safety information. You can help by reporting any side effects you may get. See the end of section 4

for how to report side effects.

Read all of this leaflet carefully before you start using this medicine because it contains

important information for you.

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

If you have any further questions, ask your doctor.

If you get any side effects, talk to your doctor. This includes any possible side effects not listed

in this leaflet. See section 4.

What is in this leaflet

What VeraSeal is and what it is used for

What you need to know before you are treated with VeraSeal

How VeraSeal is used

Possible side effects

How VeraSeal is stored

Contents of the pack and other information

1.

What VeraSeal is and what it is used for

VeraSeal contains human fibrinogen and human thrombin, two proteins extracted from the blood that

form a clot when they are mixed together.

VeraSeal is used as a sealant during surgical operations in adults. It is applied to the surface of

bleeding tissue to reduce bleeding during and after the operation when standard surgical techniques are

not sufficient.

2.

What you need to know before you are treated with VeraSeal

Your surgeon must not treat you with VeraSeal

if you are allergic to human fibrinogen or human thrombin or any of the other ingredients of this

medicine (listed in section 6).

VeraSeal must not be applied inside blood vessels.

VeraSeal must not be used to treat severe or rapid bleeding from an artery.

Warnings and precautions

Allergic reactions are possible. Signs of such reactions include hives, rash, tightness of the chest,

wheezing, drop in blood pressure (e.g. light-headedness, fainting, blurred vision), and anaphylaxis (a

severe reaction with a rapid onset). If these symptoms occur during surgery, the use of the medicine

should be stopped immediately.

VeraSeal spray application should only be used if it is possible to accurately judge the spray distance.

The spray device should not be used closer than the recommended distance.

Special safety warning

For medicines such as VeraSeal that are made from human blood or plasma, certain measures are

taken to prevent infections being passed on to patients. These include carefully selecting blood and

plasma donors to make sure those at risk of carrying infections are excluded, and testing each donation

and pooled plasma for signs of virus/infections. Manufacturers also include steps in the processing of

the blood or plasma that can inactivate or remove viruses. Despite these measures, when medicines

prepared from human blood or plasma are administered, the possibility of passing on infection cannot

be totally excluded. This also applies to any unknown or emerging viruses or other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency

virus (HIV), hepatitis B virus and hepatitis C virus, and for the non-enveloped hepatitis A virus. 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

whose immune system is depressed or who have some types of anaemia (e.g. sickle cell disease or

haemolytic anaemia).

It is strongly recommended that every time you are treated with VeraSeal, the name and batch number

of the medicine are recorded in order to maintain a record of the batches used.

Children and adolescents

VeraSeal is not recommended for use in children and adolescents under 18 years of age.

Other medicines and VeraSeal

The product may be affected after contacting solutions containing alcohol, iodine or heavy metals (e.g.

antiseptic solutions).

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor for advice before being treated with this medicine. Your doctor will decide whether you

should be treated with VeraSeal.

3.

How VeraSeal is used

The use of VeraSeal is restricted to experienced surgeons who have been trained in the use of

VeraSeal.

The surgeon will apply VeraSeal to the surface of blood vessels or to the tissue surface of internal

organs using an application device during the course of the operation. This device allows equal

amounts of the two components of VeraSeal to be administered at the same time, and ensures that they

mix evenly, which is important for the sealant to work at its best.

The amount of VeraSeal that will be applied depends on a number of factors, including the type of

surgery, the size of the area to be treated during your operation and the way VeraSeal is applied. The

surgeon will decide how much is appropriate, and will apply just enough to form a thin, even layer. If

it does not seem to be enough, a second layer can be applied.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

VeraSeal contains the component of fibrin sealant. Fibrin sealants may, in rare cases (up to 1 in

1,000 people), cause an allergic reaction. If you experience an allergic reaction you might have one or

more of the following symptoms: swelling under skin (angioedema), skin rash, hives or wheals

(nettle-rash), tightness of the chest, chills, flushing, headache, low blood pressure, lethargy, nausea,

restlessness, heart rate increase, tingling, vomiting or wheezing. In isolated cases, these reactions may

progress to a severe allergic reaction. Allergic reactions may especially be seen if the preparation is

applied repeatedly, or administered to patients known to be allergic to constituents of the product. If

you experience any of these symptoms after surgery, you should immediately consult your doctor or

surgeon.

There is also a theoretical possibility that your immune system will produce proteins to attack

VeraSeal and, that these may interfere with your blood clotting. The frequency of this type of event is

not known.

If this product is accidentally placed inside a blood vessel, it can lead to blood clots, including

disseminated intravascular coagulation (DIC) (when blood clots form throughout the blood vessels in

the body). There is also a risk of a severe allergic reaction.

Side effects which were reported during clinical trials with VeraSeal included:

Most serious side effects

Uncommon (may affect up to 1 in 100 people):

Abdominal abscess (swollen area in abdomen caused by infection)

Abdominal wound dehiscence (wound breakdown due to incomplete healing)

Leak of bile (a liquid produced by the liver) after the procedure

Cellulitis (infection of the skin)

Deep vein thrombosis (blood clots in the blood vessels)

Liver abscess (swollen area in the liver caused by infection)

Peritonitis (inflammation of the wall of the abdomen)

Positive parvovirus B19 test (laboratory result showing infection with the virus)

Postoperative wound infection

Pulmonary embolism (blood clots in blood vessels in the lungs)

Wound infection

Other side effects

Common (may affect up to 1 in 10 people):

Nausea

Pain caused by the surgery

Pruritus (itching)

Uncommon (may affect up to 1 in 100 people):

Anaemia (insufficiency of red blood cells)

Anxiety

Atrial fibrillation (irregular heartbeat)

Back pain

Bladder spasm

Chills

Conjunctival irritation (eye irritation)

Constipation

Contusion (bruise)

Decreased urine output (reduced urine production)

Dyspnoea (difficulty in breathing)

Dysuria (pain or difficulty in urination)

Ecchymosis (bruising)

Erythema (reddening of the skin)

Flatulence

Headache

High body temperature

High or low blood pressure

High or low levels of white cells in blood

High potassium levels in blood

Ileus (obstruction of the intestine)

Impaired coagulation of blood

Incision site erythema (reddening of the skin at the incision site)

Incision site infection

Increased blood bilirubin

Increased levels of liver enzymes

Increased or decreased glucose levels in blood

Insomnia

Low blood pressure due to the procedure

Low calcium levels in blood

Low magnesium levels in blood

Low oxygen in blood

Low potassium levels in blood

Low protein levels in blood

Low red blood cell levels caused by blood loss

Low sodium levels in blood

Oedema peripheral (accumulation of fluid)

Pain, not specified

Pain at the incision site

Pain in extremity

Plasma cell myeloma (cancer of blood cells)

Pleural effusion (abnormal amount of fluid around the lung)

Pleurisy (inflammation of lungs wall)

Post procedural haemorrhage (bleeding after the procedure)

Post procedural infection (infection after the procedure)

Pulmonary oedema (excess of watery fluid in lungs)

Retroperitoneal haematoma (accumulation of blood in the abdomen)

Rhonchi (rattling lung sounds)

Sleepiness

Urinary retention

Vascular graft complication (complication of vessel bypass)

Vascular graft thrombosis (blood clots in blood vessel bypass)

Ventricular tachycardia (rapid heartbeats)

Vessel puncture site haematoma (bruising at site of vessel puncture)

Vomiting

Wheezing

Wound secretion

Reporting of side effects

If you get any side effects, talk to your doctor or surgeon. This includes any possible side effects not

listed in this leaflet.

You can also report side effects directly via the national reporting system listed in

Appendix V. By reporting side effects you can help provide more information on the safety of this

medicine.

5.

How VeraSeal is stored

VeraSeal must be kept out of the sight and reach of children.

This medicine must not be used after the expiry date which is stated on the label and carton after EXP.

It must be stored in a freezer at -18 ºC or colder. The cold storage chain must not be interrupted until

use. Keep the sterilized blister in the outer carton in order to protect from light. Thaw completely

before use. Do not refreeze once thawed. After thawing, it can be maintained not more than 48 hours

at 2 ºC - 8 ºC or 24 hours at room temperature (20 ºC - 25 ºC) before use.

Once the blister is opened, VeraSeal should be used immediately.

It must not be used if the solutions are cloudy or have deposits.

Discard if the package is damaged.

6.

Contents of the pack and other information

What VeraSeal contains

The active substances are:

Component 1: Human fibrinogen

Component 2: Human thrombin

The other ingredients are:

Component 1: Sodium citrate dihydrated, sodium chloride, arginine, isoleucine, glutamic acid

monosodium, water for injections.

Component 2: Calcium chloride, human albumin, sodium chloride, glycine, water for injections.

What VeraSeal looks like and contents of the pack

VeraSeal is presented as solutions for sealant. It is supplied as a single-use kit containing two

pre-filled syringes assembled in a syringe holder. Frozen solutions. After thawing the solutions are

clear or slightly opalescent and colourless or pale yellow.

One Dual Applicator with two additional Airless Spray Tips is supplied with the product, for

application by spraying or dripping. The Airless Spray Tips are radiopaque. See scheme below.

VeraSeal is available in the following pack sizes:

VeraSeal 2 ml (containing 1 ml of human fibrinogen and 1 ml of human thrombin)

VeraSeal 4 ml (containing 2 ml of human fibrinogen and 2 ml of human thrombin)

VeraSeal 6 ml (containing 3 ml of human fibrinogen and 3 ml of human thrombin)

VeraSeal 10 ml (containing 5 ml of human fibrinogen and 5 ml of human thrombin)

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Instituto Grifols, S.A.

Can Guasc, 2 - Parets del Vallès

E-08150 Barcelona - Spain

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder:

AT/BE/BG/CY/EE/EL/ES/HR/HU/IE/LV/

LT/LU/MT/NL/RO/SI/SK

Instituto Grifols, S.A.

Tel: +34 93 571 01 00

CZ

Grifols S.R.O.

Tel: +4202 2223 1415

DE

Grifols Deutschland GmbH

Tel: +49 69 660 593 100

DK/FI/IS/NO/SE

Grifols Nordic AB

Tel: +46 8 441 89 50

FR

Grifols France

Tél: +33 (0)1 53 53 08 70

IT

Grifols Italia S.p.A.

Tel: +39 050 8755 113

PL

Grifols Polska Sp. z o. o.

Tel: +48 22 378 85 60

PT

Grifols Portugal, Lda.

Tel: +351 219 255 200

UK

Grifols UK Ltd.

Tel: +44 845 2413090

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu

---------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

Posology and method of administration

The use of VeraSeal is restricted to experienced surgeons who have been trained in the use of this

medicinal product.

The volume of VeraSeal to be applied and the frequency of application should always be oriented

towards the underlying clinical needs for the patient.

The dose to be applied is governed by variables including, but not limited to, the type of surgical

intervention, the size of the area and the mode of intended application, and the number of applications.

Application of the product must be individualised by the treating physician. In clinical trials, the

individual dosages have typically ranged from 0.3 to 12 ml. For other procedures, larger volumes may

be required.

The initial volume of the product to be applied at a chosen anatomic site or target surface area should

be sufficient to entirely cover the intended application area. VeraSeal should be applied as a thin layer.

The application can be repeated, if necessary.

Incompatibilities

This medicinal product must not be mixed with other medicinal products.

Special precautions

For epilesional use only. Do not apply intravascularly.

Life threatening thromboembolic complications may occur if the preparation is unintentionally applied

intravascularly.

When using accessory tips, the instructions for use of the tips should be followed.

Before administration of VeraSeal, care must be taken that the parts of the body outside the desired

application area are sufficiently protected (covered) to prevent tissue adhesion at undesired sites.

VeraSeal should be applied as a thin layer. Excessive clot thickness may negatively interfere with the

product’s efficacy and the wound healing process.

Instructions for use

Read this leaflet before you open the package. Please see pictograms at the end of this leaflet.

Handling of VeraSeal

VeraSeal comes ready to use in sterilized packages and must be handled using sterile technique in

aseptic conditions. Discard damaged packages as re-sterilisation is not possible.

Remove carton from freezer, open it and take out the two blisters.

Place the blister containing the Dual Applicator at room temperature until the fibrin sealant is ready to

use.

Room temperature thawing (preferred method)

Thaw blister with VeraSeal pre-filled syringes at room temperature using the following steps:

Place the blister containing the syringe holder with pre-filled syringes on a surface at

room temperature (20 ºC – 25 ºC)

for approximately 70 minutes for the 2 ml and the 4 ml package sizes

for approximately 90 minutes for the 6 ml and the 10 ml package sizes

After thawing, it is not necessary to warm the product for its use.

After thawing the solutions must be clear to slightly opalescent and colourless to pale yellow.

Solutions that are cloudy or have deposits should not be used.

Post-Thawing Storage

After thawing, the kit containing the VeraSeal syringe holder with pre-filled syringes and Dual

Applicator can be stored before use for not more than 48 hours in the refrigerator at 2 – 8 ºC or

24 hours at room temperature (20 - 25 °C) if it remains sealed in the original packaging. Once

the blisters are opened, use VeraSeal immediately and discard any unused contents.

Once thawed, do not refreeze.

Transferring instructions

After thawing, remove the blister from the surface at room temperature or from the

refrigerator at 2 °C - 8 °C.

Open the blister and make the VeraSeal syringe holder with pre-filled syringes available

to a second person for transfer to the sterile field. The outside of the blister should not

come in contact with the sterile field. See Figure 1.

Sterile Water Bath (Quick Thawing)

Thaw VeraSeal pre-filled syringes inside the sterile field in a sterile thermostatic water bath at a

temperature not higher than 37 ºC using the following steps:

NOTE: Once the VeraSeal blisters are opened, use the product immediately. Use sterile

technique to avoid the possibility of contamination due to improper handling, and follow the

steps below accurately. Do not remove the syringe luer cap until thawing is complete and the

Dual Applicator is ready to be attached.

Open the blister and make the VeraSeal syringe holder with pre-filled syringes available

to a second person for transfer to the sterile field. The outside of the blister should not

come in contact with the sterile field. See Figure 1.

Place the syringe holder with pre-filled syringes directly into the sterile water bath

ensuring that it is completely immersed in the water. See Figure 2.

At 37 ºC, the time needed is approximately 5 minutes for the 2 ml, 4 ml, 6 ml, and 10 ml

package sizes, but must not be left at this temperature for longer than 10 minutes.

The temperature of the water bath must not exceed 37 ºC.

Dry the syringe holder with pre-filled syringes after thawing, using a sterile surgical

gauze.

After thawing, the solutions must be clear to slightly opalescent and colorless to pale yellow. Do

not use solutions that are cloudy or have deposits.

Use VeraSeal immediately and discard any unused contents.

Connection instructions

Open the blister and make the VeraSeal Dual Applicator and two additional Airless Spray

Tips available to a second person for transfer to the sterile field. The outside of the blister

should not come in contact with the sterile field.

Hold the VeraSeal syringe holder with syringe luer caps pointed upward. See Figure 3.

Unscrew and discard the syringe luer cap of both fibrinogen and thrombin syringes. See

Figure 3.

Hold the syringe holder with the luers pointed upward.

To remove air bubbles from

syringes, strike gently the side of the syringe holder one or two times while keeping the

syringe holder in an upright position and lightly depress the plunger to eject air. See

Figure 4.

Attach the Dual Applicator. See Figure 5.

NOTE: Do not depress plunger during attachment or prior to intended use because the

two biologic components will pre-mix in the Airless Spray Tip, forming a fibrin clot that

prevents dispensing. See Figure 6.

Tighten luer locks and ensure the Dual Applicator is firmly attached. The device is now

ready to use.

Administration

Apply VeraSeal using the syringe holder and plunger supplied.

Apply VeraSeal using the Dual Applicator provided with the product. Other CE-marked

applicator tips (including open surgery and laparoscopic use devices) intended for specific use

with VeraSeal may also be used. When using the provided Dual Applicator, follow the

connection instructions described above. When using other applicator tips, follow the

instructions for use that are provided with the applicator tips.

Application by spraying

Grasp and bend the Dual Applicator to the desired position. Tip will retain its shape.

Position the Airless Spray Tip at least 2 cm away from the target tissue. Apply firm even

pressure to the plunger to spray the fibrin sealant. Increase distance accordingly to

achieve desired coverage of the target area.

If expression is stopped for any reason, change the Airless Spray Tip. To change the

Airless Spray Tip, remove the device from the patient and unscrew the used Airless Spray

Tip. See Figure 7. Place the used Airless Spray Tip away from the spare Airless Spray

Tips. Wipe the end of the applicator using dry or moist sterile surgical gauze. Then,

connect a new Airless Spray Tip provided in the package and ensure it is firmly

connected before use.

NOTE: Red indicator will not be visible if Airless Spray Tip is properly connected. See

Figure 8.

NOTE: Do not continue pushing the plunger in an attempt to clear the fibrin clot within

the Airless Spray Tip; otherwise the applicator may become unusable.

NOTE: Do not trim the Dual Applicator to avoid exposing internal wire.

Application by dripping

Remove the Airless Spray Tip portion of the spray and drip tip by unscrewing the Airless

Spray Tip. See Figure 7.

Grasp and bend the drip tip to the desired position. Tip will retain its shape.

During dripping, keep the end of the drip tip as close to the tissue surface as possible

without touching the tissue during application.

Apply individual drops to the surface area to be treated. To prevent uncontrolled clotting,

allow the drops to separate from each other and from the end of the drip tip.

NOTE: Do not reconnect a used drip tip after it has been removed from the adapter;

otherwise a clot may form inside the drip tip and the applicator may become unusable.

Disposal

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

requirements.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8