HAEMOCOMPLETTAN P 2 G

העדוה העדוה

לע לע

הרמחה הרמחה

(

(

עדימ עדימ

ןולעב )תוחיטב ןולעב )תוחיטב

ל

ל

אפור אפור

ןכדועמ( ןכדועמ(

05.2013

05.2013

ךיראת

09/09/2014

םש

רישכת

תילגנאב

רפסמו

:םושירה

HAEMOCOMPLETTAN P 1 G (

141 35 31819 00

), HAEMOCOMPLETTAN P 2 G (

141 36 31820 00

)

םש

לעב

םושירה

Genmedix

דבלב תורמחהה טורפל דעוימ הז ספוט

תושקובמה תורמחהה ןולעב קרפ יחכונ טסקט שדח טסקט

4.2 Posology

and

method

of

administration

Posology

Before administration of Haemocomplettan P 1g/2g

the fibrinogen level should be determined using the

method of Clauss.

Furthermore, the amount to be administered and the

frequency of application of Haemocomplettan P 1g/2g

should always be oriented to the degree of bleeding

and the clinical efficacy in the individual case.

Generally, 1 to 2 g Fibrinogen is administered initially,

with subsequent infusions as required.

The critical plasma fibrinogen level below which

haemorrhages may occur is 100 mg/dl

Normal values

are in the range of 200 to 450 mg/dl.

The circulating fibrinogen level should not be raised

Treatment should be initiated under the supervision of a

physician experienced in the treatment of coagulation disorders

Posology

The dosage and duration of the substitution therapy depend on

the severity of the disorder, location and extent of bleeding and

the patient’s clinical condition

The (functional) fibrinogen level should be determined in order

to calculate individual dosage and the amount and frequency of

administration should be determined on an individual patient

basis by regular measurement of plasma fibrinogen level and

continuous monitoring of the clinical condition of the patient and

other replacement therapies used

Normal plasma fibrinogen level is in the range of 1.5 – 4.5 g/l.

The critical plasma fibrinogen level below which haemorrhages

may occur is approximately 0.5 – 1.0 g/l. In case of major

surgical intervention, precise monitoring of replacement therapy

by coagulation assays is essential

beyond the lower limit of normal to minimize the risk

of thromboembolic complications.

In cases of severe haemorrhage, e.g. after premature

shedding of the placenta, amounts of

4 to 8 g fibrinogen may be required immediately.

In the case of children, the dosage should only be

selected according to the body weight of the child and

clinical need.

Especially to avoid overdose, precise monitoring of the

substitution therapy by means of laboratory control is

indispensable (using appropriate methods for

determination of the fibrinogen activity, e.g. method of

Clauss).

Prophylaxis

patients

with

congenital

hypo-

afibrinogenaemia and known bleeding tendency.

To prevent excessive bleeding during surgical procedures,

prophylactic treatment is recommended to raise fibrinogen levels

to 1 g/l and maintain fibrinogen at this level until haemostasis is

secure and

above 0.5 g/l until wound healing is complete

Initial Dose

If the patient's fibrinogen level is not known, the recommended

dose is 70 mg per kg of body weight (bw) administered

intravenously

Subsequent Dose

The target level (1 g/l) for minor events (e.g. epistaxis,

intramuscular bleeding or menorrhagia) should be maintained for

at least three days. The target level (1.5 g/l) for major events

(e.g. head trauma or intracranial haemorrhage) should be

maintained for seven days

Dose of fibrinogen

(mg/kg b.w.) =

[Target level (g/L) - measured

level (g/L)]

0.017 (g/L per mg/kg b.w.)

Furthermore, the amount to be administered and the frequency of

application of Haemocomplettan P 1g/2g should always be

oriented to the degree of bleeding and the clinical efficacy in the

individual case

In case of major surgical intervention, precise monitoring of

replacement therapy by coagulation assays is essential

Treatment of bleeding

Adults

Generally 1-2 g is administered initially

with subsequent

infusions as required.

In case of severe haemorrhage i.e. obstetric use / abruption

placenta, large amounts (4 – 8 g) of fibrinogen may be required

Children

Limited data from clinical studies regarding the dosage of

Haemocomplettan P1 g/2g in children are available

The dosage should be determined according to the body weight

and clinical need but is usually

20-30

mg/kg

[..]

4.4 Special

Warnings

and

Precautions

for use

Patients given Haemocomplettan P 1g/2g should be

observed closely for signs or symptoms of thrombosis

or disseminated intravascular coagulation (DIC).

Especially dysfibrinogenaemia can lead to thrombotic

tendency.

Because of the potential risk of thromboembolic

complications or disseminated intravascular

coagulation (DIC), caution should be exercised when

administering Haemocomplettan P 1g/2g to patients

with a history of coronary heart disease or myocardial

infarction, to patients with liver disease, to patients

post-operatively, to neonates, or to patients at risk of

thromboembolic phenomena. In each of these

situations, the potential benefit of treatment with

Haemocomplettan P 1g/2g should be weighed against

the risk of these complications.

For treatment of disseminated intravascular

There is a risk of thrombosis when patients

with congenital deficiency are treated with

human fibrinogen, particularly with high dose

or repeated dosing. Patients given human

fibrinogen should be observed closely for signs

or symptoms of thrombosis.

In patients with a history of coronary heart

disease or myocardial infarction, in patients

with liver disease, in peri- or post-operative

patients, in neonates, or in patients at risk of

thromboembolic events or disseminated

intravascular coagulation, the potential benefit

of treatment with human plasma fibrinogen

should be weighed against the risk of

thromboembolic complications. Caution and

close monitoring should also be performed.

If allergic or anaphylactic-type reactions occur,

the injection/infusion should be stopped

coagulation note that before substitution therapy with

coagulation factors can begin the hypercoagulability

has to be compensated in advance, e.g. by

normalisation of antithrombin III levels

In the case of patients known to have a tendency

towards allergies (with symptoms like generalised

urticaria, rash, fall in blood pressure, dyspnoea),

antihistaminics and corticosteroids may be

administered prophylactically.

Note for patients on a low sodium diet

Haemocomplettan P 1g/2g contains sodium chloride

and may therefore be harmful to patients on a low

sodium diet

Virus safety

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.

These measures may possibly be of limited value

against non-enveloped viruses such as HAV and

immediately. In case of anaphylactic shock,

standard medical treatment for shock should

be implemented.

In the case of replacement therapy with

coagulation factors in other congenital

deficiencies, antibody reactions have been

observed, but there is currently no data with

fibrinogen.

Important information about specific excipients of

Haemocomplettan

Haemocomplettan contains up to 164 mg (7.1 mmol)

sodium per 1g fibrinogen. This correlates with 11.5 mg

(0.5 mmol) sodium per kg body weight of the patient if the

recommended initial dose of 70 mg/kg body weight is

applied. To be taken into consideration by patients on a

controlled sodium diet

Virus safety

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.

parvovirus B19.

Parvovirus B19 infection may be serious for pregnant

women (fetal infection) and for individuals with

immunodeficiency or increased erythropoesis (e.g.

haemolytic anaemia).

In principle, hepatitis vaccination against hepatitis A

and hepatitis B is recommended for patients in regular

receipt of medicinal products derived from human

blood or plasma (including Haemocomplettan P

1g/2g).

It is strongly recommended that every time that

Haemocomplettan P 1g/2g 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.

The measures taken are considered effective for enveloped

viruses such as human immunodeficiency virus (HIV),

hepatitis B virus (HBV) and hepatitis C virus (HCV) and

for the non-enveloped hepatitis A 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 erythropoesis (e.g.

haemolytic anaemia).

Appropriate vaccination (hepatitis A and hepatitis B)

should be considered for patients in regular/repeated

receipt of human fibrinogen products.

It is strongly recommended that every time that

Haemocomplettan 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.

4.6

Fer

tilit

y,

pre

gna

ncy

and

lact

atio

n

The safety of Haemocomplettan P 1g/2g 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.

Haemocomplettan P 1g/2g is frequently used in the

treatment of obstetrical complications. There is no

negative experience with regard to the treatment

during pregnancy and lactation.

However, Haemocomplettan P 1g/2g may only be used

during pregnancy and lactation after careful

consideration.

Pregnancy

Animal reproduction studies have not been conducted with

Haemocomplettan (see section 5.3). Since the active

substance is of human origin, it is catabolized in the same

manner as the patient’s own protein. These physiological

constituents of the human blood are not expected to induce

adverse effects on reproduction or on the fetus

The safety of human plasma fibrinogen products for use in

human pregnancy has not been established in controlled

clinical trials.

Clinical experience with fibrinogen products in the

treatment of obstetric complications suggests that no

harmful effects on the course of the pregnancy or health of

the fetus or the neonate are to be expected.

Lactation

It is unknown whether Haemocomplettan is excreted in

human milk. The safety of human plasma fibrinogen

products for use during lactation has not been established

in controlled clinical trials.

A risk to the suckling child cannot be excluded. A decision

must be made whether to discontinue breast-feeding or to

discontinue/abstain from Haemocomplettan therapy taking

into account the benefit of breast-feeding for the child and

the benefit of therapy for the woman.

[…]

4.9

Ove

rdo

se

In case of overdosage, the risk for developing

thromboembolic complications is enhanced for

patients at risk for these complications.

In order to avoid overdosage, regular monitoring of the

plasma level of fibrinogen during therapy is indicated (see

4.2).

In case of overdosage, the risk of development of

thromboembolic complications is enhanced.

1.

NAME OF THE MEDICINAL PRODUCT

Haemocomplettan

®

P 1g

Haemocomplettan

®

P 2g

Powder for solution for injection / infusion

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Haemocomplettan is presented as a powder for solution for injection or infusion for

intravenous administration containing 1g or 2g human fibrinogen per vial.

The product contains approx. 20 mg/ml human fibrinogen after reconstitution with 50 or

100 ml water for injections.

The content of clottable fibrinogen is determined according to Ph. Eur. monograph for

human fibrinogen.

Excipients with known effect: Sodium up to 164 mg (7.1 mmol) per 1g fibrinogen.

For the full list of excipients, see section 6.1

3.

PHARMACEUTICAL FORM

Powder for solution for injection

/

infusion.

White powder

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Haemocomplettan P 1g/2g, Fibrinogen Concentrate (Human) is indicated for the treatment

of acute bleeding episodes in patients with congenital fibrinogen deficiency, including

afibrinogenemia and hypofibrinogenemia.

Haemocomplettan P 1g/2g is not indicated for dysfibrinogenemia.

4.2 Posology and method of administration

Treatment should be initiated under the supervision of a physician experienced in the

treatment of coagulation disorders.

Posology

The dosage and duration of the substitution therapy depend on the severity of the disorder,

location and extent of bleeding and the patient’s clinical condition.

The (functional) fibrinogen level should be determined in order to calculate individual

dosage and the amount and frequency of administration should be determined on an

individual patient basis by regular measurement of plasma fibrinogen level and continuous

monitoring of the clinical condition of the patient and other replacement therapies used.

Normal plasma fibrinogen level is in the range of 1.5 – 4.5 g/l. The critical plasma

fibrinogen level below which haemorrhages may occur is approximately 0.5 – 1.0 g/l. In

case of major surgical intervention, precise monitoring of replacement therapy by

coagulation assays is essential.

1. Prophylaxis in patients with congenital hypo- or afibrinogenaemia and known bleeding

tendency.

To prevent excessive bleeding during surgical procedures, prophylactic treatment is

recommended to raise fibrinogen levels to 1 g/l and maintain fibrinogen at this level until

haemostasis is secure and above 0.5 g/l until wound healing is complete.

Initial Dose

If the patient's fibrinogen level is not known, the recommended dose is 70 mg per kg of

body weight (bw) administered intravenously.

Subsequent Dose

The target level (1 g/l) for minor events (e.g. epistaxis, intramuscular bleeding or

menorrhagia) should be maintained for at least three days. The target level (1.5 g/l) for

major events (e.g. head trauma or intracranial haemorrhage) should be maintained for

seven days.

Dose of fibrinogen (mg/kg b.w.) =

[Target level (g/L) - measured level (g/L)]

0.017 (g/L per mg/kg b.w.)

Furthermore, the amount to be administered and the frequency of application of

Haemocomplettan P 1g/2g

should always be oriented to the degree of bleeding and the

clinical efficacy in the individual case.

In case of major surgical intervention, precise monitoring of replacement therapy by

coagulation assays is essential.

Treatment of bleeding

Adults

Generally 1-2 g is administered initially with subsequent infusions as required.

In case of severe haemorrhage i.e. obstetric use / abruption placenta, large amounts (4-8 g)

of fibrinogen may be required.

Children

Limited data from clinical studies regarding the dosage of Haemocomplettan P1 g/2g in

children are available.

The dosage should be determined according to the body weight and clinical need but is

usually 20-30 mg/kg.

Method of Administration

Intravenous infusion or injection.

Haemocomplettan should be reconstituted according to section 6.6. The reconstituted

solution should be warmed to room or body temperature before administration., then

injected or infused slowly at a rate which the patient finds comfortable. The injection or

infusion rate should not exceed approx. 5 ml per minute.

4.3

Contraindications

Known hypersensitivity to the active substances or to any of the excipients listed in section

6.1.

4.4

Special warnings and precautions for use

There is a risk of thrombosis when patients with congenital deficiency are treated with

human fibrinogen concentrate, particularly with high dose or repeated dosing. Patients given

human fibrinogen concentrate should be observed closely for signs or symptoms of

thrombosis.

In patients with a history of coronary heart disease or myocardial infarction, in patients with

liver disease, in peri- or post-operative patients, in neonates, or in patients at risk of

thromboembolic events or disseminated intravascular coagulation, the potential benefit of

treatment with human fibrinogen concentrate should be weighed against the risk of

thromboembolic complications. Caution and close monitoring should also be performed.

If allergic or anaphylactic-type reactions occur, the injection/infusion should be stopped

immediately. In case of anaphylactic shock, standard medical treatment for shock should be

implemented.

In the case of replacement therapy with coagulation factors in other congenital deficiencies,

antibody reactions have been observed, but there is currently no data available with regard

to fibrinogen.

Important information about specific excipients of Haemocomplettan

Haemocomplettan contains up to 164 mg (7.1 mmol) sodium per 1g fibrinogen. This

correlates with 11.5 mg (0.5 mmol) sodium per kg body weight of the patient if the

recommended initial dose of 70 mg/kg body weight is applied. To be taken into

consideration by patients on a controlled sodium diet.

Virus safety

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 human

immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) and

for the non-enveloped hepatitis A virus (HAV).

The measures taken may be of limited value against non-enveloped viruses such as

parvovirus B19.

Parvovirus B19 infections may be serious for pregnant women (foetal infection) and for

individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia).

Appropriate vaccination (hepatitis A and hepatitis B) should be considered for patients in

regular/repeated receipt of products from human blood or plasma.

It is strongly recommended that every time that Haemocomplettan 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.

4.5

Interaction with other medicinal products and other forms of interaction

No interactions studies have been performed.

4.6

Fertility, pregnancy and lactation

Pregnancy

Animal reproduction studies have not been conducted with Haemocomplettan (see section

5.3). Since the active substance is of human blood plasma origin, it is catabolized in the

same manner as the patient’s own protein. These physiological constituents of the human

blood are not expected to induce adverse effects on reproduction or on the foetus.

The safety of Haemocomplettan for use in human pregnancy has not been established in

controlled clinical trials.

Clinical experience with human fibrinogen concentrate in the treatment of obstetric

complications suggests that no harmful effects on the course of the pregnancy or health of

the foetus or the neonate are to be expected.

Lactation

It is unknown whether Haemocomplettan is excreted in human milk. The safety of

Haemocomplettan for use during lactation has not been established in controlled clinical

trials.

A risk to the suckling child cannot be excluded. A decision must be made whether to

discontinue breast-feeding or to discontinue/abstain from Haemocomplettan therapy taking

into account the benefit of breast-feeding for the child and the benefit of therapy for the

woman.

Fertility

There are no data on fertility available.

4.7

Effects on ability to drive and use machines

Haemocomplettan has no influence on the ability to drive and use machines.

4.8

Undesirable effects

Tabulated list of adverse drug reactions (ADRs)

This table combines the adverse reactions identified from clinical trials and post marketing

experience. Frequencies presented in the table below have been based on pooled analyses

across two company-sponsored clinical trials performed in aortic surgery with or without

other surgical procedures [BI3023_2002 (N=61) and BI3023_3002 (N=152)] and have been

evaluated

according to the following convention: 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); very rare

(< 1/10,000). For spontaneous post marketing ADRs, the reporting frequency is categorized

as unknown. In view of the fact that these trials were conducted in only the narrow

population of aortic surgery adverse drug reaction rates observed in these trials may not

reflect the rates observed in clinical practice and are unknown for clinical settings outside

the studied indication.

MedDRA

System Organ Class

Undesirable effects

Frequency

(In aortic surgery with or

without other surgical

procedures)

General Disorders and

Administration Site

Condition

Pyrexia

Very common

Immune System

Disorder

Anaphylactic reactions

(including anaphylactic

shock)

Uncommon

Allergic reactions

(including generalized

urticaria, rash, dyspnoea,

angioedema, tachycardia,

nausea, vomiting, chills,

pyrexia, chest pain,

cough, blood pressure

decreased)

Unknown

Vascular Disorder

Thromboembolic events*

Common**

* Isolated cases have been fatal.

** Based on results of two clinical trials (aortic surgery with or without other surgical procedures),

the pooled incidence rate of thromboembolic events was lower in fibrinogen treated subjects (N=8,

7.4 %) compared with placebo group (N=11, 10.4 %).

For safety with respect to transmissible agents, see section 4.4.

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.

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/

and emailed to the Registration Holder’s Patient Safety Unit at:

drugsafety@neopharmgroup.com

4.9

Overdose

In order to avoid overdosage, regular monitoring of the plasma level of fibrinogen during

therapy is indicated (see 4.2).

In case of overdosage, the risk of development of thromboembolic complications is

enhanced.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group

:

antihaemorrhagics

,

human fibrinogen,

ATC code: B02B B01

Human fibrinogen (coagulation factor I), in the presence of thrombin, activated coagulation

factor XIII (F XIIIa) and calcium ions, is converted into a stable and elastic three-

dimensional haemostatic fibrin clot.

The administration of human fibrinogen concentrate causes an increase in plasma fibrinogen

level and can temporarily correct the coagulation defect of patients with fibrinogen

deficiency.

The pivotal Phase II study evaluated the single-dose pharmacokinetics (see 5.2

Pharmacokinetic properties) and also provided efficacy data using the surrogate endpoint

maximum clot firmness (MCF) and safety data.

For each subject, the MCF was determined before (baseline) and one hour after a single

dose administration of 70 mg/kg body weight of Haemocomplettan. Haemocomplettan was

found to be effective in increasing clot firmness in patients with congenital fibrinogen

deficiency (afibrinogenaemia) as measured by thromboelastometry. Haemostatic efficacy in

acute bleeding episodes, and its correlation with MCF, are being verified in a postmarketing

study.

5.2

Pharmacokinetic properties

Human fibrinogen is a normal constituent of the human plasma and acts like endogenous

fibrinogen. In plasma, the biological half-life of fibrinogen is 3 to 4 days. Regarding

degradation Haemocomplettan behaves like the endogenous fibrinogen.

Haemocomplettan is administered intravenously and is immediately available in a plasma

concentration corresponding to the dosage administered.

A pharmacokinetic study evaluated the single-dose pharmacokinetics before and after

administration of human fibrinogen concentrate in subjects with congenital

afibrinogenaemia. This prospective, open label, uncontrolled, multicentre study consisted of

5 females and 10 males, ranging in age from 8 to 61 years (2 children, 3 adolescents, 10

adults). The median dose was 77.0 mg/kg body weight (range 76.6 – 77.4 mg/kg).

Blood was sampled from 15 subjects (14 measurable) to determine the fibrinogen activity at

baseline and up to 14 days after the infusion was complete. In addition, the incremental

in

vivo

recovery (IVR, defined as the maximum increase in fibrinogen plasma levels per mg/kg

body weight dosed), was determined from levels obtained up to 4 hours post-infusion. The

median incremental IVR was 1.7 (range 1.30-2.73) mg/dl per mg/kg body weight. The

following table provides the pharmacokinetic results:

Pharmacokinetic results for fibrinogen activity

Parameter (n=14)

Mean ± SD

Median (range)

78.7 ± 18.13

77.1 (55.73-117.26)

[g/l]

1.4 ± 0.27

1.3 (1.00-2.10)

AUC for dose of 70 mg/kg

[hmg/ml]

124.3 ± 24.16

126.8 (81.73-156.40)

Extrapolated part of AUC [%]

8.4 ± 1.72

7.8 (6.13-12.14)

Cl [ml/h/kg]

0.59 ± 0.13

0.55 (0.45-0.86)

MRT [h]

92.8 ± 20.11

85.9 (66.14-126.44)

[ml/kg]

52.7 ± 7.48

52.7 (36.22-67.67)

IVR [mg/dl per mg/kg bw]

1.8 ± 0.35

1.7 (1.30-2.73)

t

1/2

= terminal elimination half-life

h = hour

C

max

= maximum fibrinogen concentration in plasma within 4 hours

AUC = area under the plasma concentration curve

Cl = clearance

MRT = mean residence time

V

ss

= volume of distribution at steady state

SD = standard deviation

IVR = in vivo recovery

bw= body weight

5.3

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of

single dose toxicity and safety pharmacology.

Preclinical studies with repeated dose applications (chronic toxicity, cancerogenicity and

mutagenicity) cannot be reasonably performed in conventional animal models due to the

development of antibodies following the application of heterologous human proteins.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Human albumin,

L-arginine hydrochloride,

sodium chloride,

sodium citrate

6.2

Incompatibilities

This medicinal product must not be mixed with other medicinal products, diluents, or

solvents except those mentioned in section 6.6. A standard infusion set is recommended for

intravenous application of the reconstituted solution at room temperature.

6.3

Shelf life

The expiry date of the product is indicated on the packaging materials.

The physico-chemical stability for the reconstituted product has been demonstrated for 8

hours at room temperature (max. +25 °C). From a microbiological point of view the product

should be used immediately following reconstitution. If the reconstituted product is not

administered immediately, storage shall not exceed 8 hours below 25 °C. The reconstituted

product should not be stored in the refrigerator.

6.4

Special precautions for storage

Store in a refrigerator (2

C – 8

C). Do not freeze!

Keep the vial in the closed outer carton, in order to protect from light.

Stability for the reconstituted product see section 6.3.

6.5

Nature and contents of container

Vial of colourless glass (Type II Ph. Eur.) closed with a latex-free stopper (bromobutyl

rubber), and sealed with an aluminium / plastic crimp cap.

Pack with 1 or 2 g (Figure 1)

One vial containing 1 or 2 g human fibrinogen

Filter: Pall

Syringe Filter

Dispensing pin: Mini-Spike

Dispensing Pin

Figure 1

6.6

Special precautions for disposal and other handling

General instructions

Reconstitution and withdrawal should be carried out under aseptic conditions.

Reconstituted product should be inspected visually for particulate matter and

discoloration prior to administration.

The solution should be almost colourless to yellowish, clear to slightly opalescent and

of neutral pH. Do not use solutions that are cloudy or contain residues

(deposits/particles).

Reconstitution

Warm both the solvent and the powder in unopened vials to room or body temperature

(not above 37 °C).

Haemocomplettan should be reconstituted with water for injections (50 ml for 1 g and

100 ml for 2 g, respectively, not included).

Wash hands or use gloves before reconstituting the product.

Remove the cap from the Haemocomplettan vial to expose the central portion of the

infusion stopper.

Treat the surface of the infusion stopper with antiseptic solution and allow it to dry.

Transfer the solvent with an appropriate transfer device into the infusion vial. Ensure to

push straight down centrally through the infusion stopper. Transfer the solvent

completely. The powder should be completely wet.

Gently swirl the vial until the powder

is reconstituted and the solution is ready for

administration. Avoid strong shaking which causes formation of foam. The powder

should be completely reconstituted within max. 15 minutes (generally within 5 to 10

minutes).

Open the plastic blister containing the dispensing pin (Mini-Spike

Dispensing Pin)

provided with Haemocomplettan (Figure 2).

Figure 2

Take the provided dispensing pin and insert it into the stopper of the vial with the

reconstituted product (Figure 3).

Figure 3

After the dispensing pin is inserted, remove the cap. After the cap is removed, do not

touch the exposed surface.

Open the blister with the filter (Pall

Syringe Filter) provided with Haemocomplettan

(Figure 4).

Figure 4

Screw the syringe onto the filter (Figure 5).

Figure 5

Screw the syringe with the mounted filter onto the dispensing pin (Figure 6).

Figure 6

Draw the reconstituted product into the syringe (Figure 7).

Figure 7

When completed,

remove the filter, dispensing pin and empty vial from the syringe,

dispose of properly, and proceed with administration as usual.

Reconstituted product should be administered immediately by a separate injection /

infusion line (see section 6.3).

Take care that no blood enters syringes filled with product.

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

requirements.

7.

MANUFACTURER

CSL Behring GmbH

Emil-von-Behring-Str. 76

35041 Marburg

Germany

8.

REGISTRATION HOLDER:

Genmedix,

12 Beit Harishonim St., Emek-Heffer 3877701.

9.

REGISTRATION NUMBERS

141 35 31819

141 36 31820

Revised in September 2020