RIXUBIS

New Zealand - English - Medsafe (Medicines Safety Authority)

Active ingredient:
Nonacog gamma 200 IU/mL equivalent to 1000 IU/vial;  
Available from:
Takeda New Zealand Limited
INN (International Name):
Nonacog gamma 200 IU/mL (equivalent to 1000 IU/vial)
Dosage:
200 IU/mL
Pharmaceutical form:
Powder for injection
Composition:
Active: Nonacog gamma 200 IU/mL equivalent to 1000 IU/vial   Excipient: Calcium chloride dihydrate Histidine Mannitol Polysorbate 80 Sodium chloride Sucrose Water for injection
Prescription type:
General sale
Manufactured by:
Baxalta Manufacturing Sarl
Therapeutic indications:
· Routine prophylaxis of bleeding episodes in patients with haemophilia B · Treatment & prevention of bleeding episodes in patients with haemophilia B (congenital factor IX deficiency) · Peri-operative management in patients with haemophilia B
Product summary:
Package - Contents - Shelf Life: Combination pack, 1 vial active + 1 vial diluent - 1000 U - 36 months from date of manufacture stored at or below 30°C. do not freeze 3 hours reconstituted stored at or below 30°C. do not refrigerate or freeze - Vial, glass, diluent - 5 mL -   - Vial, glass, active component - 1000 U -  
Authorization number:
TT50-9281b
Authorization date:
2013-03-28

Read the complete document

RIXUBIS

RIXUBIS

®

nonacog gamma (rch) (recombinant coagulation factor IX), 250, 500, 1000, 2000, 3000 IU /vial

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common

questions about RIXUBIS. It does

not contain all of the available

information. All medicines have risks

and benefits. Your doctor has

weighed the risks of using your

medicine against the benefit that it

will have for you.

It does not take the place of talking to

your doctor or pharmacist.

If you have any concerns about

having this medicine, ask your

doctor or pharmacist.

Please read this leaflet carefully

before using your medicine as it

contains information about your

medicine.

Keep this leaflet with your

medicine.

You may need to read it again.

What RIXUBIS is

RIXUBIS, nonacog gamma (rch) is a

coagulation factor IX product that is

produced by recombinant

technology. Mammalian cells, which

have the DNA for human coagulation

factor IX put in them, are grown in

large amounts in cell culture

laboratories. These cells make

recombinant human factor IX, which

is released into cell culture media and

then very highly purified. The

recombinant factor IX does not

contain any human blood,

preservatives, or added animal or

human components.

What RIXUBIS is used

for

People with haemophilia B

(Christmas disease) are deficient in

coagulation factor IX. RIXUBIS

works by replacing factor IX to

enable blood to clot.

Your medicine is used to prevent and

control bleeding in people with

haemophilia B.

Your doctor may give you RIXUBIS

when you have surgery.

Your medicine can reduce the

number of bleeding episodes when

used regularly (prophylaxis).

Before you use

RIXUBIS

To make sure that your medicine is

suitable for you, it is important to tell

your doctor or pharmacist if any of

the points below apply to you. If

there is anything you do not

understand, ask your doctor or

pharmacist to explain.

Do not use RIXUBIS if you:

are allergic to hamsters.

are allergic to any ingredients in

RIXUBIS (see "What is in

RIXUBIS?").

What should I tell my doctor

before using RIXUBIS?

You should tell your doctor if you:

have or have had any medical

problems.

take any medicines, including

prescription and non-prescription

medicines, such as over-the-

counter medicines, supplements

or herbal remedies.

have any allergies, including

allergies to hamsters.

are breastfeeding. It is not known

if RIXUBIS passes into your milk

and if it can harm your baby.

are pregnant or planning to

become pregnant. It is not known

if RIXUBIS may harm your

unborn baby.

have been told that you have

inhibitors to factor IX (because

RIXUBIS may not work for you).

How RIXUBIS is given

Your medicine is given as an

injection directly into your veins,

usually by yourself, a doctor,

nurse, or other trained person.

Your medicine contains no

additives that would prevent the

growth of bacteria once the

powder is dissolved with sterile

water. For this reason, each vial

of RIXUBIS is for single use

only, in one patient only. Discard

any residue.

Your medicine should be

administered as ordered by your

physician. You should be trained

on how to do infusions by your

healthcare provider or

haemophilia treatment centre.

Many people with haemophilia B

learn to infuse their medicine by

themselves or with the help of a

family member.

RIXUBIS

Your doctor will tell you how

much medicine to use based on

your weight, the severity of your

haemophilia B, and where you

are bleeding.

You may have to have blood tests

done after getting your medicine

to be sure that your blood level of

factor IX is high enough to clot

your blood.

Use only the materials provided in

the box for dissolving the

RIXUBIS powder and then

injecting the RIXUBIS solution

(see INSTRUCTIONS FOR USE).

Inject your medicine as soon as

possible or within 3 hours after

dissolving the powder.

Always wash your hands before

doing the following procedures.

Use germ-free methods during the

making up procedure and during

injection.

RIXUBIS must not be mixed with

other injectable medicines.

If you miss/forget your

injection

Proceed with the next administration

immediately, and continue at regular

intervals as advised by your doctor.

Do not take a double dose to make up

the forgotten dose.

Overdose

Immediately contact your doctor,

or the Poisons Information Centre

(tel: 131 126 in Australia, or tel:

0800 764 766 in New Zealand) if

you inject more medicine than

your doctor recommends. Do this

even if there are no signs of

discomfort.

While you are using

RIXUBIS

Things you must do

See your doctor immediately if

your bleeding does not stop as

expected

Stop the infusion immediately

and contact your doctor, if you

experience allergic reactions such

as skin rash, itching, chest

discomfort, wheezing, dizziness,

hives, faintness, chills, flushing,

rapid heartbeat, shortness of

breath and/or a swollen face

Always follow your doctor's

instructions carefully

Tell all the doctors, dentists and

pharmacists who are treating you

that you are using RIXUBIS

If you are about to be started on

any new medicine, tell your

doctor and pharmacist that you

are using RIXUBIS

If you become pregnant while

you are using your medicine, tell

your doctor.

Talk to your healthcare provider

before traveling. Plan to bring

enough medicine for your

treatment during this time. It is

important to obtain a written

statement from your physician,

explaining the reasons why you

need to have this medicine and

injecting devices with you,

otherwise you may not be

allowed to bring it into the

country of travelling. Please

ensure you have multiple copies

of the letter if travelling to more

than one country.

Things you must not do

Do not give your medicine to

anyone else, even if they have the

same condition as you

Do not use your medicine to treat

any other complaints unless your

doctor tells you to

Do not stop using your medicine

or lower the dosage, without

checking with your doctor, unless

you have an allergic reaction.

Side effects

Allergic reactions may occur with

your medicine.

Call your doctor or get emergency

treatment right away if you get a

rash or hives, itching, tightness of

the throat, chest pain or tightness,

difficulty breathing,

lightheadedness, dizziness, nausea

or fainting.

Some common side effects of

RIXUBIS are stomach-flu-like

symptoms (such as nausea, vomiting

and stomach pain), runny nose, sore

throat, headache and diarrhoea.

Tell your doctor or pharmacist about

any side effects that bother you or do

not go away.

These are not all the possible side

effects with your medicine. You can

ask your doctor or pharmacist for

information that is written for

healthcare professionals.

After using RIXUBIS

RIXUBIS should be stored below

30°C for the duration of its shelf life.

Store in the original package in order

to protect from light.

RIXUBIS contains no

preservatives. Reconstituted

product (what you get after

dissolving the powder with the

sterile water) must be used within

3 hours and cannot be stored or

refrigerated.

Discard any medicine left in the vial

at the end of your infusion.

Keep out of the reach and sight of

children.

Do not use RIXUBIS after the

expiry date which is printed on the

label after the word 'EXP'.

The expiry date refers to the last day

of that month.

Dispose of all materials, including

any leftover reconstituted medicine,

in an appropriate container.

RIXUBIS

Medicines should not be disposed of

via wastewater or household waste.

Ask your pharmacist how to dispose

of medicines no longer required.

These measures will help to protect

the environment.

Instructions for use

Do not attempt to do an infusion to

yourself unless you have been

taught how by your healthcare

provider or haemophilia center.

Always follow the specific

instructions given by your healthcare

provider. The steps listed below are

general guidelines for using your

medicine. If you are unsure of the

procedures, please call your

healthcare provider before using.

Prepare a clean flat surface and

gather all the materials you will

need for the infusion. Check the

expiration date and let the vials

with the RIXUBIS concentrate

and the water for injections

(diluent) warm up to room

temperature. Wash your hands

and put on clean exam gloves. If

infusing yourself at home, the use

of gloves is optional.

Remove caps from the RIXUBIS

concentrate and diluent vials to

expose the centers of the rubber

stoppers.

Disinfect the stoppers with an

alcohol swab (or other suitable

solution suggested by your

healthcare provider or

haemophilia center) by rubbing

the stoppers firmly for several

seconds and allow them to dry

prior to use. Place the vials on a

flat surface.

Open the BAXJECT II device

package by peeling away the lid,

without touching the inside of the

package.

Do not remove the BAXJECT

II device from the package.

Turn the package with the

BAXJECT II device upside down

and place it over the top of the

diluent vial. Fully insert the clear

plastic spike of the device into the

center of the diluent vial's stopper

by pushing straight down. Grip

the package at its edge and lift it

off the device. Be careful not to

touch the white plastic spike.

Do not remove the blue cap

from the BAXJECT II device.

The diluent vial now has the

BAXJECT II device connected to

it and is ready to be connected to

the RIXUBIS vial.

To connect the diluent vial to the

RIXUBIS vial, turn the diluent

vial over and place it on top of

the vial containing RIXUBIS

concentrate. Fully insert the white

plastic spike into the RIXUBIS

vial's stopper by pushing straight

down. Diluent will flow into the

RIXUBIS vial. This should be

done right away to keep the liquid

free of germs.

Swirl the connected vials gently

and continuously until the

RIXUBIS is completely

dissolved.

Do not shake.

The RIXUBIS solution should

look clear and colorless. If not, do

not use it and notify Baxter

immediately.

Take off the blue cap from the

BAXJECT II device and connect

the syringe by screwing the

syringe clockwise into the

BAXJECT II device.

Be careful to not inject air.

Turn over the connected vials so

that the RIXUBIS vial is on top.

Draw the RIXUBIS solution into

the syringe by pulling back the

plunger slowly. Disconnect the

syringe from the vials.

10. If you are using more than one

vial of RIXUBIS, the contents of

more than one vial may be drawn

into the same syringe.

Make sure you mix each vial of

RIXUBIS with the water for

injections that is provided in

the box (Following Steps 1-9).

You will need a separate

BAXJECT II device to mix each

additional vial of RIXUBIS.

11. Attach the infusion needle to the

syringe using a winged (butterfly)

infusion set, if available. Point the

needle up and remove any air

bubbles by gently tapping the

syringe with your finger and

slowly and carefully pushing air

out of the syringe and needle.

12. Apply a tourniquet and get the

infusion site ready by wiping the

skin well with an alcohol swab

(or other suitable solution

suggested by your healthcare

provider or haemophilia center).

13. Insert the needle into the vein and

remove the tourniquet. Slowly

infuse the RIXUBIS.

Do not infuse any faster than 10

mL per minute.

14. Take the needle out of the vein

and use sterile gauze to put

pressure on the infusion site for

several minutes.

Do not recap the needle.

Place it with the used syringe in a

hard-walled Sharps container for

proper disposal.

15. Dispose of the used vials and

BAXJECT II system in your

hard-walled Sharps container

without taking them apart. Do not

dispose of these supplies in

ordinary household trash.

16. Remove the peel-off label from

the RIXUBIS vial and place it in

your logbook. Clean any spilled

blood with a freshly prepared

mixture of 1 part bleach and 9

parts water, soap and water, or

any household disinfecting

solution.

Important: Contact your

healthcare provider or local

haemophilia treatment center if

you experience any problems.

RIXUBIS

Product Description

What RIXUBIS looks like?

RIXUBIS comes as a white or off-

white powder in a glass vial.

Each vial of your medicine is

accompanied by a glass vial

containing water for injections for

dissolving the powder. The package

also comes with a device known as

the BAXJECT II which is used to

transfer the sterile water in the glass

vial to the powder vial.

An ancillary set containing alcohol

swabs, adhesive bandages, an

infusion set, a syringe and a butterfly

needle may be supplied with your

medicine.

What is in RIXUBIS?

The active substance in RIXUBIS is

nonacog gamma. Five strengths, i.e.

250 IU, 500 IU, 1000 IU, 2000 IU

and 3000 IU of RIXUBIS are

commercially available.

Inactive ingredients: histidine,

sodium chloride, calcium chloride

dihydrate, mannitol, sucrose,

polysorbate 80.

Supplier

RIXUBIS is supplied in Australia by:

Shire Australia Pty Limited

(now part of Takeda)

Level 39, 225 George Street

Sydney NSW 2000

Australia

Telephone: 1800 012 612

RIXUBIS is supplied in New

Zealand by:

Shire New Zealand Limited

(now part of Takeda)

C/o Crowe Horwath

Level 29, 188 Quay Street

Auckland Central

Auckland

Telephone: 0508 169 077

Date of preparation

This leaflet was prepared in

September 2019.

RIXUBIS is a trademark of Baxalta

Incorporated, a wholly-owned,

indirect subsidiary of Shire plc.

Shire and the Shire Logo are

trademarks of Shire Pharmaceutical

Holdings Ireland Limited or its

affiliates, each a Takeda company.

Read the complete document

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 1

1 RIXUBIS (50 IU/mL, 100 IU/mL, 200 IU/mL, 400 IU/mL and 600 IU/mL

powder for injection)

RIXUBIS is available in the following strengths:

50 IU/mL equivalent to 250 IU,

100 IU/mL equivalent to 500 IU,

200 IU/mL equivalent to 1000 IU,

400 IU/mL equivalent to 2000 IU,

600 IU/mL equivalent to 3000 IU.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active substance: Nonacog gamma (rch), Recombinant Coagulation Factor IX (rFIX).

The product concentration differs for each strength, as every strength is reconstituted with the

accompanying 5 mL of water for injections.

The specific activity of rFIX is ≥ 200 IU factor IX per mg.

Unit Formulation: after reconstitution with water for injections to 5mL

RIXUBIS

250 IU

500 IU

1000 IU

2000 IU

3000 IU

Active ingredient:

Nonacog gamma

[Recombinant Coagulation FIX (rch)]

250 IU

500 IU

1000 IU

2000 IU

3000 IU

Approximate Product Concentration:

(IU rFIX per mL of reconstituted

solution)

IU/mL

IU/mL

IU/mL

IU/mL

IU/mL

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder and solvent for solution for injection.

White, lyophilised powder and diluent for solution, for intravenous administration.

4 CLINICAL PARTICULARS

Therapeutic indications

RIXUBIS is indicated for:

Routine prophylaxis of bleeding episodes in patients with haemophilia B

Treatment and prevention of bleeding episodes in patients with haemophilia B (congenital

factor IX deficiency)

Peri-operative management in patients with haemophilia B.

Dose and method of administration

General

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

haemophilia.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 2

It is recommended that prescribed doses of RIXUBIS are expressed as ‘International Units’ (written in

full) of factor IX.

Patients and their caregivers should be adequately trained in the correct administration technique

before self-administration of

RIXUBIS in a home treatment setting can be considered.

The dosage and duration of the substitution therapy depend on the severity of the factor IX

deficiency, the location and extent of bleeding, and the patient's clinical condition, age and

pharmacokinetic parameters of factor IX, such as incremental recovery and half-life.

To ensure that the desired factor IX activity plasma level has been attained, careful monitoring using

an appropriate factor IX activity assay is advised and, if necessary, appropriate adjustments to the

dose and the frequency of repeated infusions should be performed, see section 4.4.

Inhibitors

Patients using RIXUBIS should be monitored for the development of factor IX inhibitors by appropriate

clinical observations and laboratory tests. If expected plasma factor IX activity levels are not attained,

or if bleeding is not controlled with an expected dose, an assay that measures factor IX inhibitor

concentration should be performed, see section 4.4.

Dosage

A guide for calculating the dose for treatment of bleeding episodes is provided below:

Number of factor IX

IU required

body weight

(in kg)

desired factor IX increase

(%) or (IU/dL)

reciprocal of observed

recovery (dL/kg)

Patients ≥ 12 years of age

The calculation of the required dose of RIXUBIS can be based on the empirical finding that 1 IU

RIXUBIS per kg body weight is expected to increase the circulating level of factor IX by 0.9 IU/dL of

plasma (0.9% of normal) (range from 0.5 to 1.4 IU/dL).

For an incremental recovery of 0.9 IU/dL of plasma (0.9% of normal), the dose is calculated as follows:

Number of factor IX

IU required

body weight

(in kg)

desired factor IX increase

(%) or (IU/dL)

1.1 dL/kg

Patients < 12 years of age

The calculation of the required dose of RIXUBIS can be based on the empirical finding that 1 IU

RIXUBIS per kg body weight is expected to increase the circulating level of factor IX by 0.7 IU/dL of

plasma (0.7% of normal) (range from 0.31 to 1.0 IU/dL).

For an incremental recovery of 0.7 IU/dL of plasma (0.7% of normal), the dose is calculated as follows:

Number of factor IX

IU required

body weight

(in kg)

desired factor IX

increase (%) or (IU/dL)

1.4 dL/kg

Due to the wide range of individual differences in incremental recovery, it is recommended to base

the calculation of the required dose on the patient’s individual incremental recovery using serial

factor IX activity assays.

Doses administered should be titrated to the patient's clinical response and individual

pharmacokinetics, in particular incremental recovery and half-life.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 3

Treatment of bleeding episodes and peri-operative management

In the case of the following haemorrhagic events, the factor IX activity should not fall below the

plasma factor IX activity levels (in % of normal or in IU/dL) in the corresponding period.

Degree of haemorrhage/ Type

of surgical procedure

Factor IX level

required (%) or

(IU/dL)

Frequency of doses (hours)

/Duration of therapy (days)

Haemorrhage

Early haemarthrosis, muscle

bleeding or oral bleeding

20 – 40

Repeat every 24 hours, at least 1 day, until the

bleeding episode as indicated by pain is resolved

or healing is achieved.

More extensive

haemarthrosis, muscle

bleeding, or haematoma

30 – 60

Repeat infusion every 24 hours for 3 - 4 days or

more until pain and acute disability are resolved.

Life-threatening

haemorrhages

60 – 100

Repeat infusion every 8 to 24 hours until threat is

resolved.

Surgery

Minor, including tooth

extraction

30 – 60

Every 24 hours, at least 1 day, until healing is

achieved.

Major

80 – 100

(pre- and post-

operative)

Repeat infusion every 8 – 24 hours until adequate

wound healing, then therapy for at least another

7 days to maintain a factor IX activity of 30% -

60% (IU/dL).

Careful monitoring of replacement therapy is especially important in cases of major surgery or life-

threatening haemorrhages.

Routine prophylaxis

RIXUBIS can be administered for long-term prophylaxis against bleeding in patients with severe and

moderately severe haemophilia B. The recommended dose for previously treated patients (PTPs)

≥ 12 years of age is 40 to 60 IU/kg twice weekly. The recommended dose for patients < 12 years of

age is 40 to 80 IU/kg twice weekly. Shorter dosage intervals or higher doses may become necessary

depending upon the individual patient’s pharmacokinetics, age, bleeding phenotype, and physical

activity.

Administration

RIXUBIS is administered by intravenous (IV) infusion.

Administer RIXUBIS at room temperature using a rate that ensures the comfort of the patient, up to a

maximum of 10 mL/min.

Do not administer RIXUBIS by continuous infusion.

Only use plastic syringes with this product.

Instructions for use

Administer RIXUBIS by intravenous (IV) infusion after reconstitution.

Initiate treatment under the supervision of a physician experienced in the treatment of haemophilia

and continue treatment under supervision for a period of time, see Hypersensitivity Reactions in

section 4.4.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 4

Inspect parenteral drug products for particulate matter and discolouration prior to administration,

whenever solution and container permit. The solution should be clear and colourless in appearance.

If not, do not use the solution and notify Takeda.

Administer RIXUBIS at room temperature within 3 hours of reconstitution. RIXUBIS contains no

antimicrobial preservative. It is for single use in one patient only. Discard any unused product.

Perform reconstitution, product administration, and handling of the administration set and needles

with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious

viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place

needles in a sharps container after single use. Discard all equipment, including any reconstituted

RIXUBIS, in an appropriate container.

The procedures below are provided as general guidelines for the preparation and reconstitution of

RIXUBIS. Always work on a clean surface and wash your hands before performing the following

procedures:

Use aseptic technique during reconstitution procedure.

Allow the RIXUBIS vial (dry factor concentrate) and water for injections vial (diluent) to reach

room temperature.

Remove caps from the factor concentrate and diluent vials.

Cleanse stoppers with germicidal solution and allow to dry prior to use. Place the vials on a flat

surface.

Open the BAXJECT II device package by peeling away the lid, without touching the inside

(Figure A).

Do not remove the device from the package. Note that the BAXJECT II device is

intended for use with a single vial of RIXUBIS and water for injections; therefore, reconstituting

and withdrawing a second vial into the syringe requires a second BAXJECT II device.

Turn the package over. Press straight down to fully insert the clear plastic spike through the

diluent vial stopper (Figure B).

Grip the BAXJECT II package at its edge and pull the package off the device (Figure C). Do not

remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike.

Turn the system over so that the diluent vial is on top. Quickly insert the white plastic spike fully

into the

RIXUBIS vial stopper by pushing straight down (Figure D). The vacuum will draw the

diluent into the

RIXUBIS vial.

Swirl gently until RIXUBIS is completely dissolved. Do not refrigerate after reconstitution. Use

within 3 hours of reconstitution.

Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device

(Figure E).

Do not inject air.

Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate

into the syringe by pulling the plunger back slowly (Figure F).

Disconnect the syringe; attach a suitable needle and inject intravenously as instructed by Bolus

Infusion. If a patient is to receive more than one vial of

RIXUBIS, the contents of multiple vials

may be drawn into the same syringe.

Maximum infusion rate of 10 mL/min.

Figure A

Figure B

Figure C

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 5

Figure D

Figure E

Figure F

Contraindications

Hypersensitivity to the active substance, to any of the excipients listed in section 6.1, or to hamster

protein.

Special warnings and precautions for use

Hypersensitivity reactions

Hypersensitivity has been reported with RIXUBIS. Anaphylaxis and other hypersensitivity reactions to

any type of factor IX concentrate are possible. Patients and/or their caregivers should be informed of

the early signs of hypersensitivity reactions. They should be advised to discontinue use of the product

immediately and contact their physician if such symptoms occur. The risk is highest during the early

phases of initial exposure to factor IX concentrates in previously untreated patients (PUPs), in

particular in patients with high-risk gene mutations.

There have been reports in the literature showing an association between the occurrence of a factor

IX inhibitor and allergic reactions, in particular in patients with a high risk gene mutation. Therefore,

patients experiencing allergic reactions should be evaluated for the presence of an inhibitor.

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

Inhibitors - Nephrotic syndrome

Patients with haemophilia B may develop neutralising antibodies (inhibitors) to factor IX.

Patients using RIXUBIS should be regularly evaluated for the development of factor IX inhibitors by

appropriate clinical observations and laboratory tests. If expected plasma factor IX activity levels are

not attained, or if bleeding is not controlled with an expected dose, an assay that measures factor IX

inhibitor concentration should be performed.

If a patient develops an inhibitor, it is recommended that a specialized haemophilia centre be

contacted.

In patients with high titer factor IX inhibitors, RIXUBIS therapy may not be effective and other

therapeutic options should be considered.

Patients with factor IX inhibitors are at an increased risk of severe hypersensitivity reactions or

anaphylaxis if re-exposed to factor IX.

Nephrotic syndrome has been reported following attempted immune tolerance induction in

haemophilia B patients with factor IX inhibitors. The safety and efficacy of using

RIXUBIS for immune

tolerance induction has not been established.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 6

Thromboembolism, DIC, fibrinolysis

The use of factor IX products has been associated with the development of thromboembolic

complications. Therefore, the use of factor IX-containing products may be potentially hazardous in

patients with disseminated intravascular coagulation (DIC) and in patients with signs of fibrinolysis.

Clinical surveillance for early signs of thrombotic and consumptive coagulopathy should be initiated

with appropriate biological testing, in particular when administering this product to patients with liver

disease, to patients peri- and post-operatively, to new-born infants, or to other patients at risk for

thromboembolic events or DIC.

In patients with DIC or those at risk for DIC or thromboembolic events, the benefit of treatment with

RIXUBIS should be weighed against the risk of these complications.

Monitoring laboratory tests

Monitor factor IX activity levels by the one-stage clotting assay to confirm that adequate

factor IX levels have been achieved and maintained, when clinically indicated, see section 4.2.

Monitor for the development of inhibitors if expected factor IX activity plasma levels are not

attained, or if bleeding is not controlled with the recommended dose of

RIXUBIS. Assays used

to determine if factor IX inhibitor is present should be titred in Bethesda Units (BUs).

Use in the elderly

Clinical studies of RIXUBIS did not include subjects aged 65 and over. It is not known whether they

respond differently from younger subjects. As for all patients, dose selection for an elderly patient

should be individualised.

Interaction with other medicines and other forms of interaction

No interactions of recombinant coagulation factor IX products with other medicinal products are

known.

Fertility, pregnancy and lactation

Effects on fertility

There effects of RIXUBIS on fertility have not been established.

Use in pregnancy (Category B2)

Medicines which have been taken by only a limited number of pregnant women and women of

childbearing age, without an increase in the frequency of malformation or other direct or indirect

harmful effects on the human foetus having been observed. Studies in animals are inadequate or

may be lacking, but available data show no evidence of an increased occurrence of foetal damage.

There are no data from the use of RIXUBIS in pregnant women. Healthcare providers should balance

the potential risks and only prescribe

RIXUBIS if clearly needed.

Use in lactation

There are no data from the use of RIXUBIS in lactating women. Healthcare providers should balance

the potential risks and only prescribe

RIXUBIS if clearly needed.

Effects on ability to drive and use machines

No effects on the ability to drive and use machines have been observed.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 7

Undesirable effects

Adverse reactions from clinical trials

The following adverse reactions have been identified during clinical development of RIXUBIS from 2

completed studies and 2 ongoing studies* with 99 unique, male previously treated patients PTPs with

haemophilia B receiving a total of 14018 infusions.

Clinical Trials Adverse Reactions

System Organ Class

(SOC)

Preferred

MedDRA

Term

Frequency per Patient

N = 99

Frequency per Infusion

N = 14018

Category

Number of

patients (%)

Category

Number of

occurrences (%)

NERVOUS SYSTEM

DISORDERS

Dysgeusia

Common

1 (1.01%)

Rare

2 (0.014%)

MUSCULO-SKELETAL

AND CONNECTIVE

TISSUE DISORDERS

Pain in

extremity

Common

1 (1.01%)

Very Rare

1 (0.007%)

Legend: Frequency is based upon the following scale: Very Common (≥ 1/10); Common (≥ 1/100 - < 1/10),

Uncommon (≥ 1/1,000 - < 1/100), Rare (≥ 1/10,000 - < 1/1,000), Very Rare (< 1/10,000)

The frequency per patient is based on the number of patients experiencing an adverse event with an investigator

assessment of at least possibly related, or when an investigator assessment of causality was unknown, considered at

least possibly related by the investigator.

The frequency per infusion is based on the number of occurrences of adverse events with an investigator assessment

of at least possibly related, or when an investigator assessment of causality was unknown, considered at least possibly

related by the investigator.

Clinical Study 250901 (Pivotal) Completed

Clinical Study 251101 (Paediatric) Completed

Clinical Study 251001 (Continuation) Data cut-off date = 14 June 2013

Clinical Study 251002 (Surgery) Data cut-off date = 14 June 2013.

Immunogenicity

Of the 99 PTPs exposed to RIXUBIS during clinical development, none developed inhibitory or

treatment-related† total binding antibodies† to factor IX or antibodies to Chinese hamster ovary

(CHO) proteins. One subject had a positive titer for rfurin that was not present when checked at a

later time point and was therefore considered transient. No clinical adverse findings were observed

in this subject.

†Defined as a more than 2 dilution-steps increase in specific titer compared to pre-study level.

Post-marketing adverse reactions

The following adverse reactions have been reported, listed by MedDRA (Version 17.1) System Organ

Class (SOC), then by Preferred Term in order of severity.

IMMUNE SYSTEM DISORDERS: Hypersensitivity (including symptoms such as dyspnoea, pruritus)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS: Urticaria, rash

Class Reactions

Disseminated intravascular coagulation, embolism (e.g., pulmonary embolism, venous

thrombosis, arterial thrombosis)

Anaphylactic reaction or other hypersensitivity reactions (including symptoms such as

angioedema, chest discomfort, hypotension, lethargy, nausea, vomiting, paraesthesia,

restlessness, wheezing, dyspnoea)

See section 4.4.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 8

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked

to report any suspected adverse reactions

https://nzphvc.otago.ac.nz/reporting/

Overdose

No symptoms of overdose have been reported.

For advice on the management of overdose please contact the National Poisons Centre on phone

number: 0800 764 766 [0800 POISON] in New Zealand (or the Poison Information Centre on 131126

in Australia).

5 PHARMACOLOGICAL PROPERTIES

Pharmacodynamic properties

Pharmacotherapeutic group: Blood Coagulation Factors

ATC Code: B02BD09.

The recombinant human factor IX (rFIX) is a glycoprotein consisting of 415 amino acids. RIXUBIS is

synthesised by a genetically engineered Chinese hamster ovary (CHO) cell line. No exogenous

materials of human or animal origin are employed in the manufacture, purification, or formulation of

the final product. The growth medium is chemically defined and the downstream process does not

use monoclonal antibodies for the purification of

RIXUBIS. The production process also includes two

independent viral removal/inactivation steps: solvent detergent treatment and nanofiltration.

Biological potency is determined by a one-stage clotting assay, which employs a factor IX concentrate

standard that is referenced to the World Health Organization (WHO) International Standard for factor

IX concentrates.

Pharmacodynamics

RIXUBIS contains recombinant coagulation factor IX.

Recombinant coagulation factor IX is a single chain glycoprotein that is a member of the serine

protease family of vitamin K-dependent coagulation factors. Recombinant coagulation factor IX is a

recombinant DNA-based protein therapeutic which has structural and functional characteristics

comparable to endogenous factor IX. Factor IX is activated by factor VIIa/tissue factor complex in the

extrinsic pathway and by factor XIa in the intrinsic coagulation pathway. Activated factor IX, in

combination with activated factor VIII, activates factor X. This results ultimately in the conversion of

prothrombin to thrombin. Thrombin then converts fibrinogen into fibrin, and a clot can be formed.

Factor IX activity is absent or greatly reduced in patients with haemophilia B, and substitution therapy

may be required.

Haemophilia B is an X chromosome-linked recessive congenital disorder of blood coagulation due to

decreased levels or complete lack of factor IX and results in profuse bleeding into joints, muscles or

internal organs, either spontaneously or as a result of accidental or surgical trauma. Replacement

therapy increases the plasma level of factor IX, providing a temporary correction of the factor

deficiency and the bleeding tendency.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 9

Pharmacokinetic properties

Clinical trials

Prophylaxis and control of bleeding in PTPs ≥ 12 years of age

The efficacy of RIXUBIS has been evaluated in the open-label, uncontrolled part of a combined phase

1/3 study, in which a total of 73 male, previously treated patients (PTPs) between 12 and 59 years of

age received

RIXUBIS either for the prophylaxis and/or for the treatment of bleeding episodes on an on-

demand basis. PTPs were defined as subjects who were exposed to a factor IX-containing product on

≥ 150 days. All subjects had severe (factor IX level < 1%) or moderately severe (factor IX level

≤ 2%) haemophilia B. Subjects with a history of or a detectable FIX inhibitor ≥ 0.6 BU, a history with

severe allergic reactions following exposure to FIX, evidence of a severe chronic liver disease

(INR > 1.4), impaired renal function, a CD4 count < 200 cells/mm3 or any haemostatic effect other than

haemophilia B were excluded from participation. Fifty-nine (59) PTPs received

RIXUBIS for prophylaxis.

Fifty six (56) of these PTPs who received

RIXUBIS for a minimum of 3 months, were included in the

efficacy evaluation for prophylaxis (see Table 5). An additional 14 PTPs received

RIXUBIS for treatment

of bleeding episodes only. Subjects in the on-demand cohort had to have at least 12 documented

bleeding episodes requiring treatment within 12 months prior to enrolment. The mean treatment

duration in the on-demand cohort was 3.5 ± 1.00 months (median 3.4, ranging from 1.2 to 5.1 months),

the mean annualized bleeding rate (ABR) was 33.9 ± 17.37 ranging from 12.9 to 73.1.

Prophylaxis

The mean ABR on prophylaxis for all bleeds was 4.3, for spontaneous bleeds 1.7 and for joint bleeds

2.9, see the following table.

Efficacy of prophylaxis with RIXUBIS in 56 PTPs ≥ 12 years of age*

Treatment duration (months)

Mean ± SD

Median (range)

6.0 ± 0.65

6.0 (5.4 - 9.1)

Number of infusions per week*

Mean ± SD

Median (range)

1.8 ± 0.11

1.8 (1.5 - 1.9)

Dose per infusion (IU/kg)

Mean ± SD

Median (range)

49.4 ± 4.92

50.5 (40.0 - 62.8)

Total annualized bleeding rate (ABR)

Mean ± SD

Median (range)

4.3 ± 5.80

2.0 (0.0 - 23.4)

ABR for joint bleeds

Mean ± SD

Median (range)

2.9 ± 4.25

0.0 (0.0 - 21.5)

ABR for spontaneous bleeds

Mean ± SD

Median (range)

1.7 ± 3.26

0.0 (0.0 - 15.6)

Subjects with zero bleeds

% (n)

42.9% (24)

The prophylactic regimen consisted of 40 to 60 IU/kg RIXUBIS twice weekly.

The individual dose could be increased up to 75 IU/kg twice weekly.

Comparison with historical control

The mean total ABR of a historical control was compared with the mean total ABR resulting from

twice-weekly treatment with

RIXUBIS. The historical control is based on a meta-analysis of data from

12 studies published from 1976 to 2011 with a total of 276 haemophilia B patients (children and

adults) treated on-demand with various factor IX products for a mean duration of 19.6 months. The

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 10

mean total ABR was 20.0 (SD 39.4; 95% CI 15.3; 24.6, whereas the mean total ABR in the RIXUBIS

prophylactic cohort (based on data of an interim analysis with n = 56 with at least 3 months

treatment), was 4.20 ± 5.75 (95% CI 2.66; 5.74). The difference was statistically significant (p < 0.001)

with a reduction of total ABR by 79%.

Treatment of bleeding episodes

A total of 249 bleeding episodes were treated with RIXUBIS, of which 197 were joint bleeds and 52

non-joint bleeds (soft tissue, muscle, body cavity, intracranial and other). Of a total of 249 bleeding

episodes, 163 were moderate, 71 were minor, and 15 were major. Treatment was individualized

based on the severity, cause and site of bleed. Of the 249 bleeding episodes, the majority (211;

84.7%) were treated with 1 - 2 infusions.

Haemostatic efficacy at resolution of bleed was rated excellent or good in 95.4% of all treated

bleeding episodes. No bleeding episode had an efficacy rating of ‘none’.

Prophylaxis and control of bleeding in PTPs < 12 years of age

The efficacy of RIXUBIS has been evaluated in a combined phase 2/3 study, in which a total of 23 male

(PTPs) between 1.8 and 11.8 years (median age 7.10 years) with 11 patients < 6 years, received

RIXUBIS for prophylaxis and control of bleeding episodes. PTPs were defined as subjects who were

exposed to a factor IX-containing product on ≥ 150 days for subjects aged 6 to < 12 years, and on ≥ 50

days for subjects aged < 6 years. All subjects had severe (factor IX level < 1%) or moderately severe

(factor IX level ≤ 2%)

haemophilia B. Subjects with a history of or a detectable FIX inhibitor

0.6 BU, a

history of severe allergic reactions following exposure to FIX, evidence of severe chronic liver disease

(INR > 1.4), impaired renal function, a CD4 count < 200 cells/mm3 or any haemostatic effect other

than haemophilia

B were excluded from participation. All 23 subjects received prophylactic

treatment with

RIXUBIS for a minimum of 3 months and were included in the efficacy evaluation for

prophylaxis, see the following table.

Efficacy of prophylaxis of RIXUBIS in 23 PTPs < 12 years of age

Treatment duration (months)

Mean ± SD

Median (range)

5.98 ± 0.712

5.95 (3.3 - 7.7)

Number of infusions per week*

Mean ± SD

Median (range)

1.97 ± 0.082

1.97 (1.8 - 2.2)

Dose per infusion (IU/kg)*

Mean ± SD

Median (range)

56.25 ± 8.341

55.63 (43.0 - 75.5)

Total annualized bleeding rate (ABR)

Mean ± SD

Median (range)

2.7 ± 3.14

2.0 (0.0 - 10.8)

ABR for joint bleeds

Mean ± SD

Median (range)

0.8 ± 1.76

0.0 (0.0 - 7.2)

ABR for spontaneous bleeds

Mean ± SD

Median (range)

0.2 ± 0.66

0.0 (0.0 - 2.0)

Subjects with zero bleeds

% (n)

39.1.% (9)

Subjects with spontaneous bleeds or bleeds of unknown origin

% (n)

13.0% (3)

* The prophylactic regimen consisted of 40 to 80 IU/kg RIXUBIS twice weekly.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 11

Treatment of bleeding episodes in PTPs < 12 years of age

A total of 26 bleeding episodes were treated with RIXUBIS, of which 23 bleeds were due to injury, 2

spontaneous and 1 of unknown origin; 19 bleeds were non-joint (soft tissue, muscle, body cavity,

intracranial and other) and 7 were joint bleeds of which 1 was a bleed into a target joint. Of the 26

bleeding episodes, 15 were minor, 9 moderate, and 2 major. Treatment was individualized based on

the severity, cause and site of bleed. The majority (23; 88.5%) were treated with 1 – 2 infusions. The

actual breakdown was (15; 57.7%) received 1 infusion, (8; 30.8%) received 2 infusions, and (3; 11.5%)

were treated with 3 infusions.

Haemostatic efficacy at resolution of a bleed was rated excellent or good in 96.2% of all treated

bleeding episodes.

Perioperative management

The safety and efficacy in the perioperative setting was evaluated in an ongoing phase 3 prospective,

open-label, uncontrolled, multicentre study in male PTPs with severe and moderately severe

haemophilia B using

RIXUBIS. The per-protocol efficacy analysis includes 13 surgeries performed in 13

patients between 19 and 54 years of age undergoing major or minor surgical, dental or other surgical

invasive procedures. Ten (10) procedures were major including 6 orthopedic and 1 dental surgery.

Three procedures including 2 dental extractions, were considered minor.

Patients undergoing major surgeries had to perform a pharmacokinetic (PK) evaluation. All patients

were dosed based on their most recent individual incremental recovery. The recommended initial

loading dose of

RIXUBIS was to ensure that during surgery, factor IX activity levels of 80 - 100% for

major surgeries and 30 - 60% for minor surgeries was maintained.

RIXUBIS was administered by bolus infusions.

Haemostasis was maintained throughout the study duration.

The following table shows the types of surgical procedures and the results of the assessment of the

haemostatic response at various points in time.

Efficacy of RIXUBIS for surgical procedures in PTPs

Procedure

(# of patients/category)

Assessment of Response

Intra-

operative

At time of drain removal or on

post-operative day 3

At Time of

Discharge

Removal of intramedullary nail

(Major, n = 1)

Excellent

Good

Excellent

Joint Replacement

(Major, n = 4)

Excellent

Good (2)

Excellent (2)

Good (1)

Excellent (3)

Intra articular injection left ankle

(Minor, n = 1)

Excellent

Not applicable

Good

Open synovectomy left elbow

(Major, n = 1)

Excellent

Excellent

Excellent

Excision of neurofibroma right calf

(Major, n = 1)

Excellent

Excellent

Excellent

Hernioplastic

(Major, n = 2)

Excellent

Excellent

Good (1)

Excellent (1)

Tooth extraction

(Major, n = 1)

Excellent

Excellent

Excellent

Tooth extraction

(Minor, n = 2)

Excellent

Excellent

Excellent

Where no drain was employed, response was assessed on postoperative day 3.

Haemostatic response assessed by surgeon who performed procedure.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 12

Thrombogenicity

In all studies subjects were monitored for the presence of thrombosis. There was no clinical evidence

of thrombotic complications in any of the subjects.

Out-of-range values for thrombogenicity markers (Thrombin-antithrombin III [TAT], Prothrombin

fragment 1.2, and D-dimer), determined during the pharmacokinetic portion of the combined phase

1/3 pivotal study (see sections 5.1 and 5.2), did not reveal any pattern indicative of clinically relevant

thrombogenicity with either

RIXUBIS or the comparator, and were not associated with adverse

events.

Pharmacokinetics

Previously treated patients ≥ 12 years of age

A randomized, blinded, controlled, crossover pharmacokinetic study of RIXUBIS and a comparator was

conducted in non-bleeding male subjects (≥ 15 years of age) as part of the combined phase 1/3

pivotal study. The subjects received either of the products as a single IV infusion. The mean (± SD)

and median dose of

RIXUBIS in the per protocol analysis set (n = 25) were 74.69 ± 2.37 and 74.25

IU/kg, respectively, with a range of 71.27 to 79.38 IU/kg. The mean and median doses of the

comparator were 74.83 ± 2.51 and 74.92 IU/kg, respectively, with a range of 70.12 to 80 IU/kg. The

pharmacokinetic parameters were calculated from factor IX activity measurements in blood samples

obtained up to 72 hours following each infusion.

The pharmacokinetic evaluation was repeated for RIXUBIS in an open-label, uncontrolled study with

RIXUBIS in male subjects who participated in the initial PK crossover study and had received

prophylaxis with

RIXUBIS for 26 ± 1 weeks (mean ± SD) and accumulated at least 30 exposure days

(EDs) to

RIXUBIS. The RIXUBIS dose range in the repeat pharmacokinetics study was 64.48 to 79.18

IU/kg (n = 23).

Pharmacokinetic parameters for evaluable subjects (per-protocol analysis) are presented in the

following table.

Pharmacokinetic parameters for RIXUBIS and comparator (per-protocol analysis)

Parameter

RIXUBIS

Initial cross-over study

(N = 25)

Comparator

Initial cross-over study

(N = 25)

RIXUBIS

Repeat Evaluation

(N = 23)

0-72h

(IU·h/dL)

Mean ± SD

Median (range)

1067.81 ± 238.42

1108.35 (696.07 - 1571.16)

1007.88 ± 236.64

1024.66 (650.08 - 1545.69)

1156.15 ± 259.44

1170.26 (753.85 - 1626.81)

Incremental recovery

(IU/dL : IU/kg)

Mean ± SD

Median (range)

0.87 ± 0.22

0.88 (0.53 - 1.35)

0.76 ± 0.20

0.73 (0.44 - 1.27)

0.95 ± 0.25

0.93 (0.52 - 1.38)

Half-life (h)

Mean ± SD

Median (range)

26.70 ± 9.55

24.58 (15.83 - 52.34)

27.87 ± 9.22

26.28 (17.59 - 64.29)

25.36 ± 6.86

24.59 (16.24 - 42.20)

(IU/dL)

Mean ± SD

Median (range)

66.22 ± 15.80

68.10 (41.70 - 100.30)

58.24 ± 15.83

55.90 (33.60 - 95.80)

72.75 ± 19.73

72.40 (38.50 - 106.30)

Mean residence time (h)

Mean ± SD

Median (range)

30.82 ± 7.26

28.93 (22.25 - 47.78)

32.24 ± 7.16

30.59 (25.40 - 60.70)

29.88 ± 4.16

29.04 (21.32 - 37.52)

(dL/kg)

Mean ± SD

Median (range)

2.02 (0.77)

1.72 (1.10 - 3.94)

2.20 (0.69)

1.98 (1.19 - 3.92)

1.79 ± 0.45

1.74 (1.12 - 2.72)

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 13

Pharmacokinetic parameters for RIXUBIS and comparator (per-protocol analysis)

Parameter

RIXUBIS

Initial cross-over study

(N = 25)

Comparator

Initial cross-over study

(N = 25)

RIXUBIS

Repeat Evaluation

(N = 23)

Clearance (dL/h/kg)

Mean ± SD

Median (range)

0.0644 ± 0.0133

0.0622 (0.0426 - 0.0912)

0.0681 ± 0.0153

0.0655 (0.0438 - 0.1001)

0.0602 ± 0.0146

0.0576 (0.0413 - 0.0945)

Area under the plasma factor IX concentration x time curve from 0 to 72 hours post-infusion.

Calculated as (C

– baseline factor IX) divided by the dose in IU/kg, where C

is the maximal post-infusion

factor IX measurement.

Volume of distribution at steady state.

The 90% confidence intervals for the AUC

0 - 72h

/dose and AUC

0 - 72h

were within the margins of

equivalence defined as 80% to 125%.

Incremental recovery 30 minutes after infusion was determined for all subjects in the combined

phase 1/3 study at exposure day 1, at their week 5, 13, and 26 visits, and at the time of study

completion or termination, if it did not coincide with the week 26 visit. The data demonstrate that

the incremental recovery is consistent over time. Please see the following table.

Incremental recovery for RIXUBIS 30 minutes after infusion

Incremental

recovery 30min

after infusion

Exposure

Day 1

(N = 73)

Week 5

(N = 71)

Week 13

(N = 68)

Week 26

(N = 55)

At study

completion/

termination

(N = 23)

(IU/dL ÷ IU/kg)

Mean ± SD

Median (range)

0.79 ± 0.20

0.78 (0.26 - 1.35)

0.83 ± 0.21

0.79 (0.46 - 1.48)

0.85 ± 0.25

0.83 (0.14 - 1.47)

0.89 ± 0.12

0.88 (0.52 - 1.29)

0.87 ± 0.20

0.89 (0.52 - 1.32)

Calculated as (C

30min

-baseline factor IX) divided by the dose in IU/kg, where C

30min

is the factor IX measurement

30 minutes after infusion.

If not coinciding with week 26 visit.

Previously treated patients < 12 years of age

All 23 male subjects underwent an initial pharmacokinetic evaluation of RIXUBIS in a non-bleeding

state as part of the combined phase 2/3 paediatric study. Subjects were randomized to one of two

blood sampling sequences to reduce the burden of frequent blood draws on the individual subjects.

The mean (

SD) and median dose of

RIXUBIS in the full analysis set (n = 23) was 75.50 ± 3.016 and

75.25 IU/kg, respectively, with a range of 70.0 to 83.6 IU/kg. The pharmacokinetic parameters were

calculated from factor IX activity measurements in blood samples obtained up to 72 hours following

the infusion.

Pharmacokinetic parameters for all subjects (full analysis set) are presented in the following table.

Pharmacokinetic parameters for paediatric PTPs < 12 years of age (full analysis set)

Parameter

< 6 years

(N = 11)

6 - < 12 years

(N = 12)

(N = 23)

0-72h

(IU·h/dL)

Mean ± SD

Median (range)

723.7 ± 119.00

717.2 (488 - 947)

886.0 ± 133.66

863.7 (730 - 1138)

808.4 ± 149.14

802.9 (488 - 1138)

Half-life (h)

Mean ± SD

Median (range)

27.67 ± 2.66

27.28 (24.0 - 32.2)

23.15 ± 1.58

22.65 (21.8 - 27.4)

25.31 ± 3.13

24.48 (21.8 - 32.2)

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 14

Pharmacokinetic parameters for paediatric PTPs < 12 years of age (full analysis set)

Parameter

< 6 years

(N = 11)

6 - < 12 years

(N = 12)

(N = 23)

Mean residence time (h)

Mean ± SD

Median (range)

30.62 ± 3.27

30.08 (26.2 - 36.2)

25.31 ± 1.83

24.74 (23.7 - 30.3)

27.85 ± 3.73

26.77 (23.7 - 36.2)

V

SS

b

(dL/kg)

Mean ± SD

Median (range)

3.22 ± 0.52

3.16 (2.65 - 4.42)

2.21 ± 0.32

2.185 (1.70 - 2.70)

2.7 ± 0.67

2.69 (1.70 - 4.42)

Clearance (dL/[kg·h])

Mean ± SD

Median (range)

0.1058 ± 0.01650

0.1050 (0.081 - 0.144)

0.0874 ± 0.01213

0.0863 (0.069 – 0.108)

0.0962 ± 0.01689

0.0935 (0.069 - 0.144)

Area under the plasma concentration-time curve from time 0 to infinity.

Volume of distribution at steady state

Incremental recovery 30 minutes after infusion was determined for all subjects in the combined

phase 2/3 study at the initial pharmacokinetic evaluation (exposure day 1), at week 5, 13, and 26

visits, and at the time of study completion or termination, if it did not coincide with the week 26 visit.

The data demonstrate that the incremental recovery is consistent over time across all paediatric age

groups. Please see the following 3 tables.

Incremental recovery for RIXUBIS 30 minutes after infusion both paediatric age groups

Incremental recovery

30 min after infusion

PK (Exposure Day

1) All (N = 22)

Week 5 All

(N = 23)

Week 13 All

(N = 21)

Week 26 All

(N = 21)

(IU/dL÷IU/kg)

Mean ± SD

Median (range)

0.67 ± 0.16

0.69 (0.31 - 1.00)

0.68 ± 0.12

0.66 (0.48 - 0.92)

0.71 ± 0.13

0.66 (0.51 - 1.00)

0.72 ± 0.15

0.734 (0.51 - 1.01)

Calculated as (C

30min

–baseline factor IX) divided by the dose in IU/kg, where C

30min

is the factor IX

measurement 30 minutes after infusion.

Incremental recovery for RIXUBIS 30 min after infusion paediatric patients < 6 years of age

Incremental recovery

30 min after infusion

PK (ED 1)

(N = 10)

Week 5

(N = 11)

Week 13

(N = 10)

Week 26

(N = 10)

(IU/dL÷IU/kg)

Mean ± SD

Median (range)

0.59 ± 0.13

0.59 (0.31 - 0.75)

0.63 ± 0.10

0.6 (0.49 - 0.80)

0.68 ± 0.12

0.66 (0.51 - 0.84)

0.65 ± 0.13

0.61 (0.51 - 0.84)

Calculated as (C

30min

–baseline factor IX) divided by the dose in IU/kg, where C

30min

is the factor IX

measurement 30 minutes after infusion.

Incremental recovery for RIXUBIS 30 minutes after infusion paediatric patients 6 to < 12 years of age

Incremental recovery

30 min after infusion

PK (ED 1)

(N = 12)

Week 5

(N = 12)

Week 13

(N = 11)

Week 26

(N = 11)

(IU/dL÷IU/kg)

Mean ± SD

Median (range)

0.73 ± 0.16

0.71 (0.51 - 1.00)

0.73 ± 0.13

0.70 (0.48 - 0.92)

0.73 ± 0.14

0.70 (0.54 - 1.00)

0.8 ± 0.14

0.78 (0.56 - 1.01)

Calculated as (C

30min

–baseline factor IX) divided by the dose in IU/kg, where C

30min

is the factor IX

measurement 30 minutes after infusion.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 15

Preclinical safety data

Genotoxicity and carcinogenicity

Studies on carcinogenesis and mutagenesis of RIXUBIS, Coagulation factor IX (Recombinant), were not

conducted, since no risk is anticipated for biotechnology-derived pharmaceuticals such as Coagulation

factor IX (Recombinant).

6 PHARMACEUTICAL PARTICULARS

List of excipients

Histidine

Sodium chloride

Sodium chloride dihydrate

Mannitol

Sucrose

Polysorbate 80

The amounts of the inactive ingredients are constant in all strengths.

Incompatibilities

RIXUBIS must not be mixed with other medicinal products.

Shelf life

Prior to reconstitution: 3 years.

Following reconstitution: 3 hours.

Special precautions for storage

Store at or below 30°C. Do not freeze.

Do not use beyond the expiration date printed on the label or carton.

For storage conditions after reconstitution see section 6.3.

Nature and contents of container

RIXUBIS is a white or almost white lyophilised powder which is supplied in a single-dose Type I glass vial:

250 IU (50 IU/mL), 500 IU (100 IU/mL), 1000 IU (200 IU/mL), 2000 IU (400 IU/mL) or 3000 IU (600 IU/mL).

The vial is closed with a butyl rubber stopper. The components of this product are latex-free.

Each kit also contains 5 mL of water for injections in a Type I glass vial and BAXJECT II Transfer device.

Not all pack sizes may be marketed.

Special precautions for disposal

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

7 MEDICINE SCHEDULE

General Sale Medicine.

NEW ZEALAND DATA SHEET

RIXUBIS Data Sheet V0.1 CCDS22820150519

Page 16

8 SPONSOR

RIXUBIS is distributed in New Zealand by:

Takeda New Zealand Limited

Level 10, 21 Queen Street

Auckland 1010

New Zealand

Telephone: 0508 169 077

www.takeda.com/en-au

9 DATE OF FIRST APPROVAL

Date of publication in the New Zealand Gazette of consent to distribute the medicine:

11 June 2015.

10 DATE OF REVISION OF THE TEXT

16 December 2020

SUMMARY TABLE OF CHANGES

Section changed

Summary of new information

Change of Sponsor details

Please refer to the Medsafe website (www.medsafe.govt.nz) for most recent data sheet.

RIXUBIS® and BAXJECT® are registered trademarks of Baxalta Incorporated.

TAKEDA® and the TAKEDA Logo® are registered trademarks of Takeda Pharmaceutical Company

Limited.

Similar products

Search alerts related to this product

View documents history

Share this information