Alprolix

New Zealand - English - Medsafe (Medicines Safety Authority)

Active ingredient:
Eftrenonacog alfa 500 IU
Available from:
sanofi-aventis new zealand limited
INN (International Name):
Eftrenonacog alfa 500 IU
Dosage:
500 IU
Pharmaceutical form:
Powder for infusion
Composition:
Active: Eftrenonacog alfa 500 IU Excipient: Histidine Mannitol Polysorbate 20 Sucrose Sodium chloride Water for injection
Prescription type:
General sale
Manufactured by:
Biogen Inc
Therapeutic indications:
ALPROLIX is a long-acting anti-haemophilic factor (recombinant) indicated in adults and children with haemophilia B (congenital factor IX deficiency) for: - Control and prevention of bleeding episodes - Routine prophylaxis to prevent or reduce the frequency of bleeding episodes - Perioperative management (surgical prophylaxis)
Product summary:
Package - Contents - Shelf Life: Combination pack, vial + syringe + plunger rod + vial adaptor, with or without ancillary pack (infusion set etc) - 1 dose units - 48 months from date of manufacture stored at 2° to 8°C (Refrigerate, do not freeze) protect from light 6 months from date of manufacture stored at or below 30°C protect from light 6 hours reconstituted stored at or below 30°C - Syringe, glass, Diluent - 1 dose units -   - Vial, glass, single dose, Active, Type 1 glass with teflon coated butyl rubber stopper - 1 dose units -  
Authorization number:
TT50-9657a
Authorization date:
2014-11-10

Read the complete document

alp-ccdsv12-cmiv4-d1--jan2018

ALPROLIX

®

Eftrenonacog alfa (recombinant coagulation factor IX fusion protein) 250, 500, 1000, 2000, 3000 IU/vial

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common

questions about ALPROLIX. It does

not contain all the available

information. It does not use the place

of talking to your doctor or

pharmacist.

This leaflet was last updated on the

date at the end of this leaflet.

Speak to your pharmacist or

doctor to obtain the most up to

date information on this medicine.

All medicines have risks and

benefits. Your doctor has weighed

the risks of you taking ALPROLIX

against the benefits they expect it

will have for you.

If you have any concerns about

taking this medicine, ask your

doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What ALPROLIX is

used for

ALPROLIX is used for the

management of haemophilia B

(congenital factor IX deficiency).

ALPROLIX is used to:

control and prevent bleeding

episodes

routinely prevent and reduce the

frequency of bleeding episodes

reduce bleeding before, during,

and after surgery.

People with haemophilia B lack

sufficient factor IX to control

bleeding. ALPROLIX works by

replacing factor IX to enable blood to

clot.

Ask your doctor if you have any

questions about why this medicine

has been prescribed for you.

Your doctor may have prescribed it

for another reason.

This medicine is not addictive.

It is available only with a doctor's

prescription.

Do not give this medicine to anyone

else.

It may harm them, even if their

symptoms are the same as yours.

Before you use

ALPROLIX

When you must not use it

Do not use ALPROLIX if you have

an allergy to:

ALPROLIX or other factor IX

replacement factors

any of the ingredients listed at the

end of this leaflet.

Some of the symptoms of an allergic

reaction may include:

shortness of breath

wheezing or difficulty breathing

swelling of the face, lips, tongue

or other parts of the body

rash, itching or hives on the skin.

If any of these signs occur, stop

using ALPROLIX and see your

doctor immediately.

Do not use this medicine after the

expiry date printed on the pack or

if the packaging is torn or shows

signs of tampering.

If it has expired or is damaged, return

it to your pharmacist for disposal.

Do not use ALPROLIX if the

medicine is cloudy, contains

particles or is discoloured.

It should be clear to slightly

opalescent and colourless.

If you are not sure whether you

should start taking this medicine,

talk to your doctor.

Before you start to use it

Tell your doctor if you have

allergies to any other medicines,

foods, preservatives or dyes.

Tell your doctor if you are

pregnant or intend to become

pregnant.

There is no information on the use of

ALPROLIX during pregnancy. Your

doctor will discuss the risks and

benefits of taking it if you are

pregnant.

Tell your doctor if you are breast-

feeding or planning to breast-feed.

It is not known whether ALPROLIX

passes into breast milk. Your doctor

will discuss the risks and benefits of

taking it if you are breast-feeding.

If you have not told your doctor

about any of the above, tell them

before you start using ALPROLIX.

Taking other medicines

Tell your doctor or pharmacist if

you are taking any other

medicines, including any that you

get without a prescription from

your pharmacy, supermarket or

health food shop.

alp-ccdsv12-cmiv4-d1--jan2018

Your doctor and pharmacist have

more information on medicines to be

careful with or avoid while taking

this medicine.

How to use ALPROLIX

Follow all directions given to you

by your doctor or pharmacist

carefully.

They may differ from the

information contained in this leaflet.

If you do not understand the

instructions on the box, ask your

doctor or pharmacist for help.

How much to use

Your doctor will decide how much

ALPROLIX you use. This will

depend on your individual need for

replacement factor IX therapy. Your

doctor may change the dose you use

during your treatment.

Do not stop using ALPROLIX or

change the dosage, without

checking with your doctor unless

you have an allergic reaction.

How to use it

ALPROLIX is given by slow

injection directly into your veins.

ALPROLIX is provided as a powder

and sterile sodium chloride solution

0.325% (diluent) which need to be

mixed together before use.

It is important to not shake

ALPROLIX when mixing it.

Shaking can damage this medicine.

Mix the ALPROLIX powder with

the diluent provided only when you

are ready to use it.

If you mix the powder and diluent

and are interrupted, you can keep the

mixed product for a maximum of 6

hours when stored at room

temperature (below 30°C).

Do not put it in the freezer.

Always inspect ALPROLIX before

use and after it has been mixed.

The medicine should be clear to

slightly opalescent and colourless.

Do not inject if the solution is

discoloured or cloudy or contains

particles.

Refer to the leaflet in the pack for

step-by-step instructions about

how to prepare and inject

ALPROLIX.

Use in one patient on one occasion

only. Dispose of all unused

solution, empty vials, and used

needles and syringes into a sharps

bin.

Talk to your doctor or pharmacist,

or telephone 1800 852 289 in

Australia or 0800 852 289 in NZ, if

you have any questions about how

to use ALPROLIX.

How long to use it

Continue taking your medicine for

as long as your doctor tells you.

This medicine helps to control your

condition, but does not cure it.

If you forget to use it

Use your dose of ALPROLIX as

soon as you remember, and resume

your normal dosing schedule.

Do not use a double dose to make

up for the dose that you missed.

This may increase the chance of you

getting an unwanted side effect.

If you are not sure what to do, ask

your doctor or pharmacist.

If you have trouble remembering

to use your medicine, ask your

pharmacist for some hints.

If you use too much

(overdose)

Immediately telephone your doctor

or the Poisons Information Centre

(in Australia telephone 13 11 26, in

New Zealand telephone 0800 764

766) for advice, or go to

Emergency at the nearest hospital,

if you think that you or anyone else

may have used too much

ALPROLIX. Do this even if there

are no signs of discomfort or

poisoning.

You may need urgent medical

attention.

While you are using

ALPROLIX

Things you must do

Tell your doctor immediately if

bleeding is not controlled after

using ALPROLIX.

If you become pregnant while on

treatment with ALRPOLIX,

immediately tell your doctor.

Always talk to your doctor or

pharmacist before taking any other

medicine while you are using

ALPROLIX.

Do not use more than the

recommended dose.

Tell any other doctors, dentists and

pharmacists who treat you that

you are using this medicine.

If you are about to have any blood

tests, tell your doctor that you are

using ALPROLIX.

Keep all of your doctor's

appointments so that your progress

can be checked.

Your doctor may do some blood tests

before you start your treatment and

from time to time during your

treatment to monitor your progress.

Things you must not do

Do not use ALPROLIX to treat

any other complaints unless your

doctor tells you to.

Do not give your medicine to

anyone else, even if they appear to

have the same condition as you.

Do not stop using your medicine or

change the dosage without

checking with your doctor.

alp-ccdsv12-cmiv4-d1--jan2018

Side effects

Tell your doctor or pharmacist as

soon as possible if you do not feel

well while you are taking

ALPROLIX.

All medicines can have side effects.

Sometimes they are serious, most of

the time they are not. You may need

medical attention if you get some of

the side effects.

Do not be alarmed by the following

lists of side effects. You may not

experience any of them.

Ask your doctor or pharmacist to

answer any questions you may

have.

Tell your doctor or pharmacist if

you notice any of the following and

they worry you:

headache

tingling or numbness in your

mouth (paraesthesia)

breath odour

fatigue

dizziness

taste disturbance or loss of taste

(dysguesia)

pain at site of infusion

low blood pressure (symptoms

include dizziness or feeling

lightheaded)

fast or irregular heartbeats, also

called palpitations

pain in your side with blood in

your urine (obstructive uropathy).

The above list includes the more

common side effects of your

medicine. If any of these persist or

worsen, talk to your doctor.

If any of the following happen, tell

your doctor immediately or go to

Emergency at your nearest

hospital:

swelling of your face, lips, tongue

or other parts of the body, rash or

hives

shortness of breath, wheezing,

difficulty breathing, chest pain or

discomfort.

The above list includes very serious

side effects. You may need urgent

medical attention or hospitalisation.

These side effects are very rare.

ALPROLIX may increase the risk of

formation of abnormal blood clots in

your body if you have risk factors for

developing blood clots.

Your body can make antibodies

called “inhibitors” against

ALPROLIX, which may stop

ALPROLIX from working properly

Tell your doctor or pharmacist if

you notice anything that is making

you feel unwell.

After using ALPROLIX

Storage

Keep your ALPROLIX in the pack

until it is time to use it.

This medicine should be protected

from light.

Keep ALPROLIX in the

refrigerator at 2°C to 8°C.

If necessary, you can keep

ALPROLIX out of the refrigerator

for a single 6 month period. If out of

the refrigerator, store the sealed

carton in a cool dry place where the

temperature stays below 30°C. The

date that the product is removed from

the refrigerator should be recorded

on the carton.

Do not use any ALPROLIX that

has been out of the refrigerator for

more than 6 months (refer to

Disposal below).

Once reconstituted, you can keep

ALPROLIX at room temperature

(below 30°C) for up to 6 hours.

Protect the product from direct

sunlight.

Do not store ALPROLIX or any

other medicine in the bathroom or

near a sink. Do not leave it on a

window sill or in the car.

Heat and dampness can destroy some

medicines.

Do not freeze ALPROLIX.

Do not place in the freezer or

freezing compartment of a

refrigerator.

Keep it where children cannot

reach it.

A locked cupboard at least one-and-

a-half metres above the ground is a

good place to store medicines.

Disposal

If your doctor tells you to stop

using this medicine or the expiry

date has passed, ask your

pharmacist what to do with any

medicine that is left over.

Product description

What it looks like

ALPROLIX comes as a white to off-

white powder to cake in a glass vial.

Each pack contains:

1 vial of sterile ALPROLIX

powder

1 pre-filled syringe of diluent

1 sterile vial adapter

reconstitution device.

ALPROLIX is available in 5

strengths: 250 IU, 500 IU, 1000 IU,

2000 IU and 3000IU.

Ingredients

ALPROLIX contains eftrenonacog

alfa as the active ingredient.

Other ingredients:

sucrose

sodium chloride

histidine

mannitol

polysorbate 20.

Further information

You can obtain more information

from your doctor, pharmacist or

your Haemophilia Treatment

Centre, or by telephoning 1800 207

753 in Australia or 0800 852 289 in

New Zealand.

alp-ccdsv12-cmiv4-d1--jan2018

Sponsor

ALPROLIX is supplied in Australia

sanofi-aventis pty ltd

12-24 Talavera Road

Macquarie Park NSW 2113

Freecall No: 1800 818 806

Email:

medinfo.australia@sanofi.com

ALPROLIX is supplied in New

Zealand by:

Sanofi-aventis New Zealand limited

Level 8, 56 Cawley Street

Ellerslie, Auckland

New Zealand Free Call: 0800 283

Email:

medinfo.australia@sanofi.com

This leaflet was prepared in February

2019.

ALPROLIX 250 IU - AUST R

209227

ALPROLIX 500 IU - AUST R

209223

ALPROLIX 1000 IU - AUST R

209224

ALPROLIX 2000 IU - AUST R

209225

ALPROLIX 3000 IU - AUST R

209226

ALPROLIX® is a registered

trademark of Bioverativ Therapeutics

Inc.

Read the complete document

01-alp-ccdsv13-piv6-29jul21

Page 1 of 27

NEW ZEALAND DATA SHEET

1 ALPROLIX (POWDER FOR INFUSION)

ALPROLIX 250 International Units (IU), Powder for infusion

ALPROLIX 500 IU, Powder for infusion

ALPROLIX 1000 IU, Powder for infusion

ALPROLIX, 2000 IU, Powder for infusion

ALPROLIX, 3000 IU, Powder for infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Alprolix 250 IU: Each single-use vial contains nominally 250 IU of eftrenonacog alfa

(rhu). After reconstitution, each mL of solution for injection contains 50 IU of

eftrenonacog alfa (rhu

Alprolix 500 IU: Each single-use vial contains nominally 500 IU of eftrenonacog alfa

(rhu). After reconstitution, each mL of solution for injection contains 100 IU of

eftrenonacog alfa (rhu

Alprolix 1000 IU: Each single-use vial contains nominally 1000 IU of eftrenonacog alfa

(rhu). After reconstitution, each mL of solution for injection contains 200 IU of

eftrenonacog alfa (rhu

Alprolix 2000 IU: Each single-use vial contains nominally 2000 IU of eftrenonacog alfa

(rhu). After reconstitution, each mL of solution for injection contains 400 IU of

eftrenonacog alfa (rhu

Alprolix 3000 IU: Each single-use vial contains nominally 3000 IU of eftrenonacog alfa

(rhu). After reconstitution, each mL of solution for injection contains 600 IU of

eftrenonacog alfa (rhu

Excipient with known effect: 0.3 mmol (6.4 mg) sodium per vial.

For the full list of excipients, see Section 6.1 LIST OF EXCIPIENTS.

3 PHARMACEUTICAL FORM

Powder for infusion

ALPROLIX is formulated as a sterile, preservative-free, non-pyrogenic, lyophilised,

white to off-white powder to cake, for intravenous (IV) administration in a single-use

vial. The liquid diluent is in a pre-filled syringe.

rhu: Produced in human embryonic kidney (HEK) 293H cells by recombinant DNA technology.

01-alp-ccdsv13-piv6-29jul21

Page 2 of 27

4 CLINICAL PARTICULARS

4.1

Therapeutic Indications

ALPROLIX is a long-acting anti-haemophilic factor (recombinant) indicated in adults

and children with haemophilia B (congenital factor IX deficiency) for:

Control and prevention of bleeding episodes

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes

Perioperative management (surgical prophylaxis)

4.2

Dose and Method of Administration

For Intravenous Use Only After Reconstitution.

Treatment should be initiated and supervised by qualified healthcare professionals

experienced in the diagnosis and treatment of haemophilia B. The ability of a patient

to self-inject intravenously should be assessed.

Each vial of ALPROLIX has the recombinant FIX potency in International Units stated

on the label.

Careful control of replacement therapy is especially important in cases of life-

threatening bleeding episodes or major surgery (see Table 1 and Table 2).

Although dosing can be estimated by the guidelines below, it is recommended that

standard routine laboratory tests such as factor IX activity assays be performed (see

Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE and Section 5.2

PHARMACOKINETIC PROPERTIES).

Method of Calculating Initial Estimated Dose

1 IU of ALPROLIX per kg body weight is expected to increase the circulating level of

factor IX by approximately 1% [IU/dL] in patients 12 years of age or older.

ALPROLIX has been shown to have a prolonged circulating half-life. In patients 12

years of age or older, no dose adjustment for recovery is generally required. In

paediatric patients less than 12 years of age, recovery may be lower and dose should

be adjusted accordingly (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS

FOR USE - Paediatric use). Since patients may vary in their pharmacokinetic (e.g.,

half-life, in vivo recovery) and clinical responses to ALPROLIX, the expected in vivo

peak increase in factor IX level expressed as IU/dL (or % of normal) or the required

dose can be estimated using the following formulae:

IU/dL (or % of normal) = [Total Dose (IU)/body weight (kg)] x recovery (IU/dL per IU/kg)

Dose (IU) = body weight (kg) x Desired Factor IX Rise (IU/dL or % of normal) x

reciprocal of recovery (IU/kg per IU/dL)

Control and Prevention of Bleeding Episodes

Table 1 can be used to guide dosing in bleeding episodes:

01-alp-ccdsv13-piv6-29jul21

Page 3 of 27

Table 1: Guide to ALPROLIX Dosing for Treatment of Bleeding

Severity of Bleed

Factor IX Level Required

(IU/dL or % of normal)

Dose (IU/kg)/

Frequency of Doses

(hrs)

Minor and Moderate

For example: joint, superficial muscle/no

neurovascular

compromise

(except

iliopsoas), superficial soft tissue, mucous

membranes

30-60

30-60 IU/kg

Repeat every 48 hours if

there is further evidence of

bleeding

Major

For example: iliopsoas and deep muscle

with neurovascular injury, or substantial

blood loss, retroperitoneum, CNS

80-100

100 IU/kg

For repeat dosing, follow

guidelines for major

surgery

(see Table 2)

Adapted from: Roberts and Eberst, WFH 2008, and WFH 2012

Subsequent dosage and duration of treatment depends on the individual clinical

response, pharmacokinetic profile, the severity of the factor IX deficiency, and the

location and extent of bleeding.

Higher doses or more frequent dosing may be needed in patients less than 12 years

of age.

Perioperative Management

Table 2 can be used to guide dosing for perioperative management (surgical

prophylaxis):

Table 2: Guide to ALPROLIX Dosing for Perioperative Management (Surgical Prophylaxis)

Type of Surgery

Initial Factor IX

Level Required

(IU/dL or % of normal)

Dose (IU/kg)/

Frequency of Doses (hrs)

Minor

Minor

operations

including

uncomplicated dental extraction

50 to 80

50-80 IU/kg

single

infusion

sufficient. Repeat as needed

after 24-48 hours.

Major

60 to 100 (initial level)

Days 1-3: maintain level 40-60%

Days 4-6: maintain level 30-50%

Days 7-14: maintain level 20-

40%

100 IU/kg (initial dose)

A repeat dose at 80 IU/kg

should be considered after

6-10 hours and then every

24 hours for the first 3 days.

Based on the long half-life of

ALPROLIX, the dose may

be reduced and frequency of

dosing in the post-surgical

setting

extended

after

every

hours.

Adapted from: Roberts and Eberst, WFH 2008, and WFH 2012

01-alp-ccdsv13-piv6-29jul21

Page 4 of 27

Higher doses or more frequent dosing may be needed in patients less than 12 years

of age.

Routine Prophylaxis

The recommended starting regimens are either:

50 IU/kg once weekly or 100 IU/kg once every 10 days.

Either regimen may be adjusted based on patient

response

(see Section 5.2

PHARMACOKINETIC PROPERTIES).

Effect of Food

There is no known effect of food on exposure of ALPROLIX. Therefore, ALPROLIX

may be taken with or without food.

4.3

Contraindications

ALPROLIX is contraindicated in patients who have manifested severe hypersensitivity

reactions, including anaphylaxis, to the product or its components (excipients listed in

Section 6.1 LIST OF EXCIPIENTS).

4.4

Special Warnings and Precautions for Use

The clinical response to ALPROLIX may vary. If bleeding is not controlled with the

recommended dose, the plasma level of factor IX should be determined, and a

sufficient dose of ALPROLIX should be administered to achieve a satisfactory clinical

response. If the patient’s plasma factor IX level fails to increase as expected or if

bleeding is not controlled after ALPROLIX administration, the presence of an inhibitor

(neutralising antibodies) should be suspected, and appropriate testing performed (see

Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE - Monitoring

Laboratory Tests).

Anaphylaxis and Hypersensitivity Reactions

Allergic type hypersensitivity reactions, including anaphylaxis, are possible with factor

replacement therapies, and have been reported with ALPROLIX. The presence of

inhibitors has been associated with allergic reactions with factor IX replacement

therapies, including with ALPROLIX. Advise patients to discontinue use of ALPROLIX

if hypersensitivity symptoms occur and contact a physician and/or seek immediate

emergency care.

Thromboembolic Complications

Thrombotic events with other factor IX products have been reported including in

patients receiving continuous-infusion through a central venous catheter. The safety

and efficacy of ALPROLIX administration by continuous infusion have not been

established (see Section 4.2 DOSE AND METHOD OF ADMINISTRATION).

Neutralising Antibodies (Inhibitors)

Inhibitors have been reported with factor replacement therapy in the treatment of

haemophilia B. Patients using ALPROLIX should be monitored for the development of

factor IX inhibitors by appropriate clinical observations and laboratory tests. Inhibitors

01-alp-ccdsv13-piv6-29jul21

Page 5 of 27

have been reported with ALPROLIX in the treatment of haemophilia B, including

previously untreated patients. If the patient’s plasma factor IX level fails to increase as

expected or if bleeding is not controlled after ALPROLIX administration, the presence

of an inhibitor (neutralising antibodies) should be suspected, and appropriate testing

performed (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE -

Monitoring Laboratory Tests).

Patients with factor IX inhibitors may be at an increased risk of anaphylaxis upon

subsequent challenge with factor IX. Patients experiencing allergic reactions should

be evaluated for the presence of an inhibitor. Patients should be observed closely for

signs and symptoms of acute hypersensitivity reactions, particularly during the early

phases of exposure to product.

Monitoring Laboratory Tests

Monitor plasma factor IX activity levels by performing the one-stage clotting assay to

confirm adequate factor IX levels have been achieved and maintained, when clinically

indicated (see Section 4.2 DOSE AND METHOD OF ADMINISTRATION). Factor IX

results can be affected by the type of aPTT reagent used. Measurement with a one-

stage clotting assay utilising a kaolin-based aPTT reagent will likely result in an

underestimation of activity level.

Monitor for the development of factor IX inhibitors. If bleeding is not controlled with

ALPROLIX and the expected factor IX activity plasma levels are not attained, perform

an assay to determine if factor IX inhibitors are present (use Bethesda Units to titer

inhibitors).

Nephrotic Syndrome

Nephrotic syndrome has been reported following immune tolerance induction with

factor IX products in haemophilia B patients with factor IX inhibitors and a history of

allergic reactions to factor IX. The safety and efficacy of using ALPROLIX for immune

tolerance induction have not been established.

Use in the Elderly

Clinical studies of ALPROLIX did not include sufficient numbers of subjects aged 65

and over to determine whether they respond differently from younger subjects. Dose

selection for an elderly patient should be individualised (see Section 4.2 DOSE AND

METHOD OF ADMINISTRATION).

Paediatric Use

Safety,

efficacy,

pharmacokinetics

ALPROLIX

have

been

evaluated

previously treated paediatric patients ages 12 to less than 18 years of age from Study

1 and under 12 years of age from Study 2. No dose adjustment is required for 12 to

less than 18 years of age (see Section 5.2 PHARMACOKINETIC PROPERTIES and

Section 5.1 PHARMACODYNAMIC PROPERTIES – Clinical Efficacy and Safety). In

comparison with adolescents and adults, children less than 12 years of age may have

a lower recovery and higher body-weight normalised factor IX clearance. These

differences should be taken into account when dosing. Higher doses or more frequent

dosing may be needed in patients less than 12 years of age (see Section 5.2

PHARMACOKINETIC PROPERTIES – Paediatric pharmacokinetics).

01-alp-ccdsv13-piv6-29jul21

Page 6 of 27

Use in patients with renal impairment

ALPROLIX has not been studied in patients with renal impairment.

Use in patients with hepatic impairment

Specific studies of ALPROLIX in patients with hepatic impairment have not been

performed.

Effect on Laboratory Tests

ALPROLIX temporarily corrects partial thromboplastin time (PTT) in patients with

haemophilia B. No effect on normal prothrombin time was seen. There was no trend

observed in coagulation activation parameters, including prothrombin fragment 1+ 2,

D-dimer, and thrombin-antithrombin complex (TAT).

4.5

Interaction with Other Medicines and Other Forms of Interaction

There are no known drug interactions reported with ALPROLIX. No drug interaction

studies have been performed.

4.6

Fertility, Pregnancy and Lactation

Pregnancy

Category C

Animal reproductive studies have not been conducted with ALPROLIX. ALPROLIX

has been shown to cross the placenta in small amounts in a placental transfer study

in mice. Based on the rare occurrence of haemophilia B in women, experience

regarding the use of factor IX during pregnancy and breastfeeding is not available. It

is not known whether ALPROLIX can affect reproductive capacity. Fc fusion products,

including eftrenonacog alfa, may pass through the placenta. The effects on the

developing foetus are unknown.

ALPROLIX should be used during pregnancy only if the potential benefit justifies the

potential risk.

Breast-feeding

Lactation studies have not been conducted with ALPROLIX. It is not known whether

ALPROLIX is excreted into human milk. Caution should be exercised if ALPROLIX is

administered to nursing mothers. ALPROLIX should be used only if clinically indicated.

Fertility

No fertility studies have been conducted in animals with ALPROLIX. ALPROLIX has

not been evaluated in animal reproductive studies.

4.7

Effects on Ability to Drive and Use Machines

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

performed.

4.8

Undesirable Effects

The most common adverse reactions with an incidence ≥1% for ALPROLIX were

headache, oral paraesthesia, and obstructive uropathy.

01-alp-ccdsv13-piv6-29jul21

Page 7 of 27

ALPROLIX has been evaluated in three completed studies (Study 1, Study 2 and

Study 3) which were conducted in previously treated patients (PTPs) with severe

haemophilia B (≤ 2% endogenous FIX activity). A total of 153 subjects have been

treated. Thirty (30) (19.6%) were paediatric subjects <12 years of age, 11 (7.2%) were

adolescents (12 to <18 years of age), and 112 (73.2%) were adults (18 years of age

and older). There were 126 subjects (82.4%) treated for at least 52 weeks,107

subjects (69.9%) for at least 104 weeks. The total number of exposure days (EDs)

was 26,106 with a median of 165 (range 1-528) EDs per subject. Adverse events were

monitored for a total of 561 subject-years.

Adverse drug reactions (ADRs) were reported in 14 of 153 (9.2%) subjects treated

with ALPROLIX. Adverse drug reactions are considered adverse events assessed by

the investigator as related or possibly related to treatment with ALPROLIX. Adverse

drug reactions are summarised in Table 3. No subject was withdrawn from study due

to an adverse drug reaction. In the studies, no inhibitors were detected and no events

of anaphylaxis were reported.

Table 3: Adverse Drug Reactions reported for ALPROLIX

MedDRA

System Organ

Class

MedDRA

Preferred Term

N=153*

Number of

Subjects N (%)

Frequency Category

1

Common

(≥1/100 to <1/10)

Uncommon

(≥1/1,000 to

<1/100)

Nervous system

disorders

Headache

Dizziness

Dysgeusia

2 (1.3)

1 (0.7)

1 (0.7)

Common

Uncommon

Uncommon

Gastrointestinal

disorders

Paraesthesia

oral

Breath odour

2 (1.3)

1 (0.7)

Common

Uncommon

General

disorders and

administration

site conditions

Fatigue

Infusion site

pain

1 (0.7)

1 (0.7)

Uncommon

Uncommon

Cardiac

disorders

Palpitations

1 (0.7)

Uncommon

Renal and

urinary

disorders

Obstructive

uropathy

Haematuria

Renal colic

2 (1.3)

1 (0.7)

1 (0.7)

Common

Uncommon

Uncommon

Vascular

disorders

Hypotension

1 (0.7)

Uncommon

Metabolism and

nutrition

disorders

Decreased

appetite

1 (0.7)

Uncommon

*The ALPROLIX clinical program included 153 previously treated patients (PTPs) on ALPROLIX therapy from 3 completed

studies

1 ADR 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)

Post Marketing Experience

In post-marketing experience, the following adverse reactions have been reported:

01-alp-ccdsv13-piv6-29jul21

Page 8 of 27

Blood and Lymphatic Disorders: FIX inhibitor development

Immune System Disorders: Hypersensitivity, including anaphylaxis

Reporting of Suspected Adverse Reactions

Reporting

suspected

adverse

reactions

after

authorisation

medicine

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/

4.9

Overdose

No symptoms of overdose have been reported. For information on the management

of overdose, contact the National Poisons Centre on 0800 POISON (0800 764 766) in

New Zealand.

5 PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor IX, ATC

code: B02BD04

ALPROLIX (eftrenonacog alfa) (rhu) is a long-acting, fully recombinant fusion protein

consisting of human coagulation factor IX (FIX) covalently linked to the Fc domain of

human immunoglobulin G1 (IgG1). The factor IX portion of eftrenonacog alfa has a

primary amino acid sequence that is identical to the Thr

allelic form of plasma

derived

factor

structural

functional

characteristics

similar

endogenous factor IX. The Fc domain of eftrenonacog alfa contains the hinge, CH2

and CH3 regions of IgG1. Eftrenonacog alfa contains 867 amino acids with a

molecular weight of approximately 98 kilodaltons.

Eftrenonacog alfa is produced by recombinant DNA technology in a human embryonic

kidney (HEK) cell line, which has been extensively characterised. The HEK cell line

expresses eftrenonacog alfa into a defined cell culture medium that does not contain

any proteins derived from animal or human sources. Eftrenonacog alfa is purified by

a series of chromatography steps that does not require use of a monoclonal antibody.

The process includes multiple viral clearance steps including 15nm virus-retaining

nano-filtration. No human or animal additives are used in the cell culture, purification,

and formulation processes.

CAS registry number: 1270012-74-2

5.1

Pharmacodynamic Properties

Mechanism of Action

ALPROLIX (eftrenonacog alfa) is a long-acting, fully recombinant, fusion protein

comprising human coagulation factor IX (FIX) covalently linked to the Fc domain of

human IgG1, and produced by recombinant DNA technology.

FIX is an approximately 55 kDa vitamin K-dependent serine protease, which is an

essential clotting factor in the coagulation cascade critical to the haemostasis process.

FIX is normally converted to activated FIX (FIXa) by the activated factor VII/Tissue

01-alp-ccdsv13-piv6-29jul21

Page 9 of 27

Factor complex or by activated factor XI. FIXa forms a complex with activated factor

VIII on phospholipid surfaces to convert factor X to activated factor X, and which

ultimately converts prothrombin to thrombin and leads to the formation of a fibrin clot.

Haemophilia B patients have a deficiency of functional FIX, which results in prolonged

bleeding after trauma and recurrent spontaneous bleeds into soft tissue and joints.

portion

eftrenonacog

alfa

similar

structural

functional

characteristics as endogenous FIX, and promotes haemostasis by correcting the

deficiency of functional FIX.

The other portion of eftrenonacog alfa is the Fc region of human IgG1 which binds with

the neonatal Fc receptor (FcRn). This receptor is expressed throughout life as part of

naturally

occurring

pathway

that

protects

immunoglobulins

from

lysosomal

degradation by cycling these proteins back into circulation, resulting in their long

plasma half-life.

ALPROLIX is used as a replacement therapy to increase plasma levels of factor IX

activity, thereby enabling a temporary correction of the factor deficiency and correction

of the bleeding tendency.

Pharmacodynamics

Haemophilia B is a bleeding disorder characterized by a deficiency of functional

clotting factor IX (FIX), which leads to a prolonged clotting time in the activated partial

thromboplastin time (aPTT) assay, a conventional in vitro test for the biological activity

of FIX. Treatment with ALPROLIX shortens the aPTT over the effective dosing period.

Clinical Efficacy and Safety

The safety, efficacy and pharmacokinetics of ALPROLIX were evaluated in two

multicentre, open-label, pivotal studies: a Phase 3 study (Study 1) and a Phase 3

paediatric study (Study 2). Patients from Study 1 and Study 2 could subsequently enrol

in a long term extension study (Study 3).

Study 1 compared the efficacy of each of two prophylactic treatment regimens to

episodic (on-demand) treatment; determined haemostatic efficacy in the treatment of

bleeding

episodes;

determined

haemostatic

efficacy

during

perioperative

management of subjects undergoing major surgical procedures. A total of 123

previously treated patients (PTPs) aged 12-71 with severe haemophilia B (<2%

endogenous FIX activity) were followed for up to 77 weeks.

Sixty-three (63) subjects in the fixed weekly interval arm received ALPROLIX for

routine prophylaxis starting at an initial dose of 50 IU/kg. The dose was adjusted to

maintain trough between 1 and 3% above baseline or higher as clinically indicated to

prevent bleeding. The median average weekly dose during the last 6 months on study

in 58 subjects who were on study for at least 9 months was 40.7 IU/kg (interquartile

range, 32.3, 54.1).

Twenty-nine (29) subjects in the individualised interval arm received ALPROLIX for

routine prophylaxis at a dose of 100 IU/kg every 10 days, with the interval adjusted to

maintain trough between 1 and 3% above baseline or higher as clinically indicated to

prevent bleeding. The median average interval during the last 6 months in 26 subjects

01-alp-ccdsv13-piv6-29jul21

Page 10 of 27

who were on study for at least 9 months was 13.8 days (interquartile range, 10.5,

14.0).

Twenty-seven (27) subjects received ALPROLIX as needed for the treatment of

bleeding episodes in the episodic (on-demand) treatment arm. Twelve (12) subjects

received ALPROLIX for perioperative management in 14 major surgical procedures.

Four subjects did not participate in the other arms.

Study 2 enrolled a total of 30 previously treated male paediatric patients with severe

haemophilia B (≤2% endogenous FIX activity). Subjects were less than 12 years of

age (15 were <6 years of age and 15 were 6 to <12 years of age). All subjects received

treatment with ALPROLIX and were followed for up to 52 weeks.

All 30 subjects were treated with ALPROLIX on an individualised prophylactic dose

regimen starting with 50-60 IU/kg every 7 days, with adjustment of dose to a maximum

of 100 IU/kg and dosing interval to a minimum of once weekly and a maximum of twice

weekly. The median dosing interval was 6.99 days (interquartile range, 6.94 to 7.03)

with no difference in the median average dosing interval between age cohorts. The

median average weekly dose of ALPROLIX was 59.40 IU/kg (interquartile range,

52.95 to 64.78 IU/kg) for subjects <6 years of age and 57.78 IU/kg (interquartile range,

51.67 to 65.01 IU/kg) for subjects 6 to <12 years of age.

Study 3 was an open-label, multicentre, long-term study in previously treated patients

with haemophilia B who had completed Study 1 or Study 2. The study evaluated the

long-term safety and efficacy of rFIXFc for routine prophylaxis, on-demand treatment,

and perioperative management with ALPROLIX. During the study, subjects, could

change treatment groups. Of the 120 subjects in Study 3 (aged 3-63), 93 were from

Study 1 and 27 were from Study 2.

Thirty-six subjects from Study 1 received individualised prophylaxis, 74 received

weekly prophylaxis, 19 received personalised prophylaxis (for subjects in whom

optimal prophylaxis could not be achieved with individualised or weekly prophylaxis),

and 15 received episodic treatment with ALPROLIX. In addition, 16 subjects were also

part of the surgery subgroup. The majority of subjects stayed on their treatment

regimen throughout the extension study, with 21 subjects (22.6%) switching treatment

regimens once or twice during the study. From the start of Study 1 to the end of Study

3, subjects had a median of 189 weeks of treatment (range <1 to 338). For evaluable

subjects on prophylactic treatments in Study 3, the median average weekly dose was

48.46 IU/kg (interquartile range 39.88-61.07) for subjects in the weekly prophylaxis

arm, 50.76 IU/kg (47.34-70.68) for subjects in the individualised prophylaxis arm, and

68.23 IU/kg (43.78-100.08) for subjects in the personalised prophylaxis arm. The

median average dosing interval was 6.99 days (range 6.7 days to 7.8 days) for

subjects in the weekly prophylaxis arm, 13.61 days (range 3.5 days to 21.3 days) for

subjects in the individualised prophylaxis arm, and 6.61 days (range 3.3 days to 14.2

days) for subjects in the personalised prophylaxis arm.

Twenty-three subjects from Study 2 participated in weekly the prophylaxis arm, 5

subjects participated in the individualised prophylaxis arm and 2 subjects received

personalised prophylaxis treatment with ALPROLIX. Three subjects (11.1%) switched

treatment regimens once during the study. From the start of Study 2 to the end of

Similar products

Search alerts related to this product

View documents history

Share this information