TRAZIMERA trastuzumab 60 mg powder for injection vial

Australia - English - Department of Health (Therapeutic Goods Administration)

Buy It Now

Active ingredient:
Trastuzumab
Available from:
Pfizer Australia Pty Ltd
Authorization status:
Registered
Authorization number:
304049

TRAZIMERA™

Trastuzumab

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common

questions about TRAZIMERA. It

does not contain all the available

information.

It does not take the place of talking to

your doctor or pharmacist.

All medicines have risks and

benefits. Your doctor has weighed

the risks of you taking TRAZIMERA

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 TRAZIMERA is

used for

TRAZIMERA contains an active

ingredient called trastuzumab.

TRAZIMERA belongs to a group of

medicines known as anti-neoplastic

(or anti-cancer) agents. There are

many different classes of

antineoplastic agents. TRAZIMERA

belongs to a class called monoclonal

antibodies.

Monoclonal antibodies are proteins

made in a laboratory. These proteins

are designed to recognise and bind to

other unique proteins in the body.

TRAZIMERA binds selectively to a

protein called human epidermal

growth factor receptor 2 (HER2).

HER2 is found in large amounts on

the surface of some cancer cells.

When TRAZIMERA binds to HER2

it stops the growth and spread of the

cancer cells.

TRAZIMERA is used to treat breast

and gastric cancer. It is only used in

patients whose tumour has tested

positive to HER2.

TRAZIMERA may be used alone or

with other medicines that treat breast

cancer, such as an aromatase

inhibitor (hormone receptor positive

breast cancer) or a taxane (e.g.

paclitaxel or docetaxel).

For the treatment of gastric cancer

TRAZIMERA is used with

chemotherapy medicines cisplatin

and capecitabine (or 5FU).

For further information about the

other medicines you are receiving

with TRAZIMERA, please ask your

doctor, nurse or pharmacist for the

Consumer Medicine Information

(CMI) leaflet.

Ask your doctor if you have any

questions about why

TRAZIMERA has been prescribed

for you.

This medicine is available only with

a doctor's prescription.

Before you are given

TRAZIMERA

When you must not be given

it

Do not use TRAZIMERA if:

you have had an allergic

reaction to;

any medicine containing

trastuzumab

any of the ingredients listed at

the end of this leaflet.

any protein of Chinese

hamster origin

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.

you have breast cancer that has

not spread (non-metastatic) and

-

you have had an LVEF test

result (which measures how

well your heart can pump

blood) of less than 45% or

-

you have symptoms of heart

failure

Symptoms of heart failure may

include:

shortness of breath or tire

easily after light physical

activity (such as walking)

shortness of breath at night,

especially when lying flat

swelling of the hands or feet

due to fluid build up

abnormal or irregular

heartbeat

If you are not sure whether you

should start receiving this medicine,

talk to your doctor.

Before you are given it

Tell your doctor if:

you have a history of heart

disease with:

angina (chest pain)

cardiac arrhythmias (abnormal

beating of the heart)

TRAZIMERA™

heart failure (where the heart

cannot pump blood normally)

coronary artery disease (also

known as CAD, a condition

where plaque builds up inside

the arteries)

poorly controlled high blood

pressure

you have previously been

treated with chemotherapy

medicines known as

anthracyclines (e.g.

doxorubicin); these medicines

can damage heart muscle and

increase the risk of heart

problems with TRAZIMERA

Your doctor will monitor your

heart function closely before and

during your treatment with

TRAZIMERA. Your heart

function may also be monitored

for years after ceasing

TRAZIMERA treatment.

if you have any breathing or

lung problems

you are allergic to any other

medicines or any other

substances such as foods,

preservatives or dyes

Allergic or anaphylactic reactions

can occur with TRAZIMERA

treatment (known as infusion or

administration related reactions).

Your doctor or nurse will monitor

you for side effects during

treatment. See "side effects" for

symptoms to look out for.

you are pregnant or intend to

become pregnant

TRAZIMERA may be harmful to

an unborn baby. If there is a need

for TRAZIMERA treatment when

you are pregnant your doctor will

discuss the risks and benefits to

you and the unborn baby.

You should use effective

contraception to avoid becoming

pregnant while you are being

treated with TRAZIMERA and

for 7 months after stopping

treatment.

you are breast-feeding or plan

to breast-feed

It is not known if TRAZIMERA

passes into breast milk. It is

recommended that you

discontinue breast-feeding while

you are being treated with

TRAZIMERA and not restart

breast-feeding until 7 months

after completing TRAZIMERA

treatment.

If you have not told your doctor

about any of the above, tell him/

her before you start taking

TRAZIMERA.

Use in children

The safety and effectiveness of

TRAZIMERA in children under 18

years of age have not been

established.

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.

TRAZIMERA treatment with

gemcitabine, vinorelbine, a taxane or

radiation therapy can increase the

chance of lung problems (interstitial

lung disease).

Your doctor and pharmacist have

more information on medicines to be

careful with or avoid while receiving

TRAZIMERA.

Tell your doctor or pharmacist

that you have had TRAZIMERA if

you start any new medication in

the seven months after stopping

treatment.

It may take up to seven months for

TRAZIMERA to be removed from

your body

How TRAZIMERA is

given

Follow all directions given to you

by your doctor or nurse carefully.

They may differ from the

information contained in this leaflet.

TRAZIMERA must be prepared by a

healthcare professional and will be

given in a hospital or clinic by a

doctor or nurse.

TRAZIMERA is given by "drip" into

a vein (intravenous (IV) infusion).

The first TRAZIMERA infusion is

given over 90 minutes. If the first

infusion is well tolerated, your drip

time may be shortened to 30 minutes.

For the treatment of breast cancer,

TRAZIMERA is given either once a

week or once every three weeks. It

may be given alone or in

combination with other medicines

used to treat breast cancer.

For the treatment of gastric cancer

TRAZIMERA is given every three

weeks in combination with other

medicines used to treat gastric

cancer.

Your doctor will decide how long

you should receive TRAZIMERA,

this will depend on your response to

the medicine and the state of your

disease.

If you miss a dose

As TRAZIMERA is given under the

supervision of your doctor, you are

unlikely to miss a dose. However, if

you forget or miss your appointment

to receive TRAZIMERA, make

another appointment as soon as

possible.

Your doctor will decide when and

how much your next dose of

TRAZIMERA will be.

If you are given too much

(overdose)

As TRAZIMERA is given to you

under the supervision of your doctor

it is unlikely that you will be given

too much. However, if you

experience any side effects after

being given TRAZIMERA, tell your

doctor immediately.

TRAZIMERA™

While you are

receiving TRAZIMERA

Things you must do

Tell your doctor or nurse

immediately if you have any signs

and symptoms of an allergic or

anaphylactic reaction

Some signs and symptoms include;

swelling of your face, lips, tongue

or throat with difficulty breathing,

swelling of other parts of your

body

shortness of breath, wheezing or

trouble breathing

rash, itching or hives on the skin

feeling sick (nausea)

fever, chills

feeling tired

headache

Tell your doctor or nurse

immediately if you have any signs

and symptoms of heart problems.

Some signs and symptoms of heart

problems are

shortness of breath or getting

tired easily after light physical

activity (such as walking)

shortness of breath at night,

especially when lying flat

swelling of the hands or feet due

to fluid build up

cough

abnormal or irregular heartbeat

Please follow all your doctors'

instructions if any of these symptoms

require medication.

Tell any other doctors, dentists,

and pharmacists who treat you

that you are receiving

TRAZIMERA.

Tell your doctor if you become

pregnant or intend to start a family

while receiving TRAZIMERA.

Keep all of your doctor's

appointments so that your progress

can be checked.

Your doctor may perform regular

tests.

Things you must not do

Do not stop your TRAZIMERA

treatment without checking with

your doctor.

Tell your doctor if you feel that

TRAZIMERA is not helping your

condition.

Do not take any other medicines,

whether they require a

prescription or not, without first

telling your doctor or consulting

with a pharmacist.

Things to be careful of

Be careful driving or operating

machinery until you know how

TRAZIMERA affects you.

If you have experienced symptoms

during your treatment with

TRAZIMERA you should not drive

or operate machinery.

Side effects

Tell your doctor or pharmacist as

soon as possible if you do not feel

well while you are taking

TRAZIMERA.

This medicine helps most people

with HER2 positive breast and

gastric cancer but it may have

unwanted side effects in some

people.

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.

Ask your doctor or pharmacist to

answer any questions you may

have.

Because TRAZIMERA may be used

with other medicines that treat breast

and gastric cancer, it may be difficult

for your doctor to tell whether the

side effects are due to TRAZIMERA

or due to the other medicines.

For further information about the

side effects of any other medicines

you are receiving, please ask your

doctor, nurse or pharmacist for the

Consumer Medicine Information

(CMI) leaflets for these medicines

During an infusion

Tell your doctor or nurse

immediately if you notice any of

the following while receiving an

infusion (particularly during the

first infusion):

swelling of your face, lips, tongue

or throat with difficulty breathing

swelling of other parts of your

body such as your hands or feet

shortness of breath, wheezing or

trouble breathing

abnormal or irregular heartbeat

rash, itching or hives on the skin

feeling sick (nausea) or vomiting,

diarrhoea

pain or discomfort (including

stomach pain, back pain, chest or

neck pain)

fever or chills

headache

fatigue or tiredness

cough

These may be serious side effects.

You may require urgent medical

attention.

Your doctor may prescribe

medication to stop the side effects

from occurring.

After an infusion

Tell your doctor immediately or go

to Accident and Emergency at

your nearest hospital if you notice

any of the following:

swelling of your face, lips, tongue

or throat with difficulty breathing

severe shortness of breath,

wheezing or trouble breathing

severe chest pain spreading out to

the arms, neck, shoulder and/or

back

rash, itching or hives on the skin

fever or chills

abnormal or irregular beating of

the heart

TRAZIMERA™

severe swelling of the hands, feet

or legs

severe coughing

These are serious side effects. You

may need urgent medical attention.

Tell your doctor or nurse as soon

as possible if you notice any of the

following:

any of the side effects listed

above

getting tired more easily after

light physical activity, such as

walking

shortness of breath, especially

when lying down or being woken

from your sleep with shortness of

breath

runny or blocked nose, or

nosebleeds

insomnia (difficulty sleeping)

weakness, soreness in muscles

and/or joints

increased cough

feeling dizzy, tired, looking pale

flu and/or cold like symptoms,

frequent infections such as fever,

severe chills, sore throat or mouth

ulcers

hot flushes

diarrhoea

changes in weight (gain or loss)

redness, dryness or peeling of the

hands or feet (hand-foot

syndrome)

pain in hands or feet

unusual hair loss or thinning

nail problems

eye problems such as producing

more tears, swollen runny eyes or

conjunctivitis (discharge with

itching of the eyes and crusty

eyelids)

This is not a complete list of all

possible side effects. Your doctor or

pharmacist has a more complete list.

Others may occur in some people and

there may be some side effects not

yet known.

Tell your doctor if you notice

anything else that is making you

feel unwell, even if it is not on this

list.

Ask your doctor or pharmacist if

you don't understand anything in

this list.

Do not be alarmed by this list of

possible side effects.

You may not experience any of them.

Product description

Storage

TRAZIMERA will be stored in the

pharmacy or on the hospital ward in

a refrigerator at a temperature

between 2°C and 8°C.

Availability

TRAZIMERA is a powder for

intravenous infusion (drip into the

vein) and supplied as a single dose

vial and available in two strengths,

60 mg and 150 mg.

It is important to check the product

labels to ensure that the medicine is

being given as prescribed.

What it looks like

TRAZIMERA is a white powder

which is dissolved in sterile water

before use.

After dissolving, the TRAZIMERA

solution should appear as a clear,

colourless to pale yellow-brown

solution.

Ingredients

Each vial of TRAZIMERA contains

60 mg or 150 mg of the active

ingredient trastuzumab.

It also contains;

histidine hydrochloride

histidine

polysorbate 20

sucrose

The trastuzumab protein is made

using Chinese hamster ovary cells.

Supplier

TRAZIMERA is supplied in

Australia by:

Pfizer Australia Pty Ltd

Sydney NSW

Toll Free number: 1800 675 229

www.pfizer.com.au

Australian registration

numbers

60mg: AUST R 304049

150mg: AUST R 304050

This leaflet was prepared in August

2019.

TRAZIMERA™

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AUSTRALIAN PRODUCT INFORMATION –

TRAZIMERA

TM

(TRASTUZUMAB)

1

NAME OF THE MEDICINE

Trastuzumab

TRAZIMERA is a biosimilar medicine to the reference biological medicine HERCEPTIN

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 60mg or 150mg trastuzumab.

TRAZIMERA (trastuzumab) is a recombinant DNA-derived humanized monoclonal antibody

that selectively targets the extracellular domain of the human epidermal growth factor receptor

2 protein (HER2). The antibody is an IgG1 kappa that contains human framework regions with

the complementarity-determining regions of a murine anti-p185 HER2 antibody that binds to

HER2. Trastuzumab is composed of 1,328 amino acids and has a molecular weight of ~148

kDa.

The humanized antibody against HER2 is produced by recombinant mammalian cells (Chinese

hamster ovary (rch)) in suspension culture in a nutrient medium and purified by affinity

chromatography

exchange,

including

specific

viral

inactivation

removal

procedures.

For the full list of excipients, see section 6.1 List of excipients.

3

PHARMACEUTICAL FORM

Powder for injection for infusion.

TRAZIMERA is a sterile, white preservative-free lyophilized powder or cake for IV infusion.

4

CLINICAL PARTICULARS

4.1

T

HERAPEUTIC INDICATIONS

Early Breast Cancer

TRAZIMERA is indicated for the treatment of HER2-positive early breast cancer following

surgery, and in association with chemotherapy and, if applicable, radiotherapy.

Locally Advanced Breast Cancer

TRAZIMERA is indicated for the treatment of HER2-positive locally advanced breast cancer

in combination with neoadjuvant chemotherapy followed by adjuvant TRAZIMERA.

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Metastatic Breast Cancer

TRAZIMERA is indicated for the treatment of patients with metastatic breast cancer who have

tumours that overexpress HER2:

a) as monotherapy for the treatment of those patients who have received one or more

chemotherapy regimens for their metastatic disease;

b) in combination with taxanes for the treatment of those patients who have not received

chemotherapy for their metastatic disease; or

c) in combination with an aromatase inhibitor for the treatment of post-menopausal patients

with hormone-receptor positive metastatic breast cancer.

Advanced Gastric Cancer

TRAZIMERA is indicated in combination with cisplatin and either capecitabine or 5-FU for

the treatment of patients with HER2 positive advanced adenocarcinoma of the stomach or

gastro-oesophageal junction who have not received prior anti-cancer treatment for their

metastatic disease.

4.2

D

OSE AND METHOD OF ADMINISTRATION

HER2 testing is mandatory prior to initiation of TRAZIMERA therapy (see section 4.2 Dose

Method

Administration,

Detection

HER2

Protein

Overexpression

Gene

Amplification).

In order to prevent medication errors, it is important to check the vial labels to ensure the

medicine

being

prepared

administered

TRAZIMERA

(trastuzumab)

KADCYLA

(trastuzumab emtansine).

In order to improve traceability of biological medicinal products, the trade name and the batch

number of the administered product should be clearly recorded in the patient medical record.

Dose

Early Breast Cancer

Three-weekly schedule: the recommended initial loading dose is 8 mg/kg body weight,

followed by a maintenance dose of 6 mg/kg body weight administered at 3 weekly intervals.

Weekly schedule: the recommended initial loading dose is 4 mg/kg body weight, followed by

a maintenance dose of 2 mg/kg body weight administered at weekly intervals.

Locally Advanced Breast Cancer

Three-weekly schedule: the recommended initial loading dose is 8 mg/kg body weight,

followed by a maintenance dose of 6 mg/kg body weight administered at 3 weekly intervals.

Metastatic Breast Cancer

Three-weekly schedule: the recommended initial loading dose is 8 mg/kg body weight,

followed by a maintenance dose of 6 mg/kg body weight administered at 3 weekly intervals.

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Weekly schedule: the recommended initial loading dose is 4 mg/kg body weight, followed by

a maintenance dose of 2 mg/kg body weight administered at weekly intervals.

Advanced Gastric Cancer

Three-weekly schedule: the recommended initial loading dose is 8 mg/kg body weight,

followed by a maintenance dose of 6 mg/kg body weight administered at 3-weekly intervals.

Refer to section 5.1 Pharmacodynamic Properties, Clinical Trials (including Table 5 for early

breast cancer) for the sequence and dosing of chemotherapy medicines used in the supporting

pivotal trials. Refer also to the currently approved product information for the chemotherapy

partners.

Administration

TRAZIMERA IV solution is not to be used for subcutaneous administration and must be

administered as an IV infusion. Do not administer as an IV push or bolus.

TRAZIMERA IV loading doses should be administered over approximately 90 minutes. If the

loading dose was well tolerated, subsequent doses can be administered as a 30 minute infusion.

Patients should be observed for fever and chills or other infusion-associated symptoms (see

section

Adverse

Effects

(Undesirable

Effects)).

Interruption

infusion

and/or

medication may help to control such symptoms. The infusion may be resumed when symptoms

abate.

Duration of Treatment

Patients with early or locally advanced breast cancer should be treated for 1 year or until disease

recurrence, whichever occurs first. However, extending adjuvant treatment beyond one year is

not recommended (see section 5.1 Pharmacodynamic Properties, Clinical Trials, Early breast

cancer).

Patients with metastatic breast cancer and advanced gastric cancer should be treated until

progression of disease.

Missed Doses

If the patient has missed a dose of TRAZIMERA by one week or less, then the usual

maintenance dose of TRAZIMERA (weekly regimen: 2 mg/kg; 3-weekly: 6 mg/kg) should be

administered as soon as possible (do not wait until the next planned cycle). Subsequent

maintenance doses should then be administered 7 days or 21 days later according to the weekly

or three-weekly schedules, respectively.

If the patient has missed a dose of TRAZIMERA by more than one week, a re-loading dose of

TRAZIMERA should be administered over approximately 90 minutes (weekly regimen: 4

mg/kg; 3-weekly: 8 mg/kg) as soon as possible. Subsequent maintenance doses (weekly

regimen: 2 mg/kg; 3-weekly: 6 mg/kg) should be administered 7 days or 21 days later according

to the weekly or three-weekly schedules, respectively.

Dose Modification

If the patient develops an infusion-related reaction (IRR), the infusion rate of TRAZIMERA

IV may be slowed or interrupted (see section 4.4 Special Warnings and Precautions for Use).

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No reductions in the dose of TRAZIMERA were made during clinical trials. Patients may

continue

TRAZIMERA

therapy

during

periods

reversible,

chemotherapy-induced

myelosuppression, but they should be carefully monitored for complications of neutropenia

during this time. The specific instructions to reduce or hold the dose of chemotherapy should

be followed.

Use in Elderly:

In clinical trials, elderly patients did not receive reduced doses of trastuzumab.

Age has been shown to have no effect on the disposition of trastuzumab (see section 5.2

Pharmacokinetic Properties).

Detection of HER2 Protein Overexpression or HER2 Gene Amplification

TRAZIMERA

should

only

used

patients

whose

tumours

have

HER2

protein

overexpression or HER2 gene amplification.

To ensure accurate and reproducible results, testing must be performed in a specialized

laboratory, which can ensure validation of the testing procedures.

HER2 protein overexpression should be detected using an immunohistochemistry (IHC)-based

assessment of fixed tumour blocks. HER2 gene amplification should be detected using in situ

hybridization (ISH) of fixed tumour blocks. Examples of ISH include fluorescence in situ

hybridization (FISH), chromogenic in situ hybridization (CISH) and silver in situ hybridization

(SISH).

For any other method to be used for the assessment of HER2 protein or gene expression, the

test method must be precise and accurate enough to demonstrate overexpression of HER2 (it

must be able to distinguish between moderate (congruent with 2+) and strong (congruent with

3+) HER2 overexpression).

For full instructions on the use of these assays and interpretation of the results please refer to

the package inserts of validated FISH, CISH and SISH assays. Official recommendations on

HER2 testing may also apply.

Breast Cancer

TRAZIMERA treatment is only appropriate if there is strong HER2 overexpression, as

described by a 3+ score by IHC or a positive ISH result. For patients with an intensity score of

2+ on IHC, confirmation of HER2 positive status by ISH is mandatory.

Advanced Gastric Cancer

TRAZIMERA treatment is only appropriate if there is HER2 overexpression, as described by

a 3+ IHC score. For cases with a score of less than 3+ by IHC, confirmation of HER2 positive

status by ISH is mandatory.

Bright-field ISH technology is recommended for advanced gastric cancer samples to enable

evaluation of tumour histology and morphology in parallel. Either FISH or SISH are

recommended for detecting HER2 gene amplification in advanced gastric cancer tissue.

Preparation for IV infusion

Reconstituting the Powder

Appropriate aseptic technique should be used.

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TRAZIMERA should be carefully handled during reconstitution. Causing excessive foaming

during reconstitution or shaking the reconstituted TRAZIMERA may result in problems with

the amount of TRAZIMERA that can be withdrawn from the vial.

Each 60 mg vial should be reconstituted with 3.0 mL of sterile water for injections as the

solvent. The use of other solvents should be avoided. The resultant solution is 3.1 mL of

approximately 21 mg/mL trastuzumab. A 7.5% overage is included to ensure withdrawal of

the labelled dose of 60 mg.

Each 150 mg vial should be reconstituted with 7.2 mL of sterile water for injections as the

solvent. The use of other solvents should be avoided. The resultant solution is 7.4 mL of

approximately 21 mg/mL trastuzumab. A 4% overage is included to ensure withdrawal of the

labelled dose of 150 mg.

Instructions for Reconstitution

1) Using a sterile syringe, slowly inject 7.2 mL (for 150 mg vial) or 3.0 mL (for 60 mg

vial) of sterile water for injections in the vial containing the lyophilized TRAZIMERA,

directing the stream into the lyophilized cake.

2) Swirl vial gently to aid reconstitution. TRAZIMERA may be sensitive to shear-

induced stress, e.g. agitation or rapid expulsion from a syringe. DO NOT SHAKE.

Slight foaming of the product upon reconstitution is not unusual. Allow the vial to stand

undisturbed for approximately 5 minutes. The reconstituted preparation results in a clear to

slightly opalescent and colourless to pale yellow-brown solution and should be essentially free

of visible particulates.

Instructions for Dilution

Weekly Regimen: Determine the volume of the reconstituted solution required based on a

loading dose of trastuzumab 4 mg/kg body weight, or a maintenance dose of trastuzumab 2

mg/kg body weight:

Volume (mL) =

Body weight

(kg) x

dose

4

mg/kg for loading or 2 mg/kg for maintenance)

21

(mg/mL, concentration of reconstituted solution)

Three-Weekly Regimen: Determine the volume of the reconstituted solution required based on

a loading dose of trastuzumab 8 mg/kg body weight, or subsequent every 3 weeks dose of 6

mg/kg body weight:

Volume (mL) =

Body weight

(kg) x

dose

8

mg/kg for loading or 6 mg/kg for maintenance)

21

(mg/mL, concentration of reconstituted solution)

Preparation and Stability of the Admixture

The appropriate amount of the reconstituted solution should be withdrawn from the vial and

added to an infusion bag containing 250 mL of 0.9% sodium chloride.

Dextrose (5%) solution should not be used since it causes aggregation of the protein.

TRAZIMERA SHOULD NOT BE MIXED OR DILUTED WITH OTHER MEDICINES.

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Page 6 of 35

incompatibilities

between

TRAZIMERA

polyvinylchloride,

polyethylene,

polypropylene, or ethylene vinyl acetate bags or glass IV bottles have been observed.

The infusion bag should be gently inverted to mix the solution in order to avoid foaming.

Parenteral drug products should be inspected visually for particulates and discoloration prior

to administration.

4.3

C

ONTRAINDICATIONS

TRAZIMERA is contraindicated in patients with known hypersensitivity to trastuzumab,

Chinese hamster ovary cell proteins or to any of its excipients.

In the treatment of early or locally advanced breast cancer, TRAZIMERA is contraindicated in

patients with a left ventricular ejection fraction of less than 45% and those with symptomatic

heart failure.

4.4

S

PECIAL WARNINGS AND PRECAUTIONS FOR USE

General

TRAZIMERA

therapy

should

only

initiated

under

supervision

physician

experienced in the treatment of cancer patients. Usual clinical care should be taken to prevent

microbial contamination of the intravenous access sites used to deliver TRAZIMERA therapy.

TRAZIMERA should be administered by a healthcare professional prepared to manage

anaphylaxis and adequate life support facilities should be available. Treatment may be

administered in an outpatient setting.

If TRAZIMERA is used concurrently with cytotoxic chemotherapy, the specific guidelines

used to reduce or hold the dose of chemotherapy should be followed. Patients may continue

TRAZIMERA therapy during periods of reversible chemotherapy-induced myelosuppression,

renal toxicity or hepatic toxicity.

Cardiac Dysfunction

General considerations

Patients treated with trastuzumab are at increased risk of developing congestive heart failure

(CHF)

(New

York

Heart

Association

[NYHA]

class

II-IV)

asymptomatic

cardiac

dysfunction. These events have been observed in patients receiving trastuzumab product

therapy alone or in combination with a taxane following anthracycline (doxorubicin or

epirubicin)–containing chemotherapy. This may be moderate to severe and has been associated

with death. In addition, caution should be exercised in treating patients with increased cardiac

risk e.g. hypertension, documented coronary artery disease, CHF, diastolic dysfunction, older

age.

Population pharmacokinetic model simulations indicate that trastuzumab may persist in the

circulation

months

after

stopping

trastuzumab

treatment

(see

section

Pharmacokinetic Properties). Patients who receive anthracycline after stopping trastuzumab

may also be at increased risk of cardiac dysfunction. If possible, physicians should avoid

anthracycline-based therapy for up to 7 months after stopping trastuzumab. If anthracyclines

are used, the patient’s cardiac function should be monitored carefully.

Candidates for treatment with TRAZIMERA, especially those with prior anthracycline and

cyclophosphamide (AC) exposure, should undergo baseline cardiac assessment including

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history and physical examination, ECG echocardiogram, and/or MUGA scan. Monitoring may

help to identify patients who develop cardiac dysfunction, including signs and symptoms of

CHF. Cardiac assessments, as performed at baseline, should be repeated every 3 months during

treatment and every 6 months following discontinuation of treatment until 24 months from the

last administration of TRAZIMERA.

If left ventricular ejection fraction (LVEF) drops 10 percentage points from baseline and to

below 50%, TRAZIMERA should be withheld and a repeat LVEF assessment performed

within approximately 3 weeks. If LVEF has not improved, or declined further, or clinically

significant

developed,

discontinuation

TRAZIMERA

should

strongly

considered, unless the benefits for the individual patient are deemed to outweigh the risks.

Patients who develop asymptomatic cardiac dysfunction may benefit from more frequent

monitoring (e.g. every 6 - 8 weeks). If patients have a continued decrease in left ventricular

function, but remain asymptomatic, the physician should consider discontinuing therapy if no

clinical benefit of TRAZIMERA therapy has been seen.

The safety of continuation or resumption of trastuzumab in patients who experience cardiac

dysfunction has not been prospectively studied. If symptomatic cardiac failure develops during

trastuzumab therapy, it should be treated with the standard medications for this purpose. In the

pivotal trials, most patients who developed heart failure or asymptomatic cardiac dysfunction

improved with standard heart failure treatment consisting of angiotensin-converting enzyme

(ACE) inhibitor or angiotensin receptor blocker (ARB) and a β-blocker. The majority of

patients with cardiac symptoms and evidence of a clinical benefit of trastuzumab treatment

continued on weekly therapy with trastuzumab without additional clinical cardiac events.

Early and Locally Advanced Breast Cancer

For patients with early breast cancer, cardiac assessments, as performed at baseline, should be

repeated every 3 months during treatment and every 6 months following discontinuation of

treatment until 24 months from the last administration of trastuzumab. In patients who receive

anthracycline containing chemotherapy further monitoring is recommended and should occur

yearly up to 5 years from the last administration of trastuzumab, or longer if a continuous

decrease of LVEF is observed.

All patients should have a determination of LVEF prior to treatment. Use of trastuzumab is

contraindicated in patients with early or locally advanced disease and a LVEF of less than 45%

and those with symptomatic heart failure (see section 4.3 Contraindications). Patients with a

LVEF of 45 - 55% at baseline should be monitored regularly for symptoms of heart failure

during trastuzumab treatment.

Patients with history of myocardial infarction (MI), angina pectoris requiring medication,

history of or present CHF (NYHA Class II –IV), other cardiomyopathy, cardiac arrhythmia

requiring

medication,

clinically

significant

cardiac

valvular

disease,

poorly

controlled

hypertension (hypertension controlled by standard medication eligible), and haemodynamic

effective pericardial effusion were excluded from adjuvant and neoadjuvant breast cancer

clinical trials with trastuzumab.

Adjuvant treatment

TRAZIMERA and anthracyclines should not be given concurrently in the adjuvant treatment

setting.

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An increase in the incidence of symptomatic and asymptomatic cardiac events was observed

when trastuzumab was administered after anthracycline-containing chemotherapy compared to

administration with a non-anthracycline regimen of docetaxel and carboplatin. The incidence

was more marked when trastuzumab was administered concurrently with taxanes than when

administered sequentially to taxanes. Regardless of the regimen used, most symptomatic

cardiac events occurred within the first 18 months.

Risk factors for a cardiac event, identified in 4 large adjuvant studies, included advanced age

(> 50 years), low level of baseline and declining LVEF (< 55%), low LVEF prior to or

following the initiation of paclitaxel treatment, trastuzumab treatment, and prior or concurrent

use of anti-hypertensive medications. In patients receiving trastuzumab after completion of

adjuvant chemotherapy the risk of cardiac dysfunction was associated with a higher cumulative

dose of anthracycline given prior to initiation of trastuzumab and a high body mass index (>

25 kg/m

Neoadjuvant-adjuvant treatment

TRAZIMERA neoadjuvant-adjuvant treatment concurrent with anthracyclines should be used

with caution and only in chemotherapy-naive patients. The maximum cumulative doses of the

low-dose anthracycline regimens should not exceed 180 mg/m

(doxorubicin) or 360 mg/m

(epirubicin).

If patients have been treated concurrently with low-dose anthracyclines and TRAZIMERA in

the neoadjuvant setting, no additional cytotoxic chemotherapy should be given after surgery.

Metastatic breast cancer

TRAZIMERA and anthracyclines should be given concurrently in the metastatic breast cancer

setting.

Advanced Gastric Cancer

In advanced gastric cancer, patients with a history of documented congestive heart failure,

angina pectoris requiring medication, evidence of transmural myocardial infarction on ECG,

poorly controlled hypertension (systolic BP >180 mmHg or diastolic BP >100 mmHg),

clinically significant valvular heart disease, high risk uncontrollable arrhythmias, and baseline

LVEF <50% (measured by echocardiography or MUGA) were excluded from Study BO18255

(ToGA) according to the study protocol.

Hypersensitivity Reactions including Anaphylaxis

Severe hypersensitivity reactions have been infrequently reported in patients treated with

trastuzumab products. Signs and symptoms include anaphylaxis, urticaria, bronchospasm,

angioedema, and/or hypotension. In some cases, the reactions have been fatal. The onset of

symptoms generally occurred during an infusion, but there have also been reports of symptom

onset after the completion of an infusion. Reactions were most commonly reported in

association with the initial infusion.

Patients should be observed closely for hypersensitivity reactions, TRAZIMERA infusion

should be interrupted in all patients with severe hypersensitivity reactions. In the event of a

hypersensitivity reaction, appropriate medical therapy should be administered, which may

include adrenaline,

corticosteroids, antihistamines, bronchodilators

and oxygen. Patients

should be evaluated and carefully monitored until complete resolution of signs and symptoms.

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Infusion-Related Reactions (IRRs)

IRRs are known to occur with the administration of trastuzumab (see section 4.8 Adverse

Effects (Undesirable Effects)).

Pre-medication may be used to reduce risk of occurrence of IRRs.

Serious

IRRs

trastuzumab

infusion

including

dyspnoea,

hypotension,

wheezing,

bronchospasm,

tachycardia,

reduced

oxygen

saturation

respiratory

distress

supraventricular

tachyarrhythmia

have

been

reported

(see

section

Adverse

Effects

(Undesirable Effects)).

Patients should be observed for IRRs. Interruption of an IV infusion may help control such

symptoms and the infusion may be resumed when symptoms abate. These symptoms can be

treated with an analgesic/antipyretic such as paracetamol and an antihistamine. Serious

reactions have been treated successfully with supportive therapy such as oxygen, intravenous

fluids, beta-agonists and corticosteroids. In rare cases, these reactions are associated with a

clinical course culminating in a fatal outcome. In other patients with acute onset of signs and

symptoms, initial improvement was followed by clinical deterioration and delayed reactions

with rapid clinical deterioration have also been reported. Fatalities have occurred within hours

or up to one week following an infusion.

Patients who are experiencing dyspnoea at rest due to complications of advanced malignancy

or co-morbidities may be at increased risk of a fatal infusion reaction. Therefore, these patients

should be treated with extreme caution and the risk versus the benefit considered for each

patient (see section 4.4 Special warnings and precautions for use, Pulmonary Reactions).

Pulmonary Reactions

Severe pulmonary events leading to death have been reported with the use of trastuzumab in

the post-marketing setting. These events may occur as part of an infusion-related reaction (see

Infusion-Related Reactions

above) or with a delayed onset. In addition, cases of interstitial

lung disease including lung infiltrates, acute respiratory distress syndrome, pneumonia,

pneumonitis, pleural effusion, respiratory distress, acute pulmonary oedema, pulmonary

hypertension, pulmonary fibrosis and respiratory insufficiency have been reported.

Risk factors associated with interstitial lung disease include prior or concomitant therapy with

other anti-neoplastic therapies known to be associated with it such as taxanes, gemcitabine,

vinorelbine and radiation therapy. Patients with dyspnoea at rest due to complications of

advanced malignancy and co-morbidities may be at increased risk of pulmonary events.

Therefore, these patients should not be treated with TRAZIMERA.

Use in Hepatic Impairment

The use of trastuzumab in patients with hepatic impairment has not been studied.

Use in Renal Impairment

Formal PK studies have not been conducted in patients with renal impairment. Based on

population PK analysis, renal impairment is not expected to influence trastuzumab exposure,

however, limited data from patients with moderate to severe renal impairment were included

in the population PK analysis (see section 5.2 Pharmacokinetics Properties).

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Use in the Elderly

Clinical experience is limited in patients above 65 years of age. The risk of cardiac dysfunction

may be increased in elderly patients. The reported clinical experience is not adequate to

determine whether older patients respond differently from younger patients. Elderly patients

did not receive reduced doses of trastuzumab in clinical trials. However, greater sensitivity to

trastuzumab in some older patients cannot be ruled out.

Paediatric Use

The safety and efficacy of trastuzumab in patients under the age of 18 years have not been

established.

Effects on Laboratory Tests

No data available.

4.5

I

NTERACTION WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTIONS

No formal drug interaction studies have been performed with trastuzumab in humans.

Clinically significant interactions with concomitant medication used in clinical trials have not

been observed. A comparison of serum levels of trastuzumab given in combination with

cisplatin, doxorubicin or epirubicin-plus-cyclophosphamide has not suggested the possibility

of any interaction.

Administration of paclitaxel in combination with trastuzumab resulted in a slightly less than

two-fold decrease in trastuzumab clearance in a non-human primate study and a 1.5-fold

increase

trastuzumab

serum

levels

clinical

studies.

Paclitaxel

pharmacokinetics

determined during the fourth cycle of the alternative 3-weekly trastuzumab regimen (n = 25)

were not altered appreciably, relative to parameters determined during the initiation of

paclitaxel,

prior

introduction

trastuzumab.

Similarly,

docetaxel

pharmacokinetics

determined during the first dose of trastuzumab in the standard weekly regimen (n = 10) were

not altered appreciably relative to those determined 2 weeks earlier for docetaxel-alone.

A pharmacokinetic interaction substudy of BO18255 (ToGA) performed in male and female

Japanese patients with advanced gastric cancer showed that co-administration of trastuzumab

and capecitabine and cisplatin had no significant effects on the pharmacokinetics of the two

chemotherapy agents compared with co-administration of the two agents without trastuzumab.

The pharmacokinetics of trastuzumab were not evaluated in this study.

The administration of concomitant chemotherapy (either anthracycline or cyclophosphamide)

did not appear to influence the pharmacokinetics of trastuzumab.

4.6

F

ERTILITY

,

PREGNANCY AND LACTATION

Effects on fertility

A study in female cynomolgus monkeys revealed no evidence of impaired fertility at IV

trastuzumab doses up to 25 mg/kg twice weekly, corresponding to serum trough levels (serum

Cmin) about 15 times higher than that in humans receiving the recommended weekly dose of

2 mg/kg.

Public Summary

Summary for ARTG Entry:

304049

TRAZIMERA trastuzumab 60 mg powder for injection vial

ARTG entry for

Medicine Registered

Sponsor

Pfizer Australia Pty Ltd

Postal Address

Level 17 151 Clarence Street,Sydney, NSW, 2000

Australia

ARTG Start Date

19/08/2019

Product category

Medicine

Status

Active

Approval area

Drug Safety Evaluation Branch

Conditions

Conditions applicable to all therapeutic goods as specified in the document "Standard Conditions Applying to Registered or Listed Therapeutic Goods

Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Conditions applicable to the relevant category and class of therapeutic goods as specified in the document "Standard Conditions Applying to Registered

or Listed Therapeutic Goods Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Products

1. TRAZIMERA trastuzumab 60 mg powder for injection vial

Product Type

Single Medicine Product

Effective date

19/08/2019

Permitted Indications

Indication Requirements

No Indication Requirements included on Record

Standard Indications

No Standard Indications included on Record

Specific Indications

Early Breast Cancer ,TRAZIMERA is indicated for the treatment of HER2-positive early breast cancer following surgery, and in association with

chemotherapy and, if applicable, radiotherapy. ,Locally Advanced Breast Cancer ,TRAZIMERA is indicated for the treatment of HER2-positive locally

advanced breast cancer in combination with neoadjuvant chemotherapy followed by adjuvant TRAZIMERA. ,Metastatic Breast Cancer ,TRAZIMERA is

indicated for the treatment of patients with metastatic breast cancer who have tumours that overexpress HER2: ,a) as monotherapy for the treatment of

those patients who have received one or more chemotherapy regimens for their metastatic disease; ,b) in combination with taxanes for the treatment of

those patients who have not received chemotherapy for their metastatic disease; or ,c) in combination with an aromatase inhibitor for the treatment of

post-menopausal patients with hormone-receptor positive metastatic breast cancer. ,Advanced Gastric Cancer ,TRAZIMERA is indicated in combination

with cisplatin and either capecitabine or 5-FU for the treatment of patients with HER2 positive advanced adenocarcinoma of the stomach or

gastro-oesophageal junction who have not received prior anti-cancer treatment for their metastatic disease.

Warnings

See Product Information and Consumer Medicine Information for this product

Additional Product information

Container information

Type

Material

Life Time

Temperature

Closure

Conditions

Vial

Glass Type I Clear

48 Months

Store at 2 to 8

degrees Celsius

Neither child resistant

closure nor restricted

flow insert

Do not Freeze

Refrigerate

Pack Size/Poison information

Pack Size

Poison Schedule

(S4) Prescription Only Medicine

Components

1. TRAZIMERA trastuzumab 60 mg powder for injection vial

Dosage Form

Injection, powder for

Route of Administration

Intravenous

Visual Identification

a sterile, white, preservative-free lyophilized powder or cake for IV infusion.

Active Ingredients

Trastuzumab

60 mg

Public Summary

Page 1 of

Produced at 30.08.2019 at 03:20:53 AEST

This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

Visit www.tga.gov.au for contact information

© Commonwealth of Australia.This work is copyright.You are not permitted to re-transmit, distribute or commercialise the material without obtaining prior

written approval from the Commonwealth.Further details can be found at http://www.tga.gov.au/about/website-copyright.htm.

Public Summary

Page 2 of

Produced at 30.08.2019 at 03:20:53 AEST

This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

Visit www.tga.gov.au for contact information

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