Cisplatin Ebewe

New Zealand - English - Medsafe (Medicines Safety Authority)

Buy It Now

Active ingredient:
Cisplatin 1 mg/mL
Available from:
Novartis New Zealand Ltd
INN (International Name):
Cisplatin 1 mg/mL
Dosage:
1 mg/mL
Pharmaceutical form:
Solution for injection
Composition:
Active: Cisplatin 1 mg/mL Excipient: Hydrochloric acid Sodium chloride Water for injection
Units in package:
Vial, glass, Amber glass with butyl rubber stopper and crimp cap 10 mg in 10 mL vial, 10 mL
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Heraeus Deutschland GmbH & Co. KG
Therapeutic indications:
Cisplatin Ebewe is indicated as palliative therapy to be employed as follows: Metastatic Non-seminomatous Germ Cell Carcinoma: In established combination therapy with other approved chemotherapeutic agents in patients with metastatic non-seminomatous germ cell tumours who have already received appropriate surgical and/or radiotherapeutic procedures. Metastatic Ovarian Tumours: Cisplatin Ebewe, as a single agent, is indicated as secondary therapy in patients with metastatic ovarian tumours refractory to standard chemotherapy who have not previously received Cisplatin Ebewe therapy. Advanced and Refractory Carcinoma of the Bladder: Cisplatin Ebewe, as a single agent, is indicated as secondary therapy in patients with advanced stage bladder cancer refractory to standard chemotherapy who have not previously received Cisplatin Ebewe therapy. Squamous Cell Carcinoma of the Head and Neck (Refractory to Standard Chemotherapy): Cisplatin Ebewe, as a single agent, is indicated as secondary therapy in pati
Product summary:
Package - Contents - Shelf Life: Vial, glass, Amber glass with butyl rubber stopper and crimp cap - 10 mL - 24 months unopened stored at or below 25°C protect from light. Do not refrigerate - Vial, glass, Amber glass with butyl rubber stopper and crimp cap - 50 mL - 24 months unopened stored at or below 25°C protect from light. Do not refrigerate - Vial, glass, Amber glass with butyl rubber stopper and crimp cap - 100 mL - 24 months unopened stored at or below 25°C protect from light. Do not refrigerate
Authorization number:
TT50-7291
Authorization date:
2004-07-26

Cisplatin Ebewe

Cisplatin Ebewe_CMI_v4_Feb 2016

Page 1 of 5

Cisplatin Ebewe

Cisplatin (siss-PLAT-in) injection

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common

questions about Cisplatin Ebewe. 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 being given

Cisplatin Ebewe against the

benefits they expect it will have for

you.

If you have any concerns about

being given this medicine, ask

your doctor or pharmacist.

Keep this leaflet in a safe place.

You may need to read it again.

What Cisplatin Ebewe

is used for

Cisplatin Ebewe belongs to a group

of medicines known as

antineoplastic or cytotoxic agents.

You may also hear it referred to as

a chemotherapy medicine.

Cisplatin Ebewe is a platinum-

containing medicine and is used as

an anticancer drug to interfere with

the growth of cancer cells and

eventually destroy them. Cancer

cells are like normal cells which

have changed so that they grow out

of control in the body. Since the

growth of normal body cells may

also be affected by Cisplatin

Ebewe, other effects may also

occur (see Side Effects).

Cisplatin Ebewe may be used

alone or with other anticancer

therapies for the treatment of

ovarian, testicular and head and

neck cancers.

Cisplatin Ebewe has been chosen

as your therapy, as the benefits of

treatment are expected to be

greater than the unwanted or side

effects.

Ask your doctor if you have any

questions about why this medicine

has been prescribed for you.

This medicine is available only with

a doctor's prescription

Before you are given

Cisplatin Ebewe

When you must not be

given it

You should not be given

Cisplatin Ebewe if you have an

allergy to Cisplatin Ebewe, other

platinum-containing compounds

or any of the ingredients listed at

the end of this leaflet.

Symptoms of an allergic reaction to

Cisplatin Ebewe 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.

Cisplatin Ebewe should not be

given if:

are dehydrated

you have kidney disorders

you have impaired hearing

you have bone-marrow disease

you have nerve damage from

previous cisplatin treatment.

you are being given yellow

fever vaccine

Females: tell your doctor or

pharmacist if you are pregnant

or intend to become pregnant.

Like most cytotoxic medicines

Cisplatin Ebewe is not

recommended for use during

pregnancy. If there is any need to

consider Cisplatin Ebewe during

your pregnancy, your doctor or

pharmacist will discuss the benefits

and risks of using it.

Males: tell your doctor or

pharmacist if your partner

intends to become pregnant

while you are being given

Cisplatin Ebewe, or shortly after

you have stopped treatment with

Cisplatin Ebewe.

Cisplatin Ebewe may cause birth

defects if either the male or female

is using it at the time of conception.

It is recommended that you use

some kind of birth control while you

are using Cisplatin Ebewe and for

at least 12 weeks after you stop

treatment. A barrier method of birth

control, such as a condom, should

be used while you are being given

Cisplatin Ebewe and for the first 12

weeks after stopping treatment.

Your doctor will discuss this with

you.

Cisplatin Ebewe may have a

prolonged effect on fertility in males

and females. Your doctor should

discuss this issue with you before

you begin therapy with Cisplatin

Ebewe.

Do not breast-feed if you are

being treated with this medicine.

It is not known whether Cisplatin

Ebewe passes into breast milk and

there is a possibility that the breast-

fed baby may be affected.

Cisplatin Ebewe

Cisplatin Ebewe_CMI_v4_Feb 2016

Page 2 of 5

If you are not sure whether you

should be given Cisplatin Ebewe,

talk to your doctor.

Before you are given it

Tell your doctor or pharmacist if

you have allergies to any other

medicines, foods, preservatives

or dyes.

Tell your doctor if you have or

have had any of the following

medical conditions:

kidney disease

hearing problems

condition of the blood with a

reduced number of red blood

cells, white blood cells, or

platelets

bleeding problems or problems

with blood clotting

neurological problems

(problems with the nervous

system)

herpes zoster infections (also

known as shingles)

chicken pox (now or recently),

or if you have been in recent

contact with someone who has

chicken pox or used live virus

vaccines such as polio vaccine.

numbness or weakness of the

arms and legs

muscle weakness

bleeding gums, tooth

abscesses

severe nausea and vomiting

Tell your doctor if you have had

previous treatment with cisplatin

If you have not told your doctor

or pharmacist about any of the

above, tell him/her before you

are given Cisplatin Ebewe.

Taking other medicines

Tell your doctor or pharmacist if

you are taking/using any other

medicines, including any that

you buy without a prescription

from your pharmacy,

supermarket or health food

shop.

Some medicines and Cisplatin

Ebewe may interfere with each

other. These include:

other medicines used to

treat cancer (such as

paclitaxel and

cyclophosphamide),

radiation therapy or any

other treatment which

weakens your immune

system

some antibiotics used to

treat serious infections,

including aminoglycosides

(such as gentamicin,

tobramycin or amikacin)

some vaccines (ask your

doctor).

Fluid tablets (such as

frusemide)

Antihistamines (ask your

doctor)

Oral blood thinning

medicine

These medicines may be affected

by Cisplatin Ebewe, or may affect

how well it works. You may need

different amounts of your medicine,

or different medicines. Your doctor

or pharmacist will advise you.

Do not have any vaccinations

(immunisations) without your

doctor's approval while you are

being treated with Cisplatin

Ebewe, and for up to 12 months

after you stop treatment with it.

Cisplatin Ebewe may lower your

body's resistance to infection and

there is a chance that you may get

the infection the immunisation is

meant to prevent.

In addition, other people living in

your household should not take oral

polio vaccine (Sabin) since there is

a chance they could pass the polio

virus on to you.

Your doctor and pharmacist have

more information on medicines to

be careful with or avoid while you

are being given this medicine.

How Cisplatin Ebewe is

given

How much is given

Your doctor will decide what dose

you will receive. This depends on

your condition and other factors,

such as your weight, height, kidney

function, blood counts and other

chemotherapy medicines you are

being given.

Cisplatin Ebewe may be given

alone or in combination with other

drugs.

Several courses of Cisplatin Ebewe

therapy may be needed depending

on your response to treatment.

Additional treatment may not be

repeated until your blood cell

numbers return to acceptable levels

and any unwanted effects have

been controlled.

Ask your doctor if you want to know

more about the dose of Cisplatin

Ebewe you receive.

How it is given

Cisplatin Ebewe is diluted in a fluid

bag and then given as an infusion

(drip) into your veins, over 1 or

several hours. It must only be given

by a doctor or nurse.

How long it will be given for

Cisplatin Ebewe is usually given as

a single infusion on one day. This is

called one 'cycle' of chemotherapy.

A cycle is usually repeated every 3

to 4 weeks after the previous cycle.

Your doctor will decide how many

of these cycles you need.

Adequate fluid intake is important

so you may be given fluids

intravenously before, during and

after treatment.

If you receive too much

(

Overdose)

As Cisplatin Ebewe is

administered under the care of a

highly trained doctor, it is

unlikely that you will receive an

Cisplatin Ebewe

Cisplatin Ebewe_CMI_v4_Feb 2016

Page 3 of 5

overdose. However, if you

experience severe side effects

tell your doctor immediately or

go to the Accident and

Emergency department of your

nearest hospital.

Symptoms of a Cisplatin Ebewe

overdose include the side effects

listed below in the "Side Effects"

section, but are usually of a more

severe nature.

Ask your doctor, nurse or

pharmacist if you have any

concerns.

While you are being

given Cisplatin Ebewe

Things you must do:

Keep all of your doctor's

appointments so that your

progress can be checked.

Your doctor may want to check

your blood pressure and do some

blood, hearing and other tests from

time to time to check on your

progress and detect any unwanted

side effects.

Keep follow up appointments

with your doctor.

It is important to have your follow-

up cycles of Cisplatin Ebewe at the

appropriate times to get the best

effects from your treatments.

Tell any other doctors, dentists,

and pharmacists who treat you

that you are being given this

medicine.

If you are about to be started on

any new medicine, remind your

doctor and pharmacist that you

are being given Cisplatin Ebewe.

If you plan to be vaccinated

within a year of being given

cisplatin, tell the doctor before

you are vaccinated.

If you are going to have surgery,

tell the surgeon or anaesthetist

you are being given this

medicine.

If you become pregnant while

you are being treated with this

medicine, tell your doctor

immediately.

Cisplatin Ebewe can lower the

number of white blood cells and

platelets in your blood. This means

that you have an increased chance

of getting an infection or bleeding.

The following precautions should

be taken to reduce your risk of

infection or bleeding:

avoid people with infections.

Check with your doctor

immediately if you think you are

getting an infection, or if you

get a fever or chills, cough or

hoarseness, lower back or side

pain, or find it painful or difficult

to urinate;

check with your doctor

immediately if you notice any

unusual bleeding or bruising,

black stools, blood in urine or

stools or pinpoint red spots on

your skin;

be careful when using a regular

toothbrush, dental floss or

toothpick. Your doctor or nurse

may recommend other ways to

clean your teeth and gums.

Check with your doctor before

having any dental work done;

be careful not to cut yourself

when you are using sharp

objects such as a safety razor

or nail cutters;

avoid contact sports or other

situations where you may get

bruised or injured.

In general, precautions to protect

other people should be taken

while you are receiving

chemotherapy and for one week

after the treatment period:

Flush the toilet twice to dispose

of any body fluids and waste

Wear gloves to clean any spill

of body fluid or waste. Use

paper towels or old rags, a

strong solution of non-

bleaching detergent and large

amounts of water to mop up the

spill. Discard the towels or rags

into a separate waste bag and

dispose of fluids in the toilet.

Wash linen or clothing that is

heavily contaminated by body

fluids or waste separately from

other items. Use a strong

solution of non-bleaching

detergent and large amounts of

water.

Place soiled disposable

nappies and other pads in a

plastic bag, seal and dispose

into the garbage.

For sexual intercourse, use a

barrier method such as a

condom.

Cisplatin Ebewe and its breakdown

products may be excreted in body

fluids and waste, including blood,

urine, faeces, vomitus and semen.

While you are being given Cisplatin

Ebewe your doctor should order

regular tests to check the number

of blood cells in your blood. The

results of these tests will be used to

determine the amount of Cisplatin

Ebewe you will be given for your

next dose.

While you are being given Cisplatin

Ebewe your doctor should order

regular tests to check how well your

kidneys are working.

Your doctor should order periodic

tests to estimate how well your liver

is working, and regularly check

your hearing during treatment with

cisplatin.

Tell your doctor, nurse or

pharmacist if you have any

concerns before, during or after

administration of Cisplatin

Ebewe.

As Cisplatin Ebewe often causes

nausea and vomiting, your doctor

will give you medication to prevent

you feeling sick. Your symptoms

will be better managed if you take

your medication regularly to

prevent sickness rather than use it

only when sickness occurs.

Tell your doctor or pharmacist if

you have any concerns about

this.

Cisplatin Ebewe

Cisplatin Ebewe_CMI_v4_Feb 2016

Page 4 of 5

Things you must do

Things to be careful of

Be careful driving or operating

machinery until you know how

Cisplatin Ebewe affects you. This

medicine may cause dizziness or

light-headedness in some people. If

you have these symptoms, do not

drive, operate machinery or do

anything else that could be

dangerous.

Avoid taking alcohol and aspirin

because of the risk of

gastrointestinal bleeding.

Side effects

Tell your doctor, pharmacist or

nurse as soon as possible if you

do not feel well while you are

being treated with Cisplatin

Ebewe.

Like other medicines, Cisplatin

Ebewe may have unwanted side

effects, some of which may be

serious. You may need medical

attention if you get some of the side

effects.

If you are over 65 years of age you

may have an increased chance of

getting side effects.

The effects of Cisplatin Ebewe may

take some time to occur and

therefore the side effects may be

delayed. It is possible that the

unwanted side effects may not

occur until months after Cisplatin

Ebewe is given.

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:

nausea and vomiting

loss of appetite

temporary hair loss

feeling tired or weak

problems with movement or

reduced reflexes

skin rashes, particularly at the

site of infusion

slurred speech and loss of

taste and memory.

These are the more common

side effects of Cisplatin Ebewe

Tell your doctor or nurse as

soon as possible if you notice

any of the following:

hearing problems

muscle irritability or cramps

blurred vision or other visual

disturbances

tingling in the fingers or toes.

The above list includes serious side

effects which may require medical

attention.

If any of the following happen,

tell your doctor or nurse

immediately or go to Accident

and Emergency at your nearest

hospital:

signs of an allergic reaction

(such as 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; dizziness or light-

headedness)

signs of infection, such as

fever, chills, sore throat or

mouth ulcers

shortness of breath

shaking or tremors, foot

spasms

irregular and/or rapid heart beat

unusual bleeding or bruising,

bleeding gums, blood in the

urine or stools, or pinpoint red

spots

problems with urination e.g.

pain or difficulty

yellowing of the skin or eyeballs

severe nausea and vomiting.

The above list includes very serious

side effects. You may need urgent

medical attention or hospitalisation.

Tell your doctor, nurse or

pharmacist if you notice

anything that is making you feel

unwell.

Other side effects not listed above

may also occur in some people.

Some of these side effects can only

be found when your doctor does

tests from time to time to check

your progress.

After being given

Cisplatin Ebewe

Continue drinking plenty of

fluids.

The benefits and side effects of

Cisplatin Ebewe may take some

time to occur. Therefore, even

after you have finished receiving

your Cisplatin Ebewe treatment

you should tell your doctor

immediately if you notice any of

the side effects listed above.

Storage

Cisplatin Ebewe should be stored

in the pharmacy or ward at room

temperature (between 15-25°C)

away from light and out of reach of

children.

Product description

What it looks like

Cisplatin Ebewe is a sterile,

aqueous, preservative-free

colourless or almost colourless

solution in glass vials.

Ingredients

Active ingredient:

Cisplatin

Other ingredients:

sodium chloride

hydrochloric acid (to adjust the

acidity)

Cisplatin Ebewe does not contain

lactose, sucrose, gluten, tartrazine

or any other azo dyes.

Cisplatin Ebewe

Cisplatin Ebewe_CMI_v4_Feb 2016

Page 5 of 5

Cisplatin Ebewe is available in the

following strengths and pack sizes:

100 mg in 100 mL, single glass

vials AUST R 106461

Distributor

Cisplatin Ebewe is distributed in

Australia by:

Sandoz Pty Ltd

54 Waterloo Road

Macquarie Park

NSW 2113Australia

Tel: 1800 634 500

Cisplatin Ebewe is distributed in

New Zealand by:

Novartis New Zealand Ltd

PO Box 99102

Newmarket

Auckland 1149

Tel: 0800354 335

This leaflet was prepared in Feb

2016.

NEW ZEALAND DATA SHEET

Page 1 of 12

1 PRODUCT NAME

CISPLATIN EBEWE

1 mg/mL Solution for injection

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains cisplatin 1 mg/mL

10mg in 10mL, 50mg in 50mL and 100mg in 100mL

Excipients with known effect: None

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for injection.

Clear colourless sterile aqueous solution.

4 CLINICAL PARTICULARS

4.1

Therapeutic indications

Cisplatin Ebewe is indicated as palliative therapy to be employed as follows:

Metastatic Non-seminomatous Germ Cell Carcinoma:

In established combination therapy with other approved chemotherapeutic agents in patients

with metastatic non-seminomatous germ cell tumours who have already received appropriate

surgical and/or radiotherapeutic procedures.

Metastatic Ovarian Tumours:

Cisplatin Ebewe, as a single agent, is indicated as secondary therapy in patients with

metastatic ovarian tumours refractory to standard chemotherapy who have not previously

received Cisplatin Ebewe therapy.

Advanced and Refractory Carcinoma of the Bladder:

Cisplatin Ebewe, as a single agent, is indicated as secondary therapy in patients with

advanced stage bladder cancer refractory to standard chemotherapy who have not previously

received Cisplatin Ebewe therapy.

Squamous Cell Carcinoma of the Head and Neck (Refractory to Standard

Chemotherapy):

Cisplatin Ebewe, as a single agent, is indicated as secondary therapy in patients with

squamous cell carcinoma of the head and neck refractory to standard chemotherapy who have

not previously received Cisplatin Ebewe therapy.

NEW ZEALAND DATA SHEET

Page 2 of 12

4.2

Dose and method of administration

Note:

Needles or intravenous sets containing aluminium parts that may come in contact with

Cisplatin Ebewe should not be used for preparation or administration. Aluminium reacts with

Cisplatin Ebewe, causing precipitate formation and a loss of potency.

The solution should be used intravenously only and should be administered by I.V. infusion

only as recommended below.

Metastatic Non-seminomatous Germ Cell Carcinoma:

The usual dosage of Cisplatin Ebewe for the treatment of non-seminomatous carcinoma in

combination with other approved therapeutic agents is:

20mg/m

I.V. daily for 5 days (Days 1-5) every three weeks for three courses.

Metastatic Ovarian Tumours:

As a single agent, Cisplatin Ebewe may be administered at a dose of 100mg/m

I.V. once

every 4 weeks.

Advanced and Refractory Carcinoma of the Bladder:

Cisplatin Ebewe should be administered as a single agent at a dose of 50-70 mg/m

I.V. once

every 3 to 4 weeks depending on the extent of prior exposure to radiation therapy and/or prior

chemotherapy. For heavily pretreated patients an initial dose of 50 mg/m² repeated every 4

weeks is recommended.

Squamous Cell Carcinoma of the Head and Neck (Refractory to Standard

Chemotherapy):

As a single agent, Cisplatin Ebewe may be administered at a dose of 100mg/m

I.V. once

every 4 weeks.

The following important principles should be taken into consideration when administering

cisplatin:

Cisplatin must be administered in an intravenous solution containing at least 0.3

percent NaCl. This amount of chloride ion is essential to maintain cisplatin stability in

intravenous solution. The medicine should be diluted in Sodium Chloride Intravenous

Infusion (0.9%) or in 1/2 or 1/3 physiologic saline with 5 percent Glucose.

A urine output of 100 mL/hr or greater will tend to minimise cisplatin nephrotoxicity.

This can be accomplished by prehydration with 2 litres of an appropriate intravenous

solution, and similar post cisplatin hydration (recommended 2,500 mL/m²/24 hours).

If vigorous hydration is insufficient to maintain adequate urinary output, an osmotic

diuretic may be administered (e.g. mannitol).

Cisplatin doses of 60 mg/m² have been administered safely over 1-2 hours; doses

greater than 60 mg/m² should be administered over 6-8 hours with sufficient fluid to

maintain adequate urine output during administration and post administration.

Cisplatin administration has been associated with electrolyte imbalances including

symptomatic hypomagnesaemia. Therefore monitoring of serum electrolytes, before,

during and after every course of cisplatin is recommended.

A repeat course of Cisplatin Ebewe should not be given until the serum creatinine is below

1.5 mg/100 mL and/or the BUN is below 25 mg/100 mL. A repeat course should not be given

NEW ZEALAND DATA SHEET

Page 3 of 12

until circulating blood elements are at an acceptable level (platelets ≥ 100,000/mm

, WBC ≥

4,000/mm

). Subsequent doses of Cisplatin Ebewe should not be given until an audiometric

analysis indicates that auditory acuity is within normal limits.

For instructions on dilution of the medicine before administration, see section 6.6.

4.3

Contraindications

Cisplatin Ebewe is contraindicated in patients with pre-existing renal impairment. Cisplatin

Ebewe should not be employed in myelosuppressed patients, in patients who are dehydrated

and those with pre-existing renal impairment or patients with hearing impairment.

Cisplatin Ebewe is contraindicated in patients with a history of allergic reactions to Cisplatin

Ebewe or other platinum-containing compounds.

Cisplatin is nephrotoxic and neurotoxic (in particular ototoxic). These toxicities may be

cumulative if disorders of this type pre-exist.

Patients receiving cisplatin should not breastfeed.

Concurrent administration of yellow fever vaccine is contraindicated.

4.4

Special warnings and precautions for use

Cisplatin Ebewe should be administered only in a hospital

under

the supervision of

qualified physician experienced in the use of cancer chemotherapeutic agents.

Appropriate

management

of therapy and complications is possible only when adequate diagnostic and

treatment facilities are readily available.

As with other platinum-based products,

hypersensitivity reactions appearing in most

cases

during perfusion may occur,

and necessitate

discontinuation of

perfusion and an

appropriate symptomatic treatment. Cross reactions, sometimes fatal, have been reported with

all the platinum compounds (See section 4.3 and 4.8).

Cisplatin produces cumulative nephrotoxicity.

The serum creatinine,

BUN,

and creatinine

clearance should be measured prior to initiating therapy, and prior to each subsequent course.

At the recommended dosage, Cisplatin Ebewe should not be given more frequently than once

every 3 to 4 weeks (see section 4.8). This can be accomplished by pre-hydration with 2 liters

of an appropriate intravenous solution,

and similar post

cisplatin hydration (recommended

2,500 mL/m

/24 hours).

If vigorous hydration is insufficient

to maintain adequate urinary

output, an osmotic diuretic may be administered (eg, mannitol).

Anaphylactic-like

reactions

to cisplatin have

been reported and include facial

oedema

bronchorestriction,

tachycardia

and hypotension.

These

reactions

have

occurred within

minutes

administration to patients

with prior

exposure to cisplatin,

and have

been

alleviated by administration of adrenaline, corticosteroids and antihistamines.

There are reports of severe neuropathies in patients in whom regimens are employed using

higher

doses

cisplatin or

greater

dose

frequencies

than those

recommended.

These

neuropathies may be irreversible and are seen as paresthesias in a stocking-glove distribution,

areflexia, and loss of proprioception and vibratory sensation. A neurologic examination must

be carried out at regular intervals

Loss of motor function has also been reported.

Since ototoxicity of cisplatin is cumulative, audiometric testing should be performed prior to

initiating therapy and prior to each subsequent dose of medicine (see section 4.8).

Cisplatin has been found to have a carcinogenic potential

in animals.

The development

NEW ZEALAND DATA SHEET

Page 4 of 12

acute leukaemia co-incident with the use of cisplatin has been reported rarely in humans, as is

generally associated with other leukemogenic agents. In these reports, cisplatin was generally

given in combination with other leukaemogenic agents.

Peripheral

blood counts should be monitored weekly.

Liver function should be monitored

periodically. Neurological examination should also be performed regularly (see section 4.8).

Neurologic examination should also be performed regularly (see section 4.8).

Cisplatin

Ebewe should be administered only in a hospital

under

the supervision of

a qualified

physician experienced in the use of cancer chemotherapy agents.

Because of its high protein binding Cisplatin Ebewe may interfere with the distribution of

other protein bound medications.

cisplatin produces

cumulative

nephrotoxicity and ototoxicity,

other

nephrotoxic

ototoxic medicines should be avoided during cisplatin therapy unless unavoidable.

Following

dilution

solution

Cisplatin

Ebewe

undergoes

varying

degrees

decomposition,

depending on the diluent

used.

Normal

Saline is the preferred diluent

(see

section 4.2).

Injection site reactions may occur during the administration of cisplatin. Given the possibility

extravasation,

recommended to closely monitor

infusion site

possible

infiltration during medicine administration. A specific treatment for extravasation reactions is

unknown at this time.

4.5

Interaction with other medicines and other forms of interaction

Plasma levels of anticonvulsants may become subtherapeutic during cisplatin therapy.

In a randomised trial in advanced ovarian cancer, response duration was adversely affected

when pyridoxine was used with Altretamine (hexamethylmelamine) and cisplatin.

The renal toxicity of ifosfamide may be greater when used with cisplatin or in patients who

have previously been given cisplatin.

Ifosfamide may increase hearing loss due to cisplatin.

Oral anticoagulants. In the event of simultaneous use of oral anticoagulants, it is advisable

regularly to check the INR.

Antihistamines, Phenothiazines and others. Simultaneous use of antihistamines, buclizine,

cyclizine, loxapine, meclozine, phenothiazines, thioxanthenes or trimethobenzamides may

mask ototoxicity symptoms (such as dizziness and tinnitus).

Attenuated live vaccines.Live vaccines should not be used in patients undergoing Cisplatin

therapy. Yellow fever vaccine is strictly contraindicated because of the risk of fatal systemic

vaccinal disease (see section 4.3). In view of the risk of generalized illness, it is advisable to

use an inactivated vaccine if available.

4.6

Fertility, pregnancy and lactation

Use in pregnancy (Category D)

Cisplatin Ebewe, like several other cytotoxic agents, is likely to produce foetal damage. Safe

use in human pregnancy has not been established. Cisplatin is mutagenic in bacteria and

produces chromosome aberrations in animal cells in tissue culture. In mice cisplatin is

teratogenic and embryotoxic.

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During treatment with cisplatin and for a minimum of the following 6 months, appropriate

measures must be taken to avoid pregnancy; this applies to patients of both genders.

Genetic counselling is recommended if the patient wishes to have children after ending the

treatment.

Since a treatment with cisplatin may cause irreversible infertility, it is recommended that

men, who wish to become fathers in the future, ask for advice regarding cryo-conservation of

their sperm prior to treatment.

Use in lactation

Cisplatin is excreted in breast milk.

To avoid possible harm to the baby, breast feeding is not advised during Cisplatin Ebewe

therapy.

4.7

Effects on ability to drive and use machines

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

Nevertheless, the profile of undesirable effects (like nephrotoxicity) may influence the ability

to drive vehicles and use machinery.

4.8

Undesirable effects

Renal and urinary disorders:

Acute renal toxicity,

which was highly frequent in the past and represented the major dose-

limiting toxicity of cisplatin, has been greatly reduced by the use of 6 to 8 hour infusions as

well

by concomitant

intravenous

hydration and forced diuresis.

Cumulative toxicity,

however,

remains

problem and may be

severe.

Dose-related and

cumulative

renal

insufficiency is the major dose-limiting toxicity of cisplatin. Renal toxicity has been noted in

28 to 36% of patients treated with a single dose of 50mg/m

is first

noted during the

second week after a dose and is manifested by elevations in BUN and creatinine, serum uric

acid and/or

a decrease in creatinine clearance.

Renal

insufficiency is

generally mild to

moderate and reversible at the usual doses of the drug, however, high or repeated doses can

increase the severity and duration of renal

impairment

and may produce irreversible renal

insufficiency (sometimes fatal).

Renal

failure has been reported following intraperitoneal

instillation of the drug. Renal function must return to normal before another dose of Cisplatin

Ebewe can be given.

Impairment

of renal

function has been associated with renal

tubular

damage.

Ear and labyrinth disorders:

Ototoxicity has been observed in up to 31% of patients treated with a single dose of cisplatin

50mg/m

, and is manifested by tinnitus and/or hearing loss in the high frequency range (4,000

to 8,000 Hz). Decreased ability to hear normal conversational tones may occur occasionally.

Ototoxic effects may be more severe in children receiving cisplatin.

Hearing loss can be

unilateral or bilateral and tends to become more frequent and severe with repeated doses. It is

unclear whether cisplatin-induced ototoxicity is reversible. Ototoxicity may be enhanced with

prior or simultaneous cranial irradiation and may be related to peak plasma concentration of

cisplatin. Careful monitoring or audiometry should be performed prior to initiation of therapy

and prior to subsequent doses of Cisplatin Ebewe. Vestibular toxicity has also been reported.

Blood and lymphatic system disorders:

Myelosuppression occurs in 25 to 30% of

patients treated with cisplatin.

The nadirs in

circulating platelets and leukocytes occur between days 18 to 23 (range 7.5 to 45) with most

NEW ZEALAND DATA SHEET

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patients recovering by day 39 (range 13 to 62). Leukopenia and thrombocytopenia are more

pronounced at

higher doses (>50mg/m

Anaemia (decrease of >2g haemoglobin/100mL)

occurs at

approximately the same frequency but

with a later

onset

than leukopenia and

thrombocytopenia.

Cisplatin has

been shown to sensitise red blood cells,

sometimes

resulting in a direct

Coombs-positive haemolytic anaemia. The incidence, severity and relative importance of this

effect in relation to other haematological toxicity has not been established, but the possibility

of a haemolytic process should be considered in any person who is receiving Cisplatin Ebewe

and has an unexplained fall

in haemoglobin.

The haemolytic process is not

clearly dose

related and reverses on cessation of therapy.

The development

of acute leukemia coincident

with the use of cisplatin has been reported

rarely in humans.

In these reports,

cisplatin was

generally in combination with other

leukemogenic agents.

Gastrointestinal disorders:

This cytostatic agent

has a more marked toxicity than is usually found in antineoplastic

chemotherapy.

Marked nausea and vomiting occur

in almost

patients treated with cisplatin,

and are

occasionally so severe that the medicine must be discontinued. Nausea and vomiting usually

begin within one to four hours after treatment

and last

up to 24 hours.

Various degrees of

nausea and anorexia may persist for up to one week after treatment.

Delayed nausea and vomiting (beginning or persisting 24 hours or more after chemotherapy)

has occurred in patients attaining complete emetic control on the day of cisplatin therapy.

Diarrhoea has also been reported.

These side effects are only partially relieved by standard antiemetics.

Rare occurrence of

stomatitis has been reported. Reported toxicity includes gingival platinum line.

Nervous system disorders:

Peripheral

neuropathies

occur

infrequently with usual

doses

the medicine.

They are

generally sensory in nature (e.g. paraesthesia of the upper and lower extremities), but can also

include

motor

difficulties,

reduced

absent

reflexes

weakness.

Autonomic

neuropathy, seizures, slurred speech, loss of taste and memory loss have also been reported.

These neuropathies usually appear after prolonged therapy,

have also developed after a

single medicine dose.

Areflexia and loss of proprioception and vibratory sensation may be

seen, especially if cisplatin is given at higher doses or more frequently than recommended. In

some patients they may be irreversible however,

they have been partially or

completely

reversible in others following discontinuance of cisplatin therapy.

Cerebrovascular accident

has been reported in patients treated with cisplatin.

Convulsions,

leukoencephalopathy and

reversible posteriorleukoencephalopathy syndrome have been rarely reported.Muscle cramps

sudden onset

and short

duration have been reported.

These were usually reported in

patients who had received a relatively high dose of

cisplatin,

and who had a relatively

advanced stage of peripheral neuropathy.

Metabolism and nutritional disorders:

Hypomagnesaemia,

hypocalcaemia,

hyponatraemia,

hypokalaemia and hypophosphataemia

have been reported to occur in patients with cisplatin and are probably related to renal tubular

damage.

Tetany has occasionally been reported in those patients with hypocalcaemia and

hypomagnesaemia.

Generally,

normal serum electrolyte levels are restored by administering

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supplemental electrolytes and discontinuing cisplatin.

Inappropriate antidiuretic hormone syndrome has also been reported.

Hyperuricaemia has been reported to occur

approximately the same frequency as the

increase in BUN and serum creatinine.

more pronounced after

doses

greater

than

50mg/m

and peak levels of uric acid generally occur between 3 to 5 days after the dose.

Allopurinol therapy for hyperuricaemia effectively reduces uric acid levels.

Eye disorders:

Retinal

toxicity manifests as blurred vision and altered colour

perception.

Optic neuritis,

papilloedema and cerebral

blindness have been reported infrequently in patients receiving

standard recommended doses of cisplatin. Improvement and/or total recovery usually occurs

after discontinuing cisplatin.

Steroids with or without

mannitol

have been used;

however,

efficacy has not been established.

Blurred vision and altered colour perception have been reported after the use of regimens

with higher

doses of

cisplatin or

greater

dose frequencies than those recommended.

altered colour perception manifests as a loss of colour discrimination,

particularly in blue-

yellow axis. The only finding on fundoscopic examination is irregular retinal pigmentation of

the macular area.

Immune system disorders:

Anaphylactic-like reactions have been occasionally reported in patients previously exposed to

cisplatin.

The reactions consist

facial

oedema,

wheezing,

tachycardia and hypotension

within a few minutes of medicine administration. Reactions may be controlled by intravenous

adrenalin,

corticosteroids and antihistamines.

Patients receiving Cisplatin Ebewe should be

observed carefully for

possible anaphylactic-like reactions and supportive equipment

medication should be available to treat such a complication.

Hepatobiliary disorders:

Transient

elevations of hepatic enzymes,

and bilirubin can occur when Cisplatin Ebewe is

administered in recommended doses.

Cardiac disorders:Cardiovascular

abnormalities

(e.g.

coronary disease,

congestive heart

failure, arrhythmias, postural hypotension, thrombotic microangiopathy).

Respiratory,

Thoracic and Mediastinal

Disorders: Pulmonary toxicity has been reported

in patients treated with cisplatin in combination with bleomycin or 5-fluorouracil.

Skin

and

Subcutaneous

Tissue

Disorders:

Mild

alopecia.

Rarely,

urticarial

maculopapular skin rashes have also been observed.

Musculoskeletal and Connective Tissue Disorders: Myalgia.

Reproductive System and Breast Disorders:

Cisplatin can affect male fertility. Impairment of spermatogenesis and azoospermia have been

reported.

Although the impairment

of spermatogenesis can be reversible,

males undergoing

cisplatin treatment should be warned about the possible adverse effects on male fertility.

Neoplasm benign,

malignant,

and unspecified:

Acute leukemia has been reported as

occurring uncommonly.

Infections and infestations: Sepsis is commonly observed.

General

Disorders and Administration Site Conditions: Pyrexia occurs very commonly.

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Local

effects such as phlebitis,

cellulitis and skin necrosis (following extravasation of the

medicine) may also occur.

Other Toxicities:

Vascular

toxicities

coincident

with

cisplatin

combination

with

other

antineoplastic agents have been reported rarely.

The events are clinically heterogenous and

may include myocardial infarction, cerebrovascular accident, thrombotic microangiopathy or

cerebral arteritis. Various mechanisms have been proposed for these vascular complications.

There are also reports

Raynaud's

phenomenon occurring in patients

treated with the

combination of bleomycin,

vinblastine with or without

cisplatin.

has been suggested that

hypomagnesaemia developing coincident with the use of cisplatin may be an added, although

not essential, factor associated with this event. However, it is currently unknown if the cause

of Raynaud's phenomenon in these cases is the disease,

underlying vascular compromise,

bleomycin, vinblastine, hypomagnesaemia, or a combination of any of these factors.

Reporting of suspected adverse reactions

Reporting suspected adverse reaction after

authorisation of

the medicine is important.

allows

continued

monitoring

benefit/risk

balance

medicine.

Healthcare

professionals

asked

report

suspected

adverse

reactions

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

4.9

Overdose

Caution should be used to prevent inadvertent overdosage with Cisplatin Ebewe.

Signs and symptoms

Acute overdosage with this medicine may result in kidney failure, liver failure, deafness,

ocular toxicity (including detachment of the retina), significant myelosuppression, intractable

nausea and vomiting and/or neuritis. In addition, death can occur following overdosage.

Management

No proven antidotes have been established for cisplatin overdosage. Haemodialysis even

when initiated four hours after overdosage, appears to have little effect on removing platinum

from the body because of rapid and high degree of protein binding of cisplatin. Management

of overdosage should include general supportive measures to sustain the patient through the

period of toxicity that may occur.

Contact the Poisons Information Centre on (telephone 0800 POISON or 0800 764766) for

advice on management of overdose.

5 PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group

Antineoplastic and immunomodulating agents; antineoplastic agents; other antineoplastic

agents; Platinum compounds

ATC Code: L01XA01

Cisplatin

has the following chemical

structure:

NEW ZEALAND DATA SHEET

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Cisplatin (cis-diamminedichloroplatinum) is a heavy metal complex containing a central

atom of platinum surrounded by two chlorine atoms and two ammonia molecules in the cis

position.

Molecular formula: Cl

Molecular weight: 300.1

CAS: 15663-27-1

Cisplatin is a yellow to orange crystalline powder that is slightly soluble in water or saline at

1mg/mL and in dimethylformamide at 24mg/mL.

Mechanism of action

Cisplatin Ebewe has biochemical properties similar to that of bifunctional alkylating agents

producing interstrand and intrastrand crosslinks in DNA. It is apparently cell-cycle non-

specific.

5.2

Pharmacokinetic properties

Pharmacokinetics

Absorption

Following a single I.V.

dose,

cisplatin concentrates in liver,

kidneys,

and large and small

intestines in animals and humans.

Cisplatin apparently has poor

penetration into the CNS.

Plasma levels of radioactivity decay in a biphasic manner after an I.V. bolus dose of radioactive

cisplatin to patients.

Distribution

Following bolus injection of intravenous infusion over 2 to 7 hours, of doses ranging 50 to 100

mg/m²,

plasma cisplatin half-life is approximately 30 minutes.

The ratios of cisplatin to total,

free (ultrafilterable) platinum in the plasma range from 0.5 to 1.1 after a dose of 100 mg/m².

Metabolism

Cisplatin does not undergo instantaneous and reversible binding to plasma proteins characteristic

of normal

medicine-protein binding;

however,

the platinum from cisplatin becomes bound to

plasma proteins. These complexes are slowly eliminated with a half-life of 5 days or more.

Elimination

Over

a range of

doses

administered as

bolus

injections

infusions

up to 24 hours,

approximately 10 to 40% of the platinum administered is excreted in the urine in 24 hours.

Similar mean urinary recoveries of platinum are found following daily administration on five

consecutive days.

Intact

cisplatin accounts for the majority of platinum excreted in the urine

within one hour of administration. Renal clearance of cisplatin exceeds creatinine clearance. The

renal clearance of free (ultrafilterable) platinum also exceeds creatinine clearance, is non-linear

and depends

on dose,

urine flow rate and individual

variability in tubular

secretion and

reabsorption.

close

correlation

exists

between

renal

clearance

either

free

NEW ZEALAND DATA SHEET

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(ultrafilterable) platinum or cisplatin and creatinine clearance. Mannitol administration increases

urinary excretion of Cisplatin Ebewe following intravenous infusion and excretion of up to 75%

in 24 hours has been reported.

There is a potential

for accumulation of free (ultrafilterable)

platinum in plasma when cisplatin is

administered on a daily basis,

when it

administered on an intermittent basis.

Although small

amounts

platinum are

present

in the

bile

and large

intestine

after

administration of cisplatin, faecal excretion of platinum appears to be insignificant.

5.3

Preclinical safety data

Carcinogenicity, Mutagenicity and Impairment of Fertility

Cisplatin is mutagenic in bacteria and produces chromosome aberrations in animal cells in

tissue culture. In mice cisplatin is teratogenic and embryotoxic see section 4.6.

6 PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Hydrochloric acid for pH adjustment

Sodium chloride

Water for injections

6.2

Incompatibilities

Cisplatin reacts with aluminium which results in production of a black platinum precipitate.

Therefore any device containing aluminium that may come in contact with cisplatin (sets for

intravenous infusion, needles, catheters, syringes) must be avoided.

This medicinal product must not be mixed with other medicinal products except those

mentioned in section 6.6.

The cisplatin 1 mg/ml concentrate must not be diluted with glucose solution 5% alone or

mannitol solution 5% alone, but only with the mixtures containing additionally sodium

chloride as stated in section 6.6.

Antioxidants (such as sodium metabisulphite), bicarbonates (sodium bicarbonate), sulphates,

fluorouracil and paclitaxel may inactivate cisplatin in infusion systems.

6.3

Shelf life

2 years

Diluted solutions: 24 hours

6.4

Special precautions for storage

Unopened vials: Store at or below 25

C. Do not refrigerate. Protect from light.

Diluted solutions: Store at room temperature (25°C) and protect from light.

6.5

Nature and contents of container

Cisplatin Ebewe is supplied in a 10 mL, 50mL or 100mL glass vial.

Each box contains 1 vial.

Not all pack sizes may be marketed.

Product is for single use in one patient only.

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6.6

Special precautions for handling, reconstitution and disposal

Cisplatin Ebewe is for single use in one patient only. Contains no antimicrobial agent.

Discard any unused residue.

Solutions of Cisplatin Ebewe: Cisplatin Ebewe can be diluted to 0.10 mg/mL in either 0.9%

sodium chloride, 1:1 mixture of 5% glucose and 0.9% sodium chloride or a 1:1 mixture of

5% mannitol and 0.9% sodium chloride.

For storage conditions after dilution of the medicine, see section 6.3 and 6.4

Procedures for Handling and Disposal of Anticancer Medicines:

Procedures for proper handling and disposal of anti-cancer medicines should be considered.

Several guidelines on this subject have been published and should be used appropriately.

As with other potentially toxic compounds, caution should be exercised in handling and

preparing the solution of Cisplatin Ebewe. Skin reactions associated with accidental exposure

to Cisplatin Ebewe may occur. The use of gloves is recommended. If Cisplatin Ebewe

solution contacts skin or mucosae, immediately wash the skin or mucosae thoroughly with

soap and water.

Conforming to the procedures appropriate for the manipulation and elimination of cytostatic

agents is recommended.

Before administering the solution to the patient, verify the clarity of the solution and the

absence of particles.

Disposal

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

requirements.

7 MEDICINE SCHEDULE

Prescription Medicine.

8 SPONSOR

Novartis New Zealand Limited

PO Box 99102, Newmarket,

Auckland 1149

Telephone: 0800 354 335

9 DATE OF FIRST APPROVAL

29 June 2006

10 DATE OF REVISION OF THE TEXT

NEW ZEALAND DATA SHEET

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28 June 2017

SUMMARY TABLE OF CHANGES

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