PACKAGE LEAFLET: INFORMATION FOR THE USER

Cisplatin 1 mg/ml Sterile Concentrate

In this leaflet:

1.    What Cisplatin Sterile Concentrate is and what it is used for

2.    Before you use Cisplatin Sterile Concentrate

3.    How to use Cisplatin Sterile Concentrate

4.    Possible side effects

5.    How to store Cisplatin Sterile Concentrate

6.    Further information

1. WHAT CISPLATIN STERILE CONCENTRATE IS AND WHAT IT IS USED FOR

Cisplatin forms part of a group of medicines called cytostatics, which are used in the treatment of cancer. Cisplatin can be used alone but more commonly Cisplatin is used in combination with other cyostatics.

What is it used for?

Cisplatin can destroy cells in your body that may cause certain types of cancer (tumour of testis, tumour of ovary, tumour of the bladder, head and neck epithelial tumour, lung cancer and for cervical cancer in combination with radiotherapy).

2. BEFORE YOU USE CISPLATIN STERILE CONCENTRATE

Do not use Cisplatin Sterile Concentrate

•    if you have shown signs of hypersensitivity (severe allergy) to cisplatin or similar anti-cancer medicines in the past

•    if you have severe kidney disease

•    if you have hearing difficulties

•    if you have very low numbers of blood cells (called ‘myelosuppression'), (your doctor will check this with a blood test)

•    if you are dehydrated

•    if you are breast-feeding

•    if you need to have a vaccine for ‘yellow fever'

Tell your doctor if the above applies to you before this medicine is used.

Take special care with Cisplatin Sterile Concentrate

•    if you have any symptoms of nerve damage (peripheral neuropathy) such as pins and needles, numbness or poor sense of touch

•    if you have had radiation therapy to your head

Tell your doctor if either of the above applies to you before this medicine is used.

Taking/using other medicines

Special care is needed if you are taking/using other medicines as some could interact with cisplatin, for example:

•    some antibiotics, such as cephalosporins, aminoglycosides and amphotericin B and some substances used in medical imaging may make the side effects of cisplatin worse; particularly kidney problems

•    some water tablets called loop diuretics, antibiotics called aminoglycosides and an anti-cancer medicine called ifosfamide may make the hearing loss side effect of cisplatin worse

•    bleomycin (anti-cancer medicine), methotrexate (used to treat cancer or arthritis) and paclitaxel (anti-cancer medicine) may produce more side effects if cisplatin is also being used

•    the effectiveness of oral anticoagulants may be affected. Your doctor will monitor with blood tests

•    use of certain antihistamines may hide the symptoms of balance changes (such as dizziness or tinnitus)

•    the effectiveness of medicines used for the treatment of convulsions (e.g. phenytoin) may be reduced, so blood levels may need to be checked

•    cisplatin may make the side effects of the anti-cancer medicine ifosfamide worse

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant, trying to become pregnant or breast-feeding. Your doctor will decide if you should receive this medicine. Due to the possible risk of birth defects, male and female patients should take contraceptive measures both during treatment with cisplatin and for at least six months after treatment has ended.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Do not drive or use machines if you experience any side effect which may lessen your ability to do so.

Important information about one of the ingredients of Cisplatin Sterile Concentrate

This medicinal product contains 1.5 mmol sodium (35 mg) per vial. To be taken into consideration by patients on a controlled sodium diet.

The vial stopper contains dry natural rubber (a derivative of latex), which may cause allergic reactions.

3. HOW TO USE CISPLATIN STERILE CONCENTRATE

Dosage and method of administration

Cisplatin should only be given by a specialist in cancer treatment.

The concentrate is diluted with a sodium chloride solution.

Cisplatin is only given by injection into a vein (an intravenous infusion). Cisplatin should not come into contact with any materials that contain aluminium.

The recommended dosage of Cisplatin depends on your well-being, the anticipated effect of the treatment, and whether or not cisplatin is given on its own (monotherapy) or in combination with other agents (combination chemotherapy).

Cisplatin (monotherapy):

The following dosages are recommended:

•    a single dosage of 50 to 120 mg/m² body surface, every 3 to 4 weeks

•    15 to 20 mg/m² per day over a 5-day period, every 3 to 4 weeks Cisplatin in combination with other chemotherapeutical agents (combination chemotherapy):

•    20 mg/m² or more, once every 3 to 4 weeks.

For treatment of cervical cancer cisplatin is used in combination with radiotherapy.

A typical dose is 40 mg/m² weekly for 6 weeks.

In order to avoid, or reduce, kidney problems, you are advised to drink copious amounts of water for a period of 24 hours following treatment with Cisplatin.

If you believe you have received more Cisplatin than you should

Your doctor will ensure that the correct dose for your condition is given. In case of overdose, you may experience increased side effects. Your doctor may give you symptomatic treatment for these side effects. If you think you received too much Cisplatin, immediately contact your doctor.

If you have any further questions on the use of this medicine, ask your doctor.

4. POSSIBLE SIDE EFFECTS

Like all medicines, cisplatin can cause side effects, although not everybody gets them.

If any of the following happen, tell your doctor immediately:

• severe allergic reaction - you may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and you may feel you are going to faint

Cisplatin 1 mg/ml Sterile Concentrate

The following information is intended for medical or healthcare professionals only

Further to the information included in section 3, practical information on the preparation/handling of the medicinal product is provided here.

Incompatibilities

Cisplatin may interact with metal aluminium to form a black precipitate of platinum. All aluminium-containing IV sets, needles, catheters and syringes should be avoided.

There is a total loss of cisplatin in 30 minutes at room temperature when mixed with metoclopramide and sodium metabisulphite in concentrations equivalent to those that would be found on mixing with a commercial formulation of metoclopramide.

Cisplatin and sodium bisulphite have been known to react chemically. Such antioxidants might inactivate cisplatin before administration if they are present in intravenous fluids.

Dilution

The vials are for single use only. Discard any unused contents.

Cisplatin 1 mg/ml Sterile Concentrate should be diluted in 2 litres of 0.9% sodium chloride injection.

Following dilution in 0.9% sodium chloride injection, chemical and physical in-use stability has been demonstrated for up to 14 days at 20°C. The diluted product should not be refrigerated. From a microbiological point of view, however, the product should be used immediately. If not used immediately,

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•    severe chest pains possibly radiating to the jaw or arm with sweating, breathlessness and nausea (heart attack)

•    pain or swelling at the injection site during the injection (may be due to the injection not going into the vein properly, which can lead to serious damage to the tissues around the injection site)

These are serious side effects. You may need urgent medical attention.

Very common side effects which may affect more than 1 person in 10 are listed below:

•    decrease in bone marrow function (which can affect the production of blood cells)

•    decrease in white blood cells, which makes infections more likely (leukopenia)

•    decrease in blood platelets, which increases the risk of bruising and bleeding (thrombocytopenia)

•    reduction of red blood cells which can cause weakness and your skin to look pale (anaemia)

•    reduced level of sodium in the blood

•    high temperature

Common side effects which may affect less than 1 person in 10, but more than 1 person in 100 are listed below:

•    fast, irregular or slow heart beats

•    sepsis (blood poisoning)

Uncommon side effects which may affect less than 1 person in 100, but more than 1 person in 1,000 are listed below:

•    severe allergic reaction (see above)

•    damage to the ear (ototoxicity)

•    reduced level of magnesium in the blood

•    abnormal sperm production

Rare side effects which may affect less than 1 person in 1,000, but more than 1 person in 10,000 are listed below:

•    increased risk of acute leukaemia

•    seizures (fits)

•    fainting, headache, confusion and loss of vision

•    loss of certain types of brain function, including brain dysfunction characterised by spasms and reduced level of consciousness

•    heart attack

•    inflammation of mucous membranes of the mouth (stomatitis).

•    peripheral neuropathy of the sensory nerves, characterised by tickling, itching or tingling without cause and sometimes with loss of taste, touch, sight, sudden shooting pains from the neck through the back and into the legs when bending forward.

Very rare side effects which may affect less than 1 person in 10,000 are listed below:

•    heart arrest

Side effects where the number of people affected is not known are listed below:

•    signs of infection such as fever or sore throat

•    haemolytic anaemia

•    inappropriate release of vasopressin hormone (ADH) which may lead to low sodium in the blood and water retention

•    blood amylase (enzyme) increased

•    dehydration

•    reduced level of calcium, phosphate, potassium in the blood

•    high level of uric acid in the blood

•    muscle cramping

•    spinal disease which may cause a sensation of electric shocks passing into your limbs

•    brain dysfunction (confusion, slurred speech, sometimes blindness, memory loss, and paralysis)

•    stroke

•    loss of taste

•    problems with your eyesight (blurred vision, odd colours, loss of vision or eye pain)

•    ringing in the ears or deafness

•    heart problems

•    unusually cold or white hands and feet

•    tingling, numbness or tremor in your hands, feet, arms or legs

•    persistent headache

•    feeling or being sick

•    loss of appetite, anorexia

•    hiccups

•    diarrhoea

•    liver enzymes increased, bilirubin increased

•    difficulty breathing

•    problems with your kidneys or urine

•    hair loss

•    rash

•    extreme tiredness/weakness

•    swelling or soreness where the injection was given

•    cramps or spasms

•    burning or prickling sensation

•    unexpected bruising or bleeding

•    haemolytic uraemic syndrome which may cause changes to the kidneys and blood

Cisplatin may lead to problems with your blood, liver and kidneys. Your doctor will take blood samples to check for these problems.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Effects on fertility

Treatment with cisplatin can potentially cause permanent sterility in men.

It is recommended that those who wish to become fathers in the future discuss the possibility of cryoconservation (freezing) of their sperm prior to treatment. Tell your doctor if you have any concerns.

5. HOW TO STORE CISPLATIN STERILE CONCENTRATE

Keep out of the reach and sight of children

Expiry

This medicine must not be used after the expiry date which is stated on the vial label and carton after ‘EXP'. Where only a month and year is stated, the expiry date refers to the last day of that month.

Storage

The vials should not be refrigerated or frozen, and they should not be stored above 25°C.

The vials should be kept in the outer carton in order to protect from light. Prepared infusions should be used immediately, however, if this is not possible they can be stored for up to 14 days provided they have been prepared in a way to exclude microbial contamination. The prepared infusions should not be refrigerated.

6. FURTHER INFORMATION

What Cisplatin Sterile Concentrate contains

The active substance is cisplatin. Each millilitre (ml) of solution contains 1 milligram (mg) of cisplatin.

The other ingredients are mannitol, sodium chloride, dilute hydrochloric acid and Water for Injections.

What Cisplatin Sterile Concentrate looks like and contents of the pack

Cisplatin Sterile Concentrate is a clear, colourless to pale yellow concentrate for solution for infusion which comes in glass containers called vials.

It may be supplied in packs containing:

1 or 10 x 10 mg/10 ml vial 1 or 10 x 50 mg/50 ml vial 1 or 10 x 100 mg/100 ml vial Not all pack sizes may be marketed

Marketing authorisation holder and manufacturer responsible for batch release in Europe

Hospira UK Limited, Queensway, Royal Leamington Spa, Warwickshire, CV31 3RW

Manufacturer

Hospira Australia Pty Ltd, Lexia Place, Mulgrave, Victoria 3170, Australia This leaflet was last approved in 12/2015

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in-use storage times and conditions prior to use are the responsibility of the user and dilution should take place in controlled and validated aseptic conditions.

Cytotoxic Handling Guidelines

Administration: Should be administered only by or under the direct supervision of a qualified physician who is experienced in the use of cancer chemotherapeutic agents.

Preparation: Chemotherapeutic agents should be prepared for administration only by professionals who have been trained in the safe use of preparation.

Operations such as reconstitution of powder and transfer to syringes should be carried out only in the designated area.

The personnel carrying out these procedures should be adequately protected with clothing, gloves and eye shield.

Pregnant personnel are advised not to handle chemotherapeutic agents.

The vial stopper contains dry natural rubber (a derivative of latex), which may cause allergic reactions.

Contamination: In the event of contact with the skin or eyes, the affected area should be washed with copious amounts of water or normal saline. A bland cream may be used to treat the transient stinging of skin. Medical advice should be sought if the eyes are affected.

In the event of spillage, operators should put on gloves and mop the spilled material with a sponge kept in the area for that purpose. Rinse the area twice with water. Put all solutions and sponges into a plastic bag and seal it.

Disposal: Syringes, containers, absorbent materials, solution and any other contaminated material should be placed in a thick plastic bag or other impervious container and incinerated.    _fl79_g7g

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Component Specification

Item number:		Q79272
Request number:		AS5308
Country:		United Kingdom
OI template:	88S119
Amalia version:	6
Mulgrave version:	5	_
Dimensions:	118 x 570 mm (20 panels)
Container(s):	vial
Supplier:	Howden Printing
Stock:	Primapharm 40gsm /
	Teropaque Thin Medical 40gsm
1 Folded dimensions:28.5 x 118 mm
Printed both sides:	Yes
Perforated:	No	_
Pharma code:	46 (12222)
Pharma code length: 10.5 mm
Mulgrave 4 series no.: 434638
Colours
Black:		■ 1

Hospira

Requester

I have checked this artwork against the registered text including spelling, layout, size, colours, registration numbers and scientific equations, the name and address and trademarks. Also for any possible changes to related items.

This artwork is in conformance with the Marketing Authorisation and can now proceed to the printing stage.

Previous Item Number: Q72542 / 434060 Signed:

Date:

Version 1 Technician: Date:	LB 06/Jul/15	Version 2 Technician: Date:	KN 09/Jul/15
Version 3 Technician: Date:	JE 19/Aug/15	Version 4 Technician: Date:	KN 20/Aug/15
Version 5 Technician: Date:	JH 22/Dec/15	Version 6 Technician: Date:	JW 05/Jan/16
Version 7 Technician: Date:	XX dd/mmm/yy	Version 8 Technician: Date:	XX dd/mmm/yy
Version 9 Technician: Date:	XX dd/mmm/yy	Version 10 Technician: Date:	XX dd/mmm/yy