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Information for the Physician

Imuran® Injection

azathioprine

Please refer to the Summary of Product Characteristics (SPC) for further details on this product.

When the reconstituted solution is diluted asdirected below, the pH of the resulting solution may be expected to be within the range pH8.0to9.5(the greater thedilution, the lower the pH).

Where dilution is not practicable, the reconstituted solution should be injected slowly over a period of not lessthan one minute and followed immediately by not less than 50 ml of one of the recommended infusion solutions.

Care must be taken to avoid perivenous injection, which may produce tissue damage.

Trade Name of the Medicinal Product

Imuran Injection

Reconstitution and dilution of Imuran Injection

Qualitative and Quantitative Composition

Azathioprine EP 50 mg/vial

Pharmaceutical Form

Injection

Method of Administration

Imuran Injection should be used only when the oral route is impractical, and should be discontinued as soon as oral therapy is tolerated. It must be administered only bythe intravenous route.

Specialist medical literature should be consulted for guidance as to clinical experience in particular conditions.

Imuran Injection, when reconstituted as directed, is a very irritant solution with a pH of 10-12.

Precautions should always be taken when handling Imuran Injection (see Instructionsfor Use/Handling).

No antimicrobial preservative is included. Therefore reconstitution and dilution must be carried out under full aseptic conditions, preferably immediately before use. Any unused solution should be discarded.

The contents of each vial should be reconstituted bytheaddition of 5 mlto15ml of Water for Injections. The reconstituted solution is stable for up to 5 days when stored between 5°C and 25°C.

When diluted on the basis of 5 ml of reconstituted solution to a volume of between 20 ml and 200 ml of one of the following infusion solutions, Imuran isstable for up to 24 hours at room temperature (15°Cto25°C):

Sodium Chloride Intravenous Infusion BP (0.45% w/v and 0.9% w/v)

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Package Leaflet: Information for the User

Imuran® Injection

azathioprine

Read all of this leaflet carefully before you start using this medicine

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor, nurse or pharmacist.

•    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms arethe same asyours.

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

In this leaflet:

1    What Imuran is and what it is used for

2    Beforeyou have Imuran

3    How to have Imuran

4    Possible side effects

5    How to store Imuran

6    Further information

Ask your doctor, nurse or pharmacist if you would like any further explanation about these uses.

2 Before you have Imur

1 What Imuran is and what it is used for

Imuran injection contains a medicine called azathioprine. This belongs to a group of medicines called immunosuppressants. These medicines reducethe activity of your body's immune system.

Imuran is used to:

•    stopyour bodyrejecting an organ transplant

•    treat diseases where your immune system reacts againstyour own body (called autoimmune diseases, such as rheumatoid arthritis).

Do not have Imuran if:

•    you areallergic (hypersensitive) to azathioprine, mercaptopurine or any of the other ingredients of Imuran (listed in section 6).

If you are not sure, talk to your doctor, nurse or pharmacist before having Imuran.

Take special care with Imuran Checkwith your doctor, nurse or pharmacist beforehaving Imuran if:

•    you have liver or kidney disease

•    you have 'Lesch-Nyhan Syndrome'.

This is a rare condition that runs in families caused by a lack of something called HPRT or 'hypoxanthine-guanine-phosphoribosyltransferase'

•    you have a condition where your body produces too little of something called TPMT or 'thiopurine methyltransferase'

•    you have ever suffered from chickenpox or shingles.

If you are not sure if any of the above applyto you, talktoyour doctor, nurse or pharmacist before having Imuran.

Taking other medicines Please tell your doctor, nurse or pharmacist if you are taking or have recently taken any other medicines. This includes medicines obtainedwithouta prescription, including herbal medicines. This is because Imuran can affect the way some medicines work. Also some other medicines can affect the way Imuran works.

In particular, tell your doctor, nurse or pharmacist if you are taking any of the following medicines:

•    allopurinol - used for gout

•    tubocurarine or succinylcholine - used during operations

•    warfarin - used for blood clots

•    penicillamine - used for rheumatoid arthritis

•    co-trimoxazole-usedfor infections

•    captopril - used for high blood pressure or heart problems

•    cimetidine - used for stomach ulcers and indigestion

•    indomethacin-usedforpainand inflammation

•    furosemide - used for high blood pressure and heart problems

•    olsalazine or mesalazine - used for a bowel problem called ulcerative colitis

•    sulfasalzine or balsalazide - used for rheumatoid arthritis or ulcerative colitis.

If you are not sure if any of the above applyto you, talkto your doctor, nurse or pharmacist before having Imuran.

Having vaccines while you are using Imuran If you are going to have a vaccination speak to your doctor or nurse before you have it. This is becausevaccines may not work properly whileyou are having Imuran.

Tests you may have while having Imuran Your doctor may ask you to have a blood test whileyou are having Imuran. This isto check your blood cell count. Your doctor may change your dose of Imuran after the test. Trying for a baby, pregnancy and breast-feeding

•    Do not have Imuran if you are a man trying to have a baby. This is because it may affect the baby.

•    Do not have Imuran if you are a women who is pregnant or think you might become pregnant. This is because it may affect the baby.

•    Do not have Imuran if you are breast-feeding. This is because small amounts may pass into the mother's milk.

Ask your doctor, midwife or pharmacistfor advice before taking any medicine, if you are pregnant or breast-feeding.

Imuran and the sun

While having Imuran you may be more likely to develop some types of cancers such as skin cancer. Some peoplealso become sensitiveto sunlight which can cause skin discolouration or a rash.Take careto avoid too much sun, cover up and use sunscreen.

Chickenpox/Shingles infection Infection with chickenpox or shingles • can becomesevere in patientstaking immunosuppressive medicine. Therefore you should avoid contactwith anyone suffering from chickenpox or shingles.

Important information about some of the ingredients of Imuran Injection Imuran injection contains sodium. Each 50 mg vial contains4.5 mg of sodium. If you are on a low sodium diet, talk to your doctor, nurse or pharmacist before you have Imuran.

3 How to take Imurr

The dose of Imuran you have depends on your illness and how bad it is. The dosealso depends on your age, your weight and how well your liver and kidneys areworking. Your doctor will explain thisto you.

To stop your body rejecting an organ transplant On the first day

•    the usual dose is up to 5 mg per kg of body weight.

For the rest of your treatment

•    you will have between 1 and 4 mg per kg of body weight each day.

For other conditions

At the start of your treatment

•    you will have 1to3mg per kg of body weight each day

•    your doctor may reduce your dose later.

If you have more Imuran than you should Your doctor will give you Imuran so it is unlikelythatyou will receive too much. If you thinkyou have been given too much or have missed a dose, tell your doctor or nurse.

4 Possible side effects

Like all medicines, Imuran can cause side effects, although not everybody getsthem.

The following side effects may happen with this medicine:

If you notice any of the following serious side effects, talk to your specialist doctor or go to hospital straight away:

•    allergic reaction, the signs may include:

-    general tiredness, dizziness,feeling sick (nausea), being sick (vomiting) or diarrhoea

-    hightemperature(fever), shiveringor chills

-    redness of the skin or a skin rash

-    paininthemusclesorjoints

-    changes in the amount and colour of the urine (kidney problems)

-    dizziness, confusion, feeling light headed or weak, caused by low blood pressure

•    you bruise more easily or notice any unusual bleeding

•    you have a high temperature (fever) or other signs of an infection

•    youfeel extremelytired

•    you notice lumps anywhere on your body

•    you notice any changes to your skin, for example blisters or peeling

•    your health suddenly getsworse

•    you come into contact with anyone who is suffering from chickenpox or shingles.

If you notice any of the above, stop having Imuran and see a doctor straight away.

Other side effects include:

Very common (affects more than 1 in 10 people)

•    infections caused by a virus, fungus or bacteria

•    reduction in your bone marrow function, which may make you feel unwell or show upin your blood tests

•    low white blood cell level in your blood tests, which may cause an infection.

Common (affects lessthan 1 in 10people)

•    low blood platelet level, which may cause you to bruise or bleed easily.

Uncommon (affects lessthan 1 in 100people)

•    low red blood cell level, which may cause you to be tired, get headaches, be short of breath when exercising, feel dizzy and look pale

•    inflammation of the pancreas, which may cause you severe upper stomach pain, with feeling sick (nausea) and being sick (vomiting)

•    liver problems, which may cause pale stools, dark urine, itchiness and yellowing of your skin and eyes.

Rare (affects less than 1 in 1,000 people)

•    problems with your blood and bone marrow which may cause weakness, tiredness, paleness, headaches, soretongue, breathlessness, bruising or infections

•    problems with your bowel leading to diarrhoea, abdominal pain, constipation, feeling sick (nausea) and being sick (vomiting)

•    hair loss which may get better even though you continue to take Imuran

•    severe liver damage which can be life-threatening

•    varioustypes of cancers including blood, lymph and skin cancers

•    sensitivity to sunlightwhich can cause skin discolouration or a rash.

Very rare (affects less than 1 in 10,000 people)

•    inflammation of your lungs causing breathlessness, cough and a fever.

If any of the side effects gets serious, or if

you notice any other side effects not listed in

this leaflet, please tell your doctor, nurse or

pharmacist.

• Medicines should not be disposed ot via wastewater or household waste. Ask your pharmacist howtodispose of medicines no longer required. These measures will help to protect the environment.

6 Further Information

What Imuran contains

•    The active substance is azathioprine.

Each Imuran injection contains 50 mg of azathioprine.

•    The other ingredient is sodium hydroxide.

•    Before Imuran is injected it is diluted in sterile water.

What Imuran looks like and contents of the pack

•    Each pack contains one Imuran injection in glass vial.

Marketing Authorisation Holder and Manufacturer

Aspen Pharma Trading Limited,

3016 LakeDrive,

Citywest Business Campus,

Dublin 24, Ireland Service-Tel: +800 00404142 Manufacturer: GlaxoSmithKline Manufacturing S.p.A., San Polo Di Torrile, Parma, Italy PL 39699/0003

Leaflet date: November 2013

Imuran is a trademark of Aspen. All rights reserved.

"Sodium Chloride (0.18% w/v) and Glucose (4.0% w/v) Intravenous Infusion BP.

Should any visible turbidity or crystallisation appear in the reconstituted or diluted solution the preparation must bediscarded.

Imuran Injection should only be reconstituted with the recommended volume of Water for Injections BP and should be diluted as specified above. Imuran Injection should not bemixed with other drugs or fluids, except those specified above, before administration.

Information for the physician leaflet date: November 2013

Imuran is a trademark of Aspen.AII rights reserved.

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5 How to store Imuran

•    Do not store above25°C.

•    Protect from light and keep dry.

•    Keep out of the reach and sight of children.

•    Do not use Imuran after the expiry date which is stated on the label. The expiry date refers to the last day of that month.

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Shelf Life

3 years unopened

5 dayswhen reconstituted with 5mlto 15 ml water for injections and stored at 5 to 25°C.

1 dayfor 5mlofthe reconstituted injection further diluted with between 20 ml and 200 ml of an appropriate infusion solution and stored at 15°C to25°C.

Special Precautions for Storage

•    Store below25°C

•    Keep dry

•    Protectfrom light

Instructions for Use/Handling

Health professionalswho handle Imuran Injection should follow guidelines for the handling of cytotoxic drugs according to prevailing local recommendations and/or regulations (e.g., the Royal Pharmaceutical Society of Great Britain Working Party Report on the Handling of Cytotoxic Drugs, 1983).