Patient leaflet - Azathioprine tablets 50 mg

1. WHAT AZATHIOPRINE TABLETS ARE AND WHAT THEY ARE USED FOR

Azathioprine Tablets contain the active ingredient Azathioprine which belongs to a group of medicines called immunosuppressants.

Azathioprine Tablets may be used to help your body accept an organ transplant, such as a new kidney, heart or liver, or to treat some diseases where your immune system is reacting against your own body (autoimmune diseases).

Autoimmune diseases may include:

! severe rheumatoid arthritis (a disease where

the immune system attacks cells lining the joints causing swelling, pain, stiffness of the joints),

! systemic lupus erythematosus (a disease

where the immune system attacks many of the body's organs and tissues, including skin, joints, kidneys, brain, and other organs causing severe fatigue, fever, stiffness and joint pain),

! dermatomyositis and polymyositis (a group of

diseases causing inflammation of the muscles, muscle weakness and skin rash), ! auto-immune chronic active hepatitis (a

disease in which the immune system attacks liver cells causing liver inflammation, fatigue, muscle aches, yellowing of the skin and fever),

! pemphigus vulgaris (a disease in which the

immune system attacks skin cells causing severe blistering of the skin, mouth, nose, throat and genitals),

! polyarteritis nodosa (a rare disease that

causes inflammation of the blood vessels), ! auto-immune haemolytic anaemia (a serious

blood disorder where the body destroys red blood cells quicker than it can produce them, with symptoms of weakness and shortness of breath),

! chronic refractory idiopathic

thrombocytopenic purpura (a condition with low platelet counts, that can cause easy or excessive bruising and bleeding).

Azathioprine Tablets may also be used to treat inflammatory bowel disease (Crohn's disease or ulcerative colitis).

Your doctor has chosen this medicine to suit you and your condition.

Azathioprine Tablets may be used on its own, but it is more often used in combination with other medicines.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE AZATHIOPRINE TABLETS

Do not take this medicine if:

! You are allergic (hypersensitive) to

azathioprine or any of the other ingredients of this medicine (listed in section 6) ! You have had an allergic reaction before to 6-

mercaptopurine (6-MP) as you are more likely to be hypersensitive to Azathioprine.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Azathioprine Tablets if:

! You have recently received, or are due to

receive, a vaccination (vaccine). If you take Azathioprine Tablets, you should not have a live organism vaccine (for example; flu vaccine, measles vaccine, BCG vaccine, etc.) until advised it is safe to do so by your doctor. This is because some vaccines may give you an infection if you receive them while you are taking Azathioprine Tablets. ! You have the inherited deficiency of the

enzyme thiopurine methyltransferase (TPMT) or Lesch-Nyhan Syndrome (hypoxanthine-guanine-phosphoribosyltransferase deficiency)

! You have kidney or liver disease

! You have ever had chickenpox or shingles ! You have had hepatitis B (a liver disease

caused by a virus)

! You are going to have an operation (this is

because medicines including tubocurarine, or succinylcholine used as muscle relaxants during operations may interact with Azathioprine Tablets. You should inform your anaesthesiologist of your treatment with Azathioprine Tablets prior to surgery.

If you are not sure if any of the above applies to you, talk to your doctor, nurse or pharmacist before taking Azathioprine Tablets.

Your doctor will want to take regular blood samples while you are taking Azathioprine Tablets, to check for any changes (see section 3 "How to take Azathioprine Tablets.") The frequency of your blood tests will usually decrease the longer you continue to take Azathioprine Tablets.

NUDT15-gene mutation

If you have an inherited mutation in the NUDT15-gene (a gene which is not involved in the break-down of azathioprine in the body), you have a higher risk of infections and hair loss, and your doctor may in this case give you a lower dose.

Liver damage

Treatment with Azathioprine Tablets may affect the liver and your doctor will monitor your liver function regularly. Tell your doctor if you experience symptoms of liver damage (see section 4 "Possible side effects").

Chromaturia

This product may cause you to experience abnormally coloured urine, such as bright yellow urine. Although bright yellow urine is generally not

concerning, you should discuss any change in the colour of your urine - including other

discolourations or darkening - with your doctor, as this may indicate kidney or liver problems.

If you are receiving immunosuppressive therapy, taking Azathioprine Tablets could put you at greater risk of:

! Tumours, including skin cancer. Therefore,

when taking Azathioprine Tablets, avoid excessive exposure to sunlight, wear protective clothing and use protective sunscreen with a high protection factor ! Lymphoproliferative disorders

, Treatment with Azathioprine Tablets

increases your risk of getting a type of cancer called lymphoproliferative disorder. With treatment regimen containing multiple immunosuppressants (including thiopurines), this may lead to death

, A combination of multiple

immunosuppressants, given concomitantly increases the risk of disorders of the lymph system due to a viral infection (Epstein-Barr virus (EBV) - associated lymphoproliferative disorders).

! Developing a serious condition called

Macrophage Activation Syndrome (excessive activation of white blood cells associated with inflammation), which usually occurs in people who have certain types of arthritis, severe chickenpox, or shingles infection. ! Therefore, when taking Azathioprine Tablets,

avoid contact with people who have chickenpox or shingles,

! A previous hepatitis B infection becoming

active again.

! Other infections such as PML (Progressive

Multifocal Leukoencephalopathy) which is an opportunistic infection. If you experience any signs of infection, please contact your doctor (see section 4 “Possible side effects”).

Vitamin B3 deficiency (pellagra)

Talk to your doctor immediately if you experience diarrhoea, localised pigmented rash (dermatitis), decline in your memory, reasoning or other thinking skills (dementia) as these symptoms may suggest vitamin B3 deficiency (nicotinic acid deficiency/pellagra).

Other medicines and Azathioprine Tablets Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Azathioprine Tablets can affect the way some medicines work. Also some other medicines can affect the way Azathioprine works.

In particular tell your doctor if you are taking any of the following:

! ribavirin (used to treat viral infections) ! methotrexate (mainly used to treat cancers) ! allopurinol, oxipurinol, thiopurinol or other

xanthine oxidase inhibitors, such as febuxostat (mainly used to treat gout) ! penicillamine (mainly used in the treatment of

rheumatoid arthritis)

! ACE inhibitor (mainly used to treat high blood

pressure - hypertension)

! anticoagulants such as warfarin or

acenocoumarol (used to prevent blood clots) ! cimetidine (used to treat stomach ulcers and

indigestion)

! indomethacin (used as a pain killer and anti-

inflammatory)

! cytostatic drugs (drugs used to treat various

types of cancer)

! aminosalicylates e.g. olsalazine, mesalazine

or sulfasalazine (mainly used in the treatment of ulcerative colitis and Crohn's disease) ! trimethoprim/sulfamethoxazole (an antibiotic,

used to treat infections caused by bacteria) ! infliximab (mainly used in the treatment of

ulcerative colitis and Crohn's disease) ! muscle relaxants e.g. tubocurarine or

succinylcholine (used during operations) as they may interact with Azathioprine Tablets. You should inform your anaesthesiologist of your treatment with Azathioprine Tablets prior to surgery.

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before taking Azathioprine Tablets.

Having vaccines whilst taking Azathioprine Tablets

If you are due to receive a vaccination (vaccine) speak to your doctor or nurse before you do so. If you take Azathioprine Tablets, you should not have a live vaccine (for example; flu vaccine, measles vaccine, BCG vaccine, etc.) until advised it is safe to do so by your doctor. This is because some vaccines may give you an infection if you receive them while you are taking Azathioprine Tablets.

Azathioprine Tablets with food and drink

You should take your medicine at least 1 hour before or 2 hours after having milk or dairy products.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to become pregnant, ask your doctor for advice before taking this medicine.

Pregnancy

Reliable contraceptive precautions must be taken to avoid pregnancy whilst you or your partner is taking Azathioprine Tablets.

If you are pregnant your doctor will carefully consider whether you should take this medicine, based on the risks and benefits of treatment. Talk to your doctor immediately if you experience intense itching without a rash during your pregnancy. You may also experience nausea, and loss of appetite together with itching, which indicates that you have a condition called cholestasis of pregnancy (condition affecting the liver during pregnancy). This condition can cause harm to your unborn child.

Breast-feeding

Small amounts of Azathioprine Tablets may pass into the breast milk. It is recommended that women receiving Azathioprine Tablets should avoid breastfeeding unless the benefits outweigh the potential risks to the child. Ask your doctor for advice before breastfeeding.

Fertility

The effects of Azathioprine Tablets on fertility are not known.

Driving and using machines

Azathioprine Tablets are not known to affect your ability to drive or use machinery. If you experience any side effect from this medicine, you may not be able to drive or operate machinery.

Azathioprine Tablets contain lactose

This medicine contains lactose (a type of sugar), if you have been told by your doctor that you have an intolerance to some sugars talk to your doctor before taking this medicine.

Sodium content

This medicine contains less than 1mmol sodium (23mg) per tablet, this is to say essentially 'sodium free'.

3. HOW TO TAKE AZATHIOPRINE TABLETS

Always take Azathioprine Tablets exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure.

The dose of Azathioprine you take depends on your illness and how bad it is.

You can take Azathioprine Tablets with food or on an empty stomach, but the choice of method should be consistent from day to day. Some patients feel nausea (sick) when first given Azathioprine Tablets, this may be relieved by taking the tablets after food.

! When you take Azathioprine Tablets, your

doctor will take regular blood tests. This is to check the number and type of cells in your blood, and to ensure your liver is working correctly.

! Your doctor may also ask for other blood and

urine tests to monitor how your kidneys are working and to measure uric acid levels. Uric acid is a natural substance made in your body and levels of uric acid can rise while you are taking Azathioprine Tablets. High levels of uric acid may damage your kidneys.

Your doctor may sometimes change your dose of Azathioprine Tablets as a result of these tests. Swallow your tablets whole. Do not chew the tablets. The tablets should not be broken or crushed.

It is important that carers are aware of the need for safe handling of this medicine. If you or your caregiver does handle broken tablets, wash your hands immediately. Please consult your doctor or pharmacist for advice.

The recommended dose is:

Adults who have had an organ transplant: On the first day of treatment, the usual dose is up to 5 mg per kilogram of body weight, then a usual daily dose of 1 mg to 4 mg per kilogram of body weight. During treatment, your doctor will adjust the dose depending on your reaction to the medicine.

Adults with other conditions: The usual starting dose is 1 mg to 3 mg per kilogram of body weight, then a usual daily dose of less than 1 mg to 3 mg per kilogram of body weight. During treatment your doctor will adjust the dose depending on your reaction to the medicine.

Elderly patients may need a reduced dose. Patients with kidney or liver problems may need a reduced dose.

Use in children

Children who have had an organ transplant: The dosing for children who have had an organ transplant is the same as adults.

Children with other conditions: The dosing for children with other conditions is the same as adults.

Children who are considered overweight may require a higher dose.

If you take more Azathioprine Tablets than you should

If you take too many tablets, contact your doctor or pharmacist immediately.

If you stop taking Azathioprine Tablets

Before you stop taking Azathioprine Tablets, consult with your doctor or pharmacist. Do not stop taking Azathioprine Tablets until your doctor tells you it is safe to do so.

If you forget to take Azathioprine Tablets

Do not take a double dose to make up for the dose that you missed. Inform your doctor if you do miss a dose.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember, then go back to taking it as you would normally.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everyone gets them.

Stop taking Azathioprine Tablets and see a doctor straight away, if you notice any of the following serious side effects, you may need urgent medical treatment:

! Allergic reactions (these are uncommon side

effects which may affect up to 1 in 100 people) these signs may include: , general tiredness, dizziness, feeling sick

(nausea), being sick (vomiting), diarrhoea or abdominal pain

, swelling of the eyelids, face or lips , redness of the skin, skin nodules or a

skin rash (including blisters, itching or peeling skin)

, pain in the muscles or joints

, sudden wheeziness, coughing or

difficulty breathing

, chest pain, shortness of breath or

swollen legs (heart problems) ! Reversible swelling of the brain with

symptoms including severe headache, vision changes, seizures, confusion and reduced consciousness, with or without high blood pressure (Posterior Reversible

Encephalopathy Syndrome or PRES).

In severe cases these reactions may be life-threatening (this is rare which may affect up to 1 in 10,000 people):

! Skin rashes or redness, which may develop

into life-threatening skin reactions including widespread rash with blisters and peeling skin, particularly occurring around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome), extensive peeling of the skin (toxic epidermal necrolysis) (these may be very rare side effects which may affect up to 1 in 10,000 people).

! Reversible pneumonitis (inflammation of your

lungs causing breathlessness, cough and fever) (these may be very rare side effects which may affect up to 1 in 10,000 people) ! Problems with your blood and bone marrow,

signs include weakness, tiredness, paleness, bruising easily, unusual bleeding or infections (these may be very common side effects which may affect more than 1 in 10 people) ! When Azathioprine Tablets are used in

combination with other immunosuppressives you may get a virus which causes damage to your brain. This may cause headaches, changes in behaviour, impaired speech, worsening of abilities such as memory, attention and decision making (cognitive decline) and may be fatal (condition known as JC virus associated Progressive Multifocal Leukoencephalopathy) (these may be very rare side effects which may affect more than 1 in 10,000 people)

If you get any of the following serious side effects, talk to your doctor or specialist doctor immediately, you may need urgent medical treatment:

! You have a high temperature (fever) or other signs of an infection such as sore throat, sore mouth, urinary problems, or chest infection causing breathlessness and cough (these may be very common side effects which may affect more than 1 in 10 people)

! Problems with your liver, signs include your skin, or the whites of your eyes turn yellow (jaundice) (these may be uncommon side effects which may affect up to 1 in 100 people)

! Various types of cancers including blood, lymph and skin cancers (see section 2 Warnings and precautions) (these may be rare side effects which may affect up to 1 in 1000 people)

! Sweet's syndrome (also known as acute febrile neutrophilic dermatosis). You may develop a rash (raised red, pink or purple lumps which are sore to touch), particularly on your arms, hands, fingers, face and neck, which may also be accompanied by a fever (high temperature) (the rate at which these side effects occur is not known – cannot be estimated from available data)

! A certain type of lymphomas (hepatosplenic

T-cell lymphoma). You may develop nose bleeds, fatigue, significant night sweats, weight loss and unexplained fevers (high temperature) (the rate at which these side effects occur is not known – cannot be estimated from available data)

! Severe liver damage which can be life threatening, especially in patients who receive long-term treatment (like liver injury, non-cirrhotic portal hypertension, portosinusoidal vascular disease). Tell your doctor if you experience any of the following symptoms: yellowing of the skin and the whites of the eyes (jaundice), bruising easily, abdominal discomfort, loss of appetite, fatigue, nausea, or vomiting (the rate at which these side effects occur is not known –cannot be estimated from available data).

If you notice any of the above, stop taking Azathioprine Tablets and see a doctor straight away.

Other side effects include:

Very common (may affect more than 1 in 10 people)

! Low white blood cell level in your blood tests, which may cause an infection

Common (may affect up to 1 in 10 people)

! Nausea (feeling sick)

Uncommon (may affect up to 1 in 100 people)

! Anaemia (low red blood cell level) ! Pancreatitis (inflammation of the pancreas), which may cause severe upper stomach pain ! Cholestasis of pregnancy, which can cause intense itching, especially on the hands and feet

Rare (may affect up to 1 in 1,000 people)

! You might notice some hair loss while taking

Azathioprine Tablets. Often hair does grow again, even if you carry on taking Azathioprine Tablets. If you are worried ask your doctor.

Very Rare (may affect up to 1 in 10,000 people)

! Problems with your bowels leading to diarrhoea, abdominal pain, constipation, feeling or being sick (bowel perforation) ! Inflammation of your lungs causing breathlessness, cough, and a fever

Not known (frequency cannot be estimated from the available data)

! Photosensitivity (sensitivity to light or sunlight)

! You may develop a rash (raised red, pink or purple lumps which are sore to touch), particularly on your arms, hands, fingers, face and neck, which may also be accompanied by a fever (Sweet's syndrome, also known as acute febrile neutrophilic dermatosis). The rate at which these side effects occur is not known (cannot be estimated from available data)

! Vitamin B3 deficiency (pellagra) associated with a localised pigmented skin rash, diarrhoea and decrease in memory, reasoning or other thinking skills

! Inflammation of a salivary gland

(Sialoadenitis)

! Tremor.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. HOW TO STORE AZATHIOPRINE TABLETS

Check the expiry date printed on the label or side of the box. Do not use after the expiry date stated on the label. Store in a dry place, below 25°C. Protect from light.

In case of any visible signs of deterioration you should discard the package.

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

Keep out of the sight and reach of children.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Azathioprine Tablets contain: Each tablet contains 50mg azathioprine. The other ingredients are: lactose, starch maize, microcrystalline cellulose, magnesium stearate, purified talc, and sodium starch glycollate.

What Azathioprine Tablets look like and contents of the pack

Azathioprine Tablets are pale yellow, biconvex tablets, scored on one side and engraved with 'A10' on the other side. The score line is not intended for breaking the tablet.

These tablets are supplied in packs of 28, 50, 56, 100 or 250 tablets or in securitainers of 50 or 100 tablets. Not all pack sizes may be marketed.

Marketing Authorisation Holder:

Ennogen IP Ltd

Unit G4, Riverside Industrial Estate,

Riverside Way, Dartford, DA1 5BS, UK

Manufacturer:

Ennogen Pharma Limited