Azathioprine Hexal: detailed information

Package leaflet: Information for the patient

Azathioprine Hexal 50 mg film-coated tablets

Generic medicine
Please read this leaflet carefully before taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Azathioprine Hexal is and what it is used for
What you need to know before taking Azathioprine Hexal
How to take Azathioprine Hexal
Possible side effects
How to store Azathioprine Hexal
Contents of the pack and other information

1. What Azathioprine Hexal is and what it is used for

Azathioprine Hexal contains the active substance azathioprine.
It belongs to a group of medicines called immunosuppressants. This means that it reduces the response of the
immune system.
Azathioprine Hexal is used to help the body accept a transplanted organ, such as a new kidney, heart or liver, or to treat certain diseases in which the immune system reacts against the body itself (autoimmune diseases).

Autoimmune diseases may include: severe rheumatoid arthritis (a disease in which the immune system attacks the cells lining the joints, causing swelling, pain and joint stiffness),
systemic lupus erythematosus (a disease in which the immune system attacks many organs and tissues of the body, including skin, joints, kidneys, brain and other organs, causing severe fatigue, fever, joint stiffness and pain),
dermatomyositis and polymyositis (a group of diseases causing inflammation of the muscles, muscle weakness and skin rash),
autoimmune chronic active hepatitis (a disease in which the immune system attacks liver cells, causing liver inflammation, fatigue, muscle pain, 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 causing inflammation of the blood vessels),
autoimmune haemolytic anaemia (a serious blood disorder in which the body destroys red blood cells faster than it can produce them, with symptoms such as weakness and shortness of breath),
chronic refractory idiopathic thrombocytopenic purpura (a condition in which the platelet count is low and may cause easy or excessive bruising and bleeding).

Azathioprine Hexal may also be used for the treatment of inflammatory bowel diseases
(Crohn’s disease or ulcerative colitis).
Your doctor has chosen this medicine because it is suitable for you and your condition.
Azathioprine Hexal may be used alone, but is very often used in combination with other medicines.

2. What you need to know before taking Azathioprine Hexal

Do not take Azathioprine Hexal

if you are allergic to azathioprine or to any of the other ingredients of this medicine (listed in section 6)
if you are allergic to mercaptopurine (a medicine similar to azathioprine, the active substance contained in Azathioprine Hexal).

Warnings and precautions
Talk to your doctor or pharmacist before taking Azathioprine Hexal:

if you have recently been vaccinated or are about to be vaccinated. If you are taking Azathioprine Hexal, you must not be vaccinated with live vaccines (for example: influenza vaccine, measles vaccine, BCG vaccine, etc.) until your doctor tells you it is safe to do so. This is because some vaccines may transmit the infection to you if administered while you are being treated with Azathioprine Hexal.
if you have a genetic condition known as Lesch-Nyhan syndrome. This is a rare inherited condition caused by the lack of a substance called “hypoxanthine-guanine-phosphoribosyl-transferase” (HPRT)
if you have liver or kidney problems
if you have a genetic condition called TPMT deficiency (in which your body produces too little of an enzyme called thiopurine methyltransferase)
if you have or have ever had chickenpox or herpes zoster
if you have had hepatitis B (a liver disease caused by a virus)
if you are scheduled for surgery (because medicines such as tubocurarine or succinylcholine, used as muscle relaxants during surgery, may interact with Azathioprine Hexal. You must inform the anaesthetist that you are being treated with Azathioprine Hexal before the procedure).
If you are unsure whether any of these conditions apply to you, consult your doctor, pharmacist or nurse before taking Azathioprine Hexal.

During treatment with Azathioprine Hexal, your doctor will prescribe regular blood tests to monitor for any changes (see section 3 “How to take Azathioprine Hexal”). The frequency of blood tests will decrease as treatment with Azathioprine Hexal continues.
If you are receiving immunosuppressive therapy, taking Azathioprine Hexal may increase the risk of developing:

Tumours, including skin tumours. Therefore, while taking Azathioprine Hexal, avoid excessive exposure to sunlight, wear protective clothing and use sunscreen with a high protection factor
Lymphoproliferative disorders – treatment with Azathioprine Hexal increases the risk of developing a type of tumour called lymphoproliferative disorder. When treatment regimens include multiple immunosuppressants (including thiopurines), this may lead to death. The combination of several immunosuppressants taken simultaneously increases the risk of lymphatic system diseases due to viral infections (Epstein-Barr virus (EBV)-associated lymphoproliferative disorders)
a serious condition called macrophage activation syndrome (excessive activation of white blood cells associated with inflammation), which usually occurs in people with certain types of arthritis
severe chickenpox or herpes zoster infection. Therefore, while taking Azathioprine Hexal, avoid contact with people who have chickenpox or herpes zoster
reactivation of a previous hepatitis B infection
other infections such as PML (progressive multifocal leukoencephalopathy), which is an opportunistic infection. If you experience any signs of infection, contact your doctor (see section 4 "Possible side effects").

Infections
During treatment with azathioprine, the risk of viral, fungal and bacterial infections is increased, and infections may be more severe. See also section 4.
Before starting treatment, inform your doctor if you have had chickenpox, herpes zoster or hepatitis B (a liver disease caused by a virus).
NUDT15 gene mutation
If you have an inherited mutation of the NUDT15 gene (a gene involved in the metabolism of azathioprine in the body), you are at higher risk of infections and hair loss, and in this case your doctor may prescribe a lower dose.
Vitamin B3 deficiency (pellagra)
Contact your doctor immediately if you experience diarrhoea, pigmented skin rash (dermatitis), memory loss, impaired reasoning or other cognitive functions (dementia), as these symptoms may indicate a deficiency of vitamin B3 (nicotinic acid deficiency/pellagra).
Liver damage
Treatment with Azathioprine Hexal may affect the liver, and your doctor will regularly monitor your liver function. Inform your doctor if you experience symptoms of liver damage (see section 4 “Possible side effects”).

Other medicines and Azathioprine Hexal
Tell your doctor if you are taking, have recently taken or might take any other medicines. This is because this medicine may affect how some medicines work. Also, other medicines may affect how this medicine works. In particular, inform your doctor if you have taken or plan to take:

Ribavirin (used to treat viral infections)
Methotrexate (mainly used to treat cancers)
Allopurinol, oxipurinol, thiopurinol and other xanthine oxidase inhibitors such as febuxostat (mainly used to treat gout)
Penicillamine (mainly used to treat rheumatoid arthritis)
ACE inhibitors (mainly used to treat high blood pressure - hypertension)
Anticoagulants such as warfarin or acenocoumarol (used to prevent blood clots)
Cimetidine (used to treat gastric ulcers and indigestion)
Indomethacin (used as a painkiller and anti-inflammatory)
Cytostatic medicines (drugs used to treat various types of cancer)
Aminosalicylates such as olsalazine, mesalazine or sulfasalazine (mainly used to treat ulcerative colitis and Crohn's disease)
Co-trimoxazole (an antibiotic used to treat bacterial infections)
Infliximab (mainly used to treat ulcerative colitis and Crohn's disease)
Muscle relaxants such as tubocurarine or succinylcholine (used during surgery), as they may interact with Azathioprine Hexal. Before undergoing surgery, inform the anaesthetist that you are taking azathioprine, as muscle relaxants used during anaesthesia may interact with Azathioprine Hexal.

If you are unsure whether any of these conditions apply to you, consult your doctor or pharmacist before taking Azathioprine Hexal.
Vaccinations during treatment with Azathioprine Hexal
If you are due to be vaccinated, inform your doctor or nurse beforehand. If you are taking Azathioprine Hexal, you must not be vaccinated with live vaccines (for example: influenza vaccine, measles vaccine, BCG vaccine, etc.) until your doctor tells you it is safe to do so. This is because some vaccines may transmit the infection to you if administered while you are being treated with Azathioprine Hexal.

Azathioprine Hexal with food and drink
Azathioprine Hexal should be taken at least 1 hour before or 2 hours after consuming milk or dairy products.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine (see section 2, “Warnings and precautions”).

Pregnancy
Reliable contraceptive measures must be used to avoid pregnancy while you or your partner are taking Azathioprine Hexal.
If you are pregnant, your doctor will carefully evaluate whether to prescribe this medicine, weighing the risks and benefits of treatment.
Contact your doctor immediately if you experience intense itching without a rash during pregnancy. You may also experience nausea and loss of appetite along with itching, which may indicate a condition called obstetric cholestasis (a condition affecting the liver during pregnancy). This condition may cause harm to the unborn child.
Women of childbearing age must use an effective contraceptive method during treatment with azathioprine and for 6 months after the last dose.
Men are advised not to father a child during and up to 3 months after treatment with azathioprine, and should therefore use an effective contraceptive method during treatment with azathioprine and for up to 3 months afterwards.

Breastfeeding
Small amounts of Azathioprine Hexal may pass into breast milk. Women taking Azathioprine Hexal should avoid breastfeeding unless the benefits outweigh the potential risks to the infant. Consult your doctor before breastfeeding.

Fertility
The effects of Azathioprine Hexal on fertility are unknown.

Driving and using machines
It is not known whether Azathioprine Hexal affects the ability to drive or use machines. If you experience any side effects with this medicine, you may be unable to drive or use machinery.

Azathioprine Hexal contains lactose
Azathioprine Hexal contains lactose monohydrate.
If your doctor has diagnosed you with an intolerance to certain sugars, contact him or her before taking this medicine.

3. How to take Azathioprine Hexal

Take this medicine exactly as prescribed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The dose of Azathioprine Hexal may vary from patient to patient and will be determined by your doctor.
The dose depends on the condition being treated.
You may take Azathioprine Hexal with or without food, but you should consistently use the same method every
day. Some patients experience nausea (feeling unwell) when first taking Azathioprine Hexal; this may be reduced
by taking the tablets after a meal.

While taking Azathioprine Hexal, your doctor will regularly perform blood tests. These are to monitor the number and types of blood cells, and to ensure your liver is functioning properly.
Your doctor may also request additional blood and urine tests to monitor kidney function and measure uric acid levels. Uric acid is a natural substance produced by your body, and its levels may increase during treatment with Azathioprine Hexal. High levels of uric acid can damage the kidneys.

Your doctor may occasionally adjust your dose of Azathioprine Hexal based on the results of these
tests.
The score line on the tablet is only intended to assist in breaking the tablet if you have difficulty swallowing it whole.
It is important that caregivers are aware of the need to handle this medicine with caution. If you or someone caring for you handles broken tablets, wash hands immediately. Consult your doctor or pharmacist for advice.

Recommended dose:
Adults who have undergone organ transplantation: On the first day of treatment, the usual dose is up to 5
mg per kilogram of body weight. Subsequently, the daily dose ranges from 1 mg to 4 mg per
kilogram of body weight. During treatment, your doctor will adjust the dose according to your response
to the medicine.
Adults with other conditions: The usual initial dose is between 1 mg and 3 mg per kilogram of body
weight. The usual daily maintenance dose ranges from less than 1 mg to 3 mg per kilogram of
body weight. During treatment, your doctor will adjust the dose according to your response to the medicine.
Elderly patients may require a reduced dose.
Patients with kidney or liver problems may require a reduced dose.

Use in children
Children who have undergone transplantation: The dose for children who have received an organ
transplant is the same as for adults.
Children with other conditions: The dose for children with other conditions is the same as for adults.
Children who are considered overweight may require a higher dose.

If you take more Azathioprine Hexal than you should
If you take too many tablets, contact your doctor or pharmacist immediately.

If you forget to take Azathioprine Hexal
Do not take a double dose to make up for a forgotten dose. Inform your doctor if you have
missed a dose.
If it is almost time for your next dose, skip the missed dose and take the next dose at the usual time. Otherwise, take the missed dose as soon as you remember, then return to your regular dosing schedule.

If you stop taking Azathioprine Hexal
Before stopping treatment with Azathioprine Hexal, consult your doctor or pharmacist. Do not stop taking
Azathioprine Hexal unless your doctor tells you it is safe to do so.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

The following side effects may occur with this medicine:

Stop taking this medicine and consult a doctor immediately if you notice any of the following serious side effects, as you may urgently need medical attention:

Allergic reactions (these are uncommon side effects that may affect up to 1 in 100 people). Symptoms may include: general fatigue, dizziness, feeling unwell (nausea), discomfort (vomiting), diarrhoea or abdominal pain or swelling of the eyelids, face or lips or skin redness, skin nodules or skin rash (including blisters, itching or peeling skin) or muscle or joint pain or sudden dizziness, cough or difficulty breathing or chest pain, shortness of breath or swelling of the legs (heart problems) or reversible brain swelling with symptoms including severe headache, vision changes, seizures, confusion and reduced consciousness, with or without high blood pressure (reversible posterior encephalopathy syndrome or PRES).

In severe cases, these reactions can be life-threatening (these may be rare side effects occurring in up to 1 in 10,000 people).

Skin rashes or redness which may progress to life-threatening skin reactions including widespread rashes with blisters and skin peeling, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome), extensive skin peeling (toxic epidermal necrolysis) (these may be very rare side effects occurring in up to 1 in 10,000 people)
Reversible pneumonia (lung inflammation causing shortness of breath, cough and fever) (these may be very rare side effects occurring in up to 1 in 10,000 people)
Blood and bone marrow problems, signs include weakness, fatigue, paleness, bruising, unusual bleeding or infections (these may be very common side effects occurring in more than 1 in 10 people)
When Azathioprine Hexal is used in combination with other immunosuppressive medicines, you may develop a virus infection that can damage the brain. This may cause headache, changes in behaviour, difficulty speaking, worsening of certain functions such as memory, attention and decision-making ability (cognitive decline) and may be fatal (a condition known as progressive multifocal leukoencephalopathy (PML) associated with JC virus) (these may be very rare side effects occurring in up to 1 in 10,000 people).

If you notice any of these side effects, inform your doctor or specialist immediately as you may need urgent medical treatment:

High temperature (fever) or other signs of infection such as sore throat, mouth pain, problems urinating or chest infection causing shortness of breath and cough (these may be very common side effects occurring in more than 1 in 10 people)
Liver problems, signs include yellowing of the skin or whites of the eyes (jaundice) (these may be uncommon side effects occurring in up to 1 in 100 people)
Various types of tumours including blood cancers, lymph node cancers, skin cancers (see section 2 “Warnings and precautions”)
You may develop a skin rash (painful red, pink or purple raised lumps), particularly on arms, hands, fingers, face and neck, which may also be accompanied by fever (Sweet’s syndrome, also known as acute febrile neutrophilic dermatosis). The frequency of occurrence of these side effects is unknown – cannot be estimated from the available data.
A certain type of lymphoma (hepatosplenic T-cell lymphoma). You may experience nosebleeds, fatigue, significant night sweats, weight loss and unexplained fever (high temperature). The frequency of these side effects is unknown – frequency cannot be determined from the available data.

If you notice any of these side effects, stop treatment with Azathioprine Hexal and contact your doctor immediately.

Other side effects include:

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

Low levels of white blood cells in the blood which may lead to infections

Common (may affect up to 1 in 10 people)

nausea (feeling unwell)

Uncommon (may affect up to 1 in 100 people)

anaemia (low levels of red blood cells in the blood)
cholestatic pregnancy (may cause intense itching, especially on hands and feet)
pancreatitis (inflammation of the pancreas), which may cause severe pain in the upper abdomen

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

You may notice hair loss while taking Azathioprine Hexal. Hair often regrows even if you continue taking Azathioprine Hexal. If you are concerned, ask your doctor.
Severe liver damage which may be potentially life-threatening, particularly in patients receiving long-term treatment (e.g. liver damage, non-cirrhotic portal hypertension, porto-sinusoidal vascular disease). Inform your doctor if you experience any of the following symptoms: yellowing of the skin and whites of the eyes (jaundice), easy bruising, abdominal discomfort, loss of appetite, fatigue, nausea or vomiting.

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

intestinal problems causing diarrhoea, abdominal pain, constipation, feeling unwell or discomfort (intestinal perforation)

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

photosensitivity (sensitivity to light or sunlight)
pellagra (deficiency of vitamin B3 (niacin)) associated with localized pigmented skin rash, diarrhoea, memory loss, difficulty reasoning and changes in cognitive abilities
inflammation of a salivary gland (sialoadenitis)
tremor

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Azathioprine Hexal

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the blister and the carton, following “Exp.”.
The expiry date refers to the last day of that month.
If it is necessary to split the Azathioprine 50 mg film-coated tablet, avoid contact of the skin with the powder or the broken surface of the tablet.
Any residue must be disposed of with the same caution.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Azathioprine Hexal contains

The active substance is azathioprine. Each film-coated tablet contains 50 mg of azathioprine.
The other components are: monohydrate lactose, maize starch, povidone K25, colloidal silicon dioxide, magnesium stearate, hypromellose, microcrystalline cellulose, macrogol stearate 400, talc. Colourant: titanium dioxide (E171).

Description of the appearance of Azathioprine Hexal and contents of the pack
Azathioprine Hexal 50 mg film-coated tablets are biconvex, film-coated tablets, white to yellowish in colour, with a break line on one side.
Pack sizes: 30, 50, 56, 90 or 100 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Sandoz S.p.A.
Viale Luigi Sturzo 43
20154 Milan
Italy
Manufacturer
SALUTAS Pharma GmbH Otto-von-Guericke-Allee, 1 - 39179 Barleben (Germany)

This medicinal product is authorised in the European Economic Area countries and in the United Kingdom (Northern Ireland) under the following names:
AT: Azathioprin "Hexal" 50 mg - Filmtabletten
BE: Azathioprine Sandoz 25/50 mg filmomhulde tabletten
DE: Azathioprin HEXAL® 25/50 mg Filmtabletten
IT: Azatioprina Hexal

The following information is intended for medical or healthcare professionals only:

Instructions for use, handling and disposal

There are no risks associated with handling tablets with intact coating. In this case,
no special safety precautions are required.
However, immunosuppressive agents must be handled in strict accordance with the instructions when
healthcare personnel split the tablets (see sections 4.2 and 4.4 of the Summary of Product Characteristics).
Excess medicines, as well as contaminated devices, must be temporarily stored in
clearly labelled containers. Unused product or waste materials must be disposed of in
accordance with current local regulations.
Incompatibilities
Not applicable.
Administration
For oral use.
The tablet should be taken with at least one glass of liquid (200 ml).
Shelf life
3 years
Special precautions for storage
This medicinal product requires no special storage conditions.