PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE PHARMACISTS’

REGULATIONS (PREPARATIONS) - 1986The medicine is dispensed

with a doctor’s prescription only.

Imuran Tablets25 mg, 50 mgEach tablet contains: 25 mg or 50 mg azathioprine.* Inactive ingredients and allergens in the preparation - see section 6 in the leaflet.Read this leaflet carefully in its entirety before using the medicine. This leaflet contains concise information about the medicine. If you have further questions, refer to the doctor or pharmacist.This medicine has been prescribed to treat you. Do not pass it on to others. It may harm them even if it seems to you that their medical condition is similar.

1. WHAT IS THE MEDICINE INTENDED FOR?Therapeutic activity: Immunosuppression.This effect is important after an organ transplantation, so that the immune system will not reject the transplanted organ. Imuran is also used to treat rheumatoid arthritis that does not respond to other treatments – only by a rheumatologist in a hospital or clinic.Therapeutic group: Immunosuppressants.

2. BEFORE USING THE MEDICINE Do not use the medicine if:• you are sensitive (allergic) to the active ingredient

azathioprine or to any of the other ingredients included in the medicine (see section 6).

•you are sensitive (allergic) to mercaptopurine (6-MP).

Special warnings regarding use of the medicine•Before treatment with Imuran, inform the doctor if⚪you suffer from a liver or kidney disease.⚪you suffer from a syndrome called Lesch-

Nyhan. This is a rare hereditary condition of deficiency of an agent called HGPRT (hypoxanthine-guanine-phosphoribosyltransferase).

⚪your body produces too little TPMT (thiopurine methyltransferase).

⚪you have suffered from chickenpox or herpes zoster, since the disease may recur.

⚪you are due to be vaccinated, as the vaccine may not act as required while taking Imuran.

⚪you are a carrier or have had hepatitis B; since there is a risk of an outbreak of hepatitis.

While taking Imuran, the doctor will tell you to undergo regular blood tests to monitor your condition.

Additional warnings:•While under treatment with Imuran, you are at greater

risk of developing different kinds of cancer, including skin cancer. Avoid overexposure to the sun; cover yourself and use sunscreens with a high sun protection factor.

•There is risk of severe infection of chickenpox or herpes zoster. Avoid contact with anyone who has these diseases.

•There is risk of other infections, such as progressive multifocal leukoencephalopathy (PML). Progressive multifocal leukoencephalopathy may occur in cases of an inadequate immune system. If there is a sign of infection, refer to the doctor.

•The tablets contain lactose. If you have been told that you have an intolerance to certain sugars, inform the doctor before commencing treatment with Imuran. If you are taking or have recently taken other

medicines, including non-prescription medicines and nutritional supplements, inform the doctor or pharmacist. It is especially important to inform the doctor or pharmacist if you are taking or plan to take:•Vaccinations.•Ribavirin for treatment of viral diseases.•Methotrexate.•Allopurinol, oxipurinol, thiopurinol used to treat gout.•Penicillamine used to treat rheumatoid arthritis.•ACE inhibitors for treatment of hypertension (e.g.,

captopril).•Furosemide for treatment of high blood pressure and

heart problems.•Warfarin for treatment of blood clots.•Cimetidine for treatment of gastric ulcers and digestive

problems.•Indomethacin to relieve pain and inflammation.•Cytostatic medicines, such as certain antibiotics and

medicines to treat certain types of cancer.•Aminosalicylates such as olsalazine, mesalazine,

balsalazide and sulfasalazine used to treat rheumatoid arthritis or intestinal problems called ulcerative colitis or Crohn’s disease.

•Tubocurarine or succinylcholine used for surgeries.•Co-trimoxazole an antibiotic for treatment of bacterial

infections. Use of the medicine and food

Do not take Imuran less than one hour before or less than three hours after food or drinking milk.

Pregnancy and breastfeeding•If you are pregnant, think you may become pregnant or

are planning to become pregnant, consult the doctor before commencing treatment with Imuran.

•Do not take Imuran if you are breastfeeding, as small quantities of it may pass into the breast milk. Consult the doctor or pharmacist.

•Imuran may increase fertility of men and women. During the course of treatment, exercise extra caution and use proper contraceptives. This applies to a man or woman under treatment with the medicine. Driving and use of machines

If you experience any side effect as a result of using this medicine, be careful and if necessary, abstain from driving and using machines.

3. HOW SHOULD YOU USE THE MEDICINE?Always use according to the doctor's instructions. Check with the doctor or pharmacist if you are unsure. The dosage and treatment regimen will be determined by the doctor only, in accordance with the severity of your disease, age, weight and kidney and liver functions. The elderly or patients with a kidney or liver disease may need lower dosages.Take the tablet with a little water. Do not halve, break or crush the tablet.The product is cytotoxic.Do not exceed the recommended dose.If you accidentally took a higher dosageIf you took an overdose or if a child accidentally swallowed the medicine, immediately refer to a doctor or proceed to a hospital emergency room and bring the package of the medicine with you.The immediate signs of overdose are: nausea, vomiting and diarrhea, lower white blood cell count, unexplained infection, throat ulcer, bleeding and bruising.If you forgot to take the medicineIf you forgot to take the medicine at the designated time, do not take a double dose. If it is almost time for the next dose, take the next dose at the regular time and consult the doctor. If not, take the tablet as soon as you remember and continue treatment as required.Adhere to the treatment regimen as recommended by the doctor. Even if there is an improvement in your health, do not discontinue or change the treatment regimen of the medicine without consulting a doctor.•Do not take medicines in the dark! Check the label and

the dose each time you take medicine. Wear glasses if you need them.

Tests and follow-upDuring the course of treatment with this medicine, and afterwards, be sure to perform blood tests – in the first eight weeks of taking the medicine, weekly blood tests should be performed.When using a high dosage or if there is liver or kidney failure, perform blood tests more frequently. Afterwards, perform blood tests once a month or at least once in three months.

Perform liver function tests in patients with impaired liver function.If you have further questions regarding use of this medicine, consult the doctor or pharmacist.

4. SIDE EFFECTSAs with any medicine, use of Imuran may cause side effects in some users. Do not be alarmed when reading the list of side effects. You may not experience any of them.Discontinue treatment and refer to the doctor immediately if you notice the following side effects; there may be a need for urgent medical care: •An allergic reaction; the signs may include: ⚪General tiredness, dizziness, nausea, vomiting or

diarrhea⚪High fever, tremor or chills⚪Skin rash or redness⚪Muscle or joint pain⚪Changes in the amount and color of the urine (kidney

problems)⚪Confusion, weakness – caused by low blood

pressure•You bruise more easily or notice unusual bleeding.•You have fever or any other sign of infection.•You feel extremely tired.•You notice lumps anywhere on your body.•You notice any changes in your skin, such as blisters

or peeling.•Your health condition suddenly declines.•You have come into contact with someone who is sick

with chickenpox or herpes zoster.•In case of hepatitis.Additional side effectsOccurring very frequently •An infection caused by a virus, fungus or bacterium

in patients who have undergone an organ transplantation.

•Reduction in your bone marrow function, which may cause you to feel unwell or which may show up in your blood tests.

•Low level of white blood cells in blood tests, which may cause infection.

Occurring frequently•Nausea.•Low levels of platelets, which may cause you to bruise

or bleed easily.Occurring infrequently•Effects of hypersensitivity to the medicine (allergic

reactions).•Anemia, low level of red blood cells, which may cause

tiredness, headache, breathlessness during physical activity, dizziness, paleness.

•Pancreatitis, which may cause severe upper abdominal pain with nausea and vomiting.

•Infection caused by a virus, fungus or bacterium in patients who are not after an organ transplantation.

•Liver problems, which may cause light-colored stool, dark urine, yellow and itchy skin and eyes, abnormal liver function test results.

Occurring rarely•Problems in your blood and bone marrow, which may

cause weakness, tiredness, paleness, headache, sores on the tongue, breathlessness, hemorrhages or infections.

•Intestinal problems leading to diarrhea, abdominal pain, constipation, nausea and vomiting.

•Hair loss (may improve with time, despite continued treatment with Imuran).

•Severe damage to the liver, which may be life-threatening.

•Different types of cancer, including: cancer of the blood, lymph and skin.

Occurring very rarely•Infection in the lungs, which may cause breathlessness,

cough and fever.•Intestinal damage, which may cause diarrhea,

abdominal pain, constipation, nausea and vomiting (can indicate intestinal perforation).

•Skin redness or rash – may develop into a life-threatening skin reaction which includes a widespread rash with blisters and skin peeling that occurs primarily around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome) or widespread skin peeling (toxic epidermal necrolysis).

•Progressive multifocal leukoencephalopathy (PML).•Different clinical syndromes, which are seemingly

a manifestation of hypersensitivity (allergy) to the medicine, such as acute febrile neutrophilic dermatosis (Sweet's Syndrome). The clinical characteristics include: general weakness, dizziness, nausea, vomiting, diarrhea, fever, tremor, roseola, rash, vasculitis, muscle pain, joint pain, reduced blood pressure, impaired kidney function, impaired liver function and cholestasis. Immediate discontinuation of treatment with Imuran, and if necessary, support therapy, may lead to recovery in the vast majority of cases, but rare cases of death have been reported due to hypersensitivity to Imuran; therefore, carefully weigh the need for prolonged treatment with the medicine.

If any of the side effects worsens, or if you suffer from a side effect not mentioned in this leaflet, consult the doctor.Reporting side effects:Side effects can be reported to the Ministry of Health by clicking on the link “Report Side Effects of Drug Treatment” found on the Ministry of Health homepage (www.health.gov.il) that directs you to the online form for reporting side effects, or by entering the link: https://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.gov.ilIn addition, you can report to Perrigo via the following address:www.perrigo-pharma.co.il

5. HOW SHOULD THE MEDICINE BE STORED?•Avoid poisoning! This medicine and any other medicine

must be kept in a closed place out of the sight and reach of children and/or infants to avoid poisoning. Do not induce vomiting without explicit instruction from the doctor.

•Do not use the medicine after the expiry date (exp. date) that appears on the package and blister. The expiry date refers to the last day of that month.

•Store below 25°C. Protect from light.

6. FURTHER INFORMATIONIn addition to the active ingredient, the medicine also contains -Lactose monohydrate, pregelatinised starch, maize starch, magnesium stearate, stearic acid.The Imuran 25 mg tablet coating contains:Opadry Orange 06B230003 (Titanium dioxide, Hypromellose, Iron oxide yellow, Iron oxide red, Macrogol 400).The Imuran 50 mg tablet coating contains:Hypromellose, macrogol 400.Important information regarding some of the ingredients of the medicine –Each 25 mg tablet contains 37 mg lactose.Each 50 mg tablet contains 74 mg lactose.•What the medicine looks like and the contents of the

package – The Imuran 25 mg tablet is an orange, round tablet

marked with GX EL5. The Imuran 50 mg tablet is a yellow, round tablet

marked with GX CH1. The tablets come in blister packages. Each package

contains 100 tablets.•Registration holder: Perrigo Israel Agencies Ltd.,

29 Lehi Street, Bnei-Brak 51200.•Manufacturer: Excella GmbH, Feucht, Germany.•This leaflet was checked and approved by the Ministry

of Health in September 2013.•Registration number of the medicine in the National

Drug Registry of the Ministry of Health: Imuran 25 mg tablets: 3479.25384 Imuran 50 mg tablets: 4265.22964