Azathioprine Vis

Package Leaflet: Information for the Patient

AZATHIOPRINE VIS, 50 mg, tablets

Azathioprine

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Leaflet

• 1. What is AZATHIOPRINE VIS and what is it used for
• 2. Important information before taking AZATHIOPRINE VIS
• 3. How to take AZATHIOPRINE VIS
• 4. Possible side effects
• 5. How to store AZATHIOPRINE VIS
• 6. Contents of the pack and other information

1. What is AZATHIOPRINE VIS and what is it used for

Azathioprine is an immunosuppressive medicine. It is used alone or more often in combination with other medicines (usually corticosteroids):

in autoimmune diseases, such as systemic lupus erythematosus, severe rheumatoid arthritis, dermatomyositis, polymyositis, nodular polyarteritis, common pemphigus-pyoderma gangrenosum, autoimmune hemolytic anemia, chronic refractory thrombocytopenia, autoimmune chronic hepatitis.

Azathioprine is used when these diseases do not respond to corticosteroid treatment, cannot be treated with corticosteroids, or require doses of corticosteroids that cause severe side effects. In the latter case, the use of azathioprine allows for a reduction in the maintenance doses of steroids;

for the treatment of moderate to severe inflammatory bowel diseases, such as Crohn's disease or ulcerative colitis - in patients who require corticosteroid treatment, in patients who do not tolerate corticosteroid treatment, or in patients whose disease is resistant to standard basic treatment;

after organ transplantation, such as kidneys, heart, and liver, azathioprine is used to prolong the survival of transplanted organs, after kidney transplantation - to reduce the doses of corticosteroids.

The action of the medicine leads to the prevention of the proliferation of cells involved in the immune response.

Due to its mechanism of action, the therapeutic effect of the medicine may occur only after weeks or months of treatment.

2. Important information before taking AZATHIOPRINE VIS

When not to take AZATHIOPRINE VIS:

• if you are allergic to azathioprine, 6-mercaptopurine, or any of the other ingredients of this medicine (listed in section 6);
• if you have leukopenia, i.e., a decrease in the number of white blood cells (leukocytes) in the peripheral blood morphology test;
• if you have low activity of the enzyme called thiopurine methyltransferase (TPMT);
• if you are pregnant or breastfeeding.

Warnings and precautions

Before starting treatment with AZATHIOPRINE VIS, discuss it with your doctor, pharmacist, or nurse.

Liver damage

Treatment with AZATHIOPRINE VIS may affect the liver. Your doctor will regularly check your liver function. If you experience symptoms of liver damage, inform your doctor (see section 4 "Possible side effects").

Infections

Patients treated with AZATHIOPRINE VIS have an increased risk of viral, fungal, and bacterial infections, and these infections can be more severe. See also section 4.

Before starting treatment, tell your doctor if you have had chickenpox, shingles, or viral hepatitis B (liver disease caused by the hepatitis B virus).

NUDT15 gene mutation

If you have a congenital mutation in the NUDT15 gene (a gene responsible for the breakdown of AZATHIOPRINE VIS in the body), you have an increased risk of infections and hair loss, so your doctor may decide to reduce the dose.

When taking immunosuppressive treatment with AZATHIOPRINE VIS, there is an increased risk of:

• tumors, including skin cancer; therefore, during treatment with AZATHIOPRINE VIS, you should avoid excessive exposure to sunlight, wear protective clothing, and use sunscreens with a high protection factor.
• lymphoproliferative disorders: treatment with AZATHIOPRINE VIS increases the risk of developing a type of tumor called lymphoproliferative disorder; concurrent use of treatment regimens containing multiple immunosuppressive drugs (including thiopurines) can lead to death; concurrent use of multiple immunosuppressive drugs increases the risk of lymphatic system disorders caused by viral infection [Epstein-Barr virus (EBV)-dependent lymphoproliferative disorders].

Taking AZATHIOPRINE VIS may increase the risk of:

• developing a severe condition called macrophage activation syndrome (excessive activation of white blood cells associated with inflammation), usually occurring in people with certain types of arthritis.

Particular caution should be exercised when taking AZATHIOPRINE VIS:

• in patients with liver failure; your doctor will regularly perform a full quantitative blood test and liver function tests. Depending on the results, the dose of azathioprine may be reduced.
• in people with a deficiency of hypoxanthine-guanine phosphoribosyltransferase (Lesch-Nyhan syndrome); azathioprine has incomplete therapeutic efficacy and is not recommended for use in people with this syndrome.

Taking AZATHIOPRINE VIS in elderly patients

In elderly patients, it is recommended to administer smaller doses, within the lower range of recommended dosing. Particular caution should be exercised when combining azathioprine with immunosuppressive drugs with a different mechanism of action, such as steroids, cyclosporine, or antithymocyte globulin (ATG).

AZATHIOPRINE VIS with other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take.

In particular, inform your doctor if you are taking:

• muscle relaxants, such as tubocurarine, pancuronium, and succinylcholine (used during surgery);
• anticoagulant medicines, such as warfarin (medicines that prevent blood clots);
• aminosalicylates, such as olsalazine, mesalazine, or sulfasalazine (medicines used, among others, in the treatment of ulcerative colitis and Crohn's disease);
• allopurinol, oxypurinol, thiopurinol, or other xanthine oxidase inhibitors, such as febuxostat (medicines used mainly in the treatment of gout). The dose of azathioprine should be reduced, even to 1/4 of the usual dose;
• cytarabine (used in the treatment of leukemia and some types of lymphoma);
• cimetidine (used in the treatment of peptic ulcer disease);
• other medicines that suppress bone marrow function, such as penicillamine (used, among others, in the treatment of rheumatoid arthritis);
• cysteine - the effect of azathioprine may be weakened;
• co-trimoxazole (an antibiotic used in the treatment of bacterial infections);
• captopril (used, among others, in hypertension);
• indomethacin (a pain reliever and anti-inflammatory medicine);
• gold salts and antimalarial medicines;

Vaccination during treatment with AZATHIOPRINE VIS

During treatment with azathioprine, patients should not be vaccinated with live vaccines. It is possible that the response to a killed vaccine, such as hepatitis B, may be weakened.

AZATHIOPRINE VIS with food and drink

The medicine is best taken after a meal, with a glass of water.

Pregnancy, breastfeeding, and fertility

If you are pregnant, breastfeeding, or think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

The medicine is contraindicated in pregnant women.

During treatment, breastfeeding should be discontinued.

Driving and using machines

No studies have been conducted on the effect of the medicine on the ability to drive and use machines. However, you should be cautious due to possible side effects.

AZATHIOPRINE VIS contains lactose

If you have been diagnosed with an intolerance to some sugars, you should contact your doctor before taking the medicine.

3. How to take AZATHIOPRINE VIS

Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

Dosing in transplants

The medicine is taken orally after a meal, and the daily dose can be given once. The dose will be determined by your doctor, depending on your clinical condition and bone marrow function.

On the first day after organ transplantation- 5 mg/kg body weight per day, then a maintenance dose of 1 to 4 mg/kg body weight per day.

This dose should be adjusted according to the clinical response and hematological tolerance. Due to the risk of transplant rejection, treatment with azathioprine should be continued for life, although sometimes using small doses of the medicine.

Dosing in other indications

In other indications, the medicine is used in adults and children at a daily dose of 1 to 3 mg/kg body weight.

After a significant clinical effect has occurred, your doctor will consider reducing the maintenance dose to the smallest possible dose. The dose may be less than 1 mg/kg body weight to 3 mg/kg body weight. If after 3 months of treatment your condition does not improve, your doctor will consider discontinuing AZATHIOPRINE VIS. However, in patients with inflammatory bowel disease, your doctor will consider a treatment duration of at least 12 months, and the response to treatment may only be clinically visible after 3 to 4 months of treatment.

Dosing in elderly patients

In elderly patients, your doctor will recommend smaller doses of the medicine, within the lower range of recommended dosing. Particular caution should be exercised when combining azathioprine with immunosuppressive drugs with a different mechanism of action, such as steroids, cyclosporine, or antithymocyte globulin (ATG).

Dosing in patients with renal and/or hepatic impairment

Patients with impaired liver or kidney function should be given the smallest recommended doses (1 mg/kg body weight per day) and have their blood count and liver function monitored. If symptoms of bone marrow or liver damage occur (infection symptoms, unexplained bruising, bleeding, or other signs of bone marrow suppression), you should contact your doctor.

If you feel that the effect of the medicine is too strong or too weak, you should consult your doctor.

Taking a higher dose of AZATHIOPRINE VIS than recommended

If you have taken more of the medicine than prescribed, you should contact your doctor or pharmacist immediately.

Procedure in case of overdose

As a result of an overdose, there is initially a decrease in the number of leukocytes and platelets. Further consequences may include stronger bone marrow suppression and pancytopenia (decrease in the number of all blood cell elements: red blood cells, white blood cells, and platelets). More severe other side effects, caused by the effect on the bone marrow, may also occur.

In extreme cases, in the event of cytopenia (decrease in the number of blood cells) threatening complications (severe thrombocytopenia, agranulocytosis), symptomatic hematologic treatment may be necessary.

Missing a dose of AZATHIOPRINE VIS

If you miss a dose of azathioprine, you should take it as soon as possible, unless it is close to the time of the next dose, and then return to your normal treatment schedule. Do not take a double dose to make up for a missed dose.

Stopping treatment with AZATHIOPRINE VIS

Do not stop taking the medicine unless your doctor tells you to. If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

You should immediately contact your doctor or go to the hospital emergency department, as you may need urgent medical attention, if you experience any of the following serious side effects:

• allergic reactions, including: frequently - fever, muscle and joint pain; not very frequently - skin nodules; rarely - rash and skin eruptions; with unknown frequency - malaise, dizziness, chills, skin itching. Immediate withdrawal of the medicine or reduction of the dose to half usually caused the symptoms to disappear;
• rash (elevated, red, pink, or purple painful bumps on the skin), especially on the arms, hands, fingers, face, and neck, with concurrent fever (Sweet's syndrome, also known as acute febrile neutrophilic dermatosis). The frequency of these side effects is unknown (cannot be estimated from available data);
• liver function disorders and bile stasis, with symptoms such as yellowing of the skin or whites of the eyes (these symptoms may also be related to allergic reactions). Patients, especially those undergoing long-term treatment, have reported cases of severe liver damage, which can be life-threatening (e.g., liver damage, non-cirrhotic portal hypertension, vascular and bile duct diseases). You should tell your doctor if you experience any of the following symptoms: yellowing of the skin and whites of the eyes (jaundice), easy bruising, discomfort in the abdominal cavity, loss of appetite, fatigue, nausea, or vomiting. The frequency of these side effects is unknown (cannot be estimated from available data);
• blood or bone marrow problems, symptoms include: weakness, fatigue, pallor, easy bruising, unusual bleeding, or signs of bone marrow suppression.
• any symptom indicating fever or infection (sore throat, mouth pain, or problems urinating)

Also reported are the following side effects: Very common (may affect more than 1 in 10 people)

• leukopenia (decrease in the number of white blood cells)

Common (may affect up to 1 in 10 people)

• thrombocytopenia (decrease in the number of platelets)
• decrease in blood pressure
• heart rhythm disorders
• nausea, vomiting, loss of appetite

Uncommon (may affect up to 1 in 100 people)

• granulocytopenia (decrease in the number of granulocytes), anemia
• diarrhea (in patients with inflammatory bowel disease, cases of severe diarrhea have been reported, recurring after re-administration of the medicine .

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

• viral, bacterial, and fungal infections, especially in the respiratory tract (especially in transplant patients),
• various types of tumors, including blood, lymphatic, and skin cancer.

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

• agranulocytosis (significant decrease in the number of granulocytes), pancytopenia (deficiency of blood cells and platelets), and aplastic anemia
• vasculitis
• pancreatitis (especially after kidney transplantation or in patients with inflammatory bowel disease)
• colitis, diverticulitis, and intestinal perforation (observed in transplant patients)
• reversible, drug-induced interstitial pneumonia
• hair loss (in many cases, it resolved on its own despite continued treatment with a lower dose of the medicine).

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49-21-301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl

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

Side effects can also be reported to the marketing authorization holder.

5. How to store AZATHIOPRINE VIS

Keep the medicine out of the sight and reach of children.

Store in a temperature below 25°C, in the original packaging.

Do not use the medicine after the expiry date stated on the packaging (label and carton). The expiry date refers to the last day of the specified month.

6. Contents of the pack and other information

What AZATHIOPRINE VIS contains

• The active substance of the medicine is azathioprine. One tablet contains 50 mg of azathioprine.
• The other ingredients (excipients) are: potato starch, lactose monohydrate, povidone, talc, magnesium stearate.

What AZATHIOPRINE VIS looks like and contents of the pack

AZATHIOPRINE VIS is a light yellow, biconvex tablet with the marking "A/50" and a score line on one side. The tablet can be divided into equal doses.

Packaging: an orange glass bottle with a polyethylene cap, containing 30 or 50 or 100 tablets, in a cardboard box.

Marketing authorization holder and manufacturer

Zakłady Chemiczno-Farmaceutyczne "VIS" Spółka z o.o.

ul. Św. Elżbiety 6a

41-905 Bytom

Date of last revision of the leaflet: