Azathioprine Doc Generici: detailed information

Patient Information Leaflet

AZATIOPRINA DOC 50mg film-coated tablets

Equivalent medicine
Please read all of this leaflet carefully before you start using 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 others, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What AZATIOPRINA DOC is and what it is used for

AZATIOPRINA DOC is a medicine used to suppress the body's defence reaction (immune response).
AZATIOPRINA DOC is used

to prevent rejection reactions following kidney, liver, heart, lung, or pancreas transplantation, in combination with other medicines that suppress the immune response (immunosuppressants). In these cases, azathioprine, the active substance of AZATIOPRINA DOC, is generally used in combination with other immunosuppressive agents which constitute the essential component of treatment.
in moderately severe to severe clinical courses of the following diseases, usually in combination with glucocorticoids (a type of anti-inflammatory medicine). The use of AZATIOPRINA DOC in combination with glucocorticoids generally allows for a reduction in the glucocorticoid dose. Furthermore, AZATIOPRINA DOC is also indicated in patients affected by the following diseases when glucocorticoids are not tolerated or when an adequate therapeutic effect cannot be achieved with high doses of glucocorticoids:
- severe forms of active rheumatoid arthritis/chronic polyarthritis (a particular form of chronic inflammation affecting multiple joints) that cannot be controlled by other medicines, so-called disease-modifying drugs with lower health risks
- chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis)
- chronic hepatitis (autoimmune hepatitis)
- systemic lupus erythematosus (an autoimmune disease that may affect various organs)
- certain immunological diseases (defined as collagenoses):
- dermatomyositis (muscle inflammation with skin involvement)
- polyarteritis nodosa (inflammation of blood vessels)
- pemphigus vulgaris and bullous pemphigoid (skin diseases characterized by blister formation)
- Behçet’s disease (recurrent chronic inflammation, particularly affecting the eyes and mucous membranes of the mouth and genitals)
blood disorder associated with destruction of red blood cells (refractory autoimmune haemolytic anaemia caused by warm IgG antibodies)
skin bleeding due to platelet damage and reduced platelet count (chronic refractory idiopathic thrombocytopenic purpura)
- in relapsing multiple sclerosis when modulation of the dysregulated immune response is indicated, but treatment with beta interferon is not possible, or when a stable disease course has been achieved during prior treatment with AZATIOPRINA DOC.
- for the treatment of generalized myasthenia gravis (a form of pathological muscle weakness). Depending on the severity of the disease, at the beginning of treatment AZATIOPRINA DOC must be administered in combination with glucocorticoids due to the slow onset of its effect, and the glucocorticoid dose should be gradually reduced after several months of treatment.

Several weeks or months may be required before the therapeutic effect becomes evident.

2. What you should know before using AZATIOPRINA DOC

Do not use AZATIOPRINA DOC

if you are hypersensitive (allergic) to the active substance azathioprine, to 6-mercaptopurine (a degradation product of azathioprine), or to any of the other components of this medicine (listed in section 6).
if you are breastfeeding.

Do not get vaccinated with live vaccines. In particular, during treatment with AZATIOPRINA DOC, vaccination against tuberculosis (BCG), smallpox, and yellow fever is not permitted.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using AZATIOPRINA DOC.

Special caution is required when taking AZATIOPRINA DOC

if you have a severe infection or a serious disease of the liver, bone marrow, or pancreas. In this case, inform your doctor, who will prescribe AZATIOPRINA DOC only after careful assessment of the risks and benefits.
at the beginning of treatment with AZATIOPRINA DOC. During the first 8 weeks of therapy, a complete blood count including platelet count must be performed at least once a week.

More frequent testing is required in the following cases:

Use of higher doses of azathioprine
Elderly patients
Impaired renal function. Your doctor will reduce the dose if necessary.
Impaired liver function. Your doctor will regularly monitor your liver function and reduce the dose if necessary. If you suffer from severely impaired liver function, your doctor will prescribe AZATIOPRINA DOC only after careful assessment of the risks and benefits, as potentially fatal liver damage has been reported in patients with impaired liver function.

After 8 weeks, the complete blood count should be checked once a month, and in any case at least every 3 months.

Your doctor may ask you to have blood tests while taking AZATIOPRINA DOC to monitor blood cell counts. Your doctor may also perform a genetic test (i.e., analysis of the TPMT and/or NUDT15 gene) before or during treatment to determine whether your response to this medicine may be influenced by your genetics. Your doctor may adjust the dose of azathioprine after these tests.
If unexplained bruising occurs during treatment, or if bleeding or signs of infection occur. In this case, please inform your doctor immediately.
If you have a deficiency of the enzyme thiopurine S-methyltransferase (TPMT), which leads to inadequate metabolism of the active substance azathioprine. This may lead to an increased risk of bone marrow damage caused by AZATIOPRINA DOC and possibly to malignant diseases of the hematopoietic system (blood formation) (secondary leukemia and myelodysplasia). Additionally, if you are taking medicines that inhibit this enzyme, such as olsalazine, mesalazine, or sulfasalazine (agents used to treat chronic inflammatory bowel disease), these may further increase this effect.
NUDT15 gene mutation If you have an inherited mutation of the NUDT15 gene (a gene involved in the metabolism of AZATIOPRINA DOC in the body), you have a higher risk of infections and hair loss; in this case, your doctor may administer a lower dose.
If you are taking AZATIOPRINA DOC simultaneously with medicines that impair bone marrow function, such as penicillamine and cytostatics.
If you are taking allopurinol, oxipurinol, thiopurinol, or other xanthine oxidase inhibitors, such as febuxostat (agent for the treatment of gout). If taken concurrently with allopurinol, oxipurinol, thiopurinol, or other xanthine oxidase inhibitors such as febuxostat, the dose of AZATIOPRINA DOC must be reduced to one-quarter of the normal dose.
Before undergoing surgery, inform the anesthesiologist that you are taking AZATIOPRINA DOC, because muscle relaxants used during anesthesia may interact with azathioprine.
If you have Lesch-Nyhan syndrome (inherited deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase). AZATIOPRINA DOC may not be effective in this metabolic disorder and therefore should not be used.
If you have been exposed to the varicella zoster virus (VZV) causing chickenpox and shingles (herpes zoster). Since a VZV infection during treatment with AZATIOPRINA DOC can be severe, you must avoid any contact with people affected by chickenpox or shingles. Your doctor will review your medical history regarding VZV infections, and if you are exposed to a VZV infection, will take appropriate measures, which may include antiviral therapy, interruption of azathioprine treatment, and supportive treatment.
If you are significantly exposed to sunlight, as there may be an increased risk of skin infections or skin cancer during use of AZATIOPRINA DOC. Therefore, avoid unnecessary sunlight and UV radiation, wear protective clothing, and use sunscreens with a high protection factor.
If you are of childbearing potential, because you must avoid pregnancy during treatment, even if only your partner is being treated. Therefore, you or your partner must use a contraceptive method during treatment with AZATIOPRINA DOC. As a man, you should continue using contraception for at least 6 additional months after the end of treatment. This also applies to male and female patients with limited fertility due to chronic urinary toxicity (uremia), as fertility generally returns to normal after transplantation.

There is clinical evidence that intrauterine devices (IUDs, copper T-shaped IUDs) may not function properly during azathioprine therapy. Therefore, you should use other or additional contraceptive measures.

If you are receiving treatment with immunosuppressive agents, taking AZATIOPRINA DOC may increase the risk of the following conditions:

Tumors, including skin tumors. If you are taking AZATIOPRINA DOC, avoid excessive exposure to sunlight, wear protective clothing, and use sunscreen with a high protection factor.
Lymphoproliferative disorders
Treatment with AZATIOPRINA DOC increases the risk of developing a specific type of cancer known as "lymphoproliferative disease." With therapeutic regimens containing multiple immunosuppressive agents (including thiopurines), this can be fatal.
The combination of multiple immunosuppressive agents taken simultaneously increases the risk of lymphatic system disorders due to viral infections (lymphoproliferative diseases caused by Epstein-Barr virus (EBV)).

Taking AZATIOPRINA DOC may increase the risk of:

Developing a serious condition known as "macrophage activation syndrome" (excessive activation of white blood cells associated with inflammation), which generally occurs in people affected by certain types of arthritis.

During immunosuppressive treatment, there may be an increased risk of malignant tumors when higher doses are used and depending on the duration of treatment.

Liver damage

Treatment with AZATIOPRINA DOC may affect the liver, and your doctor will regularly monitor your liver function. Inform your doctor if you develop symptoms of liver damage (see section 4 “Possible side effects”).

Vitamin B3 deficiency (pellagra)

Inform your doctor immediately if you experience diarrhea, pigmented skin rash, memory deterioration, difficulty reasoning, or cognitive changes, as these symptoms may indicate vitamin B3 deficiency (nicotinic acid deficiency/pellagra).

Other medicines and AZATIOPRINA DOC

Inform your doctor or pharmacist if you are taking, using, or have recently taken or used any other medicines, even those not requiring a prescription.

Concurrent use of AZATIOPRINA DOC may affect the effect of the medicines or groups of preparations listed below, and the effect of AZATIOPRINA DOC may be influenced by these medicines/groups of preparations:

Ribavirin – used to treat viral infections;
If you are taking allopurinol, oxipurinol, thiopurinol, or other xanthine oxidase inhibitors, such as febuxostat (agent for the treatment of gout). Allopurinol, oxipurinol, thiopurinol, or other xanthine oxidase inhibitors such as febuxostat inhibit the degradation of AZATIOPRINA DOC. Therefore, if one of these medicines is used concurrently, the dose of AZATIOPRINA DOC must be reduced to one-quarter of the normal dose.
Olsalazine, mesalazine, and sulfasalazine (medicines for the treatment of chronic inflammatory bowel disease, such as Crohn's disease) may increase the harmful effect of AZATIOPRINA DOC on the bone marrow.
The anticoagulant effect of anticoagulants such as warfarin may be reduced with concomitant use of AZATIOPRINA DOC.
ACE inhibitors for the treatment of high blood pressure and heart failure, trimethoprim/sulfamethoxazole (antibiotic), cimetidine (gastrointestinal agent), and indomethacin (medicine for rheumatism) may increase the harmful effect of AZATIOPRINA DOC on the bone marrow.
Concomitant use of penicillamine (medicine for rheumatism) or cytostatics (medicines for malignant tumors such as methotrexate) may increase the harmful effect of AZATIOPRINA DOC on the bone marrow and should therefore be avoided.
Vaccination with a live vaccine during treatment with AZATIOPRINA DOC may cause harmful reactions and should therefore be avoided. A reduced immune response to vaccination is likely in the case of vaccines with inactivated pathogens. Your doctor will check the immune response to vaccination, where applicable.
Muscle relaxants, such as tubocurarine or succinylcholine (used during surgery), may interact with azathioprine. Before surgery, it is necessary to inform the anesthesiologist that you are taking azathioprine because muscle relaxants used during anesthesia may interact with azathioprine.
Infliximab (used mainly for the treatment of ulcerative colitis and Crohn's disease).

AZATIOPRINA DOC with food and drinks

Take AZATIOPRINA DOC at least 1 hour before or at least 3 hours after any meal or after drinking milk. The tablet should be swallowed with some water (section 3 “Directions for use”).

Pregnancy, breastfeeding, and fertility

If you are pregnant, suspect you are pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

If you are pregnant, you may take AZATIOPRINA DOC only if your doctor considers it absolutely necessary. In case of pregnancy, you must therefore inform your doctor immediately.

Changes in blood counts may occur in newborns whose mothers were treated with AZATIOPRINA DOC during pregnancy. Regular monitoring of blood counts during pregnancy is therefore recommended.

Inform your doctor immediately if you experience intense itching without skin rash during pregnancy. You may also experience nausea and loss of appetite along with itching, indicating a condition called cholestatic pregnancy (a liver disease during pregnancy). This condition may cause harm to the unborn child.

During treatment with AZATIOPRINA DOC, you must avoid pregnancy as much as possible,
even if only your partner is being treated.

As a general rule, you or your partner, if of reproductive age, must use a contraceptive method during treatment with AZATIOPRINA DOC. Men must continue using contraception for at least 6 additional months after the end of treatment. This also applies to male and female patients with limited fertility due to chronic urinary toxicity (uremia), as fertility generally returns to normal after transplantation.

There is evidence that intrauterine devices (IUDs, copper T-shaped IUDs) may not function properly during therapy with AZATIOPRINA DOC. Therefore, other or additional contraceptive measures should be used.

If you are planning to have a child, you must contact your doctor, regardless of whether you are male or female.

You must not breastfeed during treatment with AZATIOPRINA DOC, as the degradation product of AZATIOPRINA DOC formed in the body passes into breast milk. If your doctor considers treatment with AZATIOPRINA DOC absolutely necessary, you must stop breastfeeding.

Driving and use of machines

Before considering driving a vehicle or operating machinery, consider your health status and the possible side effects of AZATIOPRINA DOC.

No studies have been conducted on the effects of azathioprine, the active substance in AZATIOPRINA DOC, on the ability to drive or operate machinery. However, based on current experience, AZATIOPRINA DOC is not considered to affect concentration or reaction ability.

AZATIOPRINA DOC contains lactose.

If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

AZATIOPRINA DOC contains sodium.

This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet, i.e., it is essentially “sodium-free”.

3. How to take AZATIOPRINA DOC

Take this medicine according to the following dosage recommendations.
Dosage
After organ transplantation
Depending on the treatment regimen, the initial dose is usually up to 5 mg/kg body weight/day.
The maintenance dose ranges between 1 mg/kg and 4 mg/kg body weight/day and must be adjusted according to clinical needs and hematological tolerance.
Treatment with AZATIOPRINA DOC, even at low doses, must be administered indefinitely, as transplant rejection may otherwise occur.

Multiple sclerosis
For the treatment of relapsing multiple sclerosis, the usual dosage is between 2 mg/kg and 3 mg/kg body weight/day.
A treatment period longer than one year may be necessary before a clearly evident effect appears, and at least two years may be required to achieve full efficacy.

Myasthenia gravis
The recommended dosage for the treatment of myasthenia gravis is between 2 mg/kg and 3 mg/kg body weight/day.
Therapeutic response usually occurs no earlier than 2–6 months after starting treatment.
Depending on the severity of the disease, AZATIOPRINA DOC should be administered in combination with glucocorticoids due to the slow onset of effect at the beginning of treatment. The glucocorticoid dose may be gradually reduced over the months.
Treatment with AZATIOPRINA DOC should be continued for at least 2 or 3 years.

Other therapeutic indications
For the treatment of autoimmune chronic active hepatitis, the initial dosage is usually between 1 mg/kg and 1.5 mg/kg body weight/day, and the maintenance dosage is up to 2 mg/kg body weight/day.
For other therapeutic indications, the initial dosage is generally between 1 mg/kg and 3 mg/kg body weight/day, and the maintenance dosage ranges from less than 1 mg/kg to 3 mg/kg body weight/day.
The dosage must be adjusted according to the therapeutic effect, which may only become apparent weeks or months after starting treatment, and hematological tolerance.
If a treatment response is observed, the dose should be reduced to the minimum amount necessary to maintain the therapeutic effect.
If no improvement is seen after 3–6 months of treatment, discontinuation of therapy should be considered.

Patients with impaired renal and/or hepatic function
In patients with impaired renal and/or hepatic function, the dose of AZATIOPRINA DOC should be at the lower end of the normal dosage range.

Children
For the treatment of children, especially those who are overweight, consult your doctor.
There are insufficient data to demonstrate the efficacy and safety of treating chronic arthritis in children and adolescents (juvenile idiopathic arthritis) with AZATIOPRINA DOC.
No data are available regarding the use of AZATIOPRINA DOC in children with multiple sclerosis.
Therefore, the use of AZATIOPRINA DOC in children is not recommended.
For other therapeutic indications, the same dosage recommendations as for adults apply.

Elderly patients
It is recommended that dosage for elderly patients be established at the lower end of the dosage range indicated for adults.

Use in combination with allopurinol, oxypurinol, thiopurinol, or other xanthine oxidase inhibitors, such as febuxostat (a gout treatment agent)
When taken concomitantly with allopurinol, oxypurinol, thiopurinol, or other xanthine oxidase inhibitors such as febuxostat, the dose of AZATIOPRINA DOC must be reduced to one-quarter of the normal dose.

Method of administration
AZATIOPRINA DOC must be taken orally and swallowed whole with plenty of water (at least 200 ml, equivalent to one glass). AZATIOPRINA DOC should be taken at least 1 hour before or 3 hours after a meal or after drinking milk.
You may experience nausea at the beginning of AZATIOPRINA DOC administration. If this occurs, your doctor may recommend taking AZATIOPRINA DOC after a meal to prevent it.
If the 50 mg tablet must be split, contact between the skin and the tablet powder or the break site should be avoided. Tablets must not be crushed.
Additional information for healthcare professionals regarding handling and disposal is provided in section 6 of this leaflet.

Duration of treatment
The duration of treatment must be determined by the treating physician.

If you take more AZATIOPRINA DOC than you should
Inform a doctor immediately if you suspect an overdose, so that appropriate further management can be decided.
The most common effect of an overdose with AZATIOPRINA DOC is suppression of bone marrow function, which usually peaks between 9 and 14 days after the overdose.
The main signs of bone marrow suppression are mouth and throat ulcers, bruising, unexplained fever, and inexplicable infections. Spontaneous bleeding and significant fatigue may also occur. However, harmful effects are more likely following prolonged mild overdose (e.g. due to physician-prescribed doses that are slightly too high) than after a single excessively high dose.
Additional information for physicians and healthcare professionals regarding overdose is provided in section 6 of this leaflet.

If you forget to take AZATIOPRINA DOC
Do not take a double dose to make up for the missed dose; instead, take only the next dose as prescribed. If you have missed more than one dose, consult your doctor.

If you stop taking AZATIOPRINA DOC
Treatment with AZATIOPRINA DOC must always be discontinued only under close medical supervision.
Therefore, if you wish to stop or suspend treatment, you must discuss this with your doctor.

If you have further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the serious side effects listed below, stop taking AZATIOPRINA DOC and contact your doctor or go to hospital immediately:

Numerous allergic-type reactions have been reported. Signs of such hypersensitivity reactions may include: general malaise, dizziness, lightheadedness, nausea, vomiting, diarrhoea, fever, chills, skin nodules or rashes, vasculitis, muscle and joint pain, chest pain, shortness of breath or leg swelling (cardiac problems), low blood pressure, impaired kidney and liver function, and biliary stasis (see also Hepatobiliary disorders). In very rare cases, fatal hypersensitivity reactions have been observed.
Reversible swelling of the brain with symptoms including severe headache, visual disturbances, seizures, confusion and reduced level of consciousness, with or without high blood pressure (posterior reversible encephalopathy syndrome or PRES).

Assessment of side effects is based on the following frequency data:
Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Rare: may affect up to 1 in 1,000 people
Very rare: may affect up to 1 in 10,000 people, including isolated cases
Not known: cannot be estimated from the available data

The following side effects have been observed to date:

Infections and infestations
Very common: Infections due to viruses, fungi and bacteria in transplant recipients receiving AZATIOPRINA DOC in combination with other immunosuppressive agents
Uncommon: Infections due to viruses, fungi and bacteria in other patients

If you take AZATIOPRINA DOC alone or in combination with other drugs to suppress the immune response, particularly glucocorticoids, you may be more susceptible to infections caused by viruses, fungi and bacteria, including serious or atypically progressing infections caused by varicella zoster virus (VZV), which causes chickenpox and shingles (herpes zoster), and other infectious pathogens.
If you notice signs of infection, inform your doctor immediately. You must also inform your doctor immediately if you have been in contact with someone who has chickenpox or shingles (herpes zoster).

Benign, malignant and unspecified tumours (including cysts and polyps)
Rare: Various types of cancer, including blood, lymphatic system and skin cancers, generally typical of treatments aimed at suppressing the immune response; malignant disorders of the haematopoietic system such as acute myeloid leukaemia and myelodysplasia

Disorders of the haemolymphopoietic system
Very common: Suppression of bone marrow function, decreased number of white blood cells (leucopenia)
Common: Decreased platelet count in the blood (thrombocytopenia)
Uncommon: Decreased red blood cell count (anaemia)
Rare: Decreased count of certain white or red blood cells (agranulocytosis, aplastic anaemia), decreased count of all blood cells (pancytopenia), increased presence of particularly large precursors of red blood cells (megaloblastic anaemia) and small red blood cells (erythroid hypoplasia) in the blood
Very rare: Anaemia due to increased breakdown of red blood cells (haemolytic anaemia)

The most frequent side effect of AZATIOPRINA DOC is dose-dependent suppression of bone marrow function, which usually returns to normal if the dose is appropriately adjusted.
Signs of impaired bone marrow function may include: increased susceptibility to infections, mouth and throat ulcers, increased tendency to bleed, fatigue and physical weakness.
Blood count changes usually occur early in therapy but may also develop later during treatment. Regular monitoring of blood counts is therefore advisable, even in patients who have been well controlled for a long time.

Immune system disorders
Uncommon: Hypersensitivity reactions
Very rare: Severe skin reactions with blistering and/or skin peeling, particularly on extremities, as well as in the mouth, eye and genital areas, associated with poor general condition and fever (Stevens-Johnson syndrome, toxic epidermal necrolysis).

If you notice signs of a hypersensitivity reaction, inform your doctor immediately. Immediate discontinuation of AZATIOPRINA DOC and, if necessary, circulatory support measures are generally sufficient as treatment.
After a hypersensitivity reaction to AZATIOPRINA DOC, your doctor will decide whether to continue treatment with AZATIOPRINA DOC.

Respiratory, thoracic and mediastinal disorders
Very rare: Pneumonitis, which may resolve after discontinuation of AZATIOPRINA DOC treatment

Inform your doctor immediately if you experience fever, headache and limb pain, cough or difficulty breathing (similar to a chest infection).

Gastrointestinal disorders
Common: Nausea, occasionally with vomiting
Uncommon: Pancreatitis, particularly in transplant patients and patients with inflammatory bowel disease
Very rare: Severe inflammatory diseases of the colon (colitis, diverticulitis) and intestinal perforation in transplant patients, severe diarrhoea in patients with inflammatory bowel diseases, intestinal problems that may lead to diarrhoea, abdominal pain, constipation, nausea and vomiting.

If you experience nausea with occasional vomiting, taking the film-coated tablets with food may reduce these symptoms.
Inform your doctor if you develop severe diarrhoea or nausea and vomiting.

Hepatobiliary disorders
Uncommon: Dose-dependent liver damage with biliary stasis, which usually resolves after discontinuation of treatment and may be associated with a hypersensitivity reaction (see also Immune system disorders), cholestasis of pregnancy which may cause intense itching, particularly in the hands and feet.
Rare: Severe, potentially life-threatening liver damage during prolonged periods of administration (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.

In some cases, temporary or sustained improvement of symptoms and histological liver abnormalities has been achieved by discontinuing treatment with AZATIOPRINA DOC.
Inform your doctor immediately if you notice any of the following signs: black (tarry) stools, blood in the stool, abdominal pain or yellowing of the skin and whites of the eyes.

Skin and subcutaneous tissue disorders
Rare: Hair loss

In many cases, hair loss improved spontaneously, even though treatment with AZATIOPRINA DOC was continued. The relationship between hair loss and the use of AZATIOPRINA DOC remains unclear.

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

You may develop a skin rash (painful, raised red, pink or purple nodules), particularly on the arms, hands, fingers, face and neck, which may also be accompanied by fever (Sweet’s syndrome, also known as acute febrile neutrophilic dermatosis).
Tremor
Inflammation of a salivary gland (sialoadenitis)
Vitamin B3 deficiency (pellagra) associated with localized pigmented skin rash, diarrhoea, memory loss, difficulty in reasoning and changes in cognitive abilities.
You may experience sensitivity to light or sunlight (photosensitivity).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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 AZATIOPRINA DOC

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and on the carton after “EXP” or
“expiry date”. The expiry date refers to the last day of that month.
Store in the original packaging to protect the contents from light.
Do not use this medicine if you notice the following: visible signs of damage.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. These measures will help protect the environment.

6. Package contents and other information

What AZATIOPRINA DOC contains

The active substance is azathioprine. One film-coated tablet contains 50 mg of azathioprine.
Other components are:
Tablet core: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate (type A), pregelatinized starch (maize), polysorbate 80, povidone K30, magnesium stearate [vegetable-based]
Coating film: hypromellose, macrogol 400, macrogol 6000

Description of the appearance of AZATIOPRINA DOC and contents of the pack
AZATIOPRINA DOC 50 mg are pale yellow, round, biconvex, film-coated tablets contained in a transparent PVC-PVdC/aluminum blister. On one side, the tablets are marked with "AZ50", and on the other side have a score line.
AZATIOPRINA DOC 50 mg film-coated tablets are available in packs of 50 film-coated tablets.
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
DOC Generici Srl
Via Turati 40
20121 Milan
Italy

Manufacturer
AqVida GmbH
Kaiser-Wilhelm-Str. 89
20355 Hamburg
Germany

The following information is intended exclusively for physicians and healthcare professionals:

Additional information on handling and disposal:
Azathioprine is mutagenic and potentially carcinogenic.
Appropriate precautionary measures should be taken when handling this medicinal product. If the film coating is intact, there is no risk associated with handling the film-coated tablets, and no additional precautionary measures are required.
During handling of AZATIOPRINA DOC, healthcare personnel responsible must follow the guidelines for handling cytotoxic substances in accordance with current recommendations or local regulations.
Any unused medicinal products or waste materials must be disposed of in accordance with local requirements. Excess medicines and contaminated supplies should be temporarily stored in clearly labeled containers and safely disposed of. High-temperature incineration is recommended.

Additional information on overdose
A case has been reported of a patient who ingested 7.5 g of azathioprine as a single dose. The toxic effects observed immediately after overdose were nausea, vomiting, and diarrhea, followed by moderate leukopenia and mild hepatic dysfunction. The patient recovered without complications.
There is no specific antidote for the active substance azathioprine. Gastric lavage has been used. In case of overdose, it is necessary to monitor particularly the blood count and liver function in order to treat any adverse effects promptly. In cases of severe intoxication, AZATIOPRINA DOC can be removed by hemodialysis.