PATIENT INFORMATION LEAFLET

Immufalk 100 mg Film-Coated Tablets

Azathioprine

Read this leaflet carefully before you start to take this medicine because it contains important information for you.

• Keep this leaflet, as 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 they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

6. Contents of the pack and additional information

Immufalk contains the active ingredient azathioprine, which belongs to a group of medicines called immunosuppressants, that reduce the activity of your immune system.

Immufalk can be used to help your body accept a new organ transplant, such as a kidney, heart, or liver transplant, or to treat some diseases in which your immune system is reacting against your own body (autoimmune diseases).

Immufalk may also be used alone or in combination with other medicines to treat:

• severe rheumatoid arthritis(a disease in which the immune system attacks the cells that line the joints, causing swelling, pain, and stiffness in the joints)
• severe inflammatory bowel disease(Crohn's disease or ulcerative colitis)
• systemic lupus erythematosus(a disease in which the immune system attacks many of the organs and tissues of the body, including the skin, joints, kidneys, brain, and other organs, causing intense fatigue, fever, stiffness, and pain in the joints)
• dermatomyositis and polymyositis(a group of diseases that cause muscle inflammation, muscle weakness, and skin rash)
• chronic active autoimmune hepatitis(a disease in which the immune system attacks the liver cells, causing liver inflammation, fatigue, muscle pain, yellowing of the skin, and fever)
• polyarteritis nodosa(a rare disease that causes inflammation of the blood vessels)
• autoimmune hemolytic anemia(a severe blood disorder in which the immune system destroys red blood cells faster than it can produce them, causing symptoms of weakness and difficulty breathing)
• idiopathic thrombocytopenic purpura refractory chronic(a disorder with low platelet counts, which can cause easy bruising and excessive bleeding)

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

Immufalk can be used alone, but it is used more frequently in combination with other medicines.

It may take weeks or months to observe a therapeutic effect.

Do not take Immufalk:

• If you areallergicto azathioprine, mercaptopurine, or any of the other components of this medication (listed in section 6).
• A hypersensitivity reaction may include rash, itching, difficulty breathing, or swelling of the face, lips, throat, or tongue.
• If you have aserious infection
• If you have aserious liver or bone marrow disorder
• If you havepancreatitis(inflammation of the pancreas)
• If you have beenvaccinatedrecently with alive attenuated vaccinesuch as smallpox or yellow fever
• If you arepregnant(unless your doctor tells you to)
• If you are inlactation

Warnings and precautions

Consult your doctor before starting to take Immufalk..

You should not take Immufalk unless you can be monitored to control the adverse effects. You should immediately inform your doctor if you develop mouth sores, fever, infections, bruises, or bleeding.

Consult your doctor immediately:

• if you observe any of the following signs: black stools, blood in the stools, abdominal pain, or yellowing of the skin and the white of the eyes (jaundice);
• If you experience intense itching without a rash during pregnancy. You may also experience nausea and loss of appetite along with the itching, which may indicate that you have a condition called cholestasis of pregnancy (a liver disease during pregnancy).

Consult your doctor before starting to take Immufalk:

• if you have received recently or are going to receive a vaccine. If you take Immufalk, you should not receive a live vaccine (for example, flu vaccine, measles vaccine, BCG vaccine, etc.) until your doctor tells you it is safe to do so. This is because some vaccines may cause an infection if you receive them while taking Immufalk.
• if you have liver or kidney problems
• if you have a genetic disorder called TPMT deficiency (in which your body produces too little of an enzyme called thiopurine‑methyltransferase)
• if you are going to undergo surgery (this is because medications such as tubocurarine or succinylcholine used as muscle relaxants during surgery may interact with Immufalk. You should inform your anesthesiologist of your treatment with Immufalk before surgery.
• if you have a genetic disorder known as Lesch‑Nyhan syndrome. This is a rare disorder that occurs in families and is caused by the lack of HPRT (hypoxanthine-guanine-phosphoribosyltransferase).

Infections

When you receive treatment with Immufalk, the risk of developing viral, fungal, and bacterial infections is higher, and these infections may be more severe. See section 4.

Before starting treatment, inform your doctor if you have had or not varicella, herpes, or hepatitis B (a liver disease caused by a virus).When you take Immufalk, avoid contact with people who have varicella or herpes zoster.

Pelagra

Inform your doctor immediately if you notice diarrhea, a localized pigmented rash (dermatitis), a decline in memory, reasoning, and thinking ability (dementia), as these symptoms may indicate a deficiency of vitamin B3 (deficiency of nicotinic acid/pelagra).

NUDT15 gene mutation

If you have a hereditary mutation in the NUDT15 gene (a gene involved in the breakdown of azathioprine in the body), you have a higher risk of infections and hair loss, and in this case, your doctor may give you a lower dose.

Your doctor may also perform genetic tests (for example, analyze your TPMT and/or NUDT15 genes) before or during treatment to determine if your response to this medication may be affected by your genetics. Your doctor may change your azathioprine dose after these tests.

If you are receiving immunosuppressive treatment, taking Immufalk may increase your risk of:

• cancers, including skin cancer. Therefore, when you take Immufalk, avoid excessive sun exposure, wear protective clothing, and use high-factor sunscreens.
• lymphoproliferative disorders
• • Treatment with Immufalk increases your risk of having a type of cancer called lymphoproliferative disorder. With a treatment that contains several immunosuppressants (including thiopurines), this may cause death.
  • The combination of multiple immunosuppressants, administered simultaneously, increases the risk of lymphatic system disorders due to a viral infection (lymphoproliferative disorders associated with Epstein-Barr virus(EBV)).

• re-activation of a previous hepatitis B infection
• other infections such as progressive multifocal leukoencephalopathy (PML), which is an opportunistic infection. If you experience any sign of infection, contact your doctor (see section 4 “Possible side effects”).

Taking Immufalk may increase your risk of:

developing 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.If you are unsure if anything applies to you, talk to your doctor, nurse, or pharmacist before taking Immufalk.

Blood tests

You will need to have a blood test once a week for the first 8 weeks of treatment. You may need more frequent blood tests if:

• you are elderly
• you are taking a high dose
• you have bone marrow disorders
• you have an overactive spleen
• you have kidney function disorders. Your doctor will reduce the dose if necessary
• you have liver function disorders. Your doctor will regularly monitor your liver function and reduce the dose if necessary
• you are receiving another potentially liver-damaging medication

It is essential to use effective contraception (such as condoms) since Immufalk may cause birth defects in both men and women.

Immufalk with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.This is because Immufalk may affect how some medications work. Additionally, other medications may affect how Immufalk works. In particular, inform your doctor if you are taking or plan to take:

• allopurinol, oxipurinol, thiopurinol, or other xanthine oxidase inhibitors such as febuxostat(used primarily to treat gout)
• other immunosuppressantssuch as cyclosporine or tacrolimus
• infliximab(used primarily to treat ulcerative colitis and Crohn's disease)
• aminosalicylates, for example, olsalazine, mesalazine, or sulfasalazine(used primarily to treat ulcerative colitis and Crohn's disease)
• warfarin or phenprocoumon (to thin the blood)
• ACE inhibitors(treatments for high blood pressure or heart failure)
• cimetidine(used to treat stomach ulcers and indigestion)
• indomethacin, cyclophosphamide, chlorambucil, melphalan(treatments for rheumatoid arthritis)
• cancer treatmentsor treatments that slow down or stop the production of new blood cells
• co-trimoxazole(an antibiotic used to treat bacterial infections)
• ribavirin, peginterferon(used to treat viral infections)
• methotrexate(used primarily to treat cancers)
• furosemide(a diuretic to treat heart failure)
• vaccinessuch as hepatitis B vaccine
• any live vaccine
• muscle relaxants, for example, tubocurarine or succinylcholine(used during surgery), as they may interact with Immufalk. You should inform your anesthesiologist of your treatment with Immufalk before surgery.

If you are unsure if anything applies to you, talk to your doctor, or pharmacist before taking Immufalk.

Receiving vaccines while taking Immufalk

If you need to receive a vaccine, talk to your doctor or nurse before doing so. If you take Immufalk, you should not receive a live attenuated vaccine (for example, flu vaccine, measles vaccine, BCG vaccine, etc.) until at least 3 months after the end of treatment or until your doctor tells you it is safe to do so. This is because some vaccines may cause an infection if you receive them while taking Immufalk. If you need inactivated vaccines, your doctor may need to monitor your immune response.

Immufalk with food and drinks

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

Pregnancy and lactation

If you are pregnant or breastfeeding, consult your doctor or pharmacist before taking this medication.

Do not take Immufalk if you are pregnant unless your doctor tells you to. Inform your doctor if you are pregnant or think you may be pregnant. Both male and female patients of childbearing age should adopt non-hormonal contraceptive methods (e.g., condoms). You should continue using the contraceptive for 6 months after treatment with Immufalk.

If you have fertility problems due to chronic uremia, you should know that fertility usually returns to normal after transplants, and you should use contraceptives.

You should not breastfeed during treatment with Immufalk, as the metabolites produced in the body pass into breast milk and may harm the infant.

Driving and operating machines

It is safe to drive or operate machines while taking Immufalk unless you experience dizziness. Dizziness may increase with alcohol, so you should not drive or operate machines if you have consumed alcohol.

Immufalk contains lactose

This medication contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

This medication contains less than 1 mmol of sodium (23 mg) per tablet; it is essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The amount of Immufalk may vary from one patient to another and will be prescribed by your doctor. The dose depends on the disorder being treated.

You can take Immufalk with food or on an empty stomach, but the choice of method must be the same every day. Some patients feel nausea when Immufalk is first administered, which may be alleviated by taking the tablets after meals.

When you take Immufalk, your doctor will perform blood tests regularly. This is to verify the number and type of cells present in your blood and to check that your liver is functioning correctly.

Your doctor may also request other blood and urine tests to monitor the functioning of your kidneys and measure uric acid levels. Uric acid is a natural substance produced in your body, and uric acid levels may increase while taking Immufalk. High levels of uric acid can damage your kidneys.

In some cases, your doctor may change your Immufalk dose as a result of these tests.

Swallow the tablets whole with plenty of liquid (at least 200 ml). Do not chew them. The tablets should not be broken or crushed.

It is essential that caregivers are aware of the need to handle this medication safely. If you or your caregiver handle broken tablets, wash your hands immediately. Consult your doctor or pharmacist for advice.

Dose

Adults who have received an organ transplant: the first day of treatment, the usual dose is up to 5 mg per kilogram of body weight, and subsequently the usual daily dose is between 1 mg and 4 mg per kilogram of body weight. During treatment, your doctor will adjust the dose based on your reaction to the medication.

Adults with other disorders: the initial usual dose is between 1 mg and 3 mg per kilogram of body weight, and subsequently the usual daily dose is less than between 1 mg and 3 mg per kilogram of body weight. During treatment, your doctor will adjust the dose based on your reaction to the medication.

Use in children and adolescents

Immufalk is not recommended for use in individuals under 18 years due to insufficient data on the treatment of chronic arthritis, systemic lupus erythematosus, dermatomyositis, and polyarteritis nodosa.

For other indications, the same posological recommendation is used in children and adolescents as in adults.

Children who are considered overweight may require a higher dose.

Older patients:

Older patients may need to reduce the dose.

Patients with liver or kidney disorders may need to reduce the dose.

Patients with severe liver problems should not take Immufalk.

Your doctor will decide on the duration of treatment with Immufalk.

If you think the effect of Immufalk is too strong or too weak, please consult your doctor.

If you take more Immufalk than you should

Contact your doctor, pharmacist, or the nearest hospital immediately.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 915 620 420, indicating the medication and the amount ingested.

If you forget to take Immufalk

Do not take a double dose to compensate for the missed dose. Inform your doctor if you forget to take a dose. If it is almost time for the next dose, omit the missed dose and take the next dose at the scheduled time. Otherwise, take it as soon as you remember and then resume taking the doses as you normally would.

If you interrupt treatment with Immufalk

Any suspension of Immufalk should be done gradually and under careful monitoring. Please consult your doctor.

If you have any other questions about the use of this product, ask your doctor or pharmacist.

Like all medicines, this medicinecan cause side effects, although not everyone will experience them.

Severe side effects:

Seek immediate medical attention if you suddenly experience:

tingling, difficulty breathing, swelling of the eyelids, face, or lips, rash, or itching (especially if it affects the entire body).

Contact your doctor immediately if you develop any of the following side effects:

• severe discomfort
• diarrhea
• fever, chills
• muscle or bone pain, muscle stiffness
• fatigue, dizziness
• inflammation of blood vessels
• renal disorders (symptoms may include changes in urine output and color)

• high temperature (fever) or other signs of infection such as sore throat, mouth sores, urinary problems, or chest infection that causes difficulty breathing and coughing

The following side effects have also been reported:

Very common: may affect more than 1 in 10 users

• infections caused by viruses, fungi, or bacteria in transplant patients
• blood and bone marrow problems, with signs such as weakness, fatigue, paleness, easy bruising, unusual bleeding, or infections

Common: may affect up to 1 in 10 users

• low platelet count, which may cause bruising or bleeding
• nausea and vomiting, loss of appetite (anorexia)

Uncommon: may affect up to 1 in 100 users

• infections caused by viruses, fungi, or bacteria in all patients except transplant patients
• low red blood cell count, which may cause fatigue, headaches, shortness of breath, dizziness, and paleness
• allergic reactions, which may cause general discomfort, dizziness, nausea, vomiting, diarrhea, fever, chills, skin reactions such as rash, nodules, and itching, inflammation of blood vessels, muscle and joint pain, low blood pressure, renal or hepatic disorders, and intestinal problems
• pancreatitis, which may cause severe abdominal pain, nausea, and vomiting
• liver damage, which may cause pale stools, dark urine, itching, and yellowing of the skin and eyes, and abnormalities in liver function test results
• cholestasis of pregnancy, a buildup of bile that causes liver inflammation and may cause severe itching, especially in the hands and feet

Rare: may affect up to 1 in 1000 users

• blood and bone marrow problems that may cause weakness, fatigue, paleness, headaches, tongue pain, difficulty breathing, bruising, or infections
• intestinal disorders that cause diarrhea, abdominal pain, constipation, and discomfort (nausea and vomiting)
• potentially fatal liver damage
• hair loss that may improve even if you continue taking Immufalk tablets
• different types of cancer, including skin cancer, blood cancer, and lymphomas

Very rare: may affect up to 1 in 10,000 users

• rashes or redness of the skin, which may become potentially fatal skin reactions, including widespread rash with blisters and skin peeling, especially around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome), extensive skin peeling (toxic epidermal necrolysis)
• sudden and severe allergic reaction with difficulty breathing, swelling, dizziness, rapid heartbeat, sweating, and loss of consciousness
• intestinal disorders that cause diarrhea, abdominal pain, constipation, nausea, or vomiting (intestinal perforation)
• pulmonary inflammation that causes difficulty breathing, coughing, and fever
• if Immufalk is used in combination with other immunosuppressants, you may contract a virus that damages your brain. This may cause headaches, changes in behavior, speech problems, and worsening of skills such as memory, attention, and decision-making (cognitive decline) and may be fatal (progressive multifocal leukoencephalopathy associated with JC virus)
• irregular and uncoordinated contractions of the upper heart chambers (atrial fibrillation)

Frequency not known: cannot be estimated from available data

• You may experience a skin rash (red, pink, or purple bumps that hurt when touched), especially on your arms, hands, fingers, face, and neck, which may also be accompanied by fever (Sweet syndrome, also known as acute febrile neutrophilic dermatosis).
• photosensitivity (sensitivity to light or sunlight)
• a certain type of lymphoma (hepatosplenic lymphoma of T cells). You may experience nasal bleeding, fatigue, night sweats, weight loss, and fever (high temperature) of unknown origin.
• excessive breakdown of red blood cells that causes fatigue and paleness of the skin (hemolytic anemia), excessive eosinophils (a type of white blood cell) (eosinophilia)
• excessive activation of macrophages and T lymphocytes that causes hyperinflammation and a cytokine storm associated with cytomegalovirus disease and Epstein-Barr virus infection
• drug hypersensitivity reaction with eosinophilia and systemic symptoms (DRESS)
• pellagra, a vitamin B3 deficiency (niacin deficiency), associated with pigmented rash, diarrhea, or memory loss
• generalized acute pustular exanthema (PEGA)

Reporting side effects

If you experience side effects, consult your doctor or pharmacist, even if they do not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Store in the original packaging to protect it from light.

Do not use Immufalk after the expiration date that appears on the packaging and blister after “CAD”. The expiration date is the last day of the month indicated.

Do not use Immufalk if you observe any visible sign of deterioration.

Medicines should not be thrown down the drains or in the trash. Dispose of the packaging and unused medications at the SIGRE collection point at the pharmacy.Ask your pharmacist if you are unsure how to dispose of the packaging and unused medications. By doing so, you will help protect the environment.

Composition of Immufalk

The active ingredient is azathioprine.

Each film-coated tablet contains 100 mg of azathioprine.

The other components (excipients) are:

Tablet core:sodium croscarmellose, anhydrous colloidal silica, lactose monohydrate, microcrystalline cellulose, sodium stearyl fumarate, pregelatinized cornstarch, povidone K25.

Tablet coating: macrogol 3350, polisorbate 80, polyvinyl alcohol, talc

Appearance of the product and contents of the package

Immufalk 100 mg film-coated tablets are yellow, round, biconvex tablets of 10.5 mm marked with “100” on one face.

The tablets should not be crushed.If the tablet coating is damaged or the tablet is completely flattened,avoid skin contact or inhalation of the tablet particles.For long-term adequate dosing, other medications containing 25 mg should be used, if necessary.

Packages:

The film-coated tablets are packaged in PVC/aluminum blisters in a cardboard box.

Immufalk 100 mg film-coated tablets are available in packages of: 20, 30, 50, 60, 90 or 100 film-coated tablets.

Only some package sizes may be marketed.

Marketing authorization holder and responsible manufacturer

Dr. Falk Pharma GmbH

Leinenweberstr.5

79108 Freiburg

Germany

Phone +49 (0) 761 / 1514-0

Fax +49(0) 761 / 1514-321

Email:[email protected]

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Dr. Falk Pharma España

Camino de la Zarzuela, 19

28023 Madrid

Spain

Phone +34 91 3729508

This medicinal product is authorized in the EEA member states with the following names:

Germany, Austria, Slovenia, Lithuania and Portugal: Azafalk.

Spain: Immufalk.

Last review date of this leaflet:June 2021.

For detailed and updated information about this medicinal product, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/

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The following information is intended only for healthcare professionals:

Immufalk 100 mg film-coated tablets

Instructions for handling and disposal

No risks are associated with handling tablets with intact coating. In this case, no special safety precautions are necessary.

However, if the film-coated tablets have been crushed, Immufalk film-coated tablets must be handled strictly in accordance with the guidelines for handling cytotoxic agents. Excess medication as well as contaminated devices must be temporarily stored in clearly labeled containers. Any unused product or waste must be disposed of in accordance with local requirements.