Truxima 500 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Truxima 100 mg concentrate for solution for infusion

Truxima 500 mg concentrate for solution for infusion

rituximab

Read the entire leaflet carefully before you start using 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, pharmacist or nurse.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Truxima is and what it is used for
2. What you need to know before using Truxima
3. How to use Truxima
4. Possible side effects
5. How to store Truxima
6. Contents of the pack and other information

1. What Truxima is and what it is used for

What Truxima is

Truxima contains the active substance "rituximab". This is a type of protein called a "monoclonal antibody". It binds to the surface of a type of white blood cells called "B-lymphocytes". When rituximab binds to the surface of these cells, it causes their death.

What Truxima is used for

Truxima can be used in adults and children for the treatment of several different diseases. Your doctor may prescribe Truxima for the treatment of:

• Non-Hodgkin's lymphoma

This is a disease of the lymphatic system (part of the immune system) that affects a type of white blood cells called B-lymphocytes.

Truxima may be given to adults either alone or in combination with other medicines called "chemotherapy". In adult patients who have responded to initial treatment, Truxima may be continued for 2 years after completion of the initial treatment.

In children and adolescents, Truxima is given in combination with "chemotherapy".

• Chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia in adults. B-lymphocytes are involved, which are produced in the bone marrow and mature in the lymph nodes. Patients with CLL have too many abnormal lymphocytes that accumulate mainly in the bone marrow and blood. The proliferation of these abnormal lymphocytes may be responsible for some of the symptoms you may experience. Truxima, in combination with chemotherapy, destroys these cells, which gradually disappear from the body through biological processes.

• Rheumatoid arthritis

Truxima is used in the treatment of rheumatoid arthritis. Rheumatoid arthritis is a disease affecting the joints. B-lymphocytes are involved, causing some of the symptoms you may experience. Truxima is used to treat rheumatoid arthritis in people who have already been treated with other medicines that either stopped working, did not work well enough, or caused adverse effects. Truxima is usually used together with another medicine called methotrexate. Truxima reduces the joint damage caused by rheumatoid arthritis and improves the ability to perform normal daily activities.

The best responses to Truxima are observed when the blood test for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) test is positive. Both tests are usually positive in patients with rheumatoid arthritis and help confirm the diagnosis.

• Granulomatosis with polyangiitis or microscopic polyangiitis

Truxima is used to treat adult and paediatric patients 2 years of age and older with granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) or microscopic polyangiitis, given in combination with corticosteroids. Granulomatosis with polyangiitis and microscopic polyangiitis are two forms of blood vessel inflammation that primarily affect the lungs and kidneys, but may also affect other organs. B-lymphocytes are involved in causing these diseases.

• Pemphigus vulgaris

Truxima is used to treat patients with moderate to severe pemphigus vulgaris. Pemphigus vulgaris is an autoimmune disease that causes painful blisters on the skin and the lining of the mouth, nose, throat, and genitals.

2. What you need to know before using Truxima

Do not use Truxima

• if you are allergic to rituximab, to other proteins similar to rituximab, or to any of the other ingredients of this medicine (listed in section 6)
• if you have an active, severe infection
• if you have a weakened immune system
• if you have severe heart failure or uncontrolled serious heart disease and have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris.

Do not use Truxima if any of the above apply to you. If you are unsure, ask your doctor, pharmacist, or nurse before being given Truxima.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Truxima:

• if you think you have infectious hepatitis or have had it in the past. This is because, in a few cases, patients who previously had hepatitis B may experience a relapse, which can rarely be fatal. Patients with a history of hepatitis B infection will be closely monitored by their doctor for possible signs of hepatitis B.
• if you have had any heart disease (such as chest pain, palpitations, or heart failure) or breathing problems.

If any of the above apply to you (or if you are unsure), ask your doctor, pharmacist, or nurse before receiving Truxima. Your doctor may need to monitor you during your treatment with Truxima.

Also ask your doctor if you think you may need to be vaccinated in the near future, including vaccines required for travel to other countries. Some vaccines should not be given at the same time as Truxima or in the months following its administration. Your doctor will check whether you need any vaccination before receiving Truxima.

If you have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris, you should also tell your doctor:

• if you think you may have an infection, even if it is mild, such as a cold. The cells that Truxima targets help fight infections, so you should wait until the infection has resolved before using Truxima. Also inform your doctor if you have had frequent infections in the past or if you have a serious infection.

Children and adolescents

Non-Hodgkin's lymphoma

Truxima can be used to treat children and adolescents aged 6 months and older with non-Hodgkin's lymphoma, specifically CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt leukemia (mature B-acute lymphoblastic leukemia) (B-ALL), or Burkitt-like lymphoma (BLL).

Talk to your doctor, pharmacist, or nurse before receiving this medicine if you or your child are under 18 years of age.

Granulomatosis with polyangiitis or microscopic polyangiitis

Truxima can be used to treat children and adolescents aged 2 years and older with granulomatosis with polyangiitis (previously called Wegener's granulomatosis) or microscopic polyangiitis. There is limited information on the use of Truxima in children and young people with other diseases.

Inform your doctor, pharmacist, or nurse before being given Truxima if you or your child is under 18 years of age.

Using Truxima with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take other medicines, including those obtained without a prescription or herbal medicines. This is because Truxima may affect how other medicines work. Likewise, other medicines may affect how Truxima works.

In particular, inform your doctor if:

• you are being treated for high blood pressure. You may be advised not to take your blood pressure medication during the 12 hours before receiving Truxima. This is because some people experience a drop in blood pressure during Truxima infusion.
• you have ever taken medicines that affect your immune system—such as chemotherapy or immunosuppressive medicines.

If any of the above apply to you (or if you are unsure), ask your doctor, pharmacist, or nurse before receiving Truxima.

Pregnancy and breastfeeding

You must inform your doctor or nurse if you are pregnant, think you may be pregnant, or plan to become pregnant. This is because Truxima can cross the placental barrier and may affect your baby.

If you are of childbearing age, you and your partner should use an effective method of contraception during treatment with Truxima and for at least 12 months after the last dose of Truxima.

Truxima passes into breast milk in very small amounts. As the long-term effects on infants are unknown, breastfeeding is not recommended during treatment with Truxima and for 6 months after treatment, as a precaution.

Driving and using machines

It is unknown whether Truxima has any effect on the ability to drive or operate machinery.

Truxima contains polysorbate 80

This medicine contains 7 mg of polysorbate 80 (E433) in a 10 ml vial and 35 mg of polysorbate 80 (E433) in a 50 ml vial, equivalent to 0.7 mg/ml (for a 10 ml vial) or 3.5 mg/ml (for a 50 ml vial). Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

Truxima contains sodium

This medicine contains 52.6 mg of sodium (the main component of table/cooking salt) per 10 ml vial and 263.2 mg of sodium (the main component of table/cooking salt) per 50 ml vial.

This corresponds to 2.6% (per 10 ml vial) and 13.2% (per 50 ml vial) of the maximum recommended daily sodium intake for an adult.

3. How to use Truxima

How to use Truxima

Truxima will be administered to you by a doctor or nurse experienced in the use of this medicine. You will be monitored during the administration of Truxima in case you experience any adverse effects.

Truxima will always be given by intravenous infusion (drip).

Medicines administered before each Truxima infusion

Before administration of Truxima, you will be given other medicines (pre-medication) to prevent or reduce possible adverse effects.

Dose and frequency of treatment

• If you are being treated for non-Hodgkin's lymphoma
  • If you are being treated with Truxima alone

Truxima will be administered once a week for 4 weeks. Treatment cycles with Truxima may be repeated.

• If you are being treated with Truxima in combination with chemotherapy

Truxima will be administered on the same day as chemotherapy. It is usually given every 3 weeks up to 8 times.

• If you respond well to treatment, you may continue Truxima treatment every 2 or 3 months for two years. Your doctor may modify this depending on your response to the medicine.

• If you are under 18 years of age, you will receive Truxima in combination with chemotherapy. You will receive Truxima up to 6 times over a period of 3.5 to 5.5 months.

• If you are being treated for chronic lymphocytic leukemia*

When you are being treated with Truxima in combination with chemotherapy, you will receive Truxima infusions on day 0 of cycle 1 and then on day 1 of each subsequent cycle, up to a total of 6 cycles. Each cycle lasts 28 days. Chemotherapy should be administered after the Truxima infusion. Your doctor will decide whether you should receive maintenance therapy.

• If you are being treated for rheumatoid arthritis*

Each treatment cycle consists of two infusions, both given 2 weeks apart. Treatment cycles with Truxima may be repeated. Depending on the signs and symptoms of your disease, your doctor may decide at some point to give you a higher dose of Truxima, which may occur after several months.

• If you are being treated for granulomatosis with polyangiitis or microscopic polyangiitis*

Treatment with Truxima consists of four infusions given one week apart. Corticosteroids are usually given by injection before starting Truxima treatment. To treat your disease, your doctor may start oral corticosteroids at any time.

If you are 18 years of age or older and respond well to treatment, you may be given Truxima as maintenance therapy. This will be given as two infusions 2 weeks apart, followed by one infusion every 6 months for at least 2 years. Your doctor may decide to treat you with Truxima for a longer period (up to 5 years), depending on your response to the medicine.

• If you are being treated for pemphigus vulgaris*

Each treatment cycle consists of two infusions, both given 2 weeks apart. If you respond well to treatment, you may be given Truxima as maintenance therapy. This will be given 1 year and 18 months after the initial treatment, and then every 6 months as needed. Your doctor may change this depending on your response to the medicine.

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

4. Possible adverse effects

Like all medicines, Truxima can cause adverse effects, although not everyone experiences them.

Most of these adverse effects are mild to moderate in intensity, but some may be serious and require treatment. In rare cases, some of these reactions have been fatal.

Infusion reactions

During or within 24 hours after the first infusion, you may experience fever, chills, and shivering. Other less common adverse effects that some patients may experience include: pain at the infusion site, skin blisters and itching, nausea and vomiting, fatigue, headache, difficulty breathing, increased blood pressure, wheezing, throat discomfort, swelling of the tongue or throat, itching or nasal congestion, vomiting, flushing or palpitations, heart attack, or low platelet count. If you have heart disease or angina, these reactions could worsen. Inform immediately the person administering the infusion if you or your child experience any of these symptoms, as you may require a slower infusion rate or interruption of the infusion. You may need additional treatment with antihistamines or paracetamol. Once symptoms have subsided or improved, the infusion may continue. These reactions are less likely after the second infusion. Your doctor may decide to discontinue your treatment with Truxima if you experience severe infusion reactions.

Infections

Inform your doctor immediately if, after treatment with Truxima, you or your child develop any symptoms of infection, such as:

• fever, cough, sore throat, burning sensation when urinating, or if you begin to feel tired or generally unwell.
• memory loss, difficulty concentrating, difficulty walking, or vision loss. This may be due to a very rare, serious brain infection (Progressive Multifocal Leukoencephalopathy or PML), which has been fatal.
• fever, headache, neck stiffness, lack of coordination (ataxia), personality changes, hallucinations, altered consciousness, seizures, or coma – this could be due to a serious brain infection (enteroviral meningoencephalitis), which can be fatal.

You may become more susceptible to infections after treatment with Truxima.

These are usually common colds, but cases of pneumonia, urinary tract infections, or serious viral infections have been reported. All of these are listed below under "Other adverse effects".

If you are being treated for rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris, your doctor should have provided you with a patient alert card, which also contains this information. It is important that you carry this card and show it to your partner or caregiver.

Skin reactions

Very rarely, severe blistering of the skin may occur, which can be fatal. Redness, usually associated with blisters, may appear on the skin or mucous membranes, such as inside the mouth, genital area, or eyelids, and may occur with fever. Inform your doctor immediately if you experience any of these symptoms.

Other adverse effects

• If you or your child is being treated for non-Hodgkin’s lymphoma or chronic lymphocytic leukemia

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

• bacterial or viral infections, bronchitis,
• low white blood cell count with or without fever, or low levels of blood cells called "platelets",
• nausea,
• hair loss, chills, headache,
• reduced immunity due to decreased levels of antibodies called "immunoglobulins" (IgG) in the blood, which help protect against infection.

Common (may affect up to 1 in 10 people)

• blood infections (sepsis), pneumonia, herpes, cold, bronchial infections, fungal infections, infections of unknown origin, sinus inflammation, hepatitis B,
• low red blood cell count (anemia), low levels of all blood cells,
• allergic reactions (hypersensitivity),
• high blood sugar levels, weight loss, peripheral and facial edema, increased levels of lactate dehydrogenase (LDH) enzyme in blood, decreased levels of calcium in blood,
• abnormal skin sensations such as numbness, tingling, pricking, burning, progressive increase in these sensations, reduced sense of touch,
• restlessness, difficulty falling asleep,
• facial redness and redness in other skin areas due to dilation of blood vessels,
• dizziness or anxiety,
• increased tearing, tear duct disorders, eye inflammation (conjunctivitis),
• ringing in the ears, ear pain,
• heart disorders, such as myocardial infarction, irregular heartbeat, or abnormally rapid heartbeat,
• increased or decreased blood pressure (especially decreased blood pressure upon standing),
• tightening of the muscles in the airways causing breathing difficulty (bronchospasm), inflammation, irritation in the lungs, throat and/or nasal cavities, shortness of breath, runny nose,
• vomiting, diarrhea, abdominal pain, irritation or ulcers in the throat and mouth, difficulty swallowing, constipation, indigestion,
• eating disorders: not eating enough, leading to weight loss,
• hives, increased sweating, night sweats,
• muscle problems such as muscle tension, joint or muscle pain, back and neck pain,
• tumor pain,
• general malaise or restlessness or fatigue, restlessness, catarrhal symptoms,
• multi-organ failure.

Uncommon (may affect up to 1 in 100 people)

• coagulation disorders, decreased production of red blood cells, increased destruction of red blood cells (aplastic hemolytic anemia), lymph node inflammation/swelling,
• lethargy, loss of interest in usual activities, nervousness,
• taste disturbances, such as changes in food taste,
• heart problems, such as reduced heart rate or chest pain (angina),
• asthma, low oxygen supply to organs,
• stomach swelling.

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

• temporary increase in a type of antibody in the blood (called immunoglobulins – IgM), chemical changes in the blood due to the breakdown of cancer cells,
• nerve damage in arms and legs, facial paralysis,
• heart failure,
• inflammation of blood vessels, including those causing skin symptoms,
• respiratory failure,
• damage to the intestinal wall (perforation),
• serious skin problems causing blisters that can be potentially fatal. Redness, usually associated with blisters, may appear on the skin or mucous membranes, such as inside the mouth, genital area, or eyelids, and may occur with fever,
• kidney problems,
• severe vision loss.

Frequency not known (frequency cannot be estimated from available data)

• delayed decrease in white blood cells in the blood,
• reduced platelet count after infusion – reversible, but in rare cases may be fatal,
• hearing loss, loss of other senses,
• infection/inflammation of the brain and meninges (enteroviral meningoencephalitis).

Children and adolescents with non-Hodgkin’s lymphoma

In general, adverse effects in children and adolescents with non-Hodgkin’s lymphoma were similar to those in adults with non-Hodgkin’s lymphoma or chronic lymphocytic leukemia. The most commonly observed adverse effects were fever associated with low levels of a type of white blood cells (neutrophils), inflammation or sores in the mouth, and allergic reactions (hypersensitivity).

• If you are being treated for rheumatoid arthritis

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

• infections such as pneumonia (bacterial),
• pain when urinating (urinary tract infection),
• allergic reactions most likely to occur during the infusion but may occur up to 24 hours after the infusion,
• changes in blood pressure, nausea, rashes, fever, hot flushes, nasal congestion, sneezing, shivering, rapid heartbeat, and fatigue,
• headache,
• changes in laboratory tests performed by your doctor. These include a decrease in certain specific proteins in the blood (immunoglobulins) that help protect against infection.

Common (may affect up to 1 in 10 people)

• infections such as bronchial inflammation (bronchitis),
• feeling of warmth, intermittent pain in the nose, cheeks, and eyes (sinusitis), abdominal pain, vomiting and diarrhea, breathing problems,
• fungal infection in the feet (athlete’s foot),
• increased levels of cholesterol in blood,
• abnormal skin sensations such as numbness, tingling, pricking, or burning, sciatica, headache, dizziness,
• hair loss,
• anxiety, depression,
• indigestion, diarrhea, acid reflux, irritation and/or ulceration of the throat and mouth,
• pain in the abdomen, back, muscles, and/or joints.

Uncommon (may affect up to 1 in 100 people)

• fluid retention in the face and body,
• inflammation, irritation, and/or pressure in the lungs and throat, cough,
• skin reactions including hives, pruritus, and skin rashes,
• allergic reactions including wheezing or difficulty breathing, facial and tongue swelling, collapse.

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

• a group of symptoms occurring a few weeks after Truxima infusion, including allergic reactions such as rash, pruritus, joint pain, lymph node swelling, and fever,
• formation of severe blisters on the skin that can be fatal. Redness, usually associated with blisters, may appear on the skin or mucous membranes, such as inside the mouth, genital area, or eyelids, and may occur with fever.

Frequency not known (frequency cannot be estimated from available data)

• serious viral infection,
• infection/inflammation of the brain and meninges (enteroviral meningoencephalitis).

Other rare adverse effects reported with Truxima include a decrease in the number of white blood cells (neutrophils) in the blood, which help fight infections. Some infections may be serious (see information on Infections within this section).

• If you or your child are being treated for granulomatosis with polyangiitis or microscopic polyangiitis

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

• infections, such as chest infections, urinary tract infections (pain when urinating), colds, or herpes infections,
• allergic reactions, more likely to occur during the infusion but may occur up to 24 hours after,
• diarrhea,
• cough or difficulty breathing,
• nosebleeds,
• hypertension,
• joint or back pain,
• muscle spasms or tremors,
• dizziness,
• tremors (especially in the hands),
• difficulty sleeping (insomnia),
• swelling of the hands or ankles.

Common (may affect up to 1 in 10 people)

• indigestion,
• constipation,
• skin rash, including acne or spots,
• flushing or skin redness,
• fever,
• nasal congestion or runny nose,
• tense or painful muscles,
• pain in muscles or in hands or feet,
• low red blood cell count (anemia),
• low platelet count in blood,
• increased potassium levels in blood,
• changes in heart rhythm or abnormally rapid heartbeat.

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

• formation of severe blisters on the skin that can be fatal. Redness, usually associated with blisters, may appear on the skin or mucous membranes, such as inside the mouth, genital area, or eyelids, and may occur with fever,
• reactivation of previous hepatitis B infection.

Frequency not known (frequency cannot be estimated from available data):

• serious viral infection,
• infection/inflammation of the brain and meninges (enteroviral meningoencephalitis).

Children and adolescents with granulomatosis with polyangiitis or microscopic polyangiitis

In general, side effects in children and adolescents with granulomatosis with polyangiitis or microscopic polyangiitis were of a similar type to those in adults with granulomatosis with polyangiitis or microscopic polyangiitis. The most common side effects observed were infections, allergic reactions, and malaise (nausea).

• If you are being treated for pemphigus vulgaris

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

• allergic reactions more likely to occur during the infusion, but may occur up to 24 hours after,
• headache,
• infections such as chest infections,
• persistent depression,
• hair loss.

Common (may affect up to 1 in 10 people)

• infections such as common cold, herpes infections, eye infections, oral candidiasis, and urinary tract infections (pain when urinating),
• mood disorders such as irritability and depression,
• skin disorders such as itching, hives, and benign lumps,
• feeling of fatigue or dizziness,
• fever,
• joint or muscle pain,
• stomach pain,
• muscle pain,
• abnormally rapid heartbeat.

Frequency not known (frequency cannot be estimated from available data)

• serious viral infection,
• infection/inflammation of the brain and meninges (enteroviral meningoencephalitis).

Truxima may also cause changes in laboratory tests performed by your doctor. If you are being treated with Truxima in combination with other medicines, some of the possible adverse effects may be due to the other medicines.

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Truxima

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the container after EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C). Keep the vial in the outer packaging to protect it from light.

This medicine can also be stored in its original packaging outside the refrigerator at temperatures up to 30 °C for a single period of up to 10 days, but not beyond the original expiry date. In this case, it must not be returned to refrigerated storage.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any unused medicine and its container. This will help protect the environment.

6. Contents of the container and additional information

Composition of Truxima

• The active substance of Truxima is rituximab.

The 10 ml vial contains 100 mg of rituximab (10 mg/ml).

The 50 ml vial contains 500 mg of rituximab (10 mg/ml).

• The other components are sodium chloride, trisodium citrate dihydrate, polysorbate 80, and water for injections. (see section 2 "Truxima contains sodium").

Appearance of the product and contents of the container

Truxima is a clear, colourless solution presented as a concentrate for infusion solution.

10 ml vials – Pack containing 2 vials

50 ml vials – Pack containing 1 vial or 2 vials (2 x 1) (multipack)

Not all pack sizes may be marketed.

Marketing Authorization Holder

Celltrion Healthcare Hungary Kft.

1062 Budapest

Váci út 1-3. WestEnd Office Building B tower

Hungary

Manufacturer

Nuvisan GmbH

Wegenerstrasse 13, Ludwigfeld

89231 Neu-Ulm, Bavaria

Germany

Nuvisan France SARL

2400, Route des Colles, 06410, Biot,

France

KYMOS S.L.

Ronda de Can Fatjó, 7B Parc Tecnològic del Vallès

08290 - Cerdanyola del Vallès, Barcelona

Spain

Midas Pharma GmbH

Rheinstrasse 49, West Ingelheim Am Rhein,

Rhineland-Palatinate 55218 Ingelheim,

Germany

More information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder.

Belgium/Belgium/Belgium Celltrion Healthcare Belgium BVBA Tel/Tel: +32 1528 7418 [email protected]	Lithuania Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493
	Luxembourg/Luxembourg Celltrion Healthcare Belgium BVBA Tel/Tel: +32 1528 7418 [email protected]
Czech Republic Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493	Hungary Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493
Denmark Orion Pharma A/S Tlf: +45 86 14 00 00	Malta Mint Health Ltd. Tel: +356 2093 9800
Germany Celltrion Healthcare Deutschland GmbH Tel. +49 (0)30 346494150 [email protected]	Netherlands Celltrion Healthcare Netherlands B.V Tel: +31 20 888 7300 [email protected]
Estonia Orion Pharma Eesti OÜ Tel: +372 6 644 550	Norway Orion Pharma AS Tlf: +47 40 00 42 10
Greece BIANEX S.A. Tel: +30 210 8009111	Austria Astro-Pharma GmbH Tel: +43 1 97 99 860
Spain CELLTRION FARMACEUTICA (SPAIN) S.L. Tel: +34 910 498 478	Poland Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493
France CELLTRION HEALTHCARE FRANCE SAS Tel: +33(0)1 71 25 27 00	Portugal CELLTRION PORTUGAL, UNIPESSOAL LDA Tel: +351 21 936 8542
Croatia Oktal Pharma d.o.o. Tel: +385 1 6595 777	Romania Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493
Ireland Celltrion Healthcare Ireland Limited Tel: +353 1 223 4026 [email protected]	Slovenia OPH Oktal Pharma d.o.o. Tel: +386 1 519 29 22
Iceland Vistor hf. Tel: +354 535 7000	Slovakia Celltrion Healthcare Hungary Kft Tel: +36 1 231 0493
Italy Celltrion Healthcare Italy S.R.L Tel: +39 0247 927040 [email protected]	Finland/Suomi Orion Pharma Tel/Puh: +358 10 4261
Cyprus C.A. Papaellinas Ltd Tel: +357 22741741	Sweden Orion Pharma AB Tel: +46 8 623 64 40
Latvia Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493

Date of the most recent review of this leaflet

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.