Patient Information Leaflet

Truxima 100 mg Concentrate for Solution for Infusion

Truxima 500 mg Concentrate for Solution for Infusion

rituximab

Read this 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 side effects, ask your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

What is Truxima

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

What is Truxima used for

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

a) Non-Hodgkin Lymphoma

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

Truxima may be administered to adults alone or with other medications called “chemotherapy”. In adult patients in whom the initial treatment has been effective, Truxima may be continued for 2 years after completing the initial treatment.

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

b) Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. B lymphocytes, which are produced in the bone marrow and develop in lymph nodes, are involved. 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 the cause of some of the symptoms that patients may experience. Truxima in combination with chemotherapy destroys these cells, which gradually disappear from the body through biological processes.

c) Rheumatoid Arthritis

Truxima is used in the treatment of rheumatoid arthritis. Rheumatoid arthritis is a disease of the joints. B lymphocytes are involved, causing some of the symptoms that patients may experience. Truxima is used in the treatment of rheumatoid arthritis in people who have already been treated with other medications, which have either stopped working, not worked well enough, or caused adverse effects. Truxima is usually used in combination with another medication called methotrexate. Truxima reduces the damage that rheumatoid arthritis causes to the joints 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 the test for anti-cyclic citrullinated peptide (anti-CCP) is positive. Both tests are usually positive in patients with rheumatoid arthritis and help confirm the diagnosis.

d) Granulomatosis with Polyangiitis or Microscopic Polyangiitis

Truxima is used for the treatment of adult and pediatric patients 2 years of age or older with granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) or microscopic polyangiitis, administered in combination with corticosteroids. Granulomatosis with polyangiitis or microscopic polyangiitis are two forms of inflammation of blood vessels that primarily affect the lungs and kidneys but may also affect other organs. B lymphocytes are involved in the cause of these diseases.

e) Pemphigus Vulgaris

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

Do not use Truxima

• if you are allergic to rituximab, other proteins similar to rituximab, or any of the other components of this medication (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 severe heart disease and have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris.

Do not use Truxima if you have any of the above. If you are unsure, ask your doctor, pharmacist, or nurse before Truxima is administered to you.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before using Truxima:

• if you think you have an infectious hepatitis or have had it in the past. This is because in a few cases, patients who had hepatitis B may suffer a relapse that can be fatal in rare cases. Patients with a history of hepatitis B infection will be closely monitored by their doctor to detect any signs of hepatitis B
• if you have had any heart disease (such as angina, palpitations, or heart failure) or respiratory problems.

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

If you have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgarisalso inform 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 passed before using Truxima. Also inform your doctor if you have had many infections in the past or have a severe infection
• if you think you may need to be vaccinated in the near future, including vaccinations required for travel to other countries. Some vaccines should not be administered at the same time as Truxima or in the months following its administration. Your doctor will check if you need any vaccinations before receiving Truxima.

Children and adolescents

Non-Hodgkin lymphoma

Truxima can be used to treat children and adolescents, 6 months of age and older, with non-Hodgkin lymphoma, specifically diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL) / acute leukemia (ALL-B) or Burkitt-like lymphoma (LBL).

Talk to your doctor, pharmacist, or nurse before receiving this medication if you or your child are under 18 years old.

Granulomatosis with polyangiitis or microscopic polyangiitis

Truxima can be used to treat children and adolescents, 2 years of age and older, with granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) or microscopic polyangiitis. There is little information on the use of Truxima in children and young people with other diseases.

Inform your doctor, pharmacist, or nurse before Truxima is administered to you if you or your child is under 18 years old.

Use of Truxima with other medications

Inform your doctor or pharmacist if you are using or have recently used other medications, even those purchased without a prescription or herbal medications. This is because Truxima may affect how other medications work. Other medications may also affect how Truxima works.

Particularly inform your doctor if:

• if you are being treated for hypertension. You may be told not to take your medications for 12 hours before Truxima is administered. This is because some people experience a drop in blood pressure during Truxima infusion
• if you have ever taken medications that affect your immune system – such as chemotherapy or immunosuppressive medications.

If you are affected by any of the above (or are unsure), ask your doctor, pharmacist, or nurse before Truxima is administered to you.

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 affect your baby.

If you are fertile, you and your partner must use an effective contraceptive method during treatment with Truxima and for 12 months after the last treatment with Truxima.

Truxima passes into breast milk in very small amounts. As the long-term effects on infants are unknown, it is recommended not to breastfeed during treatment with Truxima or for 6 months after treatment.

Driving and operating machinery

The influence of rituximab on the ability to drive and operate machinery is negligible or insignificant.

Truxima contains sodium

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

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

How to Use Truxima

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

Truxima will be administered to you always through intravenous infusion (drip).

Medications Given Before Each Truxima Infusion

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

Amount and Frequency of Treatment

a) If You Are Being Treated for Non-Hodgkin Lymphoma

• If You Are Being Treated with Truxima Alone

Truxima will be administered to you once a week for 4 weeks. Truxima treatment cycles can be repeated.

• If You Are Being Treated with Truxima and Chemotherapy

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

• If You Respond Well to Treatment, You May Continue Treatment with Truxima Every 2 or 3 Months for 2 Years. Your Doctor May Modify This Depending on Your Response to the Medication.
• If You Are Under 18 Years Old, You Will Receive Truxima with Chemotherapy. You Will Receive Truxima Up to 6 Times Over a Period of 3.5 to 5.5 Months.

b) If You Are Being Treated for Chronic Lymphocytic Leukemia

When 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 for a Total of 6 Cycles. Each Cycle Lasts 28 Days. Chemotherapy Must Be Administered After the Truxima Infusion. Your Doctor Will Decide If You Should Receive Supportive Therapy.

c) If You Are Being Treated for Rheumatoid Arthritis

Each Treatment Cycle Consists of Two Infusions, Both Separated by a 2-Week Interval. Truxima Treatment Cycles Can Be Repeated. Depending on the Signs and Symptoms of Your Disease, Your Doctor May Decide to Give You a Higher Dose of Truxima at Some Point, Which May Occur Months Later.

d) If You Are Being Treated for Granulomatosis with Polyangiitis or Microscopic Polyangiitis

Truxima Treatment Involves Four Infusions, Administered at Weekly Intervals. Corticosteroids Are Usually Given by Injection Before Starting Truxima Treatment. Your Doctor May Start Giving You Corticosteroids by Mouth at Any Time to Treat Your Disease.

If You Are 18 Years Old or Older and Respond Well to Treatment, You May Receive Truxima as Maintenance Treatment. This Will Be Administered in the Form of 2 Infusions Separated by 2 Weeks, Followed by 1 Infusion Every 6 Months for at Least 2 Years. Your Doctor May Decide to Continue Treating You with Truxima for Up to 5 Years, Depending on Your Response to the Medication.

e) If You Are Being Treated for Pemphigus Vulgaris

Each Treatment Cycle Consists of Two Infusions, Both Separated by a 2-Week Interval. If You Respond Well to Treatment, You May Receive Truxima as Maintenance Treatment. This Will Be Administered 1 Year and 18 Months After Initial Treatment and Then Every 6 Months as Needed. Your Doctor May Modify This Depending on Your Response to the Medication.

If You Have Any Other Questions About Using This Medication, Ask Your Doctor, Pharmacist, or Nurse.

Like all medicines, Truxima can cause side effects, although not everyone will experience them.

The majority of these side effects are of mild to moderate intensity, but some of them can be severe 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 frequent side effects that some patients may experience include: pain at the infusion site, blisters, and itching on the skin, nausea and vomiting, fatigue, headache, difficulty breathing, increased blood pressure, wheezing, joint pain, swelling of the tongue or throat, itching or congestion in the nose, vomiting, flushing, or palpitations. If you have a heart condition or angina, these reactions may worsen.Inform the person administering the infusion immediatelyif you or your child experiences any of these symptoms, as you may need a slower infusion or to stop it. You may need additional treatment with antihistamines or paracetamol. When the symptoms disappear or improve, the infusion can continue. After the second infusion, it is less likely that these reactions will occur. Your doctor may decide to stop your treatment with Truxima if you experience severe infusion reactions.

Infections

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

• fever, cough, sore throat, burning when urinating, or if you start feeling tired or generally unwell.
• memory loss, concentration problems, difficulty walking, or loss of vision. This may be due to a rare and serious brain infection (Leucoencephalopatía Multifocal Progresiva or LMP)

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

Usually, these are colds, but there have been reported cases of pneumonia, urinary tract infections, or severe viral infections. All of these are included below as “Other side effects”.

If you are being treated for rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris, your doctor should have given you a patient alert card, where you will also find this information. It is essential to carry this card and show it to your partner or caregiver.

Skin Reactions

Very rarely, severe blisters can form on the skin that can be fatal. You may experience redness, usually associated with blisters, on the skin or mucous membranes, such as in the mouth, genital area, or eyelids, and may be accompanied by fever.Inform your doctor immediately if you experience any of these symptoms.

Other Side Effects

a) If you or your child are being treated for non-Hodgkin 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 platelet count
• nausea
• hair loss, chills, headache
• decreased immunity due to a decrease in a type of antibody called immunoglobulins (IgG) in the blood that helps protect against infection.

Common (may affect up to 1 in 10 people)

• blood infections (sepsis), pneumonia, herpes, colds, bronchitis, fungal infections, unknown infections, nasal sinus inflammation, hepatitis B
• low red blood cell count (anemia), low count of all blood cells
• allergic reactions (hypersensitivity)
• high blood sugar levels, weight loss, peripheral and facial edema, increased lactate dehydrogenase (LDH) levels in the blood, decreased calcium levels in the blood
• abnormal skin sensations, such as numbness, tingling, pinching, burning, progressive increase in these sensations on the skin, decreased sense of touch
• agitation, difficulty falling asleep
• flushing of the face and other areas of the skin due to vasodilation
• dizziness or anxiety
• excessive tearing, alterations in the lacrimal duct, conjunctivitis
• tinnitus, ear pain
• cardiac alterations, such as myocardial infarction and irregular heart rate or abnormally fast heartbeats
• increased or decreased blood pressure (decreased blood pressure, especially when standing up)
• muscle tension in the respiratory tract causing difficulty breathing (bronchospasm), inflammation, irritation in the lungs, throat, and/or nasal cavities, shortness of breath, nasal congestion
• vomiting, diarrhea, abdominal pain, irritation or ulcers in the throat and mouth, difficulty swallowing, constipation, indigestion
• alimentary changes: not eating enough, leading to weight loss
• hiccups, increased sweating, nocturnal sweating
• muscle problems, such as muscle tension, joint or muscle pain, back and neck pain
• general malaise or feeling of unease or fatigue, agitation, catarrah symptoms
• multi-organ insufficiency

Uncommon (may affect up to 1 in 100 people):

• coagulation disorders, decreased production of red blood cells, increased destruction of red blood cells (aplastic anemia), lymph node inflammation/hypertrophy
• weight loss, loss of interest in usual activities, nervousness
• alterations in the sense of taste, such as changes in the taste of food
• cardiac problems, such as reduced heart rate or chest pain (angina)
• asthma, insufficient oxygen supply to organs
• gastric distension

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

• temporary increase in the amount of a type of antibody in the blood (IgM), chemical alterations in the blood caused by the rupture of cancer cells
• nerve damage in arms and legs, facial paralysis
• heart failure
• inflammation of blood vessels, including those that cause skin symptoms
• respiratory insufficiency
• intestinal wall damage (perforation)
• severe skin problems that can be potentially fatal. You may experience redness, usually associated with blisters, on the skin or mucous membranes, such as in the mouth, genital area, or eyelids, and may be accompanied by fever.
• kidney problems
• severe vision loss

Unknown frequency (the frequency cannot be estimated from the available data):

• delayed decrease in white blood cell count in the blood
• reversible decrease in platelet count after infusion, but in rare cases, it can be fatal
• loss of hearing, loss of other senses

Children and adolescents with non-Hodgkin lymphoma

In general, the side effects in children and adolescents with non-Hodgkin lymphoma were similar to those in adults with non-Hodgkin lymphoma or chronic lymphocytic leukemia. The most common side effects observed were fever associated with low neutrophil count, inflammation or sores in the oral cavity, and allergic reactions (hypersensitivity).

b) If you are being treated for rheumatoid arthritis

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

• infections, such as pneumonia (bacterial)
• urinary tract infection (painful urination)
• allergic reactions, which are 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 flashes, nasal congestion, sneezing, chills, rapid heartbeat, and fatigue.
• headache
• changes in laboratory tests performed by your doctor. These include a decrease in the amount of certain specific proteins in the blood (immunoglobulins) that help protect against infection.

Common (may affect up to 1 in 10 people):

• infections, such as bronchitis
• sensation of warmth, intermittent pain, in the nose, cheeks, and eyes (sinusitis), abdominal pain, vomiting, and diarrhea, respiratory problems
• foot fungus infection (athlete's foot)
• increased cholesterol levels in the blood
• abnormal skin sensations, such as numbness, tingling, pinching, or burning, sciatica, headache, dizziness
• hair loss
• anxiety, depression
• indigestion, diarrhea, acid reflux, irritation, or ulcers in the throat and mouth
• abdominal, back, muscle, or joint pain

Uncommon (may affect up to 1 in 100 people):

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

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

• a group of symptoms that occur a few weeks after the Truxima infusion and include allergic reactions, such as hives, itching, joint pain, lymph node inflammation, and fever
• severe blisters on the skin that can be fatal. You may experience redness, usually associated with blisters, on the skin or mucous membranes, such as in the mouth, genital area, or eyelids, and may be accompanied by fever

Unknown frequency (the frequency cannot be estimated from the available data):

• severe viral infection

Other rare side effects reported due to Truxima include a decrease in white blood cell count in the blood (neutrophils) that helps fight infections. Some infections may be severe (see information on Infections within this section).

c) 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 pneumonia, urinary tract infections (painful urination), colds, or herpes infections
• allergic reactions, which are most likely to occur during the infusion, but may occur up to 24 hours after the infusion
• diarrhea
• cough or difficulty breathing
• nasal bleeding
• high blood pressure
• joint or back pain
• muscle spasms or chills
• dizziness
• chills (especially in the hands)
• difficulty sleeping (insomnia)
• inflammation of the hands or feet

Common (may affect up to 1 in 10 people):

• indigestion
• constipation
• skin rash, including acne or spots
• flushing or redness of the skin
• fever, nasal congestion
• muscle tension or pain
• joint or muscle pain
• low red blood cell count (anemia)
• low platelet count in the blood
• increased potassium levels in the blood
• changes in heart rate or abnormally fast heartbeats

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

• severe blisters on the skin that can be fatal. You may experience redness, usually associated with blisters, on the skin or mucous membranes, such as in the mouth, genital area, or eyelids, and may be accompanied by fever.
• reappearance of a previous Hepatitis B infection

Unknown frequency (the frequency cannot be estimated from the available data):

• severe viral infection

Children and adolescents with granulomatosis with polyangiitis or microscopic polyangiitis

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

d) If you are being treated for pemphigus vulgaris

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

• allergic reactions, which are most likely to occur during the infusion, but may occur up to 24 hours after the infusion
• headache
• infections, such as pneumonia
• prolonged 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 (painful urination)
• mood disorders, such as irritability and depression
• skin disorders, such as itching, urticaria, and benign growths
• feeling tired or dizzy
• fever
• joint or muscle pain
• abdominal pain
• muscle pain
• rapid heartbeat

Unknown frequency (the frequency cannot be estimated from the available data):

• severe viral infection

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

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational reporting system included in Appendix V. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep out of sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

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

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

Composition of Truxima

• The active ingredient 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 injection. (see section 2 “Truxima contains sodium”).

Appearance of the product and contents of the pack

Truxima is a transparent and colorless solution that is presented as a concentrate for solution for infusion.

10 ml vials – Pack with 2 vials

50 ml vials – Pack with 1 vial

Marketing Authorization Holder

Celltrion Healthcare Hungary Kft.

1062 Budapest

Váci út 1-3. WestEnd Office Building B tower

Hungary

Manufacturer

Millmount Healthcare Ltd.

Block 7, City North Business Campus,

Stamullen, Co. Meath K32 YD60, Ireland

Nuvisan GmbH

Wegenerstrasse 13,

89231 Neu-Ulm,

Germany

Nuvisan France SARL

2400, Route des Colles, 06410, Biot,

France

For more information about this medicine, please contact the local representative of the marketing authorization holder.

Last update of this leaflet

Other sources of information

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