Ruxience 100 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Ruxience 100 mg concentrate for solution for infusion

Ruxience 500 mg concentrate for solution for infusion

rituximab

Read the entire leaflet carefully before starting to take this medicine, as 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, talk to your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Ruxience is and what it is used for

What Ruxience is

Ruxience contains the active substance "rituximab". This is a type of protein called a "monoclonal antibody". This protein binds to the surface of a type of white blood cell called "B-lymphocytes". When rituximab binds to the surface of this cell, it triggers its death.

What Ruxience is used for

Ruxience can be used to treat several different conditions in adults and children. Your doctor may prescribe Ruxience for the treatment of:

1. Non-Hodgkin’s lymphoma

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

Ruxience may be given to adults alone or in combination with other medicines called "chemotherapy".

In adult patients where treatment is working, Ruxience may be used as maintenance treatment for 2 years following completion of initial therapy.

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

2. Chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. CLL affects a specific type of lymphocyte, the B-lymphocyte, which originates in the bone marrow and develops in the lymph nodes. Patients with CLL have too many abnormal lymphocytes, which accumulate mainly in the bone marrow and blood. The proliferation of these abnormal B-lymphocytes causes the symptoms that patients may experience. Ruxience, in combination with chemotherapy, destroys these cells, which are gradually eliminated from the body through biological processes.

3. Rheumatoid arthritis

Ruxience is used for the treatment of rheumatoid arthritis. Rheumatoid arthritis is a disease affecting the joints. B-lymphocytes are involved and contribute to some of the symptoms patients may experience. Ruxience is used to treat rheumatoid arthritis in people who have already been treated with other medicines that either stopped working, were not effective enough, or caused adverse effects. Ruxience is usually taken together with another medicine called methotrexate.

Ruxience slows down joint damage caused by rheumatoid arthritis and improves your ability to perform normal daily activities.

The best responses to Ruxience are observed in patients who have a positive blood test for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP). Both tests are typically positive in rheumatoid arthritis and help confirm the diagnosis.

4. Granulomatosis with polyangiitis or microscopic polyangiitis

Ruxience is used to treat adult and pediatric patients aged 2 years and older with granulomatosis with polyangiitis (previously called Wegener’s granulomatosis) or microscopic polyangiitis, 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 involve other organs. B-lymphocytes are involved in the cause of these conditions.

5. Pemphigus vulgaris

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

2. What you need to know before Ruxience is administered to you

Do not use Ruxience

• 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 currently have a serious active 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 receive Ruxience if any of the above apply to you. If you are unsure, consult your doctor, pharmacist, or nurse before receiving Ruxience.

Warnings and precautions

It is important that you and your doctor record the brand and batch number of your medicine.

Consult your doctor, pharmacist, or nurse before receiving Ruxience if:

• you have ever had or think you may have infectious hepatitis. This is because, in some patients who had hepatitis B, Ruxience may cause reactivation of the disease, which can be fatal in very rare cases. Patients with a history of hepatitis B infection will be closely monitored by their doctor for possible signs of infection;
• you have ever had heart problems (such as chest pain, palpitations, or heart failure) or breathing problems.

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

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 Ruxience or in the months following its administration. Your doctor will check whether you need any vaccinations before you receive Ruxience.

Also inform your doctor if you have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris;

• if you think you may have an infection, even a mild one such as a cold. The cells targeted by Ruxience help fight infections, so you should wait until the infection has resolved before receiving Ruxience. Additionally, 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

Ruxience 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 (acute mature B-cell leukemia) (B-AL), 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

Ruxience 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 rituximab in children and young people with other diseases.

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

Other medicines and Ruxience

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might need to take any other medicines. This includes medicines obtained without a prescription and herbal medicines. This is because Ruxience may affect how other medicines work. In addition, other medicines may affect how Ruxience works.

In particular, inform your doctor:

• if you are being treated for high blood pressure. You may be asked not to take your medication for 12 hours before receiving Ruxience. This is because some people experience a drop in blood pressure during Ruxience infusion;
• if 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 Ruxience.

Pregnancy and breastfeeding

Inform your doctor or nurse if you are pregnant, think you may be pregnant, or plan to become pregnant. This is because Ruxience can cross the placenta and affect your baby.

If you can become pregnant, you and your partner should use an effective method of contraception during treatment with Ruxience and for 12 months after your last dose of Ruxience.

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

Driving and using machines

It is unknown whether rituximab affects your ability to drive or operate tools or machinery.

Sodium content of Ruxience

This medicine contains less than 1 mmol of sodium (23 mg) per dose; hence, it is essentially “sodium-free”.

3. How Ruxience is administered

How it is administered

Ruxience will be administered by a doctor or a nurse experienced in the use of this treatment. You will be closely monitored while receiving this medicine, in case you experience any adverse effects.

Ruxience is always administered as an intravenous infusion (drip).

Medications given before each administration of Ruxience

Before you receive Ruxience, you will be given other medications (premedication) to prevent or reduce possible adverse effects.

Dose and frequency of treatment

1. If you are being treated for non-Hodgkin’s lymphoma

• If you receive Ruxience alone

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

• If you are receiving Ruxience with chemotherapy

Ruxience will be administered on the same day as chemotherapy. This is usually given every 3 weeks, up to a maximum of 8 times.

• If you respond well to treatment, you may receive Ruxience as maintenance therapy every 2 or 3 months for two years. Your doctor may adjust this depending on your response to the medicine.
• If you are under 18 years of age, you will receive Ruxience with chemotherapy. You will receive Ruxience up to 6 times over a period of 3.5 to 5.5 months.

1. If you are being treated for chronic lymphocytic leukemia

When receiving Ruxience in combination with chemotherapy, you will receive Ruxience infusions on Day 0 of Cycle 1, and then on Day 1 of each cycle for a total of 6 cycles. Each cycle lasts 28 days. Chemotherapy must be administered after the Ruxience infusion. Your doctor will decide whether you should receive concomitant supportive therapy.

1. If you are being treated for rheumatoid arthritis

Each treatment cycle consists of two infusions given 2 weeks apart. Treatment cycles with Ruxience may be repeated. Depending on the signs and symptoms of your disease, your doctor will decide whether you should receive additional Ruxience at any time. This may occur several months later.

1. If you are being treated for granulomatosis with polyangiitis or microscopic polyangiitis

Treatment with Ruxience consists of four separate infusions given weekly. Corticosteroids are usually administered by injection before starting Ruxience treatment. Your doctor may start you on oral corticosteroids at any time to treat your condition.

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

1. If you are being treated for pemphigus vulgaris

Each treatment cycle consists of two infusions given 2 weeks apart. If you respond well to treatment, you may receive Ruxience as maintenance therapy. This will be administered 1 year and 18 months after initial treatment, and then every 6 months as needed; your doctor may adjust 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 side effects

Like all medicines, Ruxience can cause side effects, although not everyone gets them.

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

Infusion reactions

During or within the first 24 hours after infusion, you may experience fever, chills, and shivering. Less frequently, some patients may experience pain at the infusion site, blistering, itching, nausea, fatigue, headache, difficulty breathing, high blood pressure, wheezing, throat discomfort, swelling of the tongue or throat, nasal itching or runny nose, vomiting, flushing, palpitations, heart attack, or low platelet count. If you have heart disease or angina, these reactions may worsen. Inform immediately the healthcare professional administering the infusion if you or your child experience any of these symptoms, as it may be necessary to slow down or stop the infusion. You may require additional treatment, such as an antihistamine or paracetamol. Once these 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 Ruxience if these reactions are severe.

Infections

Inform your doctor immediately if you or your child show signs of infection, including:

• fever, cough, sore throat, burning sensation when urinating, or if you start feeling fatigued or generally unwell,
• memory loss, difficulty concentrating, difficulty walking, or vision loss. These may be due to a very rare, serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML),
• 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 meningioencephalitis), which can be fatal.

You may be more susceptible to infections during treatment with Ruxience.

These are often colds, but cases of pneumonia, urinary tract infections, and serious viral infections have also occurred. These are listed below under “Other side 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 containing this information. It is important that you keep this card and show it to your partner or caregiver.

Skin reactions

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

Other side effects include:

1. If you or your child are receiving treatment for non-Hodgkin’s lymphoma or chronic lymphocytic leukemia

Very common side effects (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”,
• feeling unwell (nausea),
• bald patches on the scalp, chills, headache,
• reduced immunity due to lower blood levels of antibodies called “immunoglobulins” (IgG), which help protect against infection.

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

• blood infections (sepsis), pneumonia, herpes, common 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, weight loss, facial and body swelling, high levels of the enzyme “LDH” in the blood, low blood calcium levels,
• abnormal skin sensations such as numbness, tingling, pricking, burning, or skin tingling, reduced sense of touch,
• restlessness, difficulty sleeping,
• redness of the face and other skin areas due to blood vessel dilation,
• dizziness or anxiety,
• excessive tearing, tear duct disorders, eye inflammation (conjunctivitis),
• ringing in the ears, ear pain,
• heart problems such as heart attack, irregular or rapid heartbeat,
• increased or decreased blood pressure (especially low blood pressure upon standing),
• muscle tension in the airways causing wheezing (bronchospasm), lung, throat, or sinus inflammation or irritation, shortness of breath, runny nose,
• vomiting, diarrhea, stomach pain, throat or mouth irritation or ulcers, 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,
• tumour pain,
• general malaise or restlessness, fatigue, tremors, flu-like symptoms,
• multi-organ failure.

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

• blood clotting problems, reduced red blood cell production and increased destruction of red blood cells (aplastic hemolytic anemia), swollen or enlarged lymph nodes,
• lethargy and loss of interest in usual activities, nervousness,
• altered sense of taste, such as changes in how things taste,
• heart problems such as reduced heart rate or chest pain (angina),
• asthma, insufficient oxygen reaching organs,
• stomach swelling.

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

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

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

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

Children and adolescents with non-Hodgkin’s lymphoma: In general, side 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 side effects were fever associated with low levels of a type of white blood cell (neutrophils), mouth inflammation or sores, and allergic reactions (hypersensitivity).

1. If you are being treated for rheumatoid arthritis

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

• infections such as pneumonia (bacterial),
• painful urination (urinary tract infection),
• allergic reactions, which are more likely to occur during infusion but may appear up to 24 hours afterwards,
• changes in blood pressure, nausea, rash, fever, itching, runny or blocked nose and sneezing, chills, rapid heartbeat, and fatigue,
• headache,
• changes in laboratory tests performed by your doctor. These include a decrease in specific proteins in the blood (immunoglobulins) that help protect against infection.

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

• infections such as bronchial inflammation (bronchitis),
• feeling of fullness or sharp pain behind the nose, cheeks, and eyes (sinusitis), abdominal pain, vomiting, and diarrhea, difficulty breathing,
• fungal foot infection (athlete’s foot),
• increased blood cholesterol levels,
• abnormal skin sensations such as numbness, tingling, pricking, or burning, sciatica, migraine, dizziness,
• hair loss,
• anxiety, depression,
• indigestion, diarrhea, acid reflux, throat and mouth irritation and/or ulceration,
• stomach, back, muscle, and/or joint pain.

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

• excessive fluid retention in the face and body,
• lung and throat inflammation, irritation, and/or tightness, cough,
• skin reactions including hives, itching, and rash,
• allergic reactions including wheezing or shortness of breath, facial and tongue swelling, fainting.

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

• a set of symptoms appearing a few weeks after a rituximab infusion, including allergic reactions such as rash, itching, joint pain, swollen lymph nodes, and fever,
• development of severe skin blistering that may be fatal. Redness, usually associated with blistering, may appear on the skin or mucous membranes such as inside the mouth, genital area, or eyelids, along with fever.

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

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

Other rare side effects due to rituximab include a decrease in white blood cells (neutrophils) that help fight infection. Some infections may be serious (see information on Infections in this section).

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

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

• infections such as chest infections, urinary tract infections (painful urination), colds, and herpes infections,
• allergic reactions, which occur more frequently during infusion but may appear up to 24 hours afterwards,
• diarrhea,
• cough or shortness of breath,
• nosebleeds,
• hypertension,
• joint or back pain,
• muscle spasms or muscle twitching,
• dizziness,
• tremors (especially in the hands),
• difficulty sleeping (insomnia),
• swelling of hands or ankles.

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

• indigestion,
• constipation,
• skin rashes, including acne or spots,
• flushing or skin redness,
• fever,
• runny or blocked nose,
• tense or sore muscles,
• muscle, hand, or foot pain,
• low red blood cell count (anemia),
• low platelet count in the blood,
• increased blood potassium levels,
• changes in heart rhythm or abnormally fast heartbeat.

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

• development of severe skin blistering that may be fatal. Redness, often associated with blistering, may appear on the skin or mucous membranes such as inside the mouth, genital area, or eyelids, along with fever,
• reactivation of a previous hepatitis B infection.

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

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

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 similar to those in adults with these conditions. The most commonly observed side effects were infections, allergic reactions, and malaise (nausea).

1. If you are being treated for pemphigus vulgaris

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

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

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

• infections such as common cold, herpes infections, eye infection, oral candidiasis, and urinary tract infections (painful urination),
• mood disorders such as irritability and depression,
• skin disorders such as itching, hives, and benign lumps,
• feeling tired or dizzy,
• fever,
• joint or back pain,
• abdominal pain,
• muscle pain,
• abnormally fast heartbeat.

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

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

Ruxience may also cause changes in laboratory tests performed by your doctor.

If you receive Ruxience with other medicines, some of the side effects you experience may be due to the other medicines.

Reporting of side effects

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

5. Storage of Ruxience

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

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

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze. Keep the vial in the outer packaging to protect it from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of unwanted medicines and their containers. This will help protect the environment.

6. Package contents and other information

Composition of Ruxience

• The active substance in Ruxience is called 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 L-histidine, L-histidine monohydrochloride monohydrate, disodium edetate, polysorbate 80, sucrose, water for injections. See section 2, Ruxience contains sodium.

Appearance of Ruxience and contents of the pack

Ruxience is a sterile concentrate supplied as a solution for infusion, which is colourless to clear yellowish brown and clear to slightly opalescent.

10 ml vial – Pack of 1 vial

50 ml vial – Pack of 1 vial

Marketing Authorisation Holder

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer

Pfizer Manufacturing Belgium NV
Rijksweg 12
2870 Puurs-Sint-Amands
Belgium

More information about this medicinal product is available upon request from the local representative of the Marketing Authorisation Holder:

Date of the most recent revision of this leaflet: <{MM/YYYY}><{month YYYY}>.

Other sources of information

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

This leaflet is available on the European Medicines Agency website in all languages of the European Union/European Economic Area.