Product Information for the Patient

Ruxience 100 mg Concentrate for Solution for Infusion

Ruxience 500 mg Concentrate for Solution for Infusion

rituximab

Read this entire product information carefully before starting to take this medicine, as it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

What is Ruxience

Ruxience contains the active ingredient “rituximab”. This is a type of protein called “monoclonal antibody”. This protein adheres to the surface of a type of white blood cell called “B lymphocyte”. When rituximab adheres to the surface of this cell, it causes its death.

For what Ruxience is used

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

a)NH Hodgkin 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 can be administered to adults alone or with other medications called “chemotherapy”.

In adult patients where treatment is working, Ruxience may be used as maintenance treatment for 2 years after completing initial treatment.

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

b)Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults. CLL affects a specific lymphatic cell, 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 is the cause of the symptoms that patients may experience. Ruxience in combination with chemotherapy destroys these cells that are gradually eliminated from the body through biological processes.

c)Rheumatoid Arthritis

Ruxience is used for the treatment of rheumatoid arthritis. Rheumatoid arthritis is a joint disease. B lymphocytes are involved in causing some of the symptoms that patients may experience. Ruxience is used to treat rheumatoid arthritis in people who have already been treated with other medications, which either have stopped working, have not worked well enough, or have caused adverse effects. Ruxience is usually taken with another medication called methotrexate.

Ruxience slows down the damage to the joints caused by rheumatoid arthritis and improves their ability to perform normal daily activities.

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

d)Granulomatosis with Polyangiitis or Microscopic Polyangiitis

Ruxience is used for the treatment of adult and pediatric patients 2 years of age or 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 can also affect other organs. B lymphocytes are involved in the cause of these conditions.

e)Pemphigus Vulgaris

Ruxience 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 take Ruxience

• if you are allergic to rituximab, other proteins similar to rituximab, or any of the other components of this medication (listed in section6);
• if you have an active severe infection at this time;
• 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 receive Ruxience if any of the above conditions apply to you. If you are unsure, consult your doctor, pharmacist, or nurse before receiving Ruxience.

Warnings and precautions

It is essential that you and your doctor note the brand name and batch number of your medication.

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

• you have ever had or think you have a hepatitis infection. This is because, in some patients who had hepatitis B, Ruxience may cause this infection to reactivate, which can be fatal in rare cases. Patients with a history of hepatitis B infection will be closely monitored by their doctor for any signs of this infection;
• you have ever had heart problems (such as angina, palpitations, or heart failure) or respiratory problems.

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

Also ask your doctorifyouthinkyoumay need to be vaccinated in the near future, including travel vaccines. Some vaccines should not be administered at the same time as Ruxience or in the monthsfollowingits administration. Your doctorwillcheckifyouneedanyvaccine before receiving Ruxience.

Inform your doctor also 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 like a cold. The cells targeted by Ruxience help fight infections, so you should wait until the infection has passed before receiving Ruxience. Additionally, inform your doctor if you have had many infections in the past or if you have a severe infection.

Children and adolescents

Non-Hodgkin lymphoma

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

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

Granulomatosis with polyangiitis or microscopic polyangiitis

Ruxience can be used to treat children and adolescents, 2years 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 rituximab in children and young people with other diseases.

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

Other medications and Ruxience

Inform your doctor, pharmacist, or nurse if you are taking, have taken recently, or may need to take any other medication. This includes over-the-counter medications and herbal medications. This is because Ruxience may affect how other medications work. Additionally, other medications may affect how Ruxience works.

Particularly, inform your doctor:

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

If any of the above points apply to you (or 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 contraceptive method while using Ruxience and for 12months after your last treatment with Ruxience.

Ruxience 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 Ruxience or for 6months after treatment.

Driving and operating machinery

The effect of rituximab on your ability to drive or use tools or machines is unknown.

Sodium content of Ruxience

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

How it is administered

Ruxience will be administered by a doctor or a nurse experienced in the use of this treatment. They will closely monitor you while administering this medication. This is to check for any adverse effects.

Ruxience will always be administered in the form of an infusion (intravenous perfusion).

Medications administered before each administration of Ruxience

Before receiving Ruxience, other medications (premedication) will be administered to prevent or reduce possible adverse effects.

Quantity and frequency of treatment

1. If you are being treated for non-Hodgkin lymphoma
   • If you are receiving Ruxience only

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

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

1. If you are being treated for chronic lymphocytic leukemia

When receiving treatment with 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 if you should receive concurrent supportive therapy.

1. If you are being treated for rheumatoid arthritis

Each treatment cycle consists of two infusions separated by a 2-week interval. Treatment cycles with Ruxience can be repeated. Depending on the signs and symptoms of your disease, your doctor will decide if, at some point, you should receive more Ruxience. 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 infusions separated by weekly intervals. Corticosteroids are usually administered via injection before starting treatment with Ruxience. Your doctor may initiate oral corticosteroids at any time to treat your condition.

If you are 18 years or older and respond well to treatment, you may be administered Ruxience as maintenance treatment. This will be administered as 2 infusions separated by a 2-week interval, followed by 1 infusion every 6 months for at least 2 years. Your doctor may decide to treat you for longer with Ruxience (up to 5 years), depending on your response to the medication.

e)If you are being treated for bullous pemphigoid

Each treatment cycle consists of two infusions separated by a 2-week interval. If you respond well to treatment, you may be administered Ruxience 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 change this depending on your response to the medication.

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

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

Most side effects are mild to moderate, but some can be severe 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 shakiness. Less frequently, some patients may experience pain at the infusion site, blisters, itching, nausea, fatigue, headache, difficulty breathing, high blood pressure, wheezing, throat discomfort, tongue or throat swelling, nasal itching or discharge, vomiting, flushing, or palpitations. If you have a heart condition or angina, these reactions may worsen.Inform the person administering the infusion immediately if you or your child experience any of these symptoms, as it may be necessary to slow down or stop the infusion. You may need additional treatment, such as an antihistamine or acetaminophen. When these symptoms subside or improve, the infusion may continue. After the second infusion, it is less likely that these reactions will occur. 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 experience signs of infection, which include:

• fever, cough, sore throat, burning while 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 potentially fatal brain infection (progressive multifocal leukoencephalopathy or PML);
• fever, headache, stiff neck, discoordination (ataxia), personality changes, hallucinations, altered consciousness, seizures, or coma – this may be due to a severe brain infection (enteroviral meningitis), which can be fatal.

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

Often, these are colds, but there have been cases of pneumonia, urinary tract infections, or severe viral infections, which 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 given you a patient information card, where you will also find this information. It is essential to keep this card and show it to your partner or caregiver.

Skin reactions

Very rarely, severe blisters may form on the skin that can be life-threatening. You may experience redness, often associated with blisters, on the skin or mucous membranes, such as the inside of the mouth, genital area, or eyelids, and fever.Inform 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 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 platelet count;
• feeling dizzy (nausea);
• hair loss, chills, headache;
• lowered immunity caused by lower levels of a type of antibody in the blood (IgG), which helps protect against infection.

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

• blood infections (sepsis), pneumonia, herpes, common cold, bronchitis infections, fungal infections, unknown infections, nasal congestion, inflammation, or irritation in the nose, hepatitis B;
• low red blood cell count (anemia), low count 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 calcium levels in the blood;
• abnormal sensations in the skin, such as numbness, tingling, pinching, burning, or a feeling of pins and needles in the skin, decreased sense of touch;
• agitation, difficulty falling asleep;
• redness of the face and other areas of the skin due to vasodilation;
• feeling of dizziness or anxiety;
• excessive tearing, alterations in the tear duct, conjunctivitis (inflammation of the eyes);
• ringing in the ears, ear pain;
• cardiac alterations, such as myocardial infarction, irregular or rapid heart rate;
• increased or decreased blood pressure;
• tension in the respiratory tract muscles causing wheezing (bronchospasm), inflammation, irritation in the lungs, throat, or nasal passages, shortness of breath, nasal discharge;
• vomiting, diarrhea, stomach pain, irritation, or ulcers in the throat and mouth, difficulty swallowing, constipation, indigestion;
• eating disorders: not eating enough, leading to weight loss;
• hiccups, excessive sweating, night sweats;
• muscle problems, such as muscle tension, joint or muscle pain, back and neck pain;
• tumor pain;
• general discomfort or feeling of restlessness or fatigue, tremors, flu-like symptoms;
• multi-organ insufficiency.

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

• blood clotting problems, decreased production of red blood cells, and increased destruction of red blood cells (hemolytic anemia aplastic), swollen or inflamed lymph nodes;
• fatigue and loss of interest in usual activities, nervousness;
• alterations in the sense of taste, such as changes in the taste of things;
• cardiac problems, such as reduced heart rate or chest pain (angina);
• asthma, insufficient oxygen reaching the organs;
• stomach swelling.

Very rare side effects (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 the arms and legs, facial paralysis;
• heart failure;
• inflammation of blood vessels, including those causing skin symptoms;
• respiratory insufficiency;
• intestinal wall damage (perforation);
• severe skin problems that can be life-threatening. You may experience redness, often associated with blisters, on the skin or mucous membranes, such as the inside of the mouth, genital area, or eyelids, and fever;
• renal insufficiency;
• severe vision loss.

Unknown frequency (cannot be estimated from available data):

• delayed decrease in white blood cell count;
• reversible decrease in platelet count after infusion, but which in rare cases can be fatal;
• loss of hearing, loss of other senses;
• brain and meninges infection (enteroviral meningitis).

Children and adolescents with non-Hodgkin lymphoma:Generally, 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 white blood cell count (neutropenia), inflammation or sores in the mouth, 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):

• bacterial infections (pneumonia);
• urinary tract infections (painful urination);
• allergic reactions that occur more frequently during infusion, but can appear up to 24 hours later;
• blood pressure changes, nausea, rash, fever, itching, nasal discharge or obstruction, and sneezing, shakiness, 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 side effects (may affect up to 1 in 10 people):

• bacterial infections, such as bronchitis;
• nasal congestion, sinusitis, abdominal pain, vomiting, and diarrhea, difficulty breathing;
• foot fungal infections (athlete's foot);
• high cholesterol levels in the blood;
• abnormal sensations in the skin, such as numbness, tingling, pinching, or burning, sciatica, migraines, dizziness;
• hair loss;
• anxiety, depression;
• indigestion, diarrhea, acid reflux, irritation, or ulcers in the throat and mouth;
• abdominal, back, muscle, or joint pain.

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

• fluid retention in the face and body;
• inflammation, irritation, or oppression in the lungs and throat, cough;
• skin reactions that include hives, itching, and rashes;
• allergic reactions that include 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 that appear a few weeks after a rituximab infusion, which includes allergic reactions such as rash, itching, joint pain, swollen lymph nodes, and fever;
• severe blisters that can be life-threatening. You may experience redness, often associated with blisters, on the skin or mucous membranes, such as the inside of the mouth, genital area, or eyelids, and fever.

Unknown frequency (cannot be estimated from available data):

• severe viral infection;
• brain and meninges infection (enteroviral meningitis).

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

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

Reporting 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 prospectus. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

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

Store in refrigerator (between 2°C and 8°C). Store the packaging in the outer container 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 containers and medications that you no longer need. This will help protect the environment.

Composition of Ruxience

• The active ingredient in Ruxience is called rituximab.

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

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

• The other components are L-histidine, L-histidine hydrochloride monohydrate, disodium edetate, polysorbate 80, sucrose, and water for injection.

Appearance of Ruxience and packaging contents

Ruxience is a colorless to light yellowish clear solution, supplied as a sterile concentrate for solution for infusion.

10ml vial – Pack of 1vial

50ml vial – Pack of 1vial

Marketing Authorization Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Responsible for manufacturing

Pfizer Manufacturing Belgium NV

Rijksweg 12

2870 Puurs-Sint-Amands

Belgium

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

Last update of this leaflet: 02/2025.

Other sources of information

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

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