RUXIENCE 100 mg CONCENTRATE FOR SOLUTION FOR INFUSION

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 all of this leaflet carefully before you start taking this medicine because it contains important information for you.

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

Contents of the pack

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

1. What is Ruxience and what is it used for

What is Ruxience

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

What Ruxience is used for

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

1. Non-Hodgkin's lymphoma

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

Ruxience can be given to adults alone or with other medicines 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 given in combination with “chemotherapy”.

1. Chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in adults. CLL affects a particular lymph 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 you may experience. Ruxience in combination with chemotherapy destroys these cells, which are gradually eliminated from the body through biological processes.

1. Rheumatoid arthritis

Ruxience is used to treat rheumatoid arthritis. Rheumatoid arthritis is a disease of the joints. B lymphocytes are involved, causing some of the symptoms you may experience. Ruxience is used to treat rheumatoid arthritis in people who have already been treated with other medicines that have either stopped working, not worked well enough, or have caused side effects. Ruxience is usually taken with another medicine called methotrexate.

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

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

1. Granulomatosis with polyangiitis or microscopic polyangiitis

Ruxience is used to treat adult and child patients aged 2 years and older with granulomatosis with polyangiitis (formerly 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 mainly affect the lungs and kidneys, but can also affect other organs. B lymphocytes are involved in the cause of these conditions.

1. 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 you are given Ruxience

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 have a severe active infection at the moment;
• if you have a weak immune system;
• if you have severe uncontrolled heart failure or severe uncontrolled heart disease and you have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris.

Do not receive Ruxience if any of the above applies to you. If you are not sure, consult your doctor, pharmacist, or nurse before receiving Ruxience.

Warnings and precautions

It is important that you and your doctor note 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 have an infectious hepatitis. This is because, in some patients who had had hepatitis B, Ruxience can cause it to become active again, which can be fatal in very rare cases. Patients with a history of hepatitis B infection will be closely monitored by their doctor for signs of this infection;
• you have ever had heart problems (such as angina, palpitations, or heart failure) or breathing problems.

If any of the above applies to you (or you are not sure), consult your doctor, pharmacist, or nurse before receiving Ruxience. Your doctor may need to monitor you during your treatment with Ruxience.

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

Tell 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 like a cold. The cells that Ruxience targets help fight infections, so you should wait until the infection has passed before receiving Ruxience. Also, tell your doctor if you have had many 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 leukaemia (mature B-cell acute leukaemia) (MBAL) 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 old.

Granulomatosis with polyangiitis or microscopic polyangiitis

Ruxience can be used to treat children and adolescents aged 2 years and older with granulomatosis with polyangiitis (formerly called Wegener's granulomatosis) or microscopic polyangiitis. There is not much information on the use of rituximab in children and young people with other diseases.

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

Other medicines and Ruxience

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines. This includes medicines bought without a prescription and herbal medicines. This is because Ruxience can affect how other medicines work. Also, other medicines can affect how Ruxience works.

In particular, tell your doctor:

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

If any of the above applies to you (or you are not sure), ask your doctor, pharmacist, or nurse before receiving Ruxience.

Pregnancy and breastfeeding

Tell 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 must use an effective method of contraception while using Ruxience and for up to 12 months after your last treatment with Ruxience.

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

Driving and using machines

It is not known if rituximab has an effect on your ability to drive or use tools or machines.

Sodium content of Ruxience

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

3. How Ruxience is given

How it is given

Ruxience will be given to you by a doctor or nurse who is experienced in the use of this treatment. You will be closely monitored while you are given this medicine. This is in case you have any side effects.

Ruxience will always be given as an infusion (intravenous infusion).

Medicines given before each administration of Ruxience

Before you receive Ruxience, you will be given other medicines (premedication) to prevent or reduce the possible side 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 given to you once a week for 4 weeks. Treatment cycles with Ruxience can be repeated.

• If you are receiving Ruxience with chemotherapy

Ruxience will be given to you 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 be given Ruxience as maintenance treatment every 2 or 3 months for 2 years. Your doctor may change this depending on your response to the medicine.
• If you are under 18 years old, you will be given 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 leukaemia

When you receive treatment with Ruxience in combination with chemotherapy, you will receive infusions of Ruxience 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 given after the infusion of Ruxience. Your doctor will decide if 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 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 happen after a few months.

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

Treatment with Ruxience consists of four infusions given at weekly intervals. Corticosteroids will usually be given by injection before starting treatment with Ruxience. Your doctor may start giving you corticosteroids by mouth at any time to treat your condition.

If you are 18 years or older and respond well to treatment, you may be given Ruxience as maintenance treatment. This will be given as 2 infusions 2 weeks apart, 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 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 be given Ruxience as maintenance treatment. This will be given 1 year and 18 months after initial treatment and then every 6 months as needed; your doctor may change this depending on how you respond to the medicine.

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

4. Possible Adverse Effects

Like all medicines, Ruxience can cause adverse effects, although not all people suffer from them.

Most adverse 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 in the first 24 hours following infusion, you may experience fever, chills, and shaking. Less frequently, some patients may experience pain at the infusion site, blisters, itching, nausea, fatigue, headache, difficulty breathing, high blood pressure, wheezing, throat irritation, swelling of the tongue or throat, itching or runny nose, vomiting, flushing or palpitations, heart attack, or low platelet count. If you have heart disease or angina, these reactions may worsen. Inform the person administering the infusion immediatelyif you or your child experience any of these symptoms, as it may be necessary to slow down or interrupt the infusion. You may need additional treatment, such as an antihistamine or paracetamol. When these 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 discontinue your treatment with Ruxience if these reactions are severe.

Infections

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

• fever, cough, sore throat, burning sensation when urinating, or if you start to feel tired or unwell,
• memory loss, concentration problems, difficulty walking, or vision loss. This could be due to a rare and serious brain infection (progressive multifocal leukoencephalopathy or PML), which can be fatal,
• fever, headache, stiff neck, 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 be more prone to infections during treatment with Ruxience.

These are often colds, but there have been cases of pneumonia, urinary tract infections, and serious viral infections. These are listed below in “Other Adverse 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, which also contains this information. It is essential that you keep this patient information card and show it to your partner or caregiver.

Skin Reactions

Very rarely, severe blisters can form on the skin, which 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 Adverse Effects Include:

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

Very common adverse 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 nauseous,
• hair loss on the scalp, chills, headache,
• lowered immunity due to low levels of antibodies called “immunoglobulins” (IgG) in the blood, which help protect against infection.

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

• blood infections (sepsis), pneumonia, herpes, colds, bronchial infections, fungal infections, infections of unknown origin, nasal passage inflammation, hepatitis B,
• low red blood cell count (anemia), low overall blood cell count,
• allergic reactions (hypersensitivity),
• high blood sugar, weight loss, swelling in the face and body, high levels of the enzyme “LDH” in the blood, low calcium levels in the blood,
• abnormal skin sensations, such as numbness, tingling, pinching, burning, or skin tingling,
• agitation, difficulty sleeping,
• flushing of the face and other areas of the skin due to dilation of blood vessels,
• feeling dizzy or anxious,
• increased tear production, changes in the tear duct, eye inflammation (conjunctivitis),
• ringing in the ears, ear pain,
• heart problems, such as heart attack, irregular or rapid heartbeat,
• increased or decreased blood pressure (decreased blood pressure, especially when standing up),
• muscle tension in the airways that causes wheezing (bronchospasm), inflammation, irritation in the lungs, throat, or nasal passages, shortness of breath, runny nose,
• 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,
• hives, increased sweating, night sweats,
• muscle problems, such as muscle tension, joint or muscle pain, back and neck pain,
• tumor pain,
• general discomfort or feeling of unease or fatigue, shivering, flu-like symptoms,
• multiple organ failure.

Uncommon adverse 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 (aplastic hemolytic anemia), inflamed or enlarged lymph nodes,
• decline and loss of interest in usual activities, nervousness,
• changes in taste, such as changes in the taste of things,
• heart problems, such as reduced heart rate or chest pain (angina),
• asthma, low oxygen levels in the blood,
• stomach swelling.

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

• temporary increase in the amount of a type of antibody in the blood (called immunoglobulins - IgM), chemical changes in the blood caused by the breakdown of cancer cells,
• nerve damage in the arms and legs, facial paralysis,
• heart failure,
• inflammation of blood vessels, including those that cause skin symptoms,
• respiratory failure,
• damage to the intestinal wall (perforation),
• severe skin problems that cause 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,
• kidney failure,
• severe vision loss.

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

• delayed decrease in white blood cell count in the blood,
• reversible decrease in platelet count after infusion, but which can be fatal in rare cases,
• hearing loss, loss of other senses,
• brain and meninges infection/inflammation (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 common adverse effects observed were fever associated with low levels of a type of white blood cell (neutrophils), inflammation or sores in the mouth, and allergic reactions (hypersensitivity).

1. If you are being treated for rheumatoid arthritis

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

• infections such as pneumonia (bacterial),
• pain when urinating (urinary tract infection),
• allergic reactions that are more likely to occur during infusion, but can occur up to 24 hours later,
• changes in blood pressure, nausea, rash, fever, itching, runny or stuffy nose, and sneezing, shaking, 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 adverse effects (may affect up to 1 in 10 people):

• infections, such as bronchitis (inflammation of the bronchi),
• feeling full or sharp pain behind the nose, cheeks, and eyes (sinusitis), abdominal pain, vomiting, and diarrhea, difficulty breathing,
• fungal infection of the foot (athlete's foot),
• increased cholesterol levels in the blood,
• abnormal skin sensations, such as numbness, tingling, pinching, or burning, sciatica, migraine, dizziness,
• hair loss,

• anxiety, depression,

• indigestion, diarrhea, acid reflux, irritation, and/or ulcers in the throat and mouth,
• abdominal pain, back pain, muscle and/or joint pain.

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

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

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

• a set of symptoms that appear a few weeks after a rituximab infusion, including allergic reactions such as rash, itching, joint pain, lymph node inflammation, and fever,
• severe blistering of 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.

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

• severe viral infection,

• brain and meninges infection/inflammation (enteroviral meningoencephalitis).

Other rare adverse effects due to rituximab include a decrease in the number of white blood cells in the blood (neutrophils) that help fight infection. Some infections can be serious (see the information on Infectionsin this section).

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

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

• infections, such as chest infections, urinary tract infections (pain when urinating), colds, and herpes infections,
• allergic reactions that occur more frequently during infusion, but can occur up to 24 hours later,
• diarrhea,
• coughing or shortness of breath,
• nasal bleeding,
• high blood pressure,
• joint or back pain,
• muscle spasms or muscle twitching,
• feeling dizzy,
• shaking (especially in the hands),
• difficulty sleeping (insomnia),
• swelling of the hands or ankles.

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

• indigestion,
• constipation,
• skin rashes, including acne or blemishes,
• flushing or redness of the skin,
• fever,
• runny or stuffy nose,
• tense or sore muscles,
• muscle pain in the hands or feet,
• low red blood cell count (anemia),
• low platelet count in the blood,
• high potassium levels in the blood,
• changes in heart rhythm or faster than normal heartbeat.

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

• severe blistering of 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,
• reactivation of a previous hepatitis B infection.

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

• severe viral infection,

• brain and meninges infection/inflammation (enteroviral meningoencephalitis).

Children and Adolescents with Granulomatosis with Polyangiitis or Microscopic Polyangiitis

In general, adverse 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 adverse effects observed were infections, allergic reactions, and discomfort (nausea).

1. If you are being treated for pemphigus vulgaris

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

• allergic reactions that occur more likely during infusion, but can occur up to 24 hours later,
• headache,
• infections such as chest infections,
• long-lasting depression,
• hair loss.

Common adverse effects (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 bumps,
• feeling tired or dizzy,
• fever,
• joint or back pain,
• abdominal pain,
• muscle pain,
• faster than normal heartbeat.

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

• severe viral infection,

• brain and meninges infection/inflammation (enteroviral meningoencephalitis).

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

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

Reporting of Adverse Effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse 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 carton after “EXP”. The expiry date is the last day of the month stated.

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 medicines that are no longer needed. This will help protect the environment.

6. Container contents and additional information

Ruxience composition

• The active ingredient 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 hydrochloride monohydrate, disodium edetate, polysorbate 80, sucrose, water for injectable preparations. See section 2, Ruxience contains sodium.

Appearance of Ruxience and container contents

Ruxience is a colorless to pale yellowish-brown solution and transparent to slightly opalescent, supplied as a concentrate for solution for infusion [sterile concentrate].

10 ml vial – Pack of 1 vial

50 ml vial – Pack of 1 vial

Marketing authorization 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

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet: <{MM/AAAA}><{month YYYY}>.

Other sources of information

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

This leaflet can be found in all languages of the European Union/European Economic Area on the European Medicines Agency website.