RIXIMYO 500 MG CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Riximyo 100mg concentrate for solution for infusion

Riximyo 500mg concentrate for solution for infusion

Rituximab

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of the leaflet contains information on how to report side effects.

Read all of this leaflet carefully before you start using 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 get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Riximyo and what is it used for

What is Riximyo

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

What is Riximyo used for

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

• 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.

Riximyo can be given to adults alone or with other medicines called “chemotherapy”. In adult patients who have responded to treatment, Riximyo can be used as maintenance treatment for 2 years after completing initial treatment.

In children and adolescents, rituximab is given in combination with “chemotherapy”.

• Chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in adults. It affects B lymphocytes, which are produced in the bone marrow and develop in the lymph nodes. Patients with CLL have too many abnormal B lymphocytes that accumulate mainly in the bone marrow and in the blood. The proliferation of these abnormal lymphocytes can cause some of the symptoms you may experience. Riximyo, in combination with chemotherapy, destroys these cells, which gradually disappear from the body through biological processes.

• Granulomatosis with polyangiitis or microscopic polyangiitis

Riximyo is used to treat adult and paediatric patients 2 years of age and older with granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) or microscopic polyangiitis, given in combination with corticosteroids.

Granulomatosis with polyangiitis or 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 diseases.

• Pemphigus vulgaris

Riximyo is used to treat patients with moderate to severe pemphigus vulgaris.

Pemphigus vulgaris is an autoimmune disease that causes painful blisters on the skin and the lining of the mouth, nose, throat, and genitals.

2. What you need to know before you are given Riximyo

Do not use Riximyo

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

Do not use Riximyo if you have any of the above. If you are not sure, ask your doctor, pharmacist, or nurse before you are given Riximyo.

Warnings and precautions

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

• 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 life-threatening in very rare cases. Patients with a history of hepatitis B infection will be closely monitored by their doctor for signs of hepatitis B.
• if you have had any heart disease (such as angina, palpitations, or heart failure) or respiratory problems.

If any of the above apply to you (or you are not sure), ask your doctor, pharmacist, or nurse before you are given Riximyo. Your doctor may need to monitor you during your treatment with Riximyo.

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

• if you think you may have an infection, even if it is mild, such as a cold. The cells that Riximyo targets help fight infections, so you should wait until the infection has passed before using Riximyo. You should also tell your doctor if you have had many infections in the past or if you have a serious infection.
• 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 Riximyo or in the months following its administration. Your doctor will check if you need any vaccinations before receiving Riximyo.

Children and adolescents

Non-Hodgkin lymphoma

Rituximab can be used to treat children and adolescents from 6 months of age and older with non-Hodgkin lymphoma, specifically CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL)/Burkitt leukaemia (mature B-cell acute leukaemia) (BAL) or Burkitt-like lymphoma (BLL).

Granulomatosis with polyangiitis or microscopic polyangiitis.

Rituximab can be used to treat children and adolescents 2 years of age 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.

There is not much information on the use of rituximab in children and adolescents with other diseases.

Tell your doctor, pharmacist, or nurse before you or your child are given rituximab if you or your child are under 18 years old.

Using Riximyo with other medicines

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription or herbal medicines. This is because Riximyo may affect the way other medicines work. Also, other medicines may affect the way Riximyo works.

In particular, tell your doctor if:

• you are being treated for high blood pressure. You may be told not to take your blood pressure medicines during the 12 hours before you are given Riximyo. This is because some people experience a drop in blood pressure during the infusion of Riximyo
• 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 you are not sure), ask your doctor, pharmacist, or nurse before you are given Riximyo.

Pregnancy and breast-feeding

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

If you are of childbearing potential, you and your partner must use an effective method of contraception during treatment with Riximyo and for up to 12 months after the last treatment with Riximyo. You must not breast-feed during treatment with Riximyo and for up to 12 months after the last treatment with Riximyo. This is because Riximyo may pass into breast milk.

Driving and using machines

It is not known if rituximab has any effects on the ability to drive or use machines.

Riximyo contains sodium

This medicine contains 52.6 mg of sodium per 10 ml vial and 263.2 mg of sodium 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 intake of sodium for an adult.

3. How Riximyo is given

How Riximyo is given

Riximyo will be given to you by a doctor or nurse who has experience in the use of this medicine. They will keep you under observation during the administration of Riximyo in case you experience any side effects.

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

Medicines given before each Riximyo infusion

Before the administration of Riximyo, you will be given other medicines (premedication) to prevent or reduce possible side effects.

Dose and frequency of treatment

• If you are being treated for non-Hodgkin lymphoma
  • If you are only being treated with Riximyo

Riximyo will be given to you once a week for 4 weeks. You may have further cycles of treatment with Riximyo.

• If you are being treated with Riximyo and chemotherapy

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

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

• If you are being treated for chronic lymphocytic leukaemia

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

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

Treatment with Riximyo uses four separate infusions, given at weekly intervals. Corticosteroids are usually given by injection before starting treatment with Riximyo. To treat your disease, your doctor may start giving you corticosteroids by mouth at any time.

If you are 18 years of age or older and respond well to treatment, you may be given Riximyo as maintenance treatment. This will be given as 2 separate infusions with 2 weeks between them, followed by 1 infusion every 6 months for at least 2 years. Your doctor may decide to treat you for longer with Riximyo (up to 5 years), depending on your response to the medicine.

• If you are being treated for pemphigus vulgaris

Each treatment cycle consists of two infusions, both given 2 weeks apart. If you respond well to treatment, you may be given Riximyo 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 your response 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, Riximyo can cause adverse effects, although not all people suffer from them.

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

Infusion Reactions

During or after the 24 hours following infusion, you may experience fever, chills, and tremors. Other less frequent adverse effects that some patients may experience are: pain at the infusion site, blisters, and itching of the skin, nausea and vomiting, fatigue, headache, difficulty breathing, increased blood pressure, wheezing, throat irritation, swelling of the tongue or throat, itching or nasal congestion, vomiting, flushing or palpitations, heart attack or low platelet count. If you have a heart condition or angina, these reactions could worsen. Immediately inform the person administering the infusionif you or your child experience any of these symptoms, as you may need a slower infusion or to interrupt 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 discontinue your treatment with Riximyo if you have severe infusion reactions.

Infections

Inform your doctor immediately if after treatment with Riximyo you or your childexperience any symptoms of infection, such as:

• 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 may be due to a very rare and serious brain infection, which can be fatal (progressive multifocal leukoencephalopathy or PML).

You may be more prone to infections after treatment with Riximyo. These are usually colds, but cases of pneumonia or urinary tract infections have been reported. All of these are included below as "Other Adverse Effects".

If you are being treated for 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 that you 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. Redness may appear, usually associated with blisters, on the skin or mucous membranes, such as inside the mouth, genital area, or eyelids, and may occur with fever. Inform your doctor immediately if you experience any of these symptoms.

Other Adverse Effects

• If you or your child are being treated for non-Hodgkin lymphoma or chronic lymphatic 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 blood cells called "platelets"
• nausea
• hair loss on the scalp, chills, headache
• reduced immunity due to decreased levels of antibodies called "immunoglobulins" (IgG) in the blood that help protect against infection.

Common (may affect up to 1 in 10 people)

• blood infections (sepsis), pneumonia, herpes, colds, bronchial infections, fungal infections, infections of unknown origin, 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 levels of LDH enzyme in the blood, decreased calcium levels in the blood
• abnormal skin sensations, such as numbness, tingling, pinching, burning, progressive increase in these skin sensations, decreased sense of touch
• agitation, difficulty staying asleep
• flushing of the face and other skin areas due to dilation of blood vessels
• dizziness or anxiety sensation
• increased tearing, lacrimal duct disorders, eye inflammation (conjunctivitis)
• ringing in the ears, ear pain
• cardiac disorders, such as myocardial infarction, irregular heartbeat, abnormally rapid heartbeats
• increased or decreased blood pressure (decreased blood pressure, especially when standing up)
• 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
• 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
• general malaise or feeling of restlessness or fatigue, agitation, catarrhal symptoms
• multi-organ failure

Uncommon (may affect up to 1 in 100 people)

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

Rare (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 arms and legs, facial paralysis
• heart failure
• inflammation of blood vessels, including those that lead to skin symptoms
• respiratory failure
• damage to the intestinal wall (perforation)
• severe skin problems that cause blisters that can be potentially fatal. Redness may appear, usually associated with blisters, on the skin or mucous membranes, such as inside the mouth, genital area, or eyelids, and may occur with fever.
• kidney problems
• severe vision loss

Frequency not known (the frequency with which these adverse effects occur is not known)

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

Children and Adolescents with Non-Hodgkin Lymphoma:

In general, the adverse effects in children and adolescents with non-Hodgkin lymphoma were similar to those in adults with non-Hodgkin lymphoma or chronic lymphatic leukemia. The most common adverse effects observed were fever associated with low levels of a type of white blood cell (neutrophils), inflammation or ulcers in the oral cavity, and allergic reactions (hypersensitivity).

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

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

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

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

• indigestion
• constipation
• skin rash, including acne or benign bumps
• flushing or redness of the skin
  • fever

• stuffy nose or nasal congestion
• tense or sore muscles
• pain in the muscles or hands or feet
• low red blood cell count (anemia)
• low platelet count in the blood
• increased potassium levels in the blood
• changes in heart rhythm or faster than normal heartbeat

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

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

Children and Adolescents with Microscopic Polyangiitis or Polyangiitis:

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

• If you are being treated for pemphigus vulgaris

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

• allergic reactions that are more likely to occur during infusion, but can occur up to 24 hours after infusion.
• headache
• infections such as chest infections
• 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 (pain when urinating).
• mood disorders, such as irritability and depression
• skin disorders, such as itching, hives, and benign bumps
• feeling of fatigue or dizziness
• fever
• joint or back pain
• stomach pain
• muscle pain
• faster than normal heartbeat

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

Reporting of Adverse Effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects that do not appear in this prospectus. You can also report them directly through the national reporting system included in Annex V. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Riximyo

Keep out of sight and reach of children.

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

Store in a refrigerator (between 2°C and 8°C).

Keep the container 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 the packaging and any unused medication. This will help protect the environment.

6. Package Contents and Additional Information

Riximyo Composition

• The active ingredient of Riximyo 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 ingredients are sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, and water for injectable preparations (see section 2).

Product Appearance and Package Contents

Riximyo is a clear, colorless to slightly yellowish solution presented as a concentrate for solution for infusion.

10 ml vial: package of 2 or 3 vials.

50 ml vial: package of 1 or 2 vials.

Marketing Authorization Holder

Sandoz GmbH

Biochemiestr, 10

6250 Kundl

Austria

Manufacturer

Sandoz GmbH Schaftenau

Biochemiestr, 10

6336 Langkampfen

Austria

Date of Last Revision of this Prospectus:{MM/YYYY}.

Other Sources of Information

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

On the European Medicines Agency website, you can find this prospectus in all the languages of the European Union.