Prospect: information for the patient

Rixathon 100mg concentrate for solution for infusion

Rixathon 500mg concentrate for solution for infusion

rituximab

Read this prospect carefully before starting to use this medication, because it contains important information for you.

1.What is Rixathon and for what it is used

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

3.How Rixathon is administered

4.Possible adverse effects

5.Storage of Rixathon

6.Contents of the package and additional information

What is Rixathon

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

For what Rixathon is used

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

a)Non-Hodgkin Lymphoma

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

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

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

b)Chronic Lymphocytic Leukemia (CLL)

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

c)Rheumatoid Arthritis

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

Rixathon reduces the damage caused by rheumatoid arthritis to the joints and improves the ability to perform normal daily activities.

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

d)Granulomatosis with Polyangiitis (GPA) or Microscopic Polyangiitis (MPA)

Rixathon is used for the treatment of adult patients and children 2 years or older with GPA (formerly known as Wegener's granulomatosis) or MPA, administered in combination with corticosteroids.

GPA and MPA are two forms of blood vessel inflammation that primarily affect lungs and kidneys, but may also affect other organs. B lymphocytes are involved in the cause of these diseases.

e)Pemphigus Vulgaris (PV)

Rixathon is used for the treatment of patients with pemphigus vulgaris of moderate to severe severity.

PV is an autoimmune disease that causes painful blisters on the skin and mucous membranes of the mouth, nose, throat, and genitals.

Do not use Rixathon

•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

•If you have a weakened immune system

•If you have severe heart failure or uncontrolled severe heart disease and have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris.

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Rixathon:

•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 hepatitisB in the past may experience a relapse that can be fatal in rare cases. Patients with a history of hepatitisB infection will be closely monitored by your doctor to detect possible signs of hepatitisB.

•If you have had any heart disease (such as angina, palpitations, or heart failure) or respiratory problems.

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

Also ask your doctor if you think you may need to be vaccinated in the near future, including travel vaccines. Some vaccines should not be administered at the same time as Rixathon or in the months following its administration. Your doctor will check if you need any vaccine before receiving Rixathon.

If you have rheumatoid arthritis, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (PAM), or pemphigus vulgaris (PV), you must also inform your doctor:

•If you think you may have an infection, even if it is mild such as a cold. The cells targeted by Rixathon help fight infections, so you should wait until the infection has passed before using Rixathon. 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

Rituximab can be used for the treatment of children and adolescents, 6 months 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).

Granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (PAM)

Rituximab can be used for the treatment of children and adolescents, 2 years of age and older, with GPA (previously known as Wegener's granulomatosis) or PAM. There is little information on the use of rituximab in children and young people with other diseases.

There is little information on the use of rituximab in children and adolescents with other diseases.

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

Other medications and Rixathon

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

In particular, inform your doctor if:

•If you are being treated for hypertension. You may be told not to take your medications for 12hours before Rixathon is administered. This is because some people experience a drop in blood pressure during Rixathon infusion.

•If you have ever taken medications that affect your immune system – such as chemotherapy or immunosuppressive medications.

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

Pregnancy and breastfeeding

You must inform your doctor or nurse if you are pregnant, if you think you may be pregnant, or if you intend to become pregnant. This is because Rixathon can cross the placental barrier and affect your baby.

If you are of childbearing age, you and your partner must use an effective contraceptive method during treatment with Rixathon and for 12months after the last treatment with Rixathon. Rixathon 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 Rixathon or for 6 months after treatment.

Driving and operating machinery

The effects of rituximab on the ability to drive vehicles or operate machinery are unknown.

Rixathon contains sodium

This medication contains 52.6mg of sodium per 10ml vial and 263.2mg of sodium per 50ml vial. This is equivalent to 2.6% (per 10ml vial) and 13.2% (per 50ml vial) of the maximum recommended daily sodium intake for an adult.

How Rixathon is administered

Rixathon will be administered by a doctor or nurse experienced in the use of this medication. They will keep you under observation during the administration of Rixathon in case you experience any adverse effects.

Rixathon will be administered always by intravenous infusion (drip).

Medications administered before each Rixathon infusion

Before the administration of Rixathon, other medications (premedication) will be administered to prevent or reduce possible adverse effects.

Quantity and frequency of treatment

a)If you are being treated for non-Hodgkin lymphoma

•If you are only being treated with Rixathon

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

•If you are being treated with Rixathon and chemotherapy

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

•If you respond well to treatment, you may continue treatment with Rixathon as maintenance every 2 or 3 months for 2 years. Your doctor may modify it depending on your response to the medication.

• If you are under 18 years old, Rixathon will be administered with chemotherapy. You will receive Rixathon up to 6 times during a period of 3.5 to 5.5 months.

b)If you are being treated for chronic lymphocytic leukemia (CLL)

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

c)If you are being treated for rheumatoid arthritis

Each treatment cycle consists of two infusions, both separated by a 2-week interval. Treatment cycles with Rixathon can be repeated. Depending on the signs and symptoms of your disease, your doctor may decide if you should receive a higher dose of Rixathon at some point, which may occur after several months.

d)If you are being treated for granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (PAM)

The treatment with Rixathon uses four separate infusions, administered at weekly intervals. Corticosteroids are usually administered by injection before starting treatment with Rixathon. To treat your disease, your doctor may start administering corticosteroids orally at any time.

If you are 18 years or older and respond well to treatment, you may be administered Rixathon as maintenance treatment. This will be administered in the form of 2 separate infusions with 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 Rixathon (up to 5 years), depending on your response to the medication.

e)If you are being treated for bullous pemphigoid (BP)

Each treatment cycle consists of two infusions, both separated by a 2-week interval. If you respond well to treatment, you may be administered Rixathon as maintenance treatment. This will be administered 1 year and 18 months after the 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, this medicine can cause side effects, although not everyone will experience them.

The majority of these side effects are of mild to moderate intensity, but some of them can be severe and require treatment. In rare cases, some of these reactions have been fatal.

Infusion Reactions

During or within 24 hours after the infusion, you may experience fever, chills, and shivering. Other less frequent side effects that some patients may experience are: pain at the infusion site, blisters, and itching on the skin, nausea and vomiting, fatigue, headache, difficulty breathing, increased blood pressure, wheezing, throat discomfort, swelling of the tongue or throat, itching or congestion in the nose, vomiting, flushing, or palpitations. If you have any heart disease or angina, these reactions may worsen.Inform the person administering the infusion immediately if you or your child experience any of these symptoms, as you may need a slower infusion or to stop it. You may need additional treatment with antihistamines or paracetamol. When the symptoms disappear or improve, the infusion can continue. After the second infusion, it is less likely that these reactions will occur. Your doctor may decide to stop your treatment with Rixathon if you have severe infusion reactions.

Infections

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

•fever, cough, sore throat, burning sensation 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 severe brain infection (leucoencephalopathy multifocal progressive or LMP).

• fever, headache, stiff neck,discoordination (ataxia), changeofpersonality, hallucinations,alteration of consciousness, convulsions, or coma– eventhough this could be dueto a severe brain infection (enteroviral meningoencephalitis), which can be fatal.

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

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

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

Skin Reactions

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

Other Side Effects

a)If you or your child are being treated for non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL)

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

•bacterial or viral infections, bronchitis

•low white blood cell count with or without fever or platelet count

•nausea

•hair loss on the scalp, chills, headache

•decreased immunity due to a decrease in the number 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, common cold, bronchitis infections, fungal infections, unknown origin infections, nasal sinus inflammation, hepatitis B

•low red blood cell count (anemia), low count of all blood cells

•allergic reactions (hypersensitivity)

•high blood sugar levels, weight loss, peripheral and facial edema, increased levels of LDH enzyme in the blood, decreased calcium levels in the blood

•abnormal sensations in the skin, numbness, tingling, pinching, burning, progressive increase of these sensations in the skin, decreased sense of touch

•agitation, difficulty falling asleep

•flushing of the face and other areas of the skin due to vasodilation

•feeling of dizziness or anxiety

•excessive tearing, alterations in the lacrimal duct, conjunctivitis inflammation of the eyes

•ringing in the ear, ear pain

•cardiac alterations, such as myocardial infarction, irregular heart rate, abnormally rapid heartbeats

•increased or decreased blood pressure, especially upon standing

•bronchospasm, inflammation, irritation in the lungs, throat, and/or nasal cavities, shortness of breath, nasal discharge

•vomiting, diarrhea, abdominal pain, irritation, or ulceration in the throat and mouth, difficulty swallowing, constipation, indigestion

•alimentary disorders: not eating enough, leading to weight loss

•hiccups, increased sweating, nocturnal sweating

•muscle problems, such as muscle tension, pain in the joints or muscles, back and neck pain

•general malaise or feeling of unease or fatigue, agitation, catarrhal symptoms

•multi-organ insufficiency

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

•coagulation disorders, decreased production of red blood cells, increased destruction of red blood cells (aplastic anemia), lymph node inflammation/hypertrophy

•decreased interest in usual activities, nervousness

•alterations in the sense of taste, such as changes in the taste of food

•cardiac problems, such as reduced heart rate or chest pain (angina)

•asthma, insufficient oxygen supply to organs

•gastric distension

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

•temporary increase in the amount of a type of antibody in the blood (called immunoglobulins – 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 that cause skin symptoms

•respiratory insufficiency

•intestinal wall damage (perforation)

•severe skin problems that can cause blisters that may be potentially fatal. You may experience redness, usually associated with blisters, on the skin or mucous membranes, such as in the mouth, genital area, or eyelids, and may be accompanied by fever.

•kidney problems

•severe vision loss

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

•delayed decrease in white blood cells in the blood

•reversible decrease in platelet count after infusion, but in rare cases, it may be fatal

• •hearing loss, loss of other sensesinfection/inflammationof the brain and meninges(enteroviral meningoencephalitis)

Children and adolescents with non-Hodgkin lymphoma (NHL):

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

b)If you are being treated for rheumatoid arthritis

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

•bacterial infections such as pneumonia (bacterial)

•urinary tract infections (painful urination)

•allergic reactions, which are more likely to occur during the infusion, but may occur up to 24 hours after the infusion

•changes in blood pressure, nausea, rashes, fever, hot flashes, nasal congestion, sneezing, shivering, rapid heartbeat, and fatigue.

•headache

•changes in laboratory tests conducted by your doctor. These include a decrease in the amount of certain specific proteins in the blood (immunoglobulins) that help protect against infection.

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

•bacterial infections such as bronchitis inflammation

•sensation of warmth, intermittent pain, in the nose, cheeks, and eyes (sinusitis), abdominal pain, vomiting, and diarrhea, respiratory problems

•foot fungal infections (athlete's foot)

•increased cholesterol levels in the blood

•abnormal sensations in the skin, such as numbness, tingling, pinching, or burning, sciatica, headache, dizziness

•hair loss

•anxiety, depression

•indigestion, diarrhea, acid reflux, irritation, or ulceration of the throat and mouth

•abdominal, back, muscle, or joint pain

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

•fluid retention in the face and body

•inflammation, irritation, or pressure in the lungs and throat, cough

•skin reactions, including urticaria, pruritus, and skin eruptions

•allergic reactions, including hives or difficulty breathing, facial and tongue swelling, collapse

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

•a group of symptoms that occur a few weeks after rituximab infusion and include allergic reactions such as urticaria, pruritus, joint pain, lymph node inflammation, and fever

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

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

•severe viral infection

• infection/inflammationof the brain and meninges(enteroviral meningoencephalitis)

Other rare side effects reported due to rituximab include a decrease in the number of white blood cells in the blood (neutrophils) that help fight infections. Some infections may be severe (see information onInfectionswithin this section).

c)If you or your child are being treated for granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (PAM)

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

•bacterial infections, such as pneumonia, urinary tract infections (painful urination), common cold, or herpes infections

•allergic reactions, which are more likely to occur during the infusion, but may occur up to 24 hours after the infusion

•diarrhea

•cough or difficulty breathing

•nasal hemorrhages

•hypertension

•joint or back pain

•muscle spasms or tremors

•dizziness

•tremors (especially in the hands)

•difficulty sleeping (insomnia)

•inflammation of the hands or feet

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

•indigestion

•constipation

•skin eruptions, including acne or spots

•flushing or redness of the skin

•fever

•nasal congestion or discharge

•muscle tension or pain

•pain in the muscles, hands, or feet

•low red blood cell count (anemia)

•low platelet count in the blood

•increased potassium levels in the blood

•changes in heart rate or abnormally rapid heartbeats

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

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

•reappearance of previous hepatitis B infection

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

•severe viral infection

• infection/inflammationof the brain and meninges(enteroviral meningoencephalitis)

Children and adolescents with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (PAM):

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

d)If you are being treated for pemphigus vulgaris

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

• allergic reactions, which are more likely to occur during the infusion, but may occur up to 24 hours after the infusion
• headache
• bacterial infections, such as pneumonia
• long-lasting depression
• hair loss

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

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

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

• severe viral infection
• infection/inflammationof the brain and meninges(enteroviral meningoencephalitis)

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

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendixV. 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 and the vial label after CAD. The expiration date is the last day of the month indicated.

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

Store the vial within the outer packaging to protect it from light.

This medication can also be stored in the original box outside the refrigerator for a maximum of 30°C for a single period of up to seven days, but not beyond the initial expiration date. In this situation, it should not be re-refrigerated. Write the new expiration date on the box including day/month/year. Dispose of this medication if it has not been used by the new expiration date or the expiration date printed on the box, whichever occurs first.

Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Rixathon

•The active principle of Rixathon is rituximab.

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

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

•The other components are sodium citrate, polisorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, and water for injection (see section2).

Appearance of the product and contents of the container

Rixathon is a transparent, colorless to slightly yellowish solution that is presented as a sterile concentrate for solution for infusion (concentrate).

10ml vial: packaging of 2or 3vials.

50ml vial: packaging of 1or 2vials.

Marketing Authorization Holder

SandozGmbH

Biochemiestr.10

6250Kundl

Austria

Responsible for Manufacturing

SandozGmbHSchaftenau

Biochemiestr.10

6336Langkampfen

Austria

Lek Pharmaceuticals d.d. Ljubljana

Verovškova 57

1526 Ljubljana

Eslovenia

Last review date of this leaflet:.

Other sources of information

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

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