B. PACKAGE LEAFLET

Package leaflet: information for the patient

MabThera 100 mg concentrate for solution for infusion, 500 mg concentrate for solution for infusion

rituximab
Please read all of this leaflet carefully before receiving this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What MabThera is and what it is used for
What you need to know before you are given MabThera
How MabThera is administered
Possible side effects
How to store MabThera
Contents of the pack and other information

1. What MabThera is and what it is used for

What MabThera is
MabThera contains the active substance "rituximab", a type of protein called a "monoclonal antibody" that binds to the surface of certain white blood cells, specifically B-lymphocytes. When rituximab binds to the surface of these cells, it causes their death.

What MabThera is used for
MabThera can be used to treat a variety of conditions in adults and children. Your doctor may prescribe MabThera for the treatment of:

a) Non-Hodgkin’s lymphoma
Non-Hodgkin’s lymphoma is a disease of the lymphatic tissue (part of the immune system) that involves B-lymphocytes, a specific type of white blood cell.
In adults, MabThera may be given as monotherapy (alone) or in combination with other medicines collectively referred to as "chemotherapy".
In adult patients who respond to treatment, MabThera may be used as maintenance therapy for 2 years following completion of initial treatment.
In children and adolescents, MabThera is administered in combination with chemotherapy.

b) Chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia. CLL involves a specific type of lymphocyte, the B-cell, which originates in the bone marrow and matures in the lymph nodes. Patients with CLL have too many abnormal lymphocytes, which accumulate mainly in the bone marrow and blood.
The proliferation of these abnormal B-lymphocytes causes the symptoms you may experience. MabThera, in combination with chemotherapy, destroys these cells, which are then gradually removed from the body by biological processes.

c) Rheumatoid arthritis
MabThera is used to treat rheumatoid arthritis. Rheumatoid arthritis is a disease that affects the joints. B-lymphocytes are responsible for some of the symptoms you have. MabThera is used to treat rheumatoid arthritis in people who have already tried other medicines that either stopped working, were not effective enough, or caused undesirable side effects. MabThera is usually taken together with another medicine called methotrexate.
MabThera slows down joint damage caused by rheumatoid arthritis and improves your ability to carry out normal daily activities.
The best response to MabThera has been observed in patients who have tested positive in blood tests for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP). Both tests are commonly positive in rheumatoid arthritis and help confirm the diagnosis.

d) Granulomatosis with polyangiitis and microscopic polyangiitis
MabThera is used to treat adults and children aged 2 years and older with granulomatosis with polyangiitis (previously known as Wegener’s disease) or microscopic polyangiitis, in combination with glucocorticoids.
Granulomatosis with polyangiitis and microscopic polyangiitis are two forms of blood vessel inflammation that primarily affect the lungs and kidneys, but may also involve other organs. B-lymphocytes play a role in causing these conditions.

e) Pemphigus vulgaris
MabThera is used to treat patients with moderate to severe pemphigus vulgaris. Pemphigus vulgaris is an autoimmune disease that causes painful blisters to form on the skin and mucous membranes (lining tissues) of the mouth, nose, throat, and genitals.

2. What you should know before being given MabThera

Do not take MabThera:

if you are allergic to rituximab, to other proteins similar to rituximab, or to any of the other ingredients of this medicine (listed in section 6);
if you currently have a severe active infection;
if your immune system is weak;
if you suffer from severe heart failure or severe uncontrolled heart disease and you have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris.

Do not take MabThera if any of the above conditions apply to you. If you have any doubts, consult your doctor, pharmacist, or nurse before receiving MabThera.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before receiving MabThera:

if you have previously had hepatitis infection or may currently have one, as in a small number of cases MabThera may cause reactivation of hepatitis B, which in very rare cases can lead to death. Patients with a prior history of hepatitis B infection will be closely monitored by the doctor for signs of reactivation;
if you have previously had heart problems (such as angina, palpitations, or heart failure) or respiratory problems.

If any of the above conditions apply to you (or if you have any doubts), speak with your doctor, pharmacist, or nurse before receiving MabThera. Your doctor may need to pay special attention during your treatment with MabThera.

Also talk to your doctor if you think you may need any vaccinations in the near future, including those required for travel to other countries. Some vaccines should not be given at the same time as MabThera or in the months following MabThera treatment. Your doctor will determine whether you can receive any vaccine before starting MabThera.

If you have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris, talk to your doctor

if you think you have an infection, even a mild one such as a cold. The cells affected by MabThera play a role in fighting infections, and it is necessary to wait until the infection has resolved before taking MabThera. Also, inform your doctor if you have had frequent infections in the past or if you suffer from severe infections.

Children and adolescents

Non-Hodgkin's lymphoma
MabThera may be used to treat children and adolescents aged 6 months and older with non-Hodgkin's lymphoma, specifically CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL)/Burkitt leukemia (acute mature B-cell leukemia; BAL), or Burkitt-like lymphoma (BLL).

Talk to your doctor, pharmacist, or nurse before administering this medicine if you or your child are under 18 years of age.

Granulomatosis with polyangiitis or microscopic polyangiitis
MabThera may be used to treat children and adolescents aged 2 years and older with granulomatosis with polyangiitis (previously called Wegener’s disease) or microscopic polyangiitis. Currently, limited information is available regarding the use of MabThera in children and adolescents with other diseases.

Talk to your doctor, pharmacist, or nurse before administering this medicine if you or your child are under 18 years of age.

Other medicines and MabThera

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines, including those without a prescription and herbal medicines, as MabThera may affect how some medicines work, and some medicines may in turn affect how MabThera works.

In particular, inform your doctor:

if you are taking medicines for high blood pressure. You may be asked to stop taking these medicines for 12 hours before receiving MabThera, as some people may experience a drop in blood pressure during MabThera infusion;
if you have previously taken medicines that affect the immune system—such as chemotherapy or immunosuppressive drugs.

If any of the above conditions apply to you (or if you have any doubts), speak with your doctor, pharmacist, or nurse before receiving MabThera.

Pregnancy and breastfeeding

You must inform your doctor or nurse if you are pregnant, suspect you may be pregnant, or are planning a pregnancy, as MabThera can cross the placenta and may affect the unborn child.

If there is a possibility you could become pregnant, you and your partner should use an effective method of contraception during treatment with MabThera and for 12 months after the last dose of MabThera.

MabThera passes into breast milk in very small amounts. Since the long-term effects on infants who are breastfed are unknown, as a precaution, breastfeeding is not recommended during treatment with MabThera and for 6 months after treatment.

Driving and using machines

It is not known whether MabThera has an effect on the ability to drive or use tools and machinery.

MabThera contains sodium

This medicine contains 52.6 mg of sodium (a key component of table salt) per 10 mL vial and 263.2 mg of sodium per 50 mL vial, equivalent to 2.6% and 13.2% of the maximum daily recommended dietary intake of sodium for an adult, respectively.

3. How MabThera is administered

Administration
MabThera will be administered to you by a doctor or a nurse experienced in the use of this treatment.
You will be closely monitored during administration of the medicine to detect any possible
adverse reactions.
MabThera is always administered by intravenous infusion (slow drip into a vein).

Medicines administered before each MabThera infusion
Before each MabThera infusion, you will be given other medicines (premedication) to prevent or reduce
the occurrence of possible adverse reactions.

Dose and frequency of treatment
a) If you are being treated for non-Hodgkin’s lymphoma

If you are receiving MabThera alone
MabThera will be administered once a week for 4 weeks. Repeated treatment cycles with MabThera may be possible.
If you are receiving MabThera in combination with chemotherapy
You will receive MabThera on the same day as your chemotherapy; administration usually occurs every 3 weeks for up to 8 times.
If you respond well to treatment, MabThera may be given as maintenance therapy every 2 or 3 months for two years. Depending on your response to the medicine, your doctor may adjust this treatment schedule.
If you are under 18 years of age, you will receive MabThera in combination with chemotherapy. You will receive MabThera up to 6 times within a period of 3.5–5.5 months.

b) If you are being treated for chronic lymphocytic leukemia
If you are being treated with MabThera in combination with chemotherapy, you will receive MabThera infusions on Day 0 of Cycle 1, then on Day 1 of each cycle for a total of 6 cycles. Each cycle lasts 28 days. Chemotherapy must be administered after the MabThera infusion. Your doctor will decide whether you should also receive concomitant supportive therapy.

c) If you are being treated for rheumatoid arthritis
Each treatment cycle consists of two separate infusions given 2 weeks apart. Repeated treatment cycles with MabThera may be given. Based on disease signs and symptoms, your doctor will determine when to administer further cycles. This may occur after several months.

d) If you are being treated for granulomatosis with polyangiitis or microscopic polyangiitis
Treatment with MabThera consists of four separate infusions given weekly. Corticosteroids will be administered by injection before starting MabThera treatment. Oral corticosteroids may be started at any time, as decided by your doctor, to manage your condition.
If you are 18 years of age or older and respond well to treatment, MabThera may be administered as maintenance therapy. This will consist of two separate infusions given 2 weeks apart, followed by one infusion every 6 months for at least 2 years. Depending on your response to the medicine, your doctor may decide to extend MabThera treatment (up to a maximum duration of 5 years).

e) If you are being treated for pemphigus vulgaris
Each treatment cycle consists of two separate infusions given 2 weeks apart. If you respond well to treatment, MabThera may be administered as maintenance therapy at 1 year and 18 months after initial treatment, and subsequently, if necessary, every 6 months. Depending on your response to the medicine, your doctor may modify this administration schedule.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most side effects are mild or moderate, but in some cases they can be serious and require treatment. Rarely, some of these reactions have been fatal.

Infusion reactions
During or within the first 24 hours after the infusion, you may develop fever, chills, and shaking. Less frequently, some patients may experience pain at the infusion site, blistering, itching, nausea, fatigue, headache, difficulty breathing, high blood pressure, wheezing, throat irritation, swelling of the tongue or throat, itchy or runny nose, vomiting, flushing, or palpitations, heart attack, or low platelet count. If you have heart disease or angina, these conditions may worsen. If you or your child experience any of these symptoms, inform immediately the person administering the infusion, as it may be necessary to slow down or stop the infusion. Additional treatment may be required, for example with an antihistamine or paracetamol. Once these symptoms have resolved or improved, the infusion may be resumed. These reactions are less likely after the second infusion. Your doctor may decide to discontinue treatment with MabThera if these reactions are severe.

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

fever, cough, sore throat, burning when urinating, feeling weak or generally unwell;
memory loss, thinking disorders, difficulty walking, or loss of vision – these may be due to a rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML);
fever, headache, stiff neck, lack of coordination (ataxia), personality changes, hallucinations, altered consciousness, seizures, or coma – these may be due to a serious brain infection (enteroviral meningoencephalitis), which can be fatal.

You may be more prone to infections during treatment with MabThera.
These are often colds, but cases of pneumonia, urinary tract infections, and serious viral infections have occurred. These conditions are listed below under the section “Other side effects”.
If you are being treated for rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or pemphigus vulgaris, you will find this information also in the Patient Alert Card provided by your doctor. It is important that you carry this alert card with you and show it to family members or anyone caring for you.

Skin reactions
Very rarely, serious skin reactions with blistering may occur, which can be life-threatening. Redness, often associated with blisters, may appear on the skin or mucous membranes, such as inside the mouth, in the genital area, or around the eyelids, and may be accompanied by fever. Inform your doctor immediately if any of these symptoms occur.

Other side effects

a) If you or your child is being treated for non-Hodgkin’s lymphoma or chronic lymphocytic leukemia

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

bacterial or viral infections, bronchitis,
low white blood cell count, with or without fever, or low platelet count (blood cells),
feeling unwell (nausea),
areas of hair loss on the scalp, chills, headache,
reduced immune defenses – due to decreased levels of certain antibodies called “immunoglobulins” (IgG) in the blood, which help the body protect against infections.

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

blood infections (sepsis), lung infection, shingles (herpes zoster), cold, bronchial infection, fungal infections, infections of unknown origin, 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, facial and body swelling, elevated levels of the enzyme “LDH” in the blood, low blood calcium levels,
abnormal skin sensations – such as numbness, tingling, prickling, burning, sensation of stretched skin, reduced sense of touch,
restlessness, difficulty falling asleep,
marked redness of the face and other skin areas, due to blood vessel dilation,
dizziness or anxiety,
increased tear production, tear duct problems, inflamed eye (conjunctivitis),
ringing in the ears, ear pain,
heart problems – such as heart attack, irregular or rapid heartbeat;
high or low blood pressure (particularly low blood pressure when standing),
tightening of the airway muscles causing wheezing (bronchospasm), inflammation, irritation of lungs, throat, and sinuses, shortness of breath, runny nose,
vomiting, diarrhea, stomach pain, irritation or ulcers in the throat and mouth, difficulty swallowing, constipation, indigestion,
eating disorders: inadequate food intake leading to weight loss,
hives, increased sweating, night sweats,
muscle problems – such as muscle tension, joint or muscle pain, back and neck pain,
tumour pain,
general discomfort, feeling uneasy or tired, tremors, flu-like symptoms,
multi-organ failure.

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

blood clotting problems, reduced red blood cell production and increased red blood cell destruction (hemolytic and aplastic anemia), swelling or enlarged lymph nodes,
depressed mood and loss of interest or pleasure in activities, nervousness,
taste disturbances – such as altered sense of taste,
heart problems – such as slow heart rate or chest pain (angina),
asthma, insufficient oxygen supply to body organs,
stomach swelling.

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

temporary increase in certain types of antibodies (immunoglobulins – IgM) in the blood, chemical imbalance in the blood due to the breakdown of dead tumor cells,
nerve damage in arms and legs, facial paralysis,
heart failure,
inflammation of blood vessels, including those causing skin symptoms,
respiratory failure,
damage to the intestinal wall (perforation),
severe skin reactions with blistering, which can be life-threatening. Redness, often associated with blisters, may appear on the skin or mucous membranes, such as inside the mouth, in the genital area, or around the eyelids, and may be accompanied by fever,
kidney failure,
severe loss of vision.

Not known (frequency cannot be estimated from available data):

delayed decrease in white blood cells,
reduced platelet count immediately after infusion – this condition may be reversible, but in rare cases can be fatal,
hearing loss, loss of other senses,
infection/inflammation of brain and meninges (enteroviral meningoencephalitis).

Children and adolescents with non-Hodgkin’s lymphoma
In general, the side effects observed in children and adolescents with non-Hodgkin’s lymphoma are similar to those seen in adults with non-Hodgkin’s lymphoma or chronic lymphocytic leukemia. The most commonly observed side effects were fever associated with low levels of a type of white blood cells (neutrophils), inflammation or mouth ulcers, and allergic reactions (hypersensitivity).

b) If you are being treated for rheumatoid arthritis

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

lung infection (bacterial),
pain when urinating (urinary tract infections),
allergic reactions, which are likely to occur during the infusion but may occur up to 24 hours after,
changes in blood pressure, nausea, skin rashes, fever, itching, stuffy or runny nose, sneezing, tremor, rapid heartbeat, and fatigue,
headache,
changes in laboratory tests required by your doctor. These include a reduction in certain specific proteins in the blood (immunoglobulins) that help protect against infections.

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

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

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

fluid retention in the face and body,
inflammation, irritation, and/or tightness in lungs and throat, cough,
skin reactions, including hives, itching, skin rashes,
allergic reactions including wheezing or shortness of breath, swelling of face and tongue, collapse.

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

a complex of symptoms occurring within a few weeks after MabThera infusion, including allergic-type reactions such as skin rashes, itching, joint pain, swollen lymph nodes, and fever,
severe skin reactions with blistering, which can be life-threatening. Redness, often associated with blisters, may appear on the skin or mucous membranes, such as inside the mouth, in the genital area, or around the eyelids, and may be accompanied by fever.

Not known (frequency cannot be estimated from available data):

serious viral infections,
infection/inflammation of brain and meninges (enteroviral meningoencephalitis).

Other side effects rarely reported with MabThera treatment include a reduction in the number of white blood cells (neutrophils) in the blood, which help fight infections. Some infections may be serious (please refer to the information on Infections within this section).

c) If you or your child is being treated for granulomatosis with polyangiitis or microscopic polyangiitis

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

infections, such as chest infections, urinary tract infections (pain when urinating), colds, and herpes infections,
allergic reactions that are likely to occur during the infusion, but may occur up to 24 hours after,
diarrhea,
cough or shortness of breath,
nosebleeds,
increased blood pressure,
joint or back pain,
muscle tension or tremors,
dizziness,
tremors (often in the hands),
difficulty sleeping (insomnia),
swelling of hands and ankles.

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

indigestion,
constipation,
skin rashes, including acne or spots,
hot flushes or skin redness,
fever,
stuffy or runny nose,
muscle tension or muscle pain,
muscle pain or pain in 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 abnormally rapid heartbeat.

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

severe skin reactions with blistering, which can be life-threatening. Redness, often associated with blisters, may appear on the skin or mucous membranes, such as inside the mouth, in the genital area, or around the eyelids, and may be accompanied by fever,
reactivation of a previous hepatitis B infection.

Not known (frequency cannot be estimated from available data):

serious viral infections;
infection/inflammation of brain and meninges (enteroviral meningoencephalitis).

Children and adolescents with granulomatosis with polyangiitis or microscopic polyangiitis
In general, side effects in children and adolescents with granulomatosis with polyangiitis or microscopic polyangiitis are similar in type to those observed in adults with these conditions. The most frequently observed side effects were infections, allergic reactions, and feeling unwell (nausea).

d) If you are being treated for pemphigus vulgaris

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

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

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

infections, such as colds, herpes infections, eye infections, oral thrush, and urinary tract infections (pain during urination),
mood disorders, such as irritability and depression,
skin disorders, such as itching, hives, and benign cysts,
fatigue or dizziness,
fever,
joint or back pain,
headache,
abdominal pain,
muscle pain,
abnormally rapid heartbeat.

Not known (frequency cannot be estimated from available data):

serious viral infections,
infection/inflammation of brain and meninges (enteroviral meningoencephalitis).

MabThera may also cause changes in laboratory tests required by your doctor.
If you are taking MabThera in combination with other medicines, some of the side effects you experience may be due to the other medicines.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MabThera

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze. Keep the vial in the outer packaging to protect it from light.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What MabThera contains

The active substance 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 excipients are sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid and water for injections. See section 2 “MabThera contains sodium”.

Description of the appearance of MabThera and contents of the pack
MabThera is a clear, colourless solution supplied as a concentrate for infusion solution.
10 mL vials are available in packs of 2 vials.
50 mL vials are available in packs of 1 vial.

Marketing Authorisation Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer
Roche Pharma AG
Emil-Barell-Str. 1
79639 Grenzach-Wyhlen
Germany

For further information on MabThera, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
N.V. Roche S.A. UAB “Roche Lietuva”
Tél/Tel: +32 (0) 2 525 82 11 Tel: +370 5 2546799

България Luxembourg/Luxemburg
Рош България ЕООД (Voir/siehe Belgique/Belgien)
Тел: +359 2 474 5444

Česká republika Magyarország
Roche s. r. o. Roche (Magyarország) Kft.
Tel: +420 - 2 20382111 Tel: +36 - 1 279 4500

Danmark Malta
Roche Pharmaceuticals A/S (See Ireland)
Tlf: +45 - 36 39 99 99

Deutschland Nederland
Roche Pharma AG Roche Nederland B.V.
Tel: +49 (0) 7624 140 Tel: +31 (0) 348 438050

Eesti Norge
Roche Eesti OÜ Roche Norge AS
Tel: + 372 - 6 177 380 Tlf: +47 - 22 78 90 00

Ελλάδα Österreich
Roche (Hellas) A.E. Roche Austria GmbH
Τηλ: +30 210 61 66 100 Tel: +43 (0) 1 27739

España Polska
Roche Farma S.A. Roche Polska Sp.z o.o.
Tel: +34 - 91 324 81 00 Tel: +48 - 22 345 18 88

France Portugal
Roche Roche Farmacêutica Química, Lda
Tél: +33 (0)1 47 61 40 00 Tel: +351 - 21 425 70 00

Hrvatska România
Roche d.o.o. Roche România S.R.L.
Tel: + 385 1 47 22 333 Tel: +40 21 206 47 01

Ireland Slovenija
Roche Products (Ireland) Ltd. Roche farmacevtska družba d.o.o.
Tel: +353 (0) 1 469 0700 Tel: +386 - 1 360 26 00

Ísland Slovenská republika
Roche Pharmaceuticals A/S Roche Slovensko, s.r.o.
c/o Icepharma hf Tel: +421 - 2 52638201
Sími: +354 540 8000

Italia Suomi/Finland
Roche S.p.A. Roche Oy
Tel: +39 - 039 2471 Puh/Tel: +358 (0) 10 554 500

Kύπρος Sverige
Roche (Hellas) A.E. Roche AB
Τηλ: +30 210 61 66 100 Tel: +46 (0) 8 726 1200

Latvija United Kingdom (Northern Ireland)
Roche Latvija SIA Roche Products (Ireland) Ltd.
Tel: +371 - 6 7 039831 Tel: +44 (0) 1707 366000

More detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu/en .
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

Package leaflet: information for the patient

MabThera 1400 mg solution for subcutaneous injection

rituximab
Please read this leaflet carefully before this medicine is administered to you, as it
contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What MabThera is and what it is used for
What you need to know before you are administered MabThera
How MabThera is administered
Possible side effects
How to store MabThera
Contents of the pack and other information

1. What MabThera is and what it is used for

What MabThera is
MabThera contains the active substance "rituximab", a type of protein called a "monoclonal antibody". Rituximab binds to the surface of a type of white blood cells called "B-lymphocytes". When rituximab binds to the surface of these cells, it causes their death.
MabThera is available as an infusion medicine (MabThera 100 mg or MabThera 500 mg, concentrate for solution for infusion) and as a medicine given by injection under the skin (MabThera 1400 mg or MabThera 1600 mg, solution for subcutaneous injection).

What MabThera is used for
MabThera 1400 mg is used to treat non-Hodgkin's lymphoma in adults,

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

MabThera 1400 mg may be given alone or together with other medicines ("chemotherapy").
At the beginning of treatment, MabThera will always be given to you by infusion (intravenous infusion).
Later, MabThera will be administered by injection under the skin. Your doctor will decide when to start MabThera injections.
After completion of the initial treatment, in patients for whom therapy proves effective, MabThera may be used as maintenance treatment for 2 years.

2. What you should know before being given MabThera

Do not take MabThera

if you are allergic to rituximab or to other proteins similar to rituximab, or to any of the other ingredients of this medicine (listed in section 6);
if you are allergic to hyaluronidase (an enzyme that helps increase the absorption of the injected active substance);
if you currently have a severe active infection;
if you have a weakened immune system.

Do not take MabThera if any of the above apply to you. If you have any doubts, consult your doctor,
pharmacist, or nurse before being administered MabThera.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before being administered MabThera:

if you think you have hepatitis or have had it in the past, as in some cases MabThera may cause reactivation of hepatitis B, a condition which in very rare cases may lead to death. Patients with a history of hepatitis B infection will be closely monitored by the doctor for signs of this infection;
if you have ever suffered from heart disease (e.g. angina, palpitations, or heart failure) or have had breathing problems.

If any of these conditions apply to you, or if you are unsure, discuss them with your doctor, pharmacist, or
nurse before being administered MabThera. Your doctor may need to pay special attention during treatment with MabThera.
Also talk to your doctor if you think you may need any vaccination in the near future, including vaccinations required for travel to other countries. Some vaccines should not be administered at the same time as MabThera or in the months following MabThera treatment. Your doctor will assess whether you can receive any vaccine before starting MabThera.
Children and adolescents
If you or your child are under 18 years of age, discuss this with your doctor, pharmacist, or
nurse before being administered this medicine, as there is limited information available on the use of MabThera in children and adolescents.
Other medicines and MabThera
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines, including non-prescription medicines and herbal remedies, as MabThera may interfere with how other medicines work, and these medicines may in turn interfere with how MabThera works.
In particular, inform your doctor:

if you are taking medicines for high blood pressure. You may be asked to stop taking them 12 hours before receiving MabThera, as during administration of this medicine some people may experience a drop in blood pressure;
if you have ever taken medicines that affect the immune system—such as chemotherapy or immunosuppressive medicines.

If any of these conditions apply to you, or if you are unsure, discuss them with your doctor, pharmacist, or
nurse before being administered MabThera.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, inform your doctor or
nurse. This is because MabThera can cross the placenta and may affect the unborn child.
If there is a possibility you could become pregnant, you must use an effective method of contraception during treatment with MabThera and for 12 months after the last dose of MabThera.
This is because MabThera passes into breast milk in very small amounts.
As the long-term effects on breastfed infants are unknown, as a precautionary measure, breastfeeding is not recommended during treatment with MabThera and for 6 months after treatment.
Driving and using machines
It is not known whether MabThera affects your ability to drive or use tools or machinery.
MabThera contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 11.7 mL vial, i.e. it is practically “sodium-free”.

3. How MabThera is administered

Administration
MabThera will be administered by a doctor or a nurse experienced in the use of this treatment. You will be closely monitored during administration of the medicine in case you experience any adverse reactions.
At the beginning of treatment, MabThera will always be given by intravenous infusion (IV infusion).
Later, MabThera will be administered by subcutaneous injection (injection under the skin) lasting approximately 5 minutes. The glass vial has a removable adhesive label displaying the drug information. The doctor or nurse will transfer this label to the syringe before injection. Your doctor will decide when to start MabThera injections.
The subcutaneous injection is given in the abdominal area, not in other body sites, avoiding areas where the skin is red, bruised, tender, or hardened, as well as areas with moles or scars.

Medicines given before each administration of MabThera
Before each administration of MabThera, you will be given other medicines (premedication) to help prevent or reduce possible side effects.

How much and how often you will receive treatment

MabThera will be administered on the same day as chemotherapy. Chemotherapy is usually given every 3 weeks up to 8 times.
If you respond well to treatment, MabThera may be given as maintenance therapy every 2 or 3 months for two years. Your doctor may modify this schedule depending on your response to the medicine.

If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most side effects are mild or moderate, but in some cases they can be severe and require treatment.
Rarely, some of these reactions have been fatal.

Reactions at the injection site
Many patients experience some local side effects at the site of MabThera injection. These include:
pain, swelling, bruising, bleeding, redness of the skin, itching, and skin rash.
Your doctor may decide to stop treatment with MabThera if these reactions are severe.

Infections
Tell your doctor immediately if you have symptoms of infection, including:

fever, cough, sore throat, burning when you urinate, feeling weak or generally unwell;
memory loss, thinking disorders, difficulty walking, or loss of vision. These could be due to a very rare and serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML);
fever, headache, stiff neck, lack of coordination (ataxia), personality changes, hallucinations, altered consciousness, seizures, or coma – these may be due to a serious brain infection (enteroviral meningoencephalitis), which can be fatal.

You may develop infections more easily during treatment with MabThera. These are often colds, but cases of lung infection or urinary tract infections have also occurred. Such infections are listed in the section “Other side effects”.

Other side effects include:

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

bacterial or viral infections, bronchitis;
low number of white blood cells, with or without fever, or low number of platelets (blood cells);
feeling unwell (nausea);
areas of hair loss on the scalp, chills, headache;
reduced immune defences – due to lower levels in the blood of antibodies called “immunoglobulins” (IgG) that help the body protect itself from infections.

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

blood infections (sepsis), lung infection, herpes zoster, common cold, infections of the bronchial tubes, fungal infections, infections of unknown origin, sinus inflammation, hepatitis B;
low number of red blood cells (anaemia) and low number of all blood cells;
allergic reactions (hypersensitivity);
high blood sugar levels, weight loss, swelling of the face and body, increased levels of the enzyme LDH in the blood, low calcium levels in the blood;
abnormal skin sensations such as numbness, tingling, prickling, burning sensation, feeling of stretched skin, reduced sense of touch;
feeling restless, difficulty falling asleep;
redness of the face and other areas of the skin, as a result of blood vessel dilation;
dizziness, anxiety;
increased tear production, problems with tear duct, inflamed eye (conjunctivitis);
ringing in the ears, ear pain;
heart problems such as heart attack, fast or irregular heartbeat;
high or low blood pressure (reduction in blood pressure especially when standing up);
tightening of the airway muscles causing wheezing (bronchospasm), inflammation, irritation of the lungs, throat or sinuses, shortness of breath, runny nose;
vomiting, diarrhoea, abdominal pain, irritation or ulcers in the throat and mouth, difficulty swallowing, constipation, indigestion;
difficulty eating, inadequate food intake leading to weight loss;
hives, increased sweating, night sweats;
muscle problems such as muscle tension, muscle or joint pain, back and neck pain;
tumour pain;
general feeling of tiredness and discomfort, tremors, flu-like symptoms;
multi-organ failure.

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

problems with blood clotting, reduced production of red blood cells and increased destruction of red blood cells (aplastic haemolytic anaemia), swelling or enlarged lymph nodes;
depressed mood and loss of interest or pleasure in usual activities, nervousness;
taste disturbances, such as altered taste;
heart problems such as slow heartbeat or chest pain (angina);
asthma, insufficient oxygen supply to the body's organs;
swelling of the abdomen.

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

temporary increase in certain types of antibodies in the blood (called immunoglobulins – IgM), chemical changes in the blood due to the breakdown of dead tumour cells;
nerve damage in arms and legs, facial paralysis;
heart failure;
inflammation of blood vessels, including those causing skin symptoms;
respiratory failure;
damage to the gastrointestinal wall (perforation);
severe skin reactions with blistering which may be life-threatening;
kidney failure;
severe loss of vision (a sign of damage to cranial nerves).

Not known (frequency cannot be estimated from the available data):

delayed reduction in white blood cells;
reduced platelet count immediately after infusion – this is reversible, but in rare cases may cause death;
hearing loss, loss of other senses;
infection/inflammation of the brain and meninges (enteroviral meningoencephalitis).

MabThera may also cause changes in the results of laboratory tests prescribed by your doctor.
If you are taking MabThera together with other medicines, some side effects may be due to the other medicines.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MabThera

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after "Exp". The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze. Keep the vial in the outer carton to protect it from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What MabThera 1400 mg solution for subcutaneous injection contains

The active substance is rituximab. Each vial contains 1400 mg/11.7 mL of rituximab. Each mL contains 120 mg of rituximab.
The other ingredients are recombinant human hyaluronidase (rHuPH20), L-histidine, monohydrochloride monohydrate of L-histidine, α,α-trehalose dihydrate, L-methionine, polysorbate 80, water for injections. See section 2 “MabThera contains sodium”.

Description of the appearance of MabThera 1400 mg solution for subcutaneous injection and contents of the pack
MabThera is a ready-to-use liquid, from clear to opalescent, colourless to slightly yellow, supplied as a solution for subcutaneous injection in a clear glass vial with a butyl rubber stopper, aluminium cap seal, and a pink plastic flip-off disk.
Each vial contains 1400 mg/11.7 mL of rituximab. Each pack contains one vial.

Marketing Authorisation Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer
Roche Pharma AG
Emil-Barell-Str. 1
79639 Grenzach-Wyhlen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
N.V. Roche S.A.
Tél/Tel: +32 (0) 2 525 82 11

България (Bulgaria)
Рош България ЕООД
Тел: +359 2 474 5444

Česká republika (Czech Republic)
Roche s. r. o.
Tel: +420 - 2 20382111

Danmark (Denmark)
Roche Pharmaceuticals A/S
Tlf: +45 - 36 39 99 99

Deutschland (Germany)
Roche Pharma AG
Tel: +49 (0) 7624 140

Eesti (Estonia)
Roche Eesti OÜ
Tel: + 372 - 6 177 380

Ελλάδα (Greece)
Roche (Hellas) A.E.
Τηλ: +30 210 61 66 100

España (Spain)
Roche Farma S.A.
Tel: +34 - 91 324 81 00

France
Roche
Tél: +33 (0)1 47 61 40 00

Hrvatska (Croatia)
Roche d.o.o.
Tel: + 385 1 47 22 333

Ireland
Roche Products (Ireland) Ltd.
Tel: +353 (0) 1 469 0700

Ísland (Iceland)
Roche Pharmaceuticals A/S
c/o Icepharma hf
Sími: +354 540 8000

Italia (Italy)
Roche S.p.A.
Tel: +39 - 039 2471

Kύπρος (Cyprus)
Roche (Hellas) A.E.
Τηλ: +30 210 61 66 100

Latvija (Latvia)
Roche Latvija SIA
Tel: +371 - 6 7039831

Lietuva (Lithuania)
UAB “Roche Lietuva”
Tel: +370 5 2546799

Luxembourg/Luxemburg
(See Belgique/Belgien)

Magyarország (Hungary)
Roche (Magyarország) Kft.
Tel: +36 - 1 279 4500

Malta
(See Ireland)

Nederland (Netherlands)
Roche Nederland B.V.
Tel: +31 (0) 348 438050

Norge (Norway)
Roche Norge AS
Tlf: +47 - 22 78 90 00

Österreich (Austria)
Roche Austria GmbH
Tel: +43 (0) 1 27739

Polska (Poland)
Roche Polska Sp.z o.o.
Tel: +48 - 22 345 18 88

Portugal
Roche Farmacêutica Química, Lda
Tel: +351 - 21 425 70 00

România (Romania)
Roche România S.R.L.
Tel: +40 21 206 47 01

Slovenija (Slovenia)
Roche farmacevtska družba d.o.o.
Tel: +386 - 1 360 26 00

Slovenská republika (Slovakia)
Roche Slovensko, s.r.o.
Tel: +421 - 2 52638201

Suomi/Finland
Roche Oy
Puh/Tel: +358 (0) 10 554 500

Sverige (Sweden)
Roche AB
Tel: +46 (0) 8 726 1200

United Kingdom (Northern Ireland)
Roche Products (Ireland) Ltd.
Tel: +44 (0) 1707 366000

More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/en .
This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.

Patient information leaflet

MabThera 1600 mg solution for subcutaneous injection

rituximab
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist or nurse.
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

What MabThera is and what it is used for
What you need to know before you are given MabThera
How MabThera is administered
Possible side effects
How to store MabThera
Contents of the pack and other information

1. What MabThera is and what it is used for

What MabThera is
MabThera contains the active substance “rituximab”, a type of protein called a “monoclonal antibody”.
Rituximab 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.
MabThera is available as an intravenous infusion (MabThera 100 mg or MabThera 500 mg, concentrate for solution for infusion) and as a subcutaneous injection called MabThera 1400 mg or MabThera 1600 mg, solution for subcutaneous injection.

What MabThera is used for
MabThera 1600 mg is used for the treatment of chronic lymphocytic leukemia in adults.

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia. CLL involves a specific type of white blood cell called B-lymphocytes, which originate in the bone marrow and mature in the lymph nodes. Patients with CLL have too many abnormal B-lymphocytes, which accumulate mainly in the bone marrow and blood. The proliferation of these abnormal B-lymphocytes causes the symptoms you may experience. MabThera, in combination with chemotherapy, destroys these cells, which are gradually eliminated from the body through biological processes.

MabThera 1600 mg will be administered to you together with other medicines collectively known as “chemotherapy”.
At the beginning of treatment, MabThera will always be given by intravenous infusion.
Later, MabThera will be administered by subcutaneous injection. Your doctor will decide when to start MabThera injections.

2. What you should know before being given MabThera

Do not take MabThera

if you are allergic to rituximab or to other proteins similar to rituximab, or to any of the other ingredients of this medicine (listed in section 6)
if you are allergic to hyaluronidase (an enzyme that helps increase absorption of the injected active substance),
if you currently have a severe active infection,
if you have a weakened immune system.

Do not take MabThera if any of the above conditions apply to you. If you have any doubts, consult your doctor, pharmacist, or nurse before being administered MabThera.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before being administered MabThera:

if you think you have hepatitis infection or have had it in the past, as in some cases MabThera may cause reactivation of hepatitis B, a condition which in very rare cases can be fatal. Patients with a history of hepatitis B infection will be closely monitored by the doctor for any signs of reactivation;
if you have ever suffered from heart disease (e.g. angina, palpitations, or heart failure) or have had breathing problems.

If any of these conditions apply to you, or if you are unsure, discuss them with your doctor, pharmacist, or nurse before receiving MabThera. Your doctor may need to monitor you particularly closely during treatment with MabThera.
Also speak with your doctor if you think you may need any vaccinations in the near future, including those required for travel to other countries. Some vaccines should not be administered at the same time as MabThera or in the months following MabThera treatment. Your doctor will determine whether you can receive any vaccine before starting MabThera.
Children and adolescents
If you or your child are under 18 years of age, discuss this with your doctor, pharmacist, or nurse before administration of this medicine, as there is limited information available on the use of MabThera in children and adolescents.
Other medicines and MabThera
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines, including non-prescription medicines and herbal products, as MabThera may interfere with how other medicines work, and vice versa.
In particular, inform your doctor:

if you are taking medicines for high blood pressure. You may be asked to stop taking them 12 hours before receiving MabThera, as during administration of this medicine some people may experience a drop in blood pressure;
if you have ever taken medicines that affect the immune system—such as chemotherapy or immunosuppressive medicines.

If any of these conditions apply to you, or if you are unsure, discuss them with your doctor, pharmacist, or nurse before receiving MabThera.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, inform your doctor or nurse. This is because MabThera can cross the placenta and may affect the unborn child.
If there is any possibility that you could become pregnant, you must use an effective method of contraception during treatment with MabThera and for 12 months after the last dose of MabThera.
As MabThera passes into breast milk in very small amounts, and because the long-term effects on breastfed infants are unknown, breastfeeding is not recommended as a precautionary measure during treatment with MabThera and for 6 months after treatment.
Driving and using machines
It is not known whether MabThera affects your ability to drive or operate tools or machinery.
MabThera contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 13.4 mL vial, i.e. it is practically “sodium-free”.

3. How MabThera is administered

Administration
MabThera will be administered by a doctor or a nurse experienced in the use of this treatment. You will be closely monitored during administration of the medicine in case you experience any adverse reactions.
At the beginning of treatment, MabThera will always be given by intravenous infusion (IV infusion).
Subsequently, MabThera will be administered by subcutaneous injection (under the skin), lasting approximately 7 minutes. A removable adhesive label containing drug information is present on the glass vial.
The doctor or nurse will transfer this label to the syringe before injection. Your doctor will decide when to start MabThera injections.
The subcutaneous injection is administered in the abdominal area only, not in other body sites, avoiding areas where the skin is red, bruised, tender, hardened, or where moles or scars are present.

Medicines administered before each dose of MabThera
Before each administration of MabThera, you will be given other medicines (premedication) to prevent or reduce possible side effects.

Dosage and frequency of treatment
If you are being treated with MabThera in combination with chemotherapy, you will receive an infusion of MabThera on Day 0 of Cycle 1, followed by subcutaneous injections on Day 1 of each subsequent cycle. The total number of cycles is 6, and each cycle lasts 28 days. Chemotherapy must be administered after MabThera administration.
Your doctor will decide whether you should receive concomitant maintenance therapy.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most side effects are mild or moderate, but in some cases they may be serious and require treatment. Rarely, some of these reactions have been fatal.

Reactions at the injection site
Many patients experience some local side effects at the injection site of MabThera. These include: pain, swelling, bruising, bleeding, redness of the skin, itching, and skin rash.
Your doctor may decide to stop treatment with MabThera if these reactions are severe.

Infections
Tell your doctor immediately if you have symptoms of infection, including:

fever, cough, sore throat, burning when you urinate, feeling weak or generally unwell;
memory loss, thinking problems, difficulty walking, or loss of vision. These could be due to a very rare and serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML);
fever, headache, stiff neck, lack of coordination (ataxia), personality changes, hallucinations, altered consciousness, seizures, or coma – these may be due to a serious brain infection (enteroviral meningoencephalitis), which can be fatal.

You may be more likely to develop infections during treatment with MabThera. These are often colds, but cases of lung infection or urinary tract infections have also occurred. These infections are listed in the section “Other side effects”.

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

bacterial or viral infections, bronchitis;
low number of white blood cells, with or without fever, or low number of platelets (blood cells);
feeling unwell (nausea);
areas of hair loss on the scalp, chills, headache;
reduced immune defences – due to lower levels in the blood of antibodies called “immunoglobulins” (IgG) that help the body protect itself from infections.

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

blood infections (sepsis), lung infection, shingles (herpes zoster), cold, infections of the bronchial tubes, fungal infections, infections of unknown origin, sinus inflammation, hepatitis B;
low number of red blood cells (anaemia) and low numbers of all blood cells;
allergic reactions (hypersensitivity);
high blood sugar levels, weight loss, swelling of the face and body, increased levels of the enzyme LDH in the blood, low calcium levels in the blood;
abnormal skin sensations such as numbness, tingling, prickling, burning sensation, feeling of tight skin, reduced sense of touch;
feeling restless, difficulty falling asleep;
redness of the face and other areas of the skin due to dilation of blood vessels;
dizziness, anxiety;
increased tear production, problems with tear duct, inflamed eye (conjunctivitis);
ringing in the ears, ear pain;
heart problems such as heart attack, fast or irregular heartbeat;
high or low blood pressure (low blood pressure especially when standing up);
tightening of the airway muscles causing wheezing (bronchospasm), inflammation, irritation of the lungs, throat or sinuses, shortness of breath, runny nose;
vomiting, diarrhoea, abdominal pain, irritation or ulcers in the throat or mouth, difficulty swallowing, constipation, indigestion;
eating disorders, inadequate food intake leading to weight loss;
hives, increased sweating, night sweats;
muscle problems such as muscle tension, muscle or joint pain, back and neck pain;
tumour pain;
general feeling of tiredness and discomfort, tremors, flu-like symptoms;
multi-organ failure.

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

blood clotting problems, reduced production of red blood cells and increased destruction of red blood cells (aplastic haemolytic anaemia), swelling or enlarged lymph nodes;
depressed mood and loss of interest or pleasure in usual activities, nervousness;
taste disturbances, such as altered taste;
heart problems such as slow heart rate or chest pain (angina);
asthma, insufficient oxygen supply to the body's organs;
stomach swelling.

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

temporary increase in certain types of antibodies in the blood (called immunoglobulins – IgM), chemical changes in the blood due to the breakdown of dead tumour cells;
nerve damage in arms and legs, facial paralysis;
heart failure;
inflammation of blood vessels, including those causing skin symptoms;
respiratory failure;
damage to the gastrointestinal wall (perforation);
severe skin reactions with blistering which may be life-threatening;
kidney failure;
severe loss of vision (a sign of damage to cranial nerves).

Not known (frequency cannot be estimated from the available data):

delayed reduction in white blood cells;
reduced platelet count, immediately after infusion – this is reversible, but in rare cases may cause death;
hearing loss, loss of other senses;
infection/inflammation of brain and meninges (enteroviral meningoencephalitis).

MabThera may also cause changes in the results of laboratory tests ordered by your doctor.
If you are taking MabThera together with other medicines, some side effects may be due to the other medicines.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MabThera

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 refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze. Keep the vial in the outer carton to protect it from light.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What MabThera 1600 mg solution for subcutaneous injection contains

The active substance is rituximab. Each vial contains 1600 mg/13.4 mL of rituximab. Each mL contains 120 mg of rituximab.
The other components are recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine monohydrochloride monohydrate, α,α-trehalose dihydrate, L-methionine, polysorbate 80, water for injections. See section 2 “MabThera contains sodium”.

Description of the appearance of MabThera 1600 mg, solution for subcutaneous injection and contents of the pack
MabThera is a ready-to-use liquid, from clear to opalescent, from colourless to yellowish, supplied as a solution for subcutaneous injection in a clear glass vial with a butyl rubber stopper, aluminium seal and blue plastic flip-off cap.
Each vial contains 1600 mg/13.4 mL of rituximab. Each pack contains one vial.

Marketing Authorization Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer
Roche Pharma AG
Emil-Barell-Str. 1
79639 Grenzach-Wyhlen
Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien
N.V. Roche S.A.
Tél/Tel: +32 (0) 2 525 82 11

България
Рош България ЕООД
Тел: +359 2 474 5444

Česká republika
Roche s. r. o.
Tel: +420 - 2 20382111

Danmark
Roche Pharmaceuticals A/S
Tlf: +45 - 36 39 99 99

Deutschland
Roche Pharma AG
Tel: +49 (0) 7624 140

Eesti
Roche Eesti OÜ
Tel: + 372 - 6 177 380

Ελλάδα
Roche (Hellas) A.E.
Τηλ: +30 210 61 66 100

España
Roche Farma S.A.
Tel: +34 - 91 324 81 00

France
Roche
Tél: +33 (0)1 47 61 40 00

Hrvatska
Roche d.o.o.
Tel: + 385 1 47 22 333

Ireland
Roche Products (Ireland) Ltd.
Tel: +353 (0) 1 469 0700

Ísland
Roche Pharmaceuticals A/S
c/o Icepharma hf
Sími: +354 540 8000

Italia
Roche S.p.A.
Tel: +39 - 039 2471

Kύπρος
Roche (Hellas) A.E.
Τηλ: +30 210 61 66 100

Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831

Lietuva
UAB “Roche Lietuva”
Tel: +370 5 2546799

Luxembourg/Luxemburg
(See Belgique/Belgien)

Magyarország
Roche (Magyarország) Kft.
Tel: +36 - 1 279 4500

Malta
(See Ireland)

Nederland
Roche Nederland B.V.
Tel: +31 (0) 348 438050

Norge
Roche Norge AS
Tlf: +47 - 22 78 90 00

Österreich
Roche Austria GmbH
Tel: +43 (0) 1 27739

Polska
Roche Polska Sp.z o.o.
Tel: +48 - 22 345 18 88

Portugal
Roche Farmacêutica Química, Lda
Tel: +351 - 21 425 70 00

România
Roche România S.R.L.
Tel: +40 21 206 47 01

Slovenija
Roche farmacevtska družba d.o.o.
Tel: +386 - 1 360 26 00

Slovenská republika
Roche Slovensko, s.r.o.
Tel: +421 - 2 52638201

Suomi/Finland
Roche Oy
Puh/Tel: +358 (0) 10 554 500

Sverige
Roche AB
Tel: +46 (0) 8 726 1200

United Kingdom (Northern Ireland)
Roche Products (Ireland) Ltd.
Tel: +44 (0) 1707 366000