MABTHERA 100 mg Injectable Solution

Зміст інструкції

1. MabThera 100 mg concentrate for solution for infusion, 500 mg concentrate for solution for infusion
   1. What is MabThera and what is it used for
   2. What you need to know before you are given MabThera
2. MabThera are used to fight infections and it is necessary to wait for the infection to
   1. How MabThera is administered
   2. Possible side effects
   3. How to store MabThera
   4. Package contents and other information
3. MabThera 1400 mg solution for subcutaneous injection
   1. What is MabThera and what is it used for
   2. What you need to know before you are given MabThera
   3. How MabThera is administered
   4. Possible side effects
   5. How to store MabThera
   6. Package contents and other information
4. MabThera 1600 mg solution for subcutaneous injection
   1. What is MabThera and what is it used for
   2. What you need to know before you are given MabThera
   3. How MabThera is administered
   4. Possible side effects
   5. How to store MabThera
   6. Contents of the pack and other information

• B. PACKAGE LEAFLETOR INSTRUCTIONS FOR USE

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

rituximab

Read all of 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, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is MabThera and what is it used for

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

What is MabThera used for
MabThera can be used for the treatment of many and diverse 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 particular type of white blood cell.
In adults MabThera can be given as monotherapy (alone) or with other medicines called collectively “chemotherapy”.
In adult patients where the treatment proves effective, MabThera can be used as maintenance therapy for 2 years after completion of the initial treatment.
In children and adolescents MabThera is given in combination with “chemotherapy”.

b)Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. CLL involves a particular lymphocyte, the B cell, which originates from 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 is the cause of the symptoms you may have. MabThera in association with chemotherapy destroys these cells which are gradually removed from the body by biological processes.

c)Rheumatoid Arthritis
MabThera is used for the treatment of 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, which have stopped working, have not worked well enough, or have caused undesirable effects. MabThera is generally taken with another medicine called methotrexate.
MabThera slows down the damage to the joints caused by rheumatoid arthritis and increases the ability to perform normal daily activities.
The best response to MabThera has been observed in those who have a blood test positive for rheumatoid factor (RF) and/or anti-Cyclic Citrullinated Peptide (anti-CCP). Both tests are commonly positive in rheumatoid arthritis and help in confirming the diagnosis.

d)Granulomatosis with Polyangiitis and Microscopic Polyangiitis
MabThera is used for the treatment of adults and children aged 2 years and older with granulomatosis with polyangiitis (previously called Wegener's disease) or microscopic polyangiitis, in association with glucocorticoids.
Granulomatosis with polyangiitis and microscopic polyangiitis are two forms of inflammation of the blood vessels that mainly affect the lungs and kidneys, but can also affect other organs. B lymphocytes are involved in the cause of these conditions.

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

2. What you need to know before you are 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 serious active infection;
• if your immune system is weak;
• if you suffer from severe heart failure or severe uncontrolled heart disease and 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 are unsure, ask your doctor, pharmacist or nurse before you are given MabThera.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you are given MabThera:

• if you have had a hepatitis infection in the past or might have it now, as in a small number of cases MabThera may cause hepatitis B to become active again, which in very rare cases can be fatal. Patients with a previous hepatitis B infection will be carefully monitored by the doctor for signs of this infection;
• if you have had heart problems in the past (such as angina, palpitations or heart failure) or have had breathing problems.

If any of the above conditions apply to you (or if you are unsure), talk to your doctor, pharmacist or nurse before you are given MabThera. Your doctor may need to pay particular attention to you during treatment with MabThera.
Also talk to your doctor if you think you may need any vaccinations in the near future, including vaccinations needed to travel to other countries. Some vaccines should not be given at the same time as MabThera or in the months following taking MabThera. Your doctor will assess whether you can have any vaccines before taking 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 like a cold. The cells that are affected by

MabThera are used to fight infections and it is necessary to wait for the infection to

heal before taking MabThera. Also, inform your doctor if you have had numerous infections in the past or if you suffer from serious infections.

Children and adolescents

Non-Hodgkin's Lymphoma
MabThera can be used for the treatment of children and adolescents aged 6 months or older with non-Hodgkin's lymphoma, specifically diffuse large B-cell lymphoma (DLBCL) CD20 positive, Burkitt's lymphoma (BL)/Burkitt's leukemia (mature B-cell acute leukemia; BAL) or Burkitt-like lymphoma (BLL).
Talk to your doctor, pharmacist or nurse before administering this medicine if you or your child is less than 18 years of age.

Granulomatosis with polyangiitis or microscopic polyangiitis
MabThera can be used for the treatment of children and adolescents, aged 2 years or older, with granulomatosis with polyangiitis (formerly called Wegener's disease) or microscopic polyangiitis. Currently, there is limited information 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 is less than 18 years of age.

Other medicines and MabThera
Inform your doctor, pharmacist or nurse if you are taking, have recently taken or may take any other medicines, including those available over the counter and herbal medicines, as MabThera may affect the way some medicines work, which in turn may interfere with the way MabThera works.
In particular, inform your doctor:

• if you are taking medicines for the treatment of high blood pressure. You may be asked to stop therapy with these medicines within 12 hours before taking MabThera, as some people experience a drop in blood pressure during the administration of MabThera;
• if you have previously taken medicines that affect the immune system - such as chemotherapy or immunosuppressant drugs.

If any of the above conditions apply to you (or if you have any doubts), talk to your doctor, pharmacist or nurse before you are given 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 have effects on the baby.
If there is a possibility that you may become pregnant, during therapy with MabThera and for 12 months after the last treatment with MabThera, you and your partner must use an effective method of contraception.
MabThera passes into breast milk in very small amounts. Because the long-term effects on breastfed infants 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 affects the ability to drive and use tools or machines.

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

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.
They will carefully monitor you during the administration of the medicine in order to detect
the possible occurrence of undesirable effects.
The administration of MabThera will always be carried out by intravenous drip infusion
(intravenous infusion).

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

Quantity and frequency with which you will receive therapy
a)If you are being treated for non-Hodgkin's lymphoma

• If you are administered only MabTheraMabThera will be administered once a week for 4 weeks. Repeated treatment cycles with MabThera are possible.
• If you are administered MabThera in combination with chemotherapyYou will receive MabThera on the same day you receive chemotherapy; their administration generally occurs every 3 weeks for a maximum of 8 times.
• If you respond well to treatment, MabThera may be administered to you as maintenance therapy every 2 or 3 months for two years. Based on your response to the medicine, the doctor may modify this administration schedule.
• If you are under 18 years of age, you will be administered MabThera with chemotherapy. You will receive MabThera up to 6 times over 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. The doctor will decide
whether you need to receive concomitant supportive therapy.

c)If you are being treated for rheumatoid arthritis
Each treatment cycle involves two separate infusions, administered at an interval of 2
weeks from each other. Repeated treatment cycles with MabThera are possible. Based on the signs and
symptoms of the disease, the doctor will determine when to administer you further cycles. This could
occur several months apart.

d)If you are being treated for granulomatosis with polyangiitis or microscopic polyangiitis
Treatment with MabThera involves four separate infusions given at weekly intervals. Corticosteroids will be administered by injection before the start of treatment with MabThera. Oral administration of corticosteroids may be started at any time by the doctor
to treat your condition.
If your age is 18 years or older and you respond well to treatment, MabThera may be
administered to you as maintenance therapy. This will consist of two separate infusions,
administered at an interval of 2 weeks from each other, followed by an infusion every 6 months for
at least 2 years. Based on your response to the medicine, the doctor may decide to extend the
treatment with MabThera (up to a maximum duration of 5 years).

e)If you are being treated for pemphigus vulgaris
Each treatment cycle involves two separate infusions, administered at an interval of 2
weeks from each other. If you respond well to treatment, MabThera may be administered to you
as maintenance therapy at 1 year and 18 months from the initial treatment and, subsequently, if
necessary, every 6 months. Based on your response to the medicine, the doctor may modify this
administration schedule.
If you have any further questions regarding the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience 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 of the infusion, you may develop fever, chills, and tremor. Less
frequently, some patients may experience pain at the infusion site, blister formation, a feeling of itching, illness (nausea), fatigue, headache, difficulty breathing,
elevated blood pressure, wheezing, throat discomfort, 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, immediately inform
the person administering the infusion, as it may be necessary to slow down or stop the infusion rate. Additional treatment may be required, for example with an
antihistamine or paracetamol. When these symptoms resolve or improve, the infusion can be resumed.
These reactions are less likely to occur after the second infusion. The doctor
may decide to discontinue treatment with MabThera if these reactions are
severe.

Infections
Immediately inform your doctor if you or your child shows signs of an infection,
including:

• fever, cough, sore throat, burning when urinating, feeling weak or unwell;
• memory loss, thinking difficulties, difficulty walking, or vision loss - these may be due to a rare and serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML);
• fever, headache, and stiff neck, lack of coordination (ataxia), personality changes, hallucinations, altered state of consciousness, seizures, or coma - these may be due to a severe 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 pneumonia, urinary tract infections, and serious viral infections have occurred. These conditions are listed below in the section
“Other side effects”.
If you are being treated for rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, or
pemphigus vulgaris, you will also find this information in the Patient Alert Card that your doctor will give you.
It is important to carry this alert card with you and show it to your
family or anyone who cares for you.

Skin reactions
Very rarely, severe skin reactions with blister formation can 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 on the
eyelids, and may be accompanied by fever. Immediately inform your doctor if any
of these symptoms occur.
Other side effects
a)If you or your child are being treated for non-Hodgkin lymphoma or chronic lymphocytic leukemia
Very common side effects (may affect more than 1 in 10 people):

• bacterial or viral infections, bronchitis,
• low number of white blood cells, with or without fever, or platelets (blood cells),
• feeling unwell (nausea),
• areas of hair loss on the scalp, chills, headache,
• weakened immune defenses - due to a decrease in the levels of certain antibodies called “immunoglobulins” (IgG) in the blood, which help the body fight off infections.

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

• blood infections (sepsis), pneumonia, herpes zoster, cold, bronchial infection, fungal infections, infections of unknown origin, sinus inflammation, hepatitis B,
• low number of red blood cells (anemia), low number of all blood cells,
• allergic reactions (hypersensitivity),
• high blood sugar levels, weight loss, swelling of the face and body, high levels of the enzyme “LDH” in the blood, low calcium levels in the blood,
• abnormal sensations on the skin - such as numbness, tingling, prickling, burning, skin tightness, reduced sense of touch,
• feeling restless, difficulty falling asleep,
• marked redness of the face and other skin areas, as a result of blood vessel dilation,
• dizziness or anxiety,
• increased tear production, problems with the tear duct, inflamed eye (conjunctivitis),
• ringing in the ears, ear pain,
• heart problems - such as heart attack, irregular or rapid heartbeat;
• high or low blood pressure (low blood pressure especially when standing up),
• tightening of the muscles of the airways causing wheezing (bronchospasm), inflammation, irritation of lungs, throat and sinuses, shortness of breath, runny nose,
• vomiting, diarrhea, stomach pain, irritation or ulcers of the throat and mouth, difficulty swallowing, constipation, indigestion, • eating disorders: insufficient food intake with resulting weight loss,
• hives, increased sweating, night sweats,
• muscle problems - such as muscle tension, joint or muscle pain, back and neck pain,
• tumor pain,
• feeling unwell, feeling uncomfortable or tired, tremors, flu-like symptoms,
• multiple organ failure.

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

• problems with blood clotting, reduced production of red blood cells and destruction of red blood cells (hemolytic and aplastic anemia) increased, swollen or enlarged lymph nodes,
• depressed mood and loss of interest or pleasure in activities, nervousness,
• taste disorders - such as changes in taste,
• heart problems - such as slowed heart rate or chest pain (angina),
• asthma, insufficient oxygen reaching the body's organs,
• stomach bloating.

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

• a temporary increase in the amount of certain types of antibodies (immunoglobulins - IgM) in the blood, chemical changes 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 blister formation, 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 on the eyelids, and may be accompanied by fever,
• kidney failure,
• severe vision loss.

Not known (the frequency with which these side effects occur is not known):

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

Children and adolescents with non-Hodgkin lymphoma
In general, the side effects recorded in children and adolescents with non-Hodgkin lymphoma
have been similar to those observed in adults with non-Hodgkin lymphoma or chronic lymphocytic leukemia.
The most common side effects observed were fever associated with low levels of a type
of white blood cells (neutrophils), inflammation or sores on the lining of the mouth, and allergic reactions (hypersensitivity).

b)If you are being treated for rheumatoid arthritis
Very common side effects (may affect more than 1 in 10 people):

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

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

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

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

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

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

• a complex of symptoms that occur within a few weeks of the MabThera infusion including allergic-type reactions such as skin rashes, itching, joint pain, swollen lymph nodes, and fever,
• severe skin reactions with blister formation that 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 on the eyelids, and may be accompanied by fever.

Not known (the frequency cannot be defined based on available data):

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

Other side effects rarely reported due to treatment with MabThera include a
reduction in the number of white blood cells in the blood (neutrophils) that help fight infections.
Some infections may be serious (please see the information regarding
Infectionswithin this section).

c)If you or your child are being treated for granulomatosis with polyangiitis or microscopic polyangiitis
Very common side effects (may affect more than 1 in 10 people):

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

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

• indigestion,
• constipation,
• rashes, including acne or spots,
• flushing or redness of the skin,
• fever,
• stuffy or runny nose,
• muscle tension or muscle pain,
• pain in muscles or hands or feet,
• low number of red blood cells (anemia),
• low number of platelets in the blood,
• increased potassium levels in the blood,
• changes in heart rate or faster heartbeat than normal.

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

• severe skin reactions with blister formation that 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 on the eyelids, and may be accompanied by fever,
• recurrence of a previous hepatitis B infection.

Not known (the frequency cannot be defined based on available data):

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

Children and adolescents affected by granulomatosis with polyangiitis or microscopic polyangiitis
In general, in children and adolescents affected by granulomatosis with polyangiitis or microscopic polyangiitis, the undesirable effects have been found to be similar in type to those observed in adults affected by granulomatosis with polyangiitis or microscopic polyangiitis. The undesirable effects observed more frequently were infections, allergic reactions and feeling unwell (nausea).

d) If being treated for pemphigus vulgaris
Very common side effects (may affect more than 1 in 10 people):

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

Common side effects (may affect 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 conditions, such as itching, hives and benign cysts,
• fatigue or dizziness,
• fever,
• joint or back pain,
• headache,
• abdominal pain,
• muscle pain,
• fast heartbeat compared to normal.

Not known (frequency cannot be estimated based on available data):

• severe viral infections,
• infection/inflammation of the brain and meninges (enteroviral meningoencephalitis).

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

Reporting of side effects
If you get any side effects, 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 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 any medicine in 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 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 and colourless solution, supplied as a concentrate for infusion solution.
The 10 mL vials are available in packs of 2 vials.
The 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, 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

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

България
Рош България ЕООД
Тел: +359 2 474 5444

Luxembourg/Luxemburg
(See/siehe Belgique/Belgien)

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

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

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

Malta
(See Ireland)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Latvija
Roche Latvija SIA
Tel: +371 - 6 7 039831

United Kingdom (Northern Ireland)
Roche Products (Ireland) Ltd.
Tel: +44 (0) 1707 366000
More detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu/en .
This leaflet is available in all official languages of the European Union/European Economic Area on the
European Medicines Agency website.

MabThera 1400 mg solution for subcutaneous injection

rituximab

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, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is MabThera and what is it used for

What is MabThera
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 a medicine to be administered by infusion (MabThera 100 mg or
MabThera 500 mg, concentrate for solution for infusion) and as a medicine to be administered
by injection under the skin (MabThera 1400 mg or MabThera 1600 mg, solution for subcutaneous
injection).

What is MabThera used for
MabThera 1400 mg is used for the treatment of 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 can be given alone or with other medicines (“chemotherapy”).
At the beginning of treatment you will always be given MabThera by infusion (intravenous
infusion).
Subsequently, you will be given MabThera by injection under the skin. The doctor
will decide when to start the MabThera injections.
After completion of the initial treatment, in patients in whom therapy proves effective,
MabThera can be used as maintenance treatment for 2 years.

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

Do not take MabThera

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

Do not take MabThera if any of the above apply to you. If you are unsure, ask your doctor, pharmacist or nurse before you are given MabThera.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you are given MabThera:

• if you think you have a hepatitis infection or have had it in the past, as in some cases MabThera may cause reactivation of hepatitis B, a condition that in very rare cases can be fatal. Patients with a previous hepatitis B infection will be carefully 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 not sure, talk to your doctor, pharmacist or nurse before you are given MabThera. Your doctor may need to pay particular attention to you during treatment with MabThera.
Talk to your doctor also if you think you need any vaccinations in the near future, including vaccinations needed to travel to other countries. Some vaccines should not be given at the same time as MabThera or in the months following taking MabThera. The doctor will assess whether you will be able to have any vaccines before taking MabThera.

Children and adolescents
If your age or that of your child is under 18 years, talk to your doctor, pharmacist or nurse before you are given this medicine, as there is limited information regarding the use of MabThera in children and adolescents.

Other medicines and MabThera
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines, including over-the-counter medicines and herbal remedies, as MabThera can interfere with the way other medicines work, and vice versa.
In particular, tell your doctor:

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

If any of these conditions apply to you, or if you are not sure, talk to your doctor, pharmacist or nurse before you are given MabThera.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, tell your doctor or nurse. This is because MabThera can cross the placenta and have effects on the baby.
If there is a possibility that you may become pregnant, you will need to use effective contraception during treatment with MabThera and for 12 months after the last treatment with MabThera.
This is because MabThera passes into breast milk in very small amounts.
As the long-term effects on breastfed infants are unknown, breastfeeding is not recommended during treatment with MabThera and for 6 months after treatment, as a precaution.

Driving and using machines
It is not known whether MabThera affects your ability to drive or use tools or machines.

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. They will keep you under close observation while the
medicinal product is administered to you, in case you experience any undesirable effect.
At the beginning of treatment, MabThera will always be administered to you via infusion (intravenous
infusion).
Subsequently, MabThera will be administered to you by injection under the skin (subcutaneous
injection) lasting approximately 5 minutes. There is a removable adhesive label on the glass vial
that contains the drug information. The doctor or nurse will place
the adhesive on the syringe before the injection. The doctor will decide when to start the injections of
MabThera.
The subcutaneous injection is performed in the abdominal region, not in other areas of the body,
avoiding areas where the skin is reddened, bruised, sensitive or hardened or where there are moles or
scars.

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

How much and how often you will receive treatment

• MabThera will be administered to you on the same day as chemotherapy. This is generally administered every 3 weeks up to 8 times.
• If you respond well to treatment, MabThera may be administered to you as maintenance treatment every 2 or 3 months for two years. The doctor may change this schedule depending on your response to the medicine.

If you have any doubts about the use of this medicinal product, please contact your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience 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.

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

Infections
Immediately inform your doctor if you experience symptoms of infection, including:

• fever, cough, sore throat, burning when urinating, if you feel weak or unwell;
• memory loss, thinking problems, difficulty walking or loss of vision. These may be due to a very rare and serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML);
• fever, headache and stiff neck, lack of coordination (ataxia), altered personality, hallucinations, altered state of 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 pneumonia or urinary tract infections have 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 platelets (blood cells);
• feeling unwell (nausea);
• areas of baldness on the scalp, chills, headache;
• weakened immune defenses - 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), pneumonia, herpes zoster, cold, infections of the bronchial tubes, fungal infections, infections of unknown origin, inflammation of the sinuses, hepatitis B;
• low number of red blood cells (anemia) and of all blood cells;
• allergic reactions (hypersensitivity);
• high blood sugar level, weight loss, swelling of the face and body, increased levels of the LDH enzyme in the blood, low calcium levels in the blood;
• abnormal skin sensations such as numbness, tingling, prickling sensation, burning sensation, skin feeling tight, reduced sense of touch;
• feeling restless, difficulty sleeping;
• redness of the face and other areas of the skin, as a result of blood vessel dilation;
• dizziness, anxiety;
• increased tear production, problems with the 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 getting up);
• tightening of the muscles of the airways causing wheezing (bronchospasm), inflammation, irritation of the lungs, throat or sinuses, shortness of breath, runny nose;
• vomiting, diarrhea, abdominal pain, irritation or ulcers of the throat and mouth, difficulty swallowing, constipation, indigestion;
• difficulty eating, insufficient food intake resulting in weight loss;
• hives, increased sweating, night sweats;
• muscle problems such as muscle tension, muscle or joint pain, back and neck pain;
• tumor 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 hemolytic anemia), swollen or enlarged lymph nodes;
• depressed mood and loss of interest or pleasure in usual activities, nervousness;
• taste disorders, such as altered taste;
• heart problems, such as slow heartbeat or chest pain (angina);
• asthma, insufficient oxygen supply to the body's organs;
• stomach swelling.

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

• temporary increase of some types of antibodies in the blood (called immunoglobulins - IgM), chemical changes 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 gastrointestinal wall (perforation);
• severe skin reactions with blistering which can be life-threatening;
• kidney failure;
• severe loss of vision (sign of damage to the cranial nerves).

Not known (the frequency of these side effects cannot be estimated from the available data):

• delayed decrease of white blood cells;
• reduced number of platelets immediately after the infusion - is reversible, but in rare cases can be fatal;
• hearing loss, loss of other senses;
• infection/inflammation of the brain and meninges (enteroviral meningoencephalitis).

MabThera can 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, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. 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 that is stated on the pack 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 in 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, L-histidine hydrochloride monohydrate, 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 presented as a ready-to-use liquid, from clear to opalescent, from colourless to pale yellow,
supplied as a solution for subcutaneous injection in a transparent glass vial with a butyl rubber stopper with aluminium on the crimp and a pink plastic flip-off disc.
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 on this medicinal product, 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

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

България
Рош България ЕООД
Тел: +359 2 474 5444

Luxembourg/Luxemburg
(Voir/siehe Belgique/Belgien)

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

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

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

Malta
(See Ireland)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831

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
website of the European Medicines Agency.

MabThera 1600 mg solution for subcutaneous injection

rituximab

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, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is MabThera and what is it used for

What is MabThera
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 a medicine to be administered by infusion (MabThera 100 mg or
MabThera 500 mg, concentrate for solution for infusion) and as a medicine to be administered
by injection under the skin called MabThera 1400 mg or MabThera 1600 mg, solution for
subcutaneous injection.

What is MabThera 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 leukemia in adults. CLL involves a particular type of white blood cell called a B lymphocyte, 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 is the cause of the symptoms you may have. MabThera in combination with chemotherapy destroys these cells, which are gradually eliminated from the body through biological processes.

MabThera 1600 mg will be given to you with other medicines called collectively “chemotherapy”.
At the beginning of treatment you will always be given MabThera by infusion (intravenous
infusion).
Subsequently, you will be given MabThera by injection under the skin. The doctor
will decide when to start the MabThera injections.

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

Do not take MabThera

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

Do not take MabThera if any of the above conditions apply to you. If you are unsure, ask your doctor, pharmacist or nurse before you are given MabThera.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you are given MabThera:

• if you think you have a hepatitis infection or have had it in the past, as in some cases MabThera may cause reactivation of hepatitis B, a condition that in very rare cases can be fatal. Patients with a previous hepatitis B infection will be carefully monitored by the doctor to detect any 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 not sure, talk to your doctor, pharmacist or nurse before you are given MabThera. Your doctor may need to pay particular attention to you during treatment with MabThera.
Talk to your doctor also if you think you may need any vaccinations in the near future, including vaccinations needed for travel to other countries. Some vaccines should not be given at the same time as MabThera or in the months following taking MabThera. The doctor will assess whether you can have any vaccines before taking MabThera.

Children and adolescents
If your age or that of your child is less than 18 years, talk to your doctor, pharmacist or nurse before you are given this medicine, as there is limited information regarding the use of MabThera in children and adolescents.

Other medicines and MabThera
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines, including over-the-counter medicines and herbal remedies, as MabThera can interfere with the way other medicines work, and vice versa.
In particular, tell your doctor:

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

If any of these conditions apply to you, or if you are not sure, talk to your doctor, pharmacist or nurse before you are given MabThera.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, tell your doctor or nurse. This is because MabThera can cross the placenta and have effects on the baby.
If there is a possibility that you may become pregnant, you should use effective contraception during treatment with MabThera and for 12 months after the last treatment with MabThera.
This is because MabThera passes into breast milk in very small amounts.
As the long-term effects on breastfed infants are unknown, for precautionary reasons, 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 machines.

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. They will keep you under close observation while the
medicinal product is administered to you, in case you experience any undesirable effect.
At the beginning of treatment, MabThera will always be administered to you via infusion (intravenous
infusion).
Subsequently, MabThera will be administered to you via injection under the skin (subcutaneous
injection) lasting approximately 7 minutes. There is a removable adhesive label on the glass vial
containing the drug information.
The doctor or nurse will place the adhesive on the syringe before the injection. The doctor will decide
when to start the MabThera injections.
The subcutaneous injection is performed in the abdominal region, not in other areas of the body,
avoiding areas where the skin is reddened, bruised, sensitive or hardened, or where there are moles or
scars.

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

How much and how often you will receive treatment
If you are being treated with MabThera in combination with chemotherapy, you will be administered
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. The
chemotherapy must be administered after the administration of MabThera.
The doctor will decide whether you should receive concomitant supportive therapy.
If you have any doubts about the use of this medicinal product, 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.

Reactions at the injection site of the medicine
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.
The doctor may decide to stop treatment with MabThera if these reactions are
serious.

Infections
Immediately inform your doctor if you experience symptoms of infection, including:

• fever, cough, sore throat, burning when urinating, if you feel weak or unwell;
• memory loss, thinking problems, difficulty walking or loss of vision. These may be due to a very rare and serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML);
• fever, headache and stiff neck, lack of coordination (ataxia), altered personality, hallucinations, altered state of 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 occurred. Such
infections are listed in the paragraph “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 platelets (blood cells);
• feeling unwell (nausea);
• areas of hair loss on the scalp, chills, headache;
• lowered immunity - due to lower levels in the blood of antibodies called “immunoglobulins” (IgG) that help the body fight infections.

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

• blood infections (sepsis), lung infection, herpes zoster, cold, infections of the bronchial tubes, fungal infections, infections of unknown origin, inflammation of the nasal sinuses, hepatitis B;
• low number of red blood cells (anemia) and of all blood cells;
• allergic reactions (hypersensitivity);
• high blood sugar level, 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 sensation, burning sensation, skin feeling tight, reduced sense of touch;
• feeling restless, difficulty sleeping;
• redness of the face and other areas of the skin as a result of blood vessel dilation;
• dizziness, anxiety;
• increased tear production, problems with the 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 muscles of the airways causing wheezing (bronchospasm), inflammation, irritation of the lungs, throat or nasal sinuses, shortness of breath, runny nose;
• vomiting, diarrhea, abdominal pain, irritation or ulcers of the throat and mouth, difficulty swallowing, constipation, indigestion;
• eating disorders, insufficient food intake with resulting weight loss;
• hives, increased sweating, night sweats;
• muscle problems such as muscle tension, muscle or joint pain, back and neck pain;
• tumor 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 hemolytic anemia), swollen or enlarged lymph nodes;
• depressed mood and loss of interest or pleasure in usual activities, nervousness;
• taste disorders, 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.

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

• temporary increase of certain types of antibodies in the blood (called immunoglobulins - IgM), chemical changes 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 gastrointestinal wall (perforation);
• severe skin reactions with blistering which can be life-threatening;
• kidney failure;
• severe loss of vision (sign of damage to the cranial nerves).

Not known (the frequency with which these side effects may occur is not known):

• delayed decrease of white blood cells;
• reduced number of platelets, immediately after the infusion - is reversible, but in rare cases can be fatal;
• hearing loss, loss of other senses;
• infection/inflammation of the brain and meninges (enteroviral meningoencephalitis).

MabThera can 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 effect, talk to your doctor, pharmacist or nurse. This includes any side effect not listed in this leaflet. 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 which is stated on the pack 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 in waste water 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 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 ingredients are recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine hydrochloride 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 presented as a ready-to-use liquid, from clear to opalescent, from colourless to yellowish,
supplied as a solution for subcutaneous injection in a transparent glass vial with a butyl rubber stopper with aluminium on the crimp and a blue plastic flip-off disc.
Each vial contains 1600 mg/13.4 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 on this medicinal product, 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

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

България
Рош България ЕООД
Тел: +359 2 474 5444

Luxembourg/Luxemburg
(Voir/siehe Belgique/Belgien)

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

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

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

Malta
(See Ireland)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831

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 official languages of the European Union/European Economic Area on the
website of the European Medicines Agency.