MabThera
rituximab
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possibleside effects not listed in this leaflet. See section 4.
What MabThera is and what it is used for
What you need to know before you use MabThera
How to use MabThera
Possible side effects
How to store MabThera
Contents of the pack and other information
MabThera contains the active substance “rituximab”. This is a type of protein called a “monoclonal antibody”. It sticks to the surface of a type of white blood cell called “B-Lymphocyte”. When rituximab sticks to the surface of this cell, the cell dies.
MabThera may be used for the treatment of several different conditions in adults and children. Your doctor may prescribe MabThera for the treatment of:
This is a disease of the lymph tissue (part of the immune system) that affects a type of white blood cell called B-Lymphocytes.
In adults MabThera can be given alone or with other medicines called “chemotherapy”.
In adult patients where the treatment is working, MabThera may be used as a maintenance treatment for 2 years after completing the initial treatment.
In children and adolescents, MabThera is given in combination with “chemotherapy”.
Chronic lymphocytic leukaemia (CLL) is the most common form of adult leukaemia. CLL affects a particular lymphocyte, the B cell, which originates from the bone marrow and develops in the lymph nodes. Patients with CLL have too many abnormal lymphocytes, which accumulate mainly in the bone marrow and blood. The proliferation of these abnormal B-lymphocytes is the cause of symptoms you may have. MabThera in combination with chemotherapy destroys these cells which are gradually removed from the body by biological processes.
MabThera is used for the treatment of rheumatoid arthritis. Rheumatoid arthritis is a disease of the joints. B lymphocytes are involved in the cause of some of the symptoms you have. MabThera is used to treat rheumatoid arthritis in people who have already tried some other medicines which have either
stopped working, have not worked well enough or have caused side effects. MabThera is usually taken together with another medicine called methotrexate.
MabThera slows down the damage to your joints caused by rheumatoid arthritis and improves your ability to do normal daily activities.
The best responses to MabThera are seen in those who have a positive blood test to rheumatoid factor (RF) and/or anti-Cyclic Citrullinated Peptide (anti-CCP). Both tests are commonly positive in rheumatoid arthritis and aid in confirming the diagnosis.
MabThera is used for the treatment of adults and children 2 years of age and older with granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis) or microscopic polyangiitis, taken in combination with corticosteroids.
Granulomatosis with polyangiitis and microscopic polyangiitis are two forms of inflammation of the blood vessels which mainly affects the lungs and kidneys, but may affect other organs as well. B lymphocytes are involved in the cause of these conditions.
MabThera is used for the treatment of patients with moderate to severe pemphigus vulgaris. Pemphigus vulgaris is an autoimmune condition that causes painful blisters on the skin and lining of the mouth, nose, throat and genitals.
you are allergic to rituximab, other proteins which are like rituximab, or any of the otheringredients of this medicine (listed in section 6)
you have a severe active infection at the moment
you have a weak immune system.
you have severe heart failure or severe uncontrolled heart disease and have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis or pemphigus vulgaris.
Do not have MabThera if any of the above apply to you. If you are not sure, talk to your doctor, pharmacist or nurse before you are given MabThera.
Talk to your doctor, pharmacist or nurse before you are given MabThera if:
you have ever had or might now have a hepatitis infection. This is because in a few cases, MabThera could cause hepatitis B to become active again, which can be fatal in very rare cases.Patients who have ever had hepatitis B infection will be carefully checked by their doctor for signs of this infection
you have ever had heart problems (such as angina, palpitations or heart failure) or breathingproblems.
If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before you are given MabThera. Your doctor may need to take special care of you during your 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 after you receive MabThera. Your doctor will check if you should have any vaccines before you receive MabThera.
if you think you may have an infection, even a mild one like a cold. The cells that are affected by MabThera help to fight infection and you should wait until the infection has passed before you are given MabThera. Also please tell your doctor if you had a lot of infections in the past orsuffer from severe infections.
Non-Hodgkin’s lymphoma
MabThera can be used for the the treatment of children and adolescents, 6 months of age and older, with non-Hodgkin’s lymphoma, specifically CD20 positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL)/Burkitt leukaemia (mature B-cell acute leukaemia) (BAL) or Burkitt-like lymphoma (BLL).
Talk to your doctor, pharmacist or nurse before you are given this medicine if you, or your child, are under 18 years of age.
Granulomatosis with polyangiitis or microscopic polyangiitis
MabThera can be used for treatment of children and adolescents, 2 years of age and older, with granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis) or microscopic polyangiitis. There is not much information about the use of MabThera in children and adolescents with other diseases.
Talk to your doctor, pharmacist or nurse before you are given this medicine if you, or your child, are under 18 years of age.
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription and herbal medicines. This is because MabThera can affect the way some other medicines work. Also some other medicines can affect the way MabThera works.
In particular, tell your doctor:
if you are taking medicines for high blood pressure. You may be asked not to take these other medicines 12 hours before you are given MabThera. This is because some people have a fall intheir blood pressure while they are being given MabThera.
if you have ever taken medicines which affect your immune system – such as chemotherapy orimmune- suppressive medicines.
If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before you are given MabThera.
You must tell your doctor or nurse if you are pregnant, think that you might be pregnant or are planning to become pregnant. This is because MabThera can cross the placenta and may affect your baby.
If you can get pregnant, you and your partner must use an effective method of contraception while using MabThera. You must also do this for 12 months after your last treatment with MabThera.
. MabThera passes into breast milk in small amounts. As the long-term effects on breastfed infants are not known, breastfeeding is not recommended during treatment with MabThera and for 12 months after the treatment.
It is not known whether MabThera has an effect on you being able to drive or use any tools or machines.
This medicine contains 52.6 mg sodium (main component of the cooking/table salt) in each 10 mL vial and 263.2 mg in each 50 mL vial.
This is equivalent to 2.6% (for 10ml vial) and 13.2% (for 50ml vial) of the recommended maximum daily dietary intake of sodium for an adult.
MabThera will be given to you by a doctor or nurse who is experienced in the use of this treatment. They will watch you closely while you are being given this medicine. This is in case you get any side effects.
You will always be given MabThera as a drip (intra-venous infusion).
Before you are given MabThera, you will be given other medicines (pre-medication) to prevent or reduce possible side effects.
If you are having MabThera alone
MabThera will be given to you once a week for 4 weeks. Repeated treatment courses with MabThera are possible.
If you are having MabThera with chemotherapy
MabThera will be given to you on the same day as your chemotherapy. This is usually given every 3 weeks up to 8 times.
If you respond well to treatment, you may be given MabThera as a maintenance treatmentevery 2 or 3 months for two years. Your doctor may change this, depending on how you respond to the medicine.
If you are less than 18 years of age, you will be given MabThera with chemotherapy. Youwill receive MabThera up to 6 times over a 3.5 – 5.5 month period.
When you are treated with MabThera in combination with chemotherapy, you will receive MabThera infusions on day 0 cycle 1 then day 1 of each cycle for 6 cycles in total. Each cycle has a duration of 28 days. The chemotherapy should be given after the MabThera infusion. Your doctor will decide if you should receive concomitant supportive therapy.
Each course of treatment is made up of two separate infusions which are given 2 weeks apart. Repeated courses of treatment with MabThera are possible. Depending on the signs and symptoms of your disease, your doctor will decide when you should receive more MabThera. This may be months from now.
Treatment with MabThera uses four separate infusions given at weekly intervals. Corticosteroids willusually be given by injection before the start of MabThera treatment. Corticosteroids given by mouthmay be started at any time by your doctor to treat your condition.
If you are 18 years of age and older and respond well to treatment, you may be given MabThera as a maintenance treatment. This will be administered as 2 separate infusions which are given 2 weeks apart, followed by 1 infusion every 6 months for at least 2 years. Your doctor may decide to treat you longer with MabThera (up to 5 years), depending on how you respond to the medicine.
Each course of treatment is made up of two separate infusions which are given 2 weeks apart. If you respond well to treatment, you may be given MabThera as a maintenance treatment. This will be administered 1 year and 18 months after the initial treatment and then every 6 months as needed or your doctor may change this, depending on how you respond to the medicine.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most side effects are mild to moderate but some may be serious and require treatment. Rarely, some of these reactions have been fatal.
During or within the first 24 hours of the infusion you may develop fever, chills and shivering. Less frequently, some patients may experience pain at the infusion site, blisters, itching, sickness (nausea), tiredness, headache, breathing difficulties, blood pressure raised, wheezing, throat discomfort, tongue or throat swelling, itchy or runny nose, vomiting, flushing or palpitations, heart attack or low number of platelets. If you have heart disease or angina, these reactions might get worse. Tell the person giving you the infusion immediately if you or your child develops any of these symptoms, as the infusion may need to be slowed down or stopped. You may require additional treatment such as an antihistamine or paracetamol. When these symptoms go away, or improve, the infusion can be continued. These reactions are less likely to happen after the second infusion. Your doctor may decide to stop your MabThera treatment if these reactions are serious.
fever, cough, sore throat, burning pain when passing urine or feeling weak or generally unwell
memory loss, trouble thinking, difficulty walking or sight loss – these may be due to a very rare,serious brain infection, which has been fatal (Progressive Multifocal Leukoencephalopathy or PML).
You might get infections more easily during your treatment with MabThera.
These are often colds, but there have been cases of pneumonia or urinary infections. These are listed below under “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 you have been given by your doctor. It is important that you keep this Alert Card and show it to your partner or caregiver.
Very rarely, severe blistering skin conditions that can be life-threatening may occur. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genital areas or the eyelids, and fever may be present. Tell your doctor immediately if you experience any of these symptoms.
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 blood cells called “platelets”
feeling sick (nausea)
bald spots on the scalp, chills, headache
lower immunity – because of lower levels of anti-bodies called “immunoglobulins” (IgG) inthe blood which help protect against infection
Common side effects (may affect up to 1 in 10 people):
infections of the blood (sepsis), pneumonia, shingles, cold, bronchial tube infections, fungalinfections, infections of unknown origin, sinus inflammation, hepatitis B
low number of red blood cells (anaemia), low number of all blood cells
allergic reactions (hypersensitivity)
high blood sugar level, weight loss, swelling in the face and body, high levels of the enzyme“LDH” in the blood, low calcium levels in the blood
unusual feelings of the skin – such as numbness, tingling, pricking, burning, a creeping skinfeeling, reduced sense of touch
feeling restless, problems falling asleep
becoming very red in the face and other areas of the skin as a consequence of dilation of theblood vessels
feeling dizzy or anxious
producing more tears, tear duct problems, inflamed eye (conjunctivitis)
ringing sound in the ears, ear pain
heart problems – such as heart attack, uneven or fast heart rate
high or low blood pressure (low blood pressure especially when standing upright)
tightening of the muscles in the airways which causes wheezing (bronchospasm), inflammation, irritation in the lungs, throat or sinuses, being short of breath, runny nose
being sick (vomiting), diarrhoea, pain in the stomach, irritation or ulcers in the throat andmouth, problems swallowing, constipation, indigestion
eating disorders, not eating enough, leading to weight loss
hives, increased sweating, night sweats
muscle problems – such as tight muscles, joint or muscle pain, back and neck pain
tumour pain
general discomfort or feeling uneasy or tired, shaking, signs of flu
multiple-organ failure.
Uncommon side effects (may affect up to 1 in 100 people):
blood clotting problems, decrease of red blood cell production and increase of red blood celldestruction (aplastic haemolytic anaemia), swollen or enlarged lymph nodes
low mood and loss of interest or enjoyment in doing things, feeling nervous
taste problems – such as changes in the way things taste
heart problems – such as reduced heart rate or chest pain (angina)
asthma, too little oxygen reaching the body organs
swelling of the stomach.
Very rare side effects (may affect up to 1 in 10, 000 people):
short term increase in the amount of some types of anti-bodies in the blood (called immunoglobulins – IgM), chemical disturbances in the blood caused by break-down of dyingcancer cells
nerve damage in arms and legs, paralysed face
heart failure
inflammation of blood vessels including those leading to skin symptoms
respiratory failure
damage to the intestinal wall (perforation)
severe skin problems causing blisters that can be life-threatening. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, thegenital areas or the eyelids, and fever may be present.
kidney failure
severe vision loss
Not known (it is not known how often these side effects happen):
a reduction in white blood cells which does not happen straight away
reduced platelets number just after the infusion – this can be reversed, but can be fatal in rarecases
hearing loss, loss of other senses
In general, side effects in children and adolescents with non-Hodgkin’s lymphoma were similar to those in adults with non-Hodgkin’s lymphoma or chronic lymphocytic leukaemia. The most common side effects seen were fever associated with low levels of a type of white blood cell (neutrophil), inflammation or sores in the lining of the mouth, and allergic reactions (hypersensitivity).
Very common side effects (may affect more than 1 in 10 people):
Infections such as pneumonia (bacterial)
Pain on passing water (urinary tract infection)
Allergic reactions that are most likely to occur during an infusion, but can occur up-to24-hours after infusion
Changes in blood pressure, nausea, rash, fever, feeling itchy, runny or blocked nose andsneezing, shaking, rapid heart beat, and tiredness
Headache
Changes in laboratory tests carried out by your doctor. These include a decrease in the amountof some specific proteins in the blood (immunoglobulins) which help protect against infection.
Common side effects (may affect up to 1 in 10 people):
Infections such as bronchial tube inflammation (bronchitis)
A feeling of fullness or a throbbing pain behind the nose, cheeks and eyes (sinusitis), pain inthe abdomen, vomiting and diarrhoea, breathing problems
Fungal foot infection (athlete’s foot)
High cholesterol levels in the blood
Abnormal sensations of the skin, such as numbness, tingling, pricking or burning, sciatica,migraine, dizziness
Loss of hair
Anxiety, depression
Indigestion, diarrhoea, acid reflux, irritation and /or ulceration of the throat and the mouth
Pain in the tummy, back, muscles and/or joints
Uncommon side effects (may affect up to 1 in 100 people):
Excess fluid retention in the face and body
Inflammation, irritation and / or tightness of the lungs, and throat, coughing
Skin reactions including hives, itching and rash
Allergic reactions including wheezing or shortness of breath, swelling of the face and tongue,collapse
Very rare side effects (may affect up to 1 in 10, 000 people):
A complex of symptoms occurring within a few weeks of an infusion of MabThera includingallergic like reactions such as rash, itching, joint pain, swollen lymph glands and fever
severe blistering skin conditions that can be life-threatening. Redness, often associated withblisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genital areas or the eyelids, and fever may be present.
Other rarely-reported side-effects due to MabThera include a decreased number of white cells in the blood (neutrophils) that help to fight against infection. Some infections may be severe (please see information on Infections within this section).
Very common side effects (may affect more than 1 in 10 people):
infections, such as chest infections, urinary tract infections (pain on passing water), colds andherpes infections
allergic reactions that are most likely to occur during an infusion, but can occur up-to 24-hoursafter infusion
diarrhoea
coughing or shortness of breath
nose bleeds
raised blood pressure
painful joints or back
muscle twitches or shakiness
feeling dizzy
tremors (shakiness, often in the hands)
difficulty sleeping (insomnia)
swelling of the hands or ankles
Common side effects (may affect up to 1 in 10 people):
indigestion
constipation
skin rashes, including acne or spots
flushing or redness of the skin
fever
blocked or runny nose
tight or painful muscles
pain in the muscles or in the hands or feet
low number of red blood cells (anaemia)
low numbers of platelets in the blood
an increase in the amount of potassium in the blood
changes in the rhythm of the heart, or the heart beating faster than normal
Very rare side effects (may affect up to 1 in 10, 000 people):
severe blistering skin conditions that can be life-threatening. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genitalareas or the eyelids, and fever may be present.
recurrence of a previous Hepatitis B infection
Very common side effects (may affect more than 1 in 10 people):
allergic reactions that are most likely to occur during an infusion, but can occur up to 24 hoursafter infusion
headache
infections such as chest infections
long lasting depression
loss of hair
Common side effects (may affect up to 1 in 10 people):
infections such as common cold, herpes infections, eye infection, oral thrush and urinary tractinfections (pain on passing urine)
mood disorders such as irritability and depression
skin disorders such as itching, hives, and benign lumps
feeling tired or dizzy
fever
painful joints or back
pain in the tummy
pain in the muscles
heart beating faster than normal
MabThera may also cause changes in laboratory tests carried out by your doctor.
If you are having MabThera with other medicines, some of the side effects you may get 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 via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine
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). Keep the container in the outer carton in order to protect from light.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines that you no longer use. These measures will help protect the environment.
The active ingredient in MabThera is called rituximab. The 10 mL vial contains 100 mg of rituximab (10 mg/mL).The 50 mL vial contains 500 mg of rituximab (10 mg/mL).
The other ingredients are sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid and water for injections.
MabThera is a clear, colourless solution, supplied as a concentrate for solution for infusion. 10 mL vial – Pack of 2 vials
50 mL vial – Pack of 1 vial
Roche Registration GmbH Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen Germany
Roche Pharma AG Emil-Barell-Str. 1
D-79639 Grenzach-Wyhlen Germany
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