PACKAGE LEAFLET: INFORMATION FOR THE PATIENTMabThera (rituximab) 100 mg concentrate for solution for infusion
Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
Keep this leaflet. You may need to read it again. If
you have any further questions, ask your doctor, pharmacist or nurse.
If you experience any of the side effects listed in section 4, or if you notice any side effects not listed here, talk to your doctor, pharmacist or nurse.
What is in this leaflet
? 1. What MabThera is and what it is used for?
2. When should you not use MabThera or be extra careful with it?
3. How to use MabThera?
4. Possible side effects
5. How to store MabThera?
6. Contents of the pack and other information
1. WHAT MABTHERA IS AND WHAT IT IS USED FOR? MabThera contains the active substance "rituximab". This is a type of protein called a monoclonal antibody. It binds to the surface of a type of white blood cell called a B-lymphocyte.
When rituximab binds to the surface of this cell, it causes it to die.
What is MabThera used for?
MabThera can be used to treat a number of different conditions in adults. Your doctor may prescribe MabThera to treat:
a) Non-Hodgkin's lymphoma
This is a disease of the lymphatic tissue (part of the immune system) that affects a type of white blood cell called a B-lymphocyte. MabThera can be given alone or in combination with medicines called chemotherapy. In patients whose treatment is effective, MabThera can also be given as maintenance treatment for 2 years after the initial treatment has been completed.
b) Chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. CLL affects a specific lymphocyte, the B cell, which originates in the bone marrow and develops in the lymph nodes. Patients with CLL have too many abnormal lymphocytes, which accumulate primarily in the bone marrow and blood. The increasing number of these abnormal B lymphocytes causes the symptoms you may be experiencing. In combination with chemotherapy, MabThera destroys these cells, which are gradually eliminated from the body through biological processes.
c) Rheumatoid arthritis
MabThera is used to treat rheumatoid arthritis. Rheumatoid arthritis is a disease of the joints. B-lymphocytes are involved in causing some of the symptoms you may experience. MabThera is used to treat rheumatoid arthritis in people who have already tried other medicines that stopped working, didn't work well enough, or caused side effects. MabThera is usually used in combination with another medicine called methotrexate.
MabThera slows the damage to your joints caused by rheumatoid arthritis and makes it easier for you to do your normal daily activities.
People who have a positive blood test for rheumatoid factor (RF) and/or anti-Cyclic Citrullinated Peptide (anti-CCP) respond best to MabThera. Both tests are often positive in rheumatoid arthritis and help in making the diagnosis.
d) Granulomatosis with polyangiitis or microscopic polyangiitis
MabThera is used to reduce disease activity in granulomatosis with polyangiitis (previously called Wegener's granulomatosis) or microscopic polyangiitis, when used in combination with corticosteroids. Granulomatosis with polyangiitis and microscopic polyangiitis are two forms of inflammation of the blood vessels, which mainly affect the lungs and kidneys, but can also affect other organs. B lymphocytes are involved in the cause of these conditions.
e) MabThera is used off-label in dermatology for rare skin conditions such as blistering diseases.
2. WHEN YOU SHOULD NOT USE MabThera OR TAKE SPECIAL CARE When you should not use MabThera:
• You are allergic to rituximab, other proteins similar to rituximab, or any of the other ingredients of this medicine (listed in section 6). These ingredients can be found in section 6.
• You currently have a serious, active infection
• You have a weakened immune system
• You have severe heart failure or serious uncontrolled heart disease and you have rheumatoid arthritis, granulomatosis with polyangiitis or microscopic polyangiitis.
Do not take MabThera if any of the above applies to you. If you are not sure, talk to your doctor, pharmacist or nurse before taking MabThera.
When should you take special care with MabThera?
Talk to your doctor, pharmacist or nurse before taking this medicine:
• if you have had a hepatitis infection in the past or think you may have one. This is because in some cases MabThera can cause hepatitis B to become active again, which can be fatal in very rare cases. Patients who have ever had a hepatitis B infection will be closely monitored by their doctor for signs of this infection.
• if you have ever had heart problems (such as angina, palpitations or heart failure) or breathing difficulties.
If any of the above applies to you (or you are not sure), tell your doctor, pharmacist or nurse before being given MabThera. Your doctor may need to pay special attention to you during your treatment with MabThera.
If you have rheumatoid arthritis, granulomatosis with polyangiitis or microscopic polyangiitis, also tell your doctor.
• if you have an infection, even a mild one like a cold. The cells affected by MabThera help to protect you against infections. You will need to wait until the infection is gone before being given MabThera. Also tell your doctor if you have had a lot of infections in the past or are suffering from serious infections.
• if you think you may need any vaccinations in the near future, including vaccinations needed to travel to other countries. Some vaccinations should not be given at the same time as MabThera or in the months after you have been given MabThera. Your doctor will check if you need any vaccinations before you are given MabThera. Children
and adolescents
Tell your doctor, pharmacist or nurse before being given this medicine if you or your child is under 18 years of age. This is because there is little information on 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. 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 medicines for 12 hours before you are given MabThera. This is because some people have a drop in their blood pressure when they are given MabThera.
• if you have ever taken medicines that affect your immune system - such as chemotherapy or immunosuppressants.
If any of the above applies to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking MabThera.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant or are planning to have a baby, talk to your doctor or nurse before taking this medicine. This is because MabThera can cross the placenta and may affect your baby.
If you are able to get pregnant, you and your partner must use an effective method of contraception while taking MabThera. This must also be done for 12 months after your last treatment with MabThera.
Do not breastfeed while you are being treated with MabThera. Also do not breastfeed for 12 months after your last treatment with MabThera. This is because MabThera can pass into breast milk.
Driving and using machines
It is not known if MabThera affects your ability to drive or use any tools or machines.
3. HOW TO USE MabThera How is MabThera given?
MabThera will be administered by a doctor or nurse who is experienced in using this treatment. They will monitor you closely while you are receiving this medicine. This is in case you experience any side effects.
You will always be given MabThera by drip (intravenous infusion).
Medicines given before each MabThera dose
Before you are given MabThera, you will be given other medicines (premedication) to prevent or reduce possible reactions to MabThera.
How much and how often will you receive treatment?
a) If you are being treated for non-Hodgkin's lymphoma
• If you are given MabThera on its own
MabThera will be given once a week for 4 weeks. Repeated courses of MabThera treatment are possible.
• If you are given MabThera with chemotherapy
MabThera will be given on the same day as your chemotherapy. This is usually every 3 weeks up to a maximum of 8 times.
• If you respond well to treatment, you may be given MabThera as a maintenance treatment, every 2 or 3 months for 2 years. Your doctor may change this depending on how you respond to treatment.
b) If you are being treated for chronic lymphocytic leukaemia
If you are being treated with MabThera in combination with chemotherapy, you will receive MabThera infusions on day 0 of cycle 1, and then on day 1 of each cycle for a total of 6 cycles. Each cycle lasts 28 days. Chemotherapy should be given after the MabThera infusion. Your doctor will decide whether you should receive concomitant supportive therapy.
c) If you are being treated for rheumatoid arthritis
Each course of treatment consists of two separate infusions given at least 2 weeks apart. Subsequent courses of MabThera treatment are possible. Depending on the symptoms of your disease, your doctor will decide when you should receive MabThera again. This may be 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 one week apart. Corticosteroids are usually administered by injection before starting MabThera treatment. To treat your condition, your doctor may also start you on oral corticosteroids at any time.
If you have any further questions on 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 everybody gets them. Most side effects are mild to moderate, but some may be serious and need treatment. Rarely, some of these reactions have been fatal.
Infusion reactions
During or within the first 2 hours after the first infusion, fever, chills, and shivering may occur. Less frequently, some patients may experience pain at the infusion site, skin blisters and itching, nausea, tiredness, headache, difficulty breathing, swelling of the tongue and throat, itchy or runny nose, vomiting, hot flashes or irregular heartbeat, heart attack, or low platelet counts. If you have heart disease or angina, these reactions may be made worse. Tell your infusion provider immediately if you experience any of these symptoms, as the infusion may need to be slowed down or interrupted. You may need to be treated with an antihistamine or paracetamol. When the symptoms disappear or improve, the infusion can be resumed. These reactions are less likely to occur after the second infusion. Your doctor may decide to discontinue MabThera treatment if these reactions are severe.
Infections:
Tell your doctor immediately if you develop symptoms of an infection, including:
• fever, cough, sore throat, burning pain when urinating, or if you feel weak or generally unwell.
• memory loss, difficulty thinking, difficulty walking or if your vision becomes worse - this may indicate a very rare, serious brain infection which can be fatal (progressive multifocal leukoencephalopathy or PML).
You may get infections more easily during your treatment with MabThera. These are often colds, but there have also been cases of pneumonia or urinary tract infections. These are listed below under "Other side effects".
If you are being treated for rheumatoid arthritis, 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 Patient Alert Card and show it to your partner or caregiver.
Skin reactions
Very rarely, skin conditions with severe blistering may occur, which may be life-threatening. Redness, often accompanied by blisters, may occur on the skin or mucous membranes, such as in the mouth, genitals, or eyelids. Fever may also occur. Tell your doctor immediately if you experience any of these symptoms.
Other side effects include:
a) if you are being treated for non-Hodgkin's lymphoma or chronic lymphocytic leukaemia.
Very common side effects (may affect more than 1 in 10 people):
• bacterial or viral infections, bronchitis
• low levels of white blood cells, with or without fever, or blood cells called platelets
• nausea
• bald patches on the scalp, chills, headache
• reduced functioning of the immune system - due to a reduced number of antibodies called "immunoglobulins" (IgG) in the blood, which help protect against infections.
Common side effects (may affect up to 1 in 10 people):
• blood infections (sepsis) pneumonia, shingles, colds, bronchitis, fungal infections, infections of unknown cause, sinus infection, hepatitis B
• low levels of red blood cells (anaemia), low levels of all blood cells
• allergic reactions (hypersensitivity reactions)
• high blood sugar levels, weight loss, swelling of the face and body, increased blood levels of the enzyme LDH, low blood calcium levels
• strange sensation of the skin - such as numbness, tingling, pricking, burning sensation, a crawling sensation of the skin, a reduced sense of touch.
• feeling restless, difficulty falling asleep
• very red of the face and other areas of the skin due to widening of the blood vessels
• dizziness or anxiety
• increased tear production, tear duct problems, inflammation of the eye (conjunctivitis)
• ringing sound in the ears, earache
• heart problems - such as heart attack, irregular or fast heart rate
• increased or decreased blood pressure, (lower blood pressure especially when standing up)
• tightening of the muscles in the airways which causes wheezing (bronchospasm), inflammation, irritation of the lungs, throat and/or sinuses, shortness of breath, runny nose
• vomiting, diarrhoea, stomach ache, irritation and/or ulceration of the throat and mouth, difficulty swallowing, constipation, indigestion
• eating disorders, not eating enough resulting in weight loss
• hives, increased sweating, night sweats
• muscle problems - such as tense muscles, joint or muscle aches, back and neck pain
• generally feeling unwell or tired feeling unwell, shaking, flu-like symptoms
• multi-organ failure
Uncommon side effects (may affect up to 1 in 100 people):
• blood clotting problems, decrease in red blood cell production and increased breakdown of red blood cells (aplastic haemolytic anaemia), swollen or enlarged lymph nodes
• depressed mood and decreased interest or pleasure in normal activities, nervousness
• taste problems - such as a change in the way things taste
• heart problems - such as slow heart rate or chest pain (angina), asthma, a lack of oxygen reaching the organs
• bloating
Very rare side effects (may affect up to 1 in 10,000 people):
• short-lived increase in certain types of antibodies in the blood (called immunoglobulins - IgM), chemical disturbances in the blood caused by breakdown of dying cancer cells
• damage to the nerves in the arms and legs, paralysed face
• heart failure
• Inflammation of blood vessels, including inflammation of the blood vessels causing skin problems
• Respiratory failure
• Damage to the intestinal wall (perforation)
• Serious skin problems with blisters that can be life-threatening. Redness, often accompanied by blisters, may occur on the skin or on mucous membranes, for example in the mouth, genitals or eyelids. Fever may also occur.
• kidney failure
• serious loss of vision
Not known (frequency cannot be estimated from the available data):
• a decrease in white blood cells that does not occur straight away
• decrease in platelets immediately after the infusion - this is reversible but can rarely be fatal
• hearing loss, loss of other senses
b) if you are being treated for rheumatoid arthritis
Very common side effects (may affect more than 1 in 10 people):
• infections such as pneumonia (bacterial)
• painful urination (urinary tract infection)
• allergic reactions which are most likely to occur during an infusion but can also occur up to 24 hours after infusion
• changes in blood pressure, nausea, rash, fever, itching, runny or blocked nose and sneezing, tremor, increased heart rate, and tiredness
• headache
• changes in laboratory tests carried out by your doctor. These include a decrease in the levels of some specific proteins in the blood (immunoglobulins) that help to protect against infections.
Common side effects (may affect up to 1 in 10 people):
• infections such as inflammation of the airways (bronchitis)
• a feeling of fullness or a throbbing pain behind the nose, cheeks and eyes (sinusitis), abdominal pain, vomiting and diarrhoea, difficulty breathing
• fungal infection of the foot (athlete's foot)
• high cholesterol in the blood
• abnormal sensations of the skin such as numbness, tingling, pricking, burning, sciatica, migraine, dizziness
• hair loss
• anxiety, depression
• digestive problems, diarrhoea, heartburn, irritation and/or ulcers in the throat and mouth
• pain in the stomach, back, muscles and/or joints
Uncommon side effects (may affect up to 1 in 100 people):
• Fluid retention in the face and body
• Inflammation, irritation and/or tightness in the lungs and throat, cough
• Skin reactions such as hives, itching and rash
• Allergic reactions such as wheezing or shortness of breath, swelling of the face and tongue, fainting
Very rare side effects (may affect up to 1 in 10,000 people):
• A group of symptoms occurring within a few weeks after an infusion of MabThera, including allergic-like reactions such as rash, itching, joint pain, swollen lymph nodes and fever
• Severe blistering of the skin which may be life-threatening. Redness, often with blisters, may occur on the skin or on mucous membranes, for example in the mouth, genitals or eyelids. Fever may also occur.
Other rarely reported side effects of MabThera include a decrease in the number of white blood cells (neutrophils) that help fight infection. Some infections can be serious (see the information on Infections in this section).
c) if you 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 bronchitis, urinary tract infections (pain on passing urine), colds and herpes infections
• allergic reactions which are most likely to occur during an infusion, but can also occur up to 24 hours after infusion
• diarrhoea
• coughing or shortness of breath
• nose bleeds
• increased blood pressure
• painful joints or back
• muscle twitching or shaking •
feeling dizzy
• tremors (shaking, 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
• rash, including acne or pimples
• flushing or redness of the skin
• stuffy nose
• stiff or aching muscles
• pain in the muscles or in the hands or feet
• low red blood cell count (anemia)
• low platelet count
• an increase in the amount of potassium in the blood
• changes in heart rhythm or the heart beating faster than normal
Very rare side effects (may affect up to 1 in 10,000 people):
• severe blistering of the skin which may be life-threatening. Redness, often accompanied by blisters, may occur on the skin or on mucous membranes, for example in the mouth, genitals or eyelids. There may also be a fever.
• recurrence of a previous hepatitis B infection
MabThera may also cause changes in the results of laboratory tests that your doctor carries out.
If you receive MabThera with other medicines, some of the side effects you 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 possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix VI*. By reporting side effects you can help provide more information on the safety of this medicine.
5. HOW TO STORE ROUTE OF THE MEDICINE Keep 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 (2-8°C). Keep the vial 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 you no longer use. These measures will help protect the environment.
6. OTHER INFORMATION What ROUTE OF THE MEDICINE contains
: The active substance is rituximab. The vial contains 100 mg rituximab (10 mg/ml).
• The other ingredients are sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid and water for injections.
What MabThera looks like and contents of the pack?
MabThera is a clear, colourless solution and is supplied as a concentrate for solution for infusion. 10 ml vials are available in a pack containing 2 vials.
Marketing Authorisation Holder
Roche Registration Limited 6 Falcon Way
Shire Park
Welwyn Garden City AL71TW
United Kingdom
Manufacturer
Roche Pharma AG Emil-Barell-Str. 1
D-79639 Grenzach-Wyhlen Germany
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Netherlands
Roche Nederland BV Tel: +31 (0) 348 438050
This leaflet was last approved in 2014
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.
This leaflet is available in all EU/EEA languages on the European Medicines Agency website. |
