MabThera 100 mg. / 10 ml. 2 vials 

What MabThera is and what it is used
MabThera contains an antibody ( rituximab ), which is a type of protein. Rituximab binds to the surface of a white blood cell - B lymphocytes . When rituximab binds to the surface of that cell , it causes her death

MabThera may be used to treat several other diseases. Your doctor may prescribe MabThera for the treatment of:
a) non-Hodgkin's lymphoma
Non-Hodgkin's lymphoma is a disease of the lymph system. B lymphocytes are part of the reason for some of the symptoms you may have . MabThera can be used alone or with other medications that your doctor can prescribe to achieve remission of your disease . MabThera may be used as a continuous (maintenance ) treatment for 2 years in patients who have responded to induction therapy .

b ) Chronic lymphocytic leukemia
Chronic lymphocytic leukemia ( CLL ) is the most common form of adult leukemia . CLL affects a particular lymphocyte - B- cells derived from the bone marrow and develop in the lymph nodes. Patients with CLL have too many abnormal lymphocytes, which accumulate mainly in the bone marrow and blood. The growth of these abnormal B- lymphocytes is the cause of the symptoms that you may have. MabThera in combination with chemotherapy destroys these cells, which are gradually removed from the body of the biological processes .

c) Rheumatoid arthritis
MabThera is used to treat rheumatoid arthritis . Rheumatoid arthritis is a disease of the joints . B lymphocytes are responsible for some of the symptoms that you have. MabThera is
used to treat rheumatoid arthritis in people who have already tried other drugs or have expired or have not worked well enough or have caused side effects . MabThera is usually taken together with another medicine called methotrexate.
MabThera slows damage to your joints caused by rheumatoid arthritis, and improve your ability to do normal daily activities.
Best respond to MabThera patients with a positive blood test for rheumatoid factor (RF ) and / or anti-cyclical citrullinated peptide (anti -CCP). Both tests are generally positive in rheumatoid arthritis and contribute to the confirmation of the diagnosis .

d) granulomatosis with polyangiitis or microscopic polyangiitis
MabThera, administered in combination with a glucocorticoid used to enter remission with granulomatosis with polyangiitis ( previously referred to as Wegener's granulomatosis ) or microscopic polyangiitis . Granulomatosis with polyangiitis and microscopic polyangiitis are two forms of blood vessel inflammation that affects mainly the lungs and kidneys, but can also affect other organs. Part of the reason for these conditions are B- lymphocytes.

2 . What you should know before using MabThera
Do not use MabThera:
if you are allergic to rituximab, to other similar proteins, or any of the other ingredients of this medicine (listed in Section 6) ;
if you have an active, severe infection or severely decreased immune system function ;
if you have severe heart failure or severe, uncontrolled cardiac disease and have rheumatoid arthritis granulomatosis with polyangiitis or microscopic polyangiitis .
If you are not sure , you should ask your doctor, who will inform you accordingly .

Before starting treatment with MabThera, tell your doctor :
If you think you have hepatitis infection now or have had it in the past. In rare cases, patients who have had hepatitis B might have a repeat attack of hepatitis, which in rare cases can be fatal . Patients who have had hepatitis B will be carefully reviewed by a doctor for signs of active hepatitis B ;
if you are being treated for high blood pressure. You may be asked not to take your medicine 12 hours before infusion of MabThera. In some people, blood pressure decreased during the infusion ;
if you have ever had heart disease (eg, angina, palpitations, or heart failure) or a history of breathing problems .
It may be necessary for your doctor to take special care of you during your treatment with MabThera ( in some cases above ) .

Warnings and Precautions
Talk to your doctor, pharmacist or nurse before using MabThera:
tell your doctor if you are taking or have taken medicines that affect your immune system , such as chemotherapy or immunosuppressive agents.
If you have rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis , your doctor also :
If you think you may have an infection , even a mild one like a cold. The cells that are affected by MabThera, help fight infection and you should wait until the infection has passed before you are given MabThera. Please tell your doctor if you have had a lot of infections or suffer from severe infections ;
if you think that you may need any vaccinations in the near future, including vaccinations needed to travel to other countries. Some vaccines should not be administered concomitantly with MabThera or in the months after the administration of MabThera. Your doctor will check if you should have any vaccines before you start treatment with MabThera.
So far there is not much information on the treatment of children and adolescents with MabThera; If you are under the age of 18 years , you or your parent / guardian should ask your doctor if MabThera is right for you.

Other medicines, MabThera
Before starting treatment , make sure to tell your doctor if you are taking or have recently taken any other medicines (including those you have bought yourself from a pharmacy , supermarket or health store) . This is extremely important , as using more than one drug may strengthen or weaken their effect. MabThera should not be used with other medicines unless your doctor has told you it is safe .

Pregnancy and lactation
You should tell your doctor if you are pregnant, think you are pregnant or planning a pregnancy . This is because MabThera is an antibody and can cross the placenta and affect your baby.
If you could get pregnant should use an effective method of birth control during treatment with MabThera and for 12 months after the last dose of MabThera.
MabThera may also pass into breast milk and therefore should not breast- feed your baby during treatment with MabThera and for 12 months after the last dose of MabThera.

Driving and using machines
It is not known whether MabThera affect your ability to drive or operate machinery.

3 . How to use MabThera
MabThera is an infusion that is given directly into your veins ( "drip " ) . While you are given MabThera, will be under the supervision of a medical professional if you have any side effects during the infusion.
Before the infusion will be given medicines to prevent or reduce possible reactions to MabThera.

a) If you are being treated for non-Hodgkin's lymphoma
If you are treated with MabThera, you will receive infusions every other week - a total of four infusions (days 1st , 8th , 15th and 22nd ) , so that the course of treatment usually lasts 22 days. Possible Repeated courses of treatment with MabThera. If you are treated with MabThera in combination with other medicines, you will receive an infusion of MabThera in the day as the other drugs , which are usually 8 times at 3-week intervals . If you have responded to treatment and MabThera is given to you further as continuous ( maintenance) treatment , you will receive one infusion of MabThera in 2 or 3 months ( as prescribed by your doctor) for two years. Depending on your condition , your doctor may change the number of infusions .

b) If you are being treated for chronic lymphocytic leukemia
When treated with MabThera in combination with chemotherapy , you will receive MabThera infusion on day 0 of cycle 1 and then on day 1 of each cycle for a total of 6 cycles . Each cycle has a duration of 28 days. Chemotherapy should be administered after infusion of MabThera. Your doctor will decide whether you should receive concomitant supportive care.

c) If you are being treated for rheumatoid arthritis
Each course of treatment consists of two separate infusions which are given 2 weeks. Possible repeated courses of treatment with MabThera. Depending on the signs and symptoms of your disease, your doctor will decide when you should receive more MabThera. This may be months .

d) If you are being treated for granulomatosis with polyangiitis and microscopic polyangiitis
Treatment with MabThera consists of four separate infusions are administered at intervals of one week. Before beginning treatment with MabThera will normally be administered corticosteroids by injection. To treat your condition , your doctor may at any time initiate treatment with corticosteroids administered orally .

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 require treatment . Rarely, some of these reactions have been fatal.

Infusion reactions
During or within the first 2 hours of the first infusion may develop fever, chills and shivering . Less frequently , some patients may experience pain at the infusion site , blisters, itching, nausea, fatigue , headache , difficulty breathing , 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 effects may be worse. Tell the person giving you the infusion if you develop any of these symptoms , as may be necessary to infusion to slow or stop. You may need additional treatment with antihistamines or acetaminophen . When these symptoms disappear or improve, the infusion can be continued. Less likely to get these reactions after the second infusion. If you have a serious infusion reaction , your doctor may decide not to continue treatment with MabThera.

infections
Tell your doctor if, after treatment with MabThera have symptoms of infection, for example . fever, cough , sore throat , burning pain when urinating , or if you feel weak or generally unwell . After treatment with MabThera may get infections more easily. Often they are cold, but there are cases of pneumonia or urinary tract infections .
Very rarely, some patients using MabThera, is a serious brain infection that has been fatal . Tell your doctor immediately if you have memory loss, difficulty thinking , difficulty walking or loss of vision .
If you are being treated for rheumatoid arthritis will also find this information in the Patient Alert Card , which is given by your doctor. It is important to keep the Patient Alert Card and show it to your partner or the person who takes care of you.

skin reactions
Very rarely occur severe skin conditions , blistering , which can be life threatening . May redness often associated with blistering or mucosa , e.g., on the inner side of the mouth , the genital area , or the eyelids, as there may be an elevated temperature. Tell your doctor immediately if you experience any of these symptoms.

other reactions
a) If you are being treated for non-Hodgkin's lymphoma or chronic lymphocytic leukemia
The most commonly reported side effects due to MabThera ( reported in more than 1 patient in 10 ) are:
infections such as pneumonia ( bacterial ) and herpes ( viral ) or bronchial inflammation ( bronchitis ) ;
low white blood cell count with or without fever, low platelet count in the blood ;
allergic reactions after infusion ;
nausea ;
skin rash , itching, bald spots on the scalp , fever , chills, physical weakness , headache ;
changes in laboratory studies directed by your doctor. These include reduction in the amount of specific proteins in the blood ( immunoglobulins ) that helps protect against infections.
Common side effects due to MabThera ( reported in more than 1 in 100 patients ) include:
infections such as sepsis and pneumonia ( bacterial ) , herpes and hepatitis B ( viral ) or candida ( fungal ), inflammation of the bronchial tubes and sinuses or other common infections of unknown origin ;
low red blood cell count , low red and white blood cells and platelets ;
allergic reactions (hypersensitivity) ;
high levels of blood sugar, weight loss, fluid retention in the face and the body , increased blood levels of the enzyme (LDH), low levels of calcium in the blood ;
abnormal skin sensations such as numbness , tingling, pricking , burning, chills, decreased sense of touch. Anxiety, difficulty in sleeping, facial redness and bruising due to dilation of blood vessels , dizziness , anxiety ;
increased lacrimation , impaired secretion and shedding , inflammation of the eye ( conjunctivitis) ;
ringing in the ears, ear pain ;
heart disorders ( heart attack, irregular heartbeat, unusually fast heart rate ) ;
high or low blood pressure , decrease in blood pressure upon standing;
inflammation, irritation of the lungs and / or chest tightness, throat and / or sinuses, shortness of breath, too little oxygen to the organs , cough ;
vomiting , diarrhea , abdominal pain, irritation and / or ulceration of the mouth and throat , difficulty swallowing, constipation , indigestion . Eating Disorders : reducing the amount of food eaten by a subsequent dangerous weight loss;
skin disorders , burning sensation of the skin, itching, increased sweating , night sweats ;
disorders of the musculoskeletal system , abnormal increase in muscle tone , pain , joint pain, muscle pain, back pain and neck ;
general disorders , tumor pain, marked redness of the face and other areas of the skin, general discomfort or uneasiness , flu syndrome , fatigue, tremors, multiorgan dysfunction.
Uncommon side effects due to MabThera ( reported in more than 1 in 1000 patients ) include:
clotting dysfunction , decreased production of blood cells , an autoimmune reduction in red blood cells , swollen / enlarged lymph nodes;
low mood and loss of interest or pleasure in usual activities , nervousness ;
changes in taste ;
cardiac disorders (myocardial , unusually fast heartbeat , slow pulse , irregular heartbeat , chest pain ) inflammation, irritation in the lungs and / or chest tightness, asthma , shortness of breath ;
enlargement of the abdomen ;
pain at the infusion site .
Very common side effects, due to MabThera (reported in less than 1 in 10 000 patients) , include:
temporary increase of the immunoglobulins , chemical blood disorders caused by decomposition of perishing cancer cells, which can also lead to renal failure;
nerve damage in the arms and legs, facial paralysis ;
heart failure ;
inflammation of blood vessels , including those that give rise to skin symptoms ;
perforation of the intestinal wall ;
renal failure ;
severe conditions with the formation of blisters on the skin , which can be life threatening . May redness often associated with blistering or mucosa , e.g., on the inner side of the mouth , the genital area , or the eyelids, as there may be an elevated temperature ;
infection caused by a fungus called Pneumocystis jirovecii.
Events occurring not known :
continuous decrease of white blood cells;
immediate reduction in platelet infusion-related ( reversible) , in rare cases can be fatal ;
hearing loss ;
loss of other sensations.
b) If you are being treated for rheumatoid arthritis
The most commonly reported side effects due to MabThera ( reported in more than 1 patient in 10 ) are:
infections , e. pneumonia ( bacterial ) ;
pain when passing urine ( urinary tract infection ) ;
allergic reactions, which often occur during the infusion , but may occur within 24 hours thereafter ;
changes in blood pressure , nausea, rash, fever , itching, runny or stuffy nose, sneezing , shaking , fast heartbeat , and fatigue ;
headache ;
changes in laboratory studies directed by your doctor. These include reduction in the amount of specific proteins in the blood ( immunoglobulins ) that helps protect against infections.
Common side effects due to MabThera ( reported in more than 1 in 100 patients ) include:
infections , e. inflammation of the bronchi ( bronchitis ) ;
feeling of fullness or throbbing pain behind the nose , cheeks and eyes ( sinusitis ) , abdominal pain , vomiting and diarrhea , breathing problems ;
fungal infection of the feet ( athlete's foot ) ;
high cholesterol levels in the blood ;
abnormal skin sensations such as numbness, tingling, pricking or burning , sciatica , migraine, dizziness ;
hair loss ;
anxiety, depression ;
indigestion, diarrhea and reflux irritation and / or ulceration of the throat and mouth ;
pain in the abdomen, back , muscles and / or joints.
Uncommon side effects due to MabThera ( reported in more than 1 in 1000 patients ) include:
retention of excessive fluid in the face and body ;
inflammation, irritation and / or tightness in the lungs and throat, cough;
skin reactions including urticaria, pruritus , and rash ;
allergic reactions including wheezing, or shortness of breath, swelling of the face and tongue , collapse .
Very common side effects, due to MabThera (reported in less than 1 in 10 000 patients) , include:
a complex of symptoms that arise after a few weeks of infusion of MabThera, including effects like allergic , e. rash , itching , joint pain , swollen lymph nodes and fever ;
severe conditions with the formation of blisters on the skin , which can be life threatening . May redness often associated with blistering or mucosa , e.g., on the inner side of the mouth , the genital area , or the eyelids, as there may be an elevated temperature.
Other frequently reported adverse effects due to MabThera, decreased number of white blood cells (neutrophils ) that help to fight infections. Some infections may be severe ( please see information on " Infections " at this point) .

c) If you are being treated for granulomatosis with polyangiitis and microscopic polyangiitis
The most commonly reported side effects due to MabThera ( reported in more than 1 patient in 10 ) are:
infections , e. chest infections , urinary tract infection ( painful urination ) , cold and herpes infections ;
allergic reactions, which is most likely to occur during the infusion , but can be up to 24 hours after infusion ;
diarrhea ;
cough or shortness of breath ;
nosebleeds ;
hypertension ;
joint pain or back ;
muscle twitching or trembling ;
dizziness ;
tremor ( often hand ) ;
difficulty sleeping ( insomnia);
swelling of the hands or ankles.
Common side effects due to MabThera ( reported in more than 1 in 100 patients ) include:
indigestion ;
constipation ;
skin rashes , including acne or spots ;
flushing or skin ;
stuffy nose ;
stiff or painful muscles ;
pain in the muscles of the arms or legs ;
low red blood cells ( anemia) ;
low number of platelets in the blood ;
increasing the amount of potassium in the blood ;
changes in heart rate or palpitations .
Very common side effects, due to MabThera (reported in less than 1 in 10 000 patients) , include:
severe conditions with the formation of blisters on the skin , which can be life threatening . May redness often associated with blistering or mucosa , e.g., on the inner side of the mouth , the genital area , or the eyelids, as there may be an elevated temperature ;
recurrence of a previous infection with hepatitis B.
MabThera may also cause changes in laboratory tests directed by your doctor. These include a reduced number of white blood cells (neutrophils ) that help fight infection and reduce the amount of specific proteins in the blood ( immunoglobulins ) that helps protect against infections.
If you are receiving MabThera in combination with other drugs , some of the side effects you may experience may be due to other medicines.

Adverse event reporting
If you get any side effects, tell your doctor, pharmacist or nurse. This includes all listed in this leaflet . You can also report side effects directly through the National Reporting System . As reported side effects , you can do your bit to get more information on the safety of this medicine.

5 . How to store MabThera
Keep out of reach of children.
Do not use this medicine after the expiry date stated on the carton after " EXP" . The expiry date refers to the last day of that month.
Store in a refrigerator (2 ° C - 8 ° C). Store in the original package to protect from light.
Do not dispose of medications in wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required . These measures will help to protect the environment.

6 . Package Contents and more information
What MabThera contains
The active substance of MabThera is called rituximab . The vial contains 100 mg of rituximab (10 mg / ml).
The other ingredients are sodium citrate, polysorbate 80, sodium chloride , sodium hydroxide, hydrochloric acid and water for injection.

MabThera looks like and contents of the pack
MabThera is a clear, colorless solution , which is available as a concentrate for solution for infusion .
Vials of 10 ml are available in pack of 2 vials .

Marketing Authorisation Holder:
Roche Registration Limited, United Kingdom.

manufacturer:
Roche Pharma AG, Germany .