Ristova Infusion

Rituximab is an antibody which is a type of protein. Rituximab binds to the surface of a type of white blood cell, the B lymphocytes. When rituximab binds to the surface of this cell it causes the cell to die. RISTOVA may be used for the treatment of two different conditions. Your doctor may prescribe RISTOVA for the treatment of:

1. Non-Hodgkin’s Lymphoma (NHL)
   Non-Hodgkin’s Lymphoma is a disease of the lymphatic system, and B lymphocytes are involved in the cause of some of the symptoms you may have. RISTOVA can be used alone or with other medicines your doctor may prescribe to induce remission of your disease. RISTOVA may be used as a continuous (maintenance) treatment in patients who have responded to induction treatment.
2. Chronic lymphocytic leukaemia (CLL)
   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 high number of these abnormal B-lymphocytes is the cause of symptoms you may have. RISTOVA in combination with chemotherapy destroys these cells which are then gradually removed from the body by biological processes.
3. Rheumatoid arthritis (RA)
   RISTOVA 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. RISTOVA is used to treat rheumatoid arthritis in people who have already tried some other medicines which have either stopped working or have not worked well enough. RISTOVA is usually taken together with another medicine called methotrexate. RISTOVA slows down the damage to your joints caused by rheumatoid arthritis and improves your ability to do normal daily activities.
4. ANCA-Associated Vasculitis (AAV)
   RISTOVA in combination with glucocorticoids is used for the treatment of patients with severely active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (inflammation of blood vessels).

Do not use RISTOVA:

• if you are allergic to rituximab, to other similar proteins, or to any of the other ingredients in the solution
• if you have an active, severe infection or have a severely decreased immune system function. If you are not sure about this, you should ask your doctor who will inform you accordingly.

Take special care with RISTOVA:

• if you think you have hepatitis infection now or have had it in the past. In a few cases, patients who have had hepatitis B might have a repeat attack of hepatitis. Patients with a history of hepatitis B infection will be carefully checked by their doctor for signs of active hepatitis B.
• if you are taking treatment for high blood pressure. You may be asked not to take your medicines 12 hours before your infusion of RISTOVA. Some people have a fall in their blood pressure during the infusion.
• if you have ever had heart disease (i.e. angina, palpitations, or heart failure) or a history of breathing problems. Your doctor will take special care of you during your treatment with RISTOVA.
• tell your doctor if you are taking or have previously taken medicines which may affect your immune system, such as chemotherapy or immunosuppressive agents.
• If you have rheumatoid arthritis also tell your doctor
• if you think you may have an infection, even a mild one like a cold. The cells that are affected by RISTOVA help to fight infection and you should wait until the infection has passed before you are given RISTOVA. Also please tell your doctor if you had a lot of infections in the past or suffer from severe infections.
• 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 RISTOVA or in the months after you receive RISTOVA. Your doctor will check if you should have any vaccines before you receive RISTOVA.

Use in children:
At present, there is not much information about RISTOVA treatment in children and adolescents; if you are under 18 years of age, you or your parent should ask your doctor if RISTOVA is right for you.

Pregnancy and Breastfeeding
Pregnancy: You must tell your doctor if you are pregnant, if you think you are pregnant or if you intend to become pregnant. This is because RISTOVA is an antibody and can cross the placenta and affect your baby. If you can get pregnant, you must use an effective method of birth control during therapy with RISTOVA and for 12 months after your last treatment RISTOVA.
Breastfeeding: If you are pregnant or breastfeeding your baby while taking RISTOVA please consult your doctor, pharmacist or other healthcare professional for advice. RISTOVA might also get into breast milk and so you should not breast-feed your baby during treatment with RISTOVA and for 12 months after your last time treatment with RISTOVA.

Driving and using machinery:
It is not known whether RISTOVA has an effect on your ability to drive a car or operate machinery.

Taking other medicines with RISTOVA:
Before starting treatment, make sure your doctor knows if you are taking other medicines (including those not prescribed by your doctor). This is extremely important, as using more than one medicine at the same time can strengthen or weaken their effect. RISTOVA should not be used with other medicines without your doctor’s consent. If you are taking medicines on a regular basis, including complementary or traditional medicines, the use of RISTOVA with these medicines may cause undesirable interactions. Please consult your doctor, pharmacist or other healthcare professional for advice.

RISTOVA is administered by a healthcare professional after dilution as an intravenous infusion (“drip”). Your doctor will give you a medicine to prevent or reduce pain and/or fever and allergy before each infusion of RISTOVA. You will be observed by a healthcare professional while you are being given RISTOVA in case you have any side effects during the infusion. Before the infusion is given you will be given medicines to prevent or reduce possible reactions to RISTOVA.

If you are being treated for non-Hodgkin’s Lymphoma
If you are treated with RISTOVA alone you will receive infusions at weekly intervals for a total of four infusions (days 1, 8, 15 and 22), so that a course of treatment usually lasts for 22 days. Repeated treatment courses with RISTOVA are possible. If you are treated with RISTOVA in combination with other medicines, you will receive an infusion of RISTOVA on the same day as the other medicines, which are usually given 8 times at 3-week intervals. If you have responded to treatment and are further treated with RISTOVA as continuous (maintenance) treatment, you will receive one infusion of RISTOVA every 2 or 3 months (as directed by your doctor) for two years. Your doctor may change the number of infusions depending on your disease.

If you are being treated for chronic lymphocytic leukemia
When you are treated with RISTOVA in combination with chemotherapy, you will receive RISTOVA infusions on day 0 (the day before chemotherapy), 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 RISTOVA infusion. Your doctor will decide if you should receive supportive therapy at that time.

If you are being treated for rheumatoid arthritis
Each course of treatment is made up of two separate infusions which are given 2 weeks apart. Repeated courses of treatment with RISTOVA are possible. Depending on the signs and symptoms of your disease, your doctor will decide when you should receive more RISTOVA. This may be months from now.

Do not share medicines prescribed for you with another person. In the event of over dosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison centre. If you have missed a dose or taken more than you should:
You will be receiving doses according to your treatment plan and therefore you should go to the oncology clinic according to your scheduled appointments.

RISTOVA can cause side effects. Side effects are mild to moderate but some may be serious and may be fatal.

Infusion reactions
During or within the first 2 hours of the first infusion you may develop fever, chills and shivering. Less frequently, some patients may experience blisters, itching, sickness, tiredness, headache, breathing difficulties, tongue or throat swelling, itchy, runny nose, vomiting, flushing or palpitations, heart attack or low number of platelets. If you have heart disease or angina, these might get worse. Tell the person giving you the infusion immediately if you develop any of these symptoms, as the infusion may need to be slowed down or stopped for a while. 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.

Infections
Tell your doctor after your RISTOVA treatment if you get any symptoms of an infection, for example fever, cough, sore throat, burning pain when passing urine, or you start to feel weak or generally unwell. You might get infections more easily following RISTOVA therapy. Often these are colds, but there have been cases of pneumonia or urinary infections. Some patients taking RISTOVA have had a serious brain infection, which has been fatal. Tell your doctor immediately if you have memory loss, trouble thinking, difficulty with walking or loss of vision.

Other reactions

a) If you are being treated for non-Hodgkin’s Lymphoma or chronic lymphocytic leukaemia
The most frequently reported side effects due to RISTOVA are:

• infections such as pneumonia (bacterial) and herpes (viral) or bronchial tube inflammation (bronchitis)
• low number of white blood cells, with or without fever, low number of platelets in the blood
• allergic reactions after infusion
• nausea
• skin rashes, itching, bald spots on the scalp, fever, chills, physical weakness, headache
• decreased immunity (decreased IgG levels).
• infections such as sepsis and pneumonia (bacterial), herpes and hepatitis B (viral) or candidal (fungal) bronchial tube and sinuses inflammation, or other general infections of unknown origin
• low number of red blood cells, low number of red and white blood cells and platelets
• allergic reactions (hypersensitivity)
• high sugar level in the blood, weight loss, excess fluid in the face and the body, increased blood levels of the enzyme (LDH), low blood level of calcium
• abnormal sensations of the skin, such as numbness, tingling, pricking, burning, a creeping skin sensation, decreased sense of touch. Feeling restless, difficulty falling asleep, becoming red in the face and bruising of the skin as a consequence of dilation of the blood vessels, dizziness, anxiety
• an increased production of tears, secretion and shedding disorders, inflammation of the eye (conjunctivitis)
• ringing sound in the ears, ear pain
• heart disorders (heart attack, irregular heart rate, abnormally fast heart rate)
• high or low blood pressure, a decrease in blood pressure upon assuming an upright posture
• inflammation, irritation and / or tightness of the lungs, throat and / or sinuses, shortness of breath, too little oxygen reaching the body organs, coughing
• vomiting, diarrhoea, pain in the abdomen, irritation and /or ulceration of the throat and the mouth, difficulties in swallowing, constipation, indigestion. Eating disorders: decrease in the amount of food eaten with a consequential dangerous loss in weight
• skin disorders, burning sensation of the skin, itching, increased perspiration, night sweats
• musculoskeletal disorders, abnormal increase in tightness of muscle tone, pain, joint pain, muscle pain, back and neck pain
• general disorders, tumour pain, becoming markedly red in the face and other areas of the skin, general discomfort or uneasiness, flu syndrome, fatigue, shaking, multi-organ dysfunction.

Less frequent side effects due to RISTOVA include:

• abnormal clotting, decrease of blood cells production, auto-immune decrease of red blood cells, swollen/enlarged lymph nodes
• low mood and loss of interest or pleasure in usual activities, nervousness
• taste changes
• heart disorder (heart attack, abnormally fast heart rate, reduced heart rate, irregular heart rate, chest pain) inflammation, irritation and/or tightness of the lungs, asthma, shortness of breath
• enlargement of the abdomen
• pain at the infusion site.

b) If you are being treated for rheumatoid arthritis
The most frequent side effects due to RISTOVA are:

• infections such as pneumonia (bacterial)
• pain on passing water (urinary tract infection)
• allergic reactions after infusion
• changes in blood pressure, nausea, rash, fever, feeling itchy, runny or block nose and sneezing, shaking, rapid heart beat, and tiredness
• headache.
• infections such as bronchial tube inflammation (bronchitis)
• a feeling of fullness or a throbbing pain behind the nose, cheeks and eyes (sinusitis), pain in the 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

Less frequent side effects due to RISTOVA include:

• 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
• a complex of symptoms occurring within a few weeks of an infusion of RISTOVA including allergic like reactions such as rash, itching, joint pain, swollen lymph glands and fever.

If you are receiving RISTOVA in combination with other medicines, some of the side effects you may experience may be due to the other medicine. If any of the side effects gets serious, or, if you notice any side effects not listed in this leaflet, please inform your doctor, nurse or pharmacist immediately.

Keep out of the reach and sight of children. Always store the vials in the closed original pack at 2 – 8 °C (in the refrigerator). Keep the container in the outer carton in order to protect from light. Do not use after the expiry date dated on the outer pack and on the vial label.