MabThera 500 mg concentrate for solution for infusion Rituxi - United Kingdom[英国药品]

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MabThera 500 mg concentrate for solution for infusion Rituxi

2014-04-19 09:48:39 来源: 作者: 【大中小】浏览:385次评论:0条

For doctors

What is it and how is it used?

MabThera contains an antibody (rituximab) which is a type of protein. Rituximab binds to the surface of a type of white blood cell, the B lymphocyte. When rituximab binds to the surface of this cell it causes the cell to die.

MabThera may be used for the treatment of three different conditions. Your doctor may prescribe MabThera for the treatment of:

a) Non-Hodgkin’s Lymphoma Non-Hodgkin’s lymphoma is a disease of the lymphatic system. B lymphocytes are involved in the cause of some of the symptoms you may have. MabThera can be used alone or with other medicines your doctor may prescribe to induce remission of your disease. MabThera may be used as a continuous (maintenance) treatment for 2 years in patients who have responded to induction treatment.

b) Chronic lymphocytic leukaemia 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 gradulally removed from the body by biological processes.

c) Rheumatoid arthritis 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.

What do you have to consider before using it?

Do not take MabThera

If you are not sure about this, you should ask your doctor who will inform you accordingly.

Tell your doctor before your MabThera treatment

Take special care with MabThera

If you have rheumatoid arthritis also tell your doctor

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

Taking other medicines
Before starting treatment, make sure your doctor knows if you are taking or have recently taken any other medicines (including those you have bought for yourself from a pharmacy, supermarket or health store). This is extremely important, as using more than one medicine at the same time can strengthen or weaken their effect. MabThera should not be used with other drugs unless your doctor has told you it is safe to do so.

Pregnancy and breast-feeding
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 MabThera 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 MabThera and for 12 months after the last time you were treated with MabThera.

MabThera might also get into breast milk and so you should not breast-feed your baby during therapy with MabThera and for 12 months after the last time you were treated with MabThera

Driving and using machines
It is not known whether MabThera has an effect on your ability to drive a car or use machines.

How is it used?

MabThera is an infusion (“drip”) which is given directly into your veins. You will be observed by a health care professional while you are being given MabThera 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 MabThera.

a) If you are being treated for non-Hodgkin’s Lymphoma If you are treated with MabThera alone you will receive infusions at weekly intervals for a total of four infusions (days 1, 8, 15 and 22), so that the a course of treatment usually lasts for 22 days. Repeated treatment courses with MabThera are possible. If you are treated with MabThera in combination with other medicines, you will receive an infusion of MabThera 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 MabThera as continuous (maintenance) treatment, you will receive one infusion of MabThera 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.

b) If you are being treated for chronic lymphocytic leukemia 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.

c) 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 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.

What are possible side effects?

Like all medicines, MabThera 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 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 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 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 MabThera 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 MabThera therapy. Often these are colds, but there have been cases of pneumonia or urinary infections.

Very rarely, some patients taking MabThera 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.

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 Alert Card and show it to your partner or caregiver.

Other reactions

a) If you are being treated for non-Hodgkin’s Lymphoma or chronic lymphocytic leukaemia The most commonly reported side effects due to MabThera (reported in more than 1 out of 10 patients are:

Common side effects due to MabThera (reported in more than 1 out of 100 patients) include:

Uncommon side effects due to MabThera (reported in more than 1 out of 1000 patients) include:

b) If you are being treated for rheumatoid arthritis The most commonly reported side effects due to MabThera (reported in more than 1 out of 10 patients) are:

Commonly side effects due to MabThera (reported in more than 1 out of 100 patients) include:

Uncommon side effects due to MabThera (reported in more than 1 out of 1000 patients) include:

If you are receiving MabThera 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 (chemist) immediately.

How should it be stored?

Keep out of the reach and sight of children.

Do not use MabThera 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.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer required. These measures will help to protect the environment.

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For doctors

What is it?

MabThera is a concentrate that is made up into a solution for infusion (drip into a vein). It contains the active substance rituximab.

What is it used for?

MabThera is used in adults to treat non-Hodgkin’s lymphoma (a cancer of the lymph tissue), chronic lymphocytic leukaemia (CLL, a cancer of the B-lymphocytes, a type of white blood cell) and rheumatoid arthritis (a disease that causes inflammation of the joints).

In non-Hodgkin’s lymphoma, MabThera is used to treat two types of the disease, both of which affect B-lymphocytes:

in patients with diffuse large B-cell lymphoma, MabThera is used in combination with a specific type of chemotherapy called CHOP cyclophosphamide, doxorubicin, vincristine and prednisolone

In CLL, MabThera is used in combination with chemotherapy in patients who have not been treated before and in patients whose disease has come back after previous treatment.

In rheumatoid arthritis, MabThera is used in adults with severe disease in combination with methotrexate (a medicine that acts on the immune system). It is used in patients who cannot take or have not responded adequately to other treatments for rheumatoid arthritis, including a tumour necrosis factor (TNF) inhibitor.

The medicine can only be obtained with a prescription.

How is it used?

MabThera should be given under the close supervision of an experienced doctor, and in an environment where facilities for resuscitating patients are immediately available. When it is given with chemotherapy, MabThera is given on the first day of each chemotherapy cycle. Patients should be given an antihistamine to prevent allergic reactions and an anti-pyreticto reduce fever before each infusion. They may also need a corticosteroid to reduce inflammation (especially in CLL patients with high levels of lymphocytes in the blood and in rheumatoid arthritis patients).

In the treatment of non-Hodgkin’s lymphoma, the usual dose of MabThera is 375mg per square metre body surface area (calculated using the patient’s height and weight). The number and frequency of infusions depends on the type of lymphoma being treated.

For CLL, MabThera is given six times: the first dose is 375mg/m , followed by 500mg/m for the remaining doses. To prevent side effects caused by destruction of the cancerous lymphocytes, patients need to be well hydrated and treated with medicines that help to stabilise uric acid levels before treatment.

For rheumatoid arthritis, MabThera is given as two infusions of 1,000mg with a two-week interval between them. Patients usually respond to treatment within 16 to 24 weeks of initial treatment. After 24 weeks, treatmentcan be repeated depending on the patient’s response. Patients who receive MabThera for rheumatoid arthritis must be given a special card that explains the symptoms of certain types of infection that can occur as a side effect of MabThera, instructing patients to seek medical care immediately if they experience them. See the summary of product characteristics (also part of the EPAR) for full details.

How does it work?

The active substance in MabThera, rituximab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) that is found on certain cells in the body. Rituximab has been designed to target an antigen called CD20, which is present on the surface of all B-lymphocytes. When rituximab attaches to the antigen, this causes cell death. This helps in lymphoma and CLL, since the cancerous B-lymphocytes are destroyed. In rheumatoid arthritis, the B-lymphocytes are destroyed in the joints, helping to reduce inflammation.

How has it been studied?

MabThera has been studied in both types of non-Hodgkin’s lymphoma:

overall response rate to MabThera in 203 patients who had failed previous treatments and the other two studiesweremaintenance studies in a total of 1353patients (334 patients whose disease had come back after previous treatment and 1019 previously untreated patients), looking at how long the patients lived without the disease getting worse;

in diffuse large B-cell lymphoma, the effectiveness of adding MabThera to CHOP chemotherapy was examined in a study involving 399 patients who were all over 60 years of age. The main measure of effectiveness was how long the patients lived without the disease getting worse or the need for a change in treatment

In CLL, the effectiveness of adding MabThera to ‘FC’ chemotherapy (fludarabine and cyclophosphamide) was studied in 817 patients who had not been treated before and in 552 whose disease had come back after previous treatment. The main measure of effectiveness was how long the patients lived without the disease getting worse. Additional studies from the published scientific literature looked at the effects of adding MabThera to other types of chemotherapy.

In rheumatoid arthritis, MabThera was studied in 517patients. The effectiveness of adding MabThera to methotrexate was compared with that of adding placebo (a dummy treatment). The study measured how many patients had experienced a 20% improvement in the key symptoms of rheumatoid arthritis after 24 weeks.

What benefits has it shown during the studies?

In non-Hodgkin’s lymphoma, patients receiving MabThera had better outcomes than those not receiving it:

What is the risk associated?

When used to treat non-Hodgkin’s lymphoma or CLL, the most common side effects with MabThera (seen in more than 1 patient in 10) are bacterial infections, viral infections, bronchitis (inflammation of the airways in the lungs), neutropenia (low levels of neutrophils, a type of white blood cell), leucopenia (low white blood cell counts), febrile neutropenia (neutropenia with fever), thrombocytopenia (low blood platelet counts), reactions related to the infusion (mainly fever, chills and shivering), angioedema (swelling beneath the skin), nausea (feeling sick), pruritus (itching), rash, alopecia (hair loss), fever, chills, asthenia (weakness), headache and decreased levels of IgG (a type of antibody).

When used to treat rheumatoid arthritis, the most common side effects (seen in more than 1 patient in 10) are headache, upper respiratory tract infection (colds), urinary tract infection (infection of the structures that carry urine), reactions related to the infusion. For the full list of all side effects reported with MabThera, see the package leaflet.

MabThera should not be used in people who may be hypersensitive (allergic) to rituximab, mouse proteins or any of the other ingredients. It must not be used in patients who have an active severe infectionor a severely weakened immune system. In addition, patients with rheumatoid arthritis must not receive MabThera if they have severe heart failure (an inability of the heart to pump enough blood around the body) or severe heart disease.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that MabThera’s benefits are greater than its risksandrecommended that it be given marketing authorisation.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for MabThera to Roche Registration Limited on 2 June 1998. The marketing authorisation is valid for an unlimited period. europa.eu/Find medicine/Human medicines/European Public Assessment Reports.For more information about treatment with MabThera, read the package leaflet (also part of the EPAR)or contact your doctor or pharmacist.

This summary was last updated in 10-2010.

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Name

MabThera 500 mg concentrate for solution for infusion

Composition

Each ml contains 10 mg of rituximab.

Each single-use vial containing 500 mg of Rituximab.

Rituximab is a genetically engineered chimeric mouse/human monoclonal antibody representing a glycosylated immunoglobulin with human IgG1 constant regions and murine light-chain and heavy-chain variable region sequences. The antibody is produced by mammalian (Chinese hamster ovary) cell suspension culture and purified by affinity chromatography and ion exchange, including specific viral inactivation and removal procedures.

For a full list of excipients, see section 6.1.