MabThera 1400 mg solution for subcutaneous injection

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

MabThera 1400mg solution for subcutaneous injection

rituximab

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What MabThera is and what it is used for
2. What you need to know before using MabThera
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

What MabThera is

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 “B-lymphocytes”. When rituximab binds to the surface of these cells, it causes their death.

MabThera is available as a medicine to be given by infusion (called MabThera 100 mg or MabThera 500 mg concentrate for solution for infusion), and as a medicine to be administered as an injection under the skin (called MabThera 1400 mg or MabThera 1600 mg solution for subcutaneous injection).

What MabThera is used for

MabThera 1400 mg is used for the treatment of non-Hodgkin's lymphoma in adults.

• It is a disease of the lymphatic system (part of the immune system) that affects a type of white blood cell called B-lymphocytes.

MabThera 1400 mg may be given alone or together with other medicines called “chemotherapy”.

At the beginning of your treatment, MabThera will always be given to you by infusion (intravenous infusion).

After this, MabThera will be given to you as an injection under the skin. Your doctor will decide when to start using MabThera as an injection.

In patients who have responded to treatment, MabThera may be used as maintenance treatment for 2 years after completing the initial treatment.

2. What you need to know before starting MabThera

Do not use MabThera

• if you are allergic to rituximab, to other proteins similar to rituximab, or to any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to hyaluronidase (an enzyme that helps increase absorption of the active substance)
• if you have an active, serious infection
• if you have a weakened immune system.

Do not use MabThera if any of the above apply to you. If you are unsure, ask your doctor, pharmacist, or nurse before receiving MabThera.

Warnings and precautions

Tell your doctor, pharmacist, or nurse before using MabThera:

• if you think you have infectious hepatitis or have had it in the past. This is because, in a few cases, patients who previously had hepatitis B may experience a relapse, which has been fatal in very rare instances. Patients with a history of hepatitis B infection will be closely monitored by their doctor for possible signs of hepatitis B reactivation.
• if you have ever had heart disease (such as angina, palpitations, or heart failure) or respiratory problems.

If any of the above apply to you (or if you are unsure), consult your doctor, pharmacist, or nurse before receiving MabThera. Your doctor must monitor you during treatment with MabThera.

Also ask your doctor if you think you may need vaccinations in the near future, including those required for travel to other countries. Some vaccines should not be given at the same time as MabThera or in the months following its administration. Your doctor will check whether you need any vaccinations before receiving MabThera.

Children and adolescents

Inform your doctor, pharmacist, or nurse before receiving MabThera if you or your child is under 18 years of age. This is because there is limited information on the use of MabThera in children and adolescents.

Other medicines and MabThera

Inform your doctor or pharmacist if you are currently using, or have recently used, any other medicines, including those obtained without a prescription. This is because MabThera may affect how other medicines work. Likewise, other medicines may affect how MabThera works.

In particular, inform your doctor:

• if you are being treated for high blood pressure. You may be advised not to take your medication during the 12 hours prior to receiving MabThera. This is because some people experience a drop in blood pressure during infusion.
• if you have ever taken medicines that affect your immune system—such as chemotherapy or immunosuppressive drugs.

If any of the above apply to you (or if you are unsure), consult your doctor, pharmacist, or nurse before receiving MabThera.

Pregnancy and breastfeeding

You must inform your doctor if you are pregnant, think you might be pregnant, or plan to become pregnant. This is because MabThera can cross the placental barrier and may affect your baby.

If you are of childbearing age, you and your partner should use an effective method of contraception during treatment with MabThera and for 12 months after the last dose.

MabThera passes into breast milk in very small amounts. As the long-term effects on infants are unknown, breastfeeding is not recommended during treatment with MabThera and for 6 months after treatment ends, as a precaution.

Driving and operating machinery

It is unknown whether MabThera has any effect on the ability to drive vehicles or operate machinery.

MabThera contains sodium

This medicine contains less than 1 mmol of sodium (23 mg per 11.7 ml vial) and is therefore considered essentially "sodium-free".

3. How to use Mabthera

How this medicine is used

MabThera will be administered to you by a doctor or nurse experienced in the use of this medicine. You will be monitored during the administration of MabThera in case you experience any adverse effects.

At the beginning of your treatment, MabThera will always be given by infusion (intravenous infusion).

Later, MabThera will be administered as an injection under the skin (subcutaneous injection), taking approximately 5 minutes. A label is included with the vials specifying the medication.

Your doctor or nurse will place the label on the syringe before the injection.

Your doctor will decide when to start administering MabThera injections to you.

The subcutaneous injection of MabThera will be given in the abdominal area only, not in other areas of your body, and never in abdominal areas where the skin is red, bruised, soft, hard, or in areas with moles or scars.

Medicines administered before each dose of MabThera

Before each administration of MabThera, you will be given medicines (premedication) to prevent or reduce possible adverse effects.

Dose and frequency of treatment

• MabThera will be administered on the same day as chemotherapy. It is generally given up to 8 times at 3-week intervals.
• If you respond well to treatment, you may continue receiving MabThera as maintenance therapy every 2 or 3 months for two years.

Your doctor may adjust this depending on your response to the medicine.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, MabThera can cause adverse effects, although not everyone will experience them.

Most of these adverse effects are mild to moderate in intensity, but some may be serious and require treatment. In rare cases, some of these reactions have been fatal.

Reactions at the injection site

Many patients experience local adverse effects at the site of MabThera injection. These include: pain, swelling, bruising, bleeding, itching, or skin rash.

Your doctor may decide to discontinue your treatment with MabThera if you experience severe infusion reactions.

Infections

• Inform your doctor immediately if you experience any symptoms of infection such as:
• fever, cough, sore throat, burning sensation when urinating, or if you begin to feel tired or generally unwell,
• memory loss, difficulty concentrating, difficulty walking, or loss of vision. This may be due to a very rare, serious brain infection (Progressive Multifocal Leukoencephalopathy or PML), which has been fatal,
• fever, headache, stiff neck, lack of coordination (ataxia), personality changes, hallucinations, altered consciousness, seizures, or coma – this could be due to a serious brain infection (enteroviral meningoencephalitis), which may be fatal.

You may become more susceptible to infections during treatment with MabThera. These are usually colds, but cases of pneumonia or urinary tract infections have been reported. All are listed below under “Other adverse effects.”

Other adverse effects

Very common (may affect more than 1 in 10 people):

• bacterial or viral infections, bronchitis,
• low white blood cell count with or without fever, or low levels of blood cells called "platelets",
• nausea,
• hair loss from the scalp, chills, headache,
• reduced immunity due to decreased levels of antibodies called "immunoglobulins" (IgG) in the blood, which help protect against infection.

Common (may affect up to 1 in 10 people):

• blood infections (sepsis), pneumonia, herpes, common cold, bronchial infections, fungal infections, infections of unknown origin, sinus inflammation, hepatitis B,
• low red blood cell count (anemia), low levels of all blood cells,
• allergic reactions (hypersensitivity),
• high blood sugar levels, weight loss, peripheral and facial edema, increased levels of LDH enzyme in blood, decreased levels of calcium in blood,
• abnormal skin sensations such as numbness, tingling, pricking, burning, progressive increase in these skin sensations, reduced sense of touch,
• restlessness, difficulty falling asleep,
• redness of the face and other skin areas due to dilation of blood vessels,
• dizziness or anxiety,
• increased tearing, lacrimal duct disorders, eye inflammation (conjunctivitis),
• ringing in the ears (tinnitus), ear pain,
• heart disorders such as myocardial infarction, irregular heartbeat, abnormally rapid heartbeat,
• increased or decreased blood pressure (especially decreased blood pressure upon standing),
• tightening of the muscles in the airways causing difficulty breathing (bronchospasm), inflammation, irritation in the lungs, throat and/or nasal cavities, shortness of breath, runny nose,
• vomiting, diarrhea, abdominal pain, throat or mouth irritation or ulceration, difficulty swallowing, constipation, indigestion,
• eating disorders: insufficient food intake leading to weight loss,
• hives, increased sweating, night sweats,
• muscle problems such as muscle tension, joint or muscle pain, back and neck pain,
• tumor pain,
• general malaise or restlessness, fatigue, restlessness, cold-like symptoms,
• multi-organ failure.

Uncommon (may affect up to 1 in 100 people):

• coagulation disorders, decreased production of red blood cells, increased destruction of red blood cells (aplastic hemolytic anemia), lymph node inflammation/swelling,
• fatigue, loss of interest in usual activities, nervousness,
• disturbances in taste sensation, such as changes in food taste,
• heart problems such as reduced heart rate or chest pain (angina),
• asthma, insufficient oxygen supply to organs,
• stomach swelling.

Rare (may affect up to 1 in 1,000 people):

• temporary increase in levels of a type of antibody in the blood (called immunoglobulins – IgM), chemical changes in the blood caused by the breakdown of cancer cells,
• nerve damage in arms and legs, facial paralysis,
• heart failure,
• inflammation of blood vessels, including those causing skin symptoms,
• respiratory failure,
• damage to the intestinal wall (perforation),
• severe skin problems causing blisters that may be life-threatening,
• kidney problems (renal failure),
• severe vision loss (signs of damage to brain nerves).

Frequency not known (the frequency with which these adverse effects occur is unknown):

• delayed decrease in white blood cells in the blood,
• reduced platelet count after infusion – reversible, but in rare cases may be fatal,
• hearing loss, loss of other senses,
• infection/inflammation of the brain and meninges (enteroviral meningoencephalitis).

MabThera may also cause changes in laboratory tests performed by your doctor.

If you are being treated with MabThera in combination with other medicines, some of the possible adverse effects may be due to the other medicines.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of MabThera

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the container after EXP. The expiry date is the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze. Keep the vial in the outer packaging to protect it from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of MabThera 1400 mg solution for subcutaneous injection

• The active substance of MabThera is rituximab. The vial contains 1400 mg/11.7 ml of rituximab. Each ml contains 120 mg of rituximab.
• The other components are recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine hydrochloride monohydrate, ?-?-trehalose dihydrate, L-methionine, polysorbate 80, water for injections. See section 2 “MabThera contains sodium”.

Appearance of the product and contents of the pack

MabThera is a ready-to-use solution, from transparent to opalescent, colourless to slightly yellowish, supplied as a solution for subcutaneous injection in a clear glass vial with a butyl rubber stopper sealed with aluminium and a pink flip-off plastic cap.

Each vial contains 1400 mg/11.7 ml of rituximab. Each pack contains one vial.

Marketing Authorization Holder

Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer

Roche Pharma AG
Emil-Barrell-Str. 1
79639 Grenzach-Wyhlen
Germany

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorization Holder.

Date of the most recent review of this leaflet

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

This leaflet is available on the European Medicines Agency website in all languages of the European Union.