MABTHERA 1400 mg SOLUTION FOR SUBCUTANEOUS INJECTION

2. What you need to know before you use 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 the absorption of the active substance)
• if you have any active, severe infection
• if you have a weak immune system.

Do not use MabThera if you have any of the above. If you are not sure, ask your doctor, pharmacist, or nurse before you are given MabThera.

Warnings and precautions

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

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

If any of the above apply to you (or you are not sure), ask your doctor, pharmacist, or nurse before you are given MabThera. Your doctor will need to monitor you during your treatment with MabThera.

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

Children and adolescents

Tell your doctor, pharmacist, or nurse before you are given MabThera if you or your child is under 18 years old. This is because there is not much information on the use of MabThera in children and adolescents.

Other medicines and MabThera

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription. This is because MabThera may affect the way other medicines work. Also, other medicines may affect the way MabThera works.

In particular, tell your doctor if:

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

If any of the above apply to you (or you are not sure), ask your doctor, pharmacist, or nurse before you are given MabThera.

Pregnancy and breastfeeding

You must tell your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant. This is because MabThera may cross the placenta and affect your baby.

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

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

Driving and using machines

It is not known if MabThera has any effects on the ability to drive or use machines.

MabThera contains sodium

This medicine contains less than 1 mmol of sodium (23 mg per 11.7 ml vial, and is therefore essentially “sodium-free”.

3. How to use MabThera

How this medicine is given

MabThera will be given to you by a doctor or nurse who is experienced in the use of this medicine. They will keep you under observation during the administration of MabThera in case you experience any side effects.

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

After this, MabThera will be given to you as an injection under your skin (subcutaneous injection), which takes about 5 minutes. A sticker is included on the vials that specifies the medication.

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

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

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

Medicines given before each administration of MabThera

Before the administration of MabThera, you will be given medicines (pre-medication) to prevent or reduce possible side effects.

Dose and frequency of treatment

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

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

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, MabThera can cause side effects, although not everybody gets them.

Most of these side effects are mild to moderate, but some of them can be serious and require treatment. In rare cases, some of these reactions have been fatal.

Reactions at the injection site

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

Your doctor may decide not to continue your treatment with MabThera if you have severe reactions to the infusion.

Infections

Tell your doctor immediately if you have any symptoms of infection, such as:

• fever, cough, sore throat, burning sensation when urinating, or if you start to feel tired or unwell,
• memory loss, concentration problems, difficulty walking, or loss of vision. This may be due to a very rare, serious infection in the brain (Progressive Multifocal Leukoencephalopathy or PML), which has been fatal,
• fever, headache, stiff neck, lack of coordination (ataxia), change in personality, hallucinations, altered consciousness, seizures, or coma – this could be due to a serious brain infection (enteroviral meningoencephalitis), which can be fatal.

You may catch infections more easily during treatment with MabThera. These are usually colds, but cases of pneumonia or urinary tract infections have been reported. All of these are listed below as “Other side effects”.

Other side 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 platelet count
• nausea,
• hair loss, chills, headache,
• low immunity due to decreased number of antibodies called “immunoglobulins” (IgG) in the blood that help protect against infection.

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

• blood infections (sepsis), pneumonia, herpes, colds, bronchitis, fungal infections, infections of unknown origin, sinusitis, hepatitis B,
• low red blood cell count (anemia), low white blood cell count,
• allergic reactions (hypersensitivity),
• high blood sugar, weight loss, peripheral and facial edema, increased LDH enzyme levels in the blood, decreased calcium levels in the blood,
• abnormal skin sensations, such as numbness, tingling, pricking, burning, increasing sensation in the skin, decreased sense of touch,
• agitation, difficulty sleeping,
• flushing of the face and other areas of the skin due to dilation of blood vessels,
• feeling of dizziness or anxiety,
• increased tear production, changes in the tear duct, eye inflammation (conjunctivitis),
• ringing in the ears, ear pain,
• heart problems, such as heart attack, irregular heartbeat, abnormally fast heartbeat,
• increased or decreased blood pressure (decreased blood pressure, especially when standing up),
• bronchospasm, inflammation, irritation in the lungs, throat, and/or nasal cavities, shortness of breath, runny nose,
• vomiting, diarrhea, abdominal pain, irritation or ulcers in the throat and mouth, difficulty swallowing, constipation, indigestion,
• eating disorders: not eating enough, 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 discomfort or feeling of unease or fatigue, agitation, cold symptoms,
• multi-organ failure.

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

• coagulation disorders, decreased red blood cell production, increased destruction of red blood cells (aplastic hemolytic anemia), inflammation/swelling of lymph nodes,
• exhaustion, loss of interest in usual activities, nervousness,
• taste disorders, such as changes in the taste of food,
• heart problems, such as decreased heart rate or chest pain (angina),
• asthma, low oxygen levels in the blood,
• stomach swelling.

Rare (may affect up to 1 in 10,000 people):

• temporary increase in the amount 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 that cause skin symptoms,
• respiratory failure,
• damage to the intestinal wall (perforation),
• serious skin problems that cause blisters that can be life-threatening,
• kidney problems (renal failure),
• severe vision loss (signs of nerve damage in the brain).

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

• delayed decrease in white blood cells in the blood,
• decrease in platelet count after infusion - reversible, but in rare cases can 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 side effects may be due to the other medicines.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of MabThera

Keep out of 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 is the last day of the month shown.

Store in a refrigerator (2°C - 8°C). Do not freeze. Keep the vial 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 no longer required. These measures will help protect the environment.

6. Container contents and additional 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, α,α-trehalose dihydrate, L-methionine, polysorbate 80, water for injectable preparations. See section 2 "MabThera contains sodium".

Appearance and container contents of the product

MabThera is a ready-to-use solution, from transparent to opalescent, from colorless to yellowish, presented as a solution for subcutaneous injection in a transparent glass vial with a butyl rubber stopper sealed with aluminum and a pink plastic flip-off disc.

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

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder.

Date of last revision of this leaflet

Other sources of information

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

This leaflet can be found in all languages of the European Union on the European Medicines Agency website.