Package Insert: Patient Information

MabThera 1400mg subcutaneous injection solution

rituximab

Read the entire package insert carefully before starting to use the medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

What is MabThera

MabThera contains the active ingredient “rituximab”. This is a type of protein called “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 medication to be administered through infusion (called MabThera 100 mg or MabThera 500 mg concentrate for infusion solution), and as a medication to be administered as a subcutaneous injection (called MabThera 1400 mg or MabThera 1600 mg subcutaneous injection solution).

What is MabThera used for

MabThera 1400 mg is used for the treatment of Non-Hodgkin 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 administered alone or with other medications called “chemotherapy”.

At the beginning of your treatment, MabThera will always be administered through infusion (intravenous perfusion).

After this, MabThera will be administered as a subcutaneous injection. Your doctor will decide when to start using MabThera as an injection.

In patients where the treatment has been effective, MabThera may be used as maintenance treatment for 2 years after completing the initial treatment.

Do not use MabThera

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

Do not use MabThera if you have any of the above points. If you are unsure, ask your doctor, pharmacist, or nurse before MabThera is administered to you.

Warnings and precautions

Inform your doctor, pharmacist, or nurse before usingMabThera:

• 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 hepatitis B may suffer a relapse that has been fatal in very rare occasions. Patients with a history of hepatitis B infection will be closely monitored by their doctor to detect any possible signs of hepatitis B
• if you have had any heart disease (such as angina, palpitations, or heart failure) or respiratory problems

If you are affected by any of the above points (or are unsure), ask your doctor, pharmacist, or nurse before MabThera is administered to you. Your doctor should 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 travel vaccines. Some vaccines should not be administered at the same time as MabThera or in the months following its administration. Your doctor will check if you need any vaccine before receiving MabThera.

Children and adolescents

Inform your doctor, pharmacist, or nurse before MabThera is administered to you if you or your child is under 18 years old. This is because there is little information about the use of MabThera in children and adolescents.

Other medications and MabThera

Inform your doctor or pharmacist if you are using or have recently used other medications, even those obtained without a prescription. This is because MabThera may affect how other medications work. Also, other medications may affect how MabThera works.

In particular, inform your doctor if:

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

If you are affected by any of the above points (or are unsure), ask your doctor, pharmacist, or nurse before MabThera is administered to you.

Pregnancy and breastfeeding

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

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

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 or for 6 months after treatment.

Driving and operating machinery

The effects of MabThera on the ability to drive vehicles or operate machinery are unknown.

MabThera contains sodium

This medication contains less than 1 mmol of sodium (23 mg per 11.7 ml vial, so it is considered essentially "sodium-free").

How to use this medication

MabThera will be administered to you by a doctor or nurse experienced in the use of this medication. They will keep you under observation during the administration of MabThera in case you experience any adverse effects.

At the beginning of your treatment, MabThera will always be administered to you through an infusion (intravenous perfusion).

Later, MabThera will be administered to you as an injection under your skin (subcutaneous injection), for approximately 5 minutes. The vials include an adhesive that specifies the medication.

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

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

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

Medications administered before each administration of MabThera

Before the administration of MabThera, you will be administered medications (pre-medication) to prevent or reduce possible adverse effects.

Quantity and frequency of treatment

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

Your doctor may modify it depending on your response to the medication.

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

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

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

Reactions at the injection site

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

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

Infections

Inform your doctor immediately if you experience any symptoms of infection, such as:

• fever, cough, sore throat, burning sensation while urinating, or if you start feeling tired or generally unwell,
• memory loss, concentration problems, difficulty walking, or loss of vision. This may be due to a rare and severe brain infection (Progressive Multifocal Leukoencephalopathy or PML),
• fever, headache, stiff neck, discoordination (ataxia), personality change, hallucinations, altered consciousness, seizures, or coma – this could be due to a severe brain infection (enteroviral meningoencephalitis), which can be fatal.

You may be more susceptible to infections 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 platelet cells called “plaquetas”
• nausea,
• hair loss on the scalp, chills, headache,
• reduced immunity by decreasing the number of antibodies called “inmunoglobulinas” (IgG) in the blood that help protect against infection.

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

• blood infections (sepsis), pneumonia, herpes, cold, bronchitis infections, fungal infections, unknown origin infections, nasal congestion, hepatitis B,
• low red blood cell count (anemia), low count of all blood cells,
• allergic reactions (hypersensitivity),
• high blood sugar levels, weight loss, peripheral and facial edema, increased levels of enzyme LDH in the blood, decreased calcium levels in the blood,
• abnormal sensations in the skin, numbness, tingling, pins and needles, progressive increase in these sensations in the skin, decreased sense of touch,
• agitation, difficulty falling asleep,
• flushing of the face and other skin areas due to vasodilation,
• feeling of dizziness or anxiety,
• increased tearing, alterations in the tear duct, conjunctivitis (inflammation of the eyes),
• ringing in the ears, ear pain,
• cardiac alterations, such as myocardial infarction, irregular heart rate, abnormally rapid heartbeats,
• increased or decreased blood pressure (decreased blood pressure especially when standing up),
• muscle tension in the respiratory tract causing difficulty breathing (bronchospasm), inflammation, irritation in the lungs, throat, and/or nasal cavities, shortness of breath, nasal discharge,
• vomiting, diarrhea, abdominal pain, irritation or ulcers in the throat and mouth, difficulty swallowing, constipation, indigestion,
• alimentary alterations: not eating enough, leading to weight loss,
• hiccups, increased sweating, nocturnal sweating,
• muscle problems, such as muscle tension, joint or muscle pain, back and neck pain,
• tumor pain,
• general malaise or feeling of restlessness or fatigue, agitation, catarrhal symptoms,
• multi-organ failure.

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

• coagulation disorders, decreased production of white blood cells, increased destruction of red blood cells (aplastic anemia), inflammation/swelling of lymph nodes,
• weakness, loss of interest in usual activities, nervousness,
• alterations in the sense of taste, such as changes in the taste of food,
• cardiac problems, such as reduced heart rate or chest pain (angina),
• asthma, insufficient oxygen supply to organs,
• gastric distension.

Very 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 alterations in the blood caused by the rupture of cancer cells,
• nerve damage in arms and legs, facial paralysis,
• heart failure,
• inflammation of blood vessels, including those that cause skin symptoms,
• respiratory insufficiency,
• intestinal wall damage (perforation),
• serious skin problems that can be life-threatening,
• renal problems (renal insufficiency),
• severe vision loss (signs of brain nerve damage).

Unknown frequency(the frequency of these side effects is unknown):

• delayed decrease in white blood cells in the blood,
• reduction in platelet count after infusion – reversible, but in rare cases, 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 treatedwith MabThera in combination with other medications, some of the possible side effects may be due to the other medications.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging after EXP. The expiration date is the last day of the month indicated.

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

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This will help protect the environment.

Composition of MabThera 1400mg solution for subcutaneous injection

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

Appearance of the product and contents of the pack

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

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

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche PharmaAG

Emil-Barrell-Str. 1

79639 Grenzach-Wyhlen

Germany

Further information about this medicinal product can be obtained by contacting the local representative of the marketing authorization holder.

Last update of this leaflet

Other sources of information

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

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