Zevalin 1,6 mg/ml, equipo reactivo para la preparacion de un radiofarmaco para perfusion

PATIENT INFORMATION LEAFLET

Zevalin 1.6 mg/ml, kit for preparation of a radiopharmaceutical for infusion

Ibritumomab tiuxetan (90Y)

Read this leaflet carefully before you receive 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, consult your doctor or pharmacist.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. Possible side effects
2. Storage of Zevalin

1. Contents of the pack and additional information

This medication is a radioisotope for therapeutic use only.

Zevalin is a kit for the preparation of the active ingredient ibritumomab tiuxetan (90Y), a monoclonal antibody labeled with the radioactive substance yttrium-90 (90Y). Zevalin binds to a protein (CD20) on the surface of certain white blood cells (B lymphocytes) and eliminates them through irradiation.

Zevalin is used to treat patients with certain types of non-Hodgkin's lymphoma of B cells (indolent B cell lymphoma CD20+ or transformed B cell lymphoma) if previous treatment with rituximab, another monoclonal antibody, has not worked or has stopped working (refractory disease or relapse).

Zevalin is also used in patients with follicular lymphoma who have not received previous treatment. It is used as a consolidation treatment to improve the reduction in lymphoma cells (remission) achieved with the initial chemotherapy regimen.

The use of Zevalin involves exposure to small amounts of radioactivity. Your doctor and the nuclear medicine doctor have considered that the clinical benefit you will obtain from the procedure with the radioisotope outweighs the risk due to radiation.

You should not receive Zevalin:

• If you areallergic(hypersensitive) to any of the following substances:

• Ibritumomab tiuxetan, yttrium chloride or any of the other components of Zevalin (listed in section 6 “Composition of Zevalin”).
• Rituximab or other murine-derived proteins.
• If you are pregnant or breastfeeding (also see the section “Pregnancy and breastfeeding”).

Be cautious with Zevalin

The following cases are not recommended for the use of Zevalin, as its safety and efficacy have not been established:

• More than one-fourthof your bone marrow is infiltrated by malignant abnormal cells.
• If you have received external beam radiation therapy that affects more than one-fourthof your bone marrow.

• If you are receiving Zevalin alone and your platelet count is less than 100,000/mm3.
• If your platelet count is less than 150,000/mm3after chemotherapy.
• If your white blood cell count is less than 1500/mm3.

• If you have undergone a bone marrow transplant or cell transplantation in the past.

If you have received treatment with other proteins(especially murine-derived proteins) before Zevalin treatment, you may have a higher risk of an allergic reaction. Therefore, you may need to undergo testing to determine specific antibodies.

Zevalin is not recommended for patients with non-Hodgkin lymphoma that affects the brain, spinal cord, or both, as these patients were not included in clinical studies.

Children

Zevalin is not recommended for children under 18 years old, as its safety and efficacy have not been established.

Older patients

There is limited data available for patients over 65 years old. In general, no differences were observed in terms of safety or efficacy between these patients and younger patients.

Use of Zevalin with other medications

Inform your doctor or pharmacist if you are using or have recently used any other medication, including those purchased without a prescription.

Especially, your doctor should discontinue treatment with growth factors, such as filgrastim, for a period of three weeks before administering Zevalin and until two weeks after Zevalin treatment.

If you receive Zevalin treatment before four months after receiving chemotherapy with the active ingredient fludarabine, you may have a higher risk of decreased blood cells. Please inform your doctor that you have received Zevalin if you are to be vaccinated after using this medication.

Pregnancy and breastfeeding

Zevalin should not be used during pregnancy. Your doctor will perform tests to rule out pregnancy before starting treatment. Women of childbearing age and male patients should use effective contraceptive methods during Zevalin treatment and for one year after treatment.

There is a potential risk that the ionizing radiation in Zevalin may damage your ovaries and testicles. Consult with your doctor about how this may affect you, especially if you plan to have children in the future.

Women should not breastfeed during treatment and for 12 months after treatment.

Driving and operating machinery

Zevalin may affect your ability to drive and operate machinery, as dizziness is a very common side effect. Be cautious until you are sure you are not affected.

Zevalin contains sodium

This medication contains up to 28 mg of sodium per dose, depending on the concentration of radioactivity. Patients with low-sodium diets should take this into account.

There are strict guidelines for the use, handling, and disposal of radioactive medications. Zevalin will only be used in specially controlled areas. This medication will only be handled and administered by trained and qualified personnel to ensure safe use. Those individuals will take special care in the safe use of this product and will inform you of their actions.

The dose of Zevalin depends on your body weight, the number of platelets in your blood, and the indication for which Zevalin is used. The maximum dose should not exceed 1200 MBq ("megabecquerel", a unit to measure radioactivity).

Zevalin is used with another medication that contains the active ingredient rituximab.

You will receive a total of three infusions over two visits to a medical center, with an interval of 7 to 9 days.

• On day 1, you will receive an infusion of rituximab.
• On days 7th, 8th, or 9th, you will receive an infusion of rituximab followed by an infusion of Zevalin immediately afterwards (within four hours).

The recommended dose is:

For consolidation treatment in patients with follicular lymphoma

• The usual dose is 15 MBq/kg body weight.

For treatment of patients with non-Hodgkin lymphoma in relapse or refractory, who do not respond to rituximab

• The usual dose is 11 or 15 MBq/kg body weight, depending on the number of platelets in the blood.

Zevalin Preparation

Zevalin is not used directly, but rather must be prepared by a healthcare professional. The equipment allows for the conjugation of the ibritumomab tiuxetan antibody with the radioactive isotope yttrium-90 (radioactively labeled).

How Zevalin is Administered

Zevalin is administered by intravenous infusion (drip in a vein), which generally lasts approximately 10 minutes.

After Zevalin Administration

The amount of radiation to which your body will be exposed due to Zevalin is less than that received with radiation therapy. Most of the radioactivity will break down within the body, but a small part will be eliminated through urine. Therefore, for one week after the Zevalin infusion, each time you urinate, you should wash your hands thoroughly after urinating.

After treatment, your doctor will perform blood tests at regular intervals to check platelet and white blood cell counts. These generally decrease approximately two months after the start of treatment.

If your doctor plans to treat you with another antibody after Zevalin treatment, they will need to perform tests to determine specific antibodies. Your doctor will inform you if this applies to you.

If You Have Received More Zevalin Than You Should

Your doctor will provide the necessary treatment if you experience any adverse effects. This may include suspension of Zevalin treatment and treatment with growth factors using your own stem cells.

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

Inform your doctor immediately if you observe symptoms of the following conditions:

• Infection:fever, chills.
• Blood infection (sepsis):fever and chills, changes in mental state, rapid breathing, increased heart rate, decreased urine production, low blood pressure, shock, bleeding or clotting problems.
• Pneumonia:difficulty breathing.
• Low white blood cell count:bruises, petechiae or hematomas, more bleeding than usual after an injury, fever, or feeling abnormally tired or having difficulty breathing.
• Intense mucous membrane reactions,which may occur days or months after the administration of Zevalin, rituximab or both. Your doctor will immediately stop treatment.
• Extravasation(leakage of the infusion into surrounding tissues): pain, itching, burning or other reaction at the infusion site during administration. Your doctor will immediately stop the infusion and restart it in another vein.
• Allergic reactions(hypersensitivity)/ infusion reactions: symptoms of allergic reactions or infusion reactions may include skin reactions, difficulty breathing, swelling, itching, redness, chills, dizziness (as a possible sign of low blood pressure). Depending on the type or severity of the reaction, your doctor will decide whether to immediately stop treatment.

The side effects marked with an asterisk (*) have caused death in some cases, either in clinical trials or during product marketing.

The side effects marked with two asterisks (**) were also observed with consolidation treatment.

Side effectsvery common(may affect more than 1 in 10 people)

• Decreased platelet, white blood cell, and red blood cell counts in the blood (thrombocytopenia, leucocitopenia, neutropenia, anemia)*.
• Unpleasant feeling (nausea).

• Weakness, fever, chills.
• Infection*.

• Tiredness**.
• Small, red spots under the skin (petechiae)**.

Side effectscommon(may affect up to 1 in 10 people)

• Blood infection (sepsis)*; pneumonia*, urinary tract infection, oral candidiasis.
• Other types of blood cancer (myelodysplastic syndrome (MDS) / acute myeloid leukemia (AML))*, **, tumor pain.
• Fever with decreased white blood cell count (febrile neutropenia), decreased counts of all blood cells (pancytopenia)*, decreased lymphocyte count (lymphocytopenia).

• Allergic reactions (hypersensitivity).
• Severe loss of appetite (anorexia).

• Anxiety, insomnia.
• Dizziness, headache.

• Bleeding due to decreased platelet count in the blood*.
• Cough, nasal discharge.
• Vomiting, abdominal pain (abdominal), diarrhea, indigestion, throat irritation, constipation.
• Rash, pruritus (pruritus).

• Joint pain (arthralgia), muscle pain (mialgia), back pain, neck pain.
• Pain, flu-like symptoms, general feeling of discomfort, swelling caused by fluid accumulation in arms and legs, and in other tissues (peripheral edema), increased sweating.

• High blood pressure (hypertension)**.
• Low blood pressure (hypotension)**.
• Absence of menstruation (amenorrhea)**.

Side effectsuncommon(may affect up to 1 in 100 people)

• Increased heart rate (tachycardia).

Side effectsrare(may affect up to 1 in 1000 people)

• Benign brain tumor (meningioma).
• Head bleeding due to decreased platelet count in the blood*.

Side effects whose frequency is unknown:

• Skin and mucous membrane reaction (includingStevens-Johnson syndrome)*.

• Extravasation(leakage of the infusion into surrounding tissues), which causes skin inflammation (dermatitis at the infusion site) and skin peeling or ulcers at the infusion site or injection site.

• Tissue damage around lymphatic system tumors and complications caused by swelling of such tumors.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAnexo V.By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging.

This medication will be stored by a healthcare professional.

Store in refrigerator (between 2°C and 8°C). Do not freeze.

Store the vials in the original packaging to protect them from light.

The storage procedures must comply with national regulations on radioactive materials.

After radioactive labeling, immediate use is recommended. Stability has been demonstrated for 8 hours at 2°C – 8°C and protected from light.

Composition of Zevalin

• The active ingredient is ibritumomab tiuxetan. Each vial contains 3.2 mg of ibritumomab tiuxetan in 2 ml of solution (1.6 mg per ml).
• The other components are:
• • Vial of ibritumomab tiuxetan: sodium chloride, water for injection.
  • Vial of sodium acetate: sodium acetate, water for injection.

-Vial of buffer solution: human albumin solution, sodium chloride, disodium phosphate dodecahydrate, sodium hydroxide, potassium dihydrogen phosphate, potassium chloride, pentetic acid, diluted hydrochloric acid for pH adjustment, water for injection.

The final formulation after radioactive marking contains 2.08 mg of ibritumomab tiuxetan marked with yttrium-90 (90Y) in a total volume of 10 ml.

Appearance of the product and content of the container

Zevalin is a reactive kit for the preparation of radiopharmaceuticals for infusion that contains:

• A glass vial of ibritumomab tiuxetan, with 2 ml of colorless and transparent solution.
• A glass vial of sodium acetate, with 2 ml of colorless and transparent solution.

• A glass vial, buffer solution, with 10 ml of transparent yellow to amber-colored solution.
• A glass vial of reaction (empty).

Marketing Authorization Holder

Ceft Biopharma s.r.o.

Trtinova 260/1

Cakovice, 196 00 Praha 9

República Checa

Responsible for manufacturing

CIS bio international

RN 306- Saclay

B.P. 32

91192 Gif-sur-Yvette Cedex

Francia

Last review date of this leaflet:

Other sources of information

Detailed information about this medicine 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/European Economic Area on the website of the European Medicines Agency.