Label: information for the user

BESPONSA 1mg powder for concentrate for solution for infusion

inotuzumab ozogamicina

Read this label carefully before starting to use this medication, because it contains important information for you.

• Keep this label, as you may need to read 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 label. See section4.

1. What is BESPONSA and for what it is used

2. What you need to know beforeyou are administered BESPONSA

3. Howto administer BESPONSA

4. Possible adverse effects

5. Storage of BESPONSA

6. Contents of the package and additional information

The active ingredient of BESPONSA is inotuzumab ozogamicin. It belongs to a group of medicines whose target are cancer cells. These medicines are called antineoplastic agents.

BESPONSA is used for the treatment of adults with acute lymphoblastic leukemia. Acute lymphoblastic leukemia is a blood cancer in which there are too many white blood cells.BESPONSA is designed for the treatment of acute lymphoblastic leukemia in adult patients who have previously used other treatments that have failed.

BESPONSA acts by binding to cells with a protein called CD22. Leukemia lymphoblastic cells have this protein. Once bound to leukemia lymphoblastic cells, the medicine releases a substance inside the cells, which interferes with the DNA of the cells and destroys them.

Do not use BESPONSA

• if you are allergic to inotuzumab ozogamicin or any of the other ingredients of this medicine (listed in section6).
• if you have had a severe confirmed veno-occlusive disease (a condition in which the blood vessels of the liver are damaged and blocked by blood clots) or have veno-occlusive disease currently.
• if you have a severe liver disease, for example, cirrhosis (a condition in which the liver does not function properly due to prolonged damage), nodular regenerative hyperplasia (a condition with signs and symptoms of portal hypertension that may be caused by chronic use of medications) or active hepatitis (a disease characterized by inflammation of the liver).

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting BESPONSA if:

• you have a history of liver problems, or if you have signs and symptoms of a serious disease called hepatic veno-occlusive disease, a condition in which the blood vessels of the liver are damaged and blocked by blood clots. Hepatic veno-occlusive disease can be fatal andis related toa rapid weight gain, pain in the upper right side of the abdomen (stomach), enlargement of the liver, accumulation of fluid causing swelling in the abdomen and blood tests with elevated bilirubin and/or liver enzymes (which can cause a yellowish discoloration of the skin and eyes). This condition can occur during treatment with BESPONSA or after subsequent stem cell transplant treatment. Stem cell transplant is a surgery to transplant stem cells (cells that become new blood cells) from another person into your bloodstream. This surgery may be performed if your disease responds completely to treatment
• you have signs or symptoms of a low number of blood cells known as neutrophils (sometimes accompanied by fever), red blood cells, white blood cells, lymphocytes or a low number of blood components known as platelets; these signs and symptoms include the development of an infection or fever, easy bruising or frequent nosebleeds
• you experience signs and symptoms of a reaction related to perfusion, such as fever and chills or breathing problems during or shortly after the infusion of BESPONSA
• you experience signs and symptoms of tumor lysis syndrome, which may be related to symptoms in the stomach and intestines (for example, nausea, vomiting, diarrhea), heart (for example,, changes in heart rhythm), kidneys (for example, decreased urine output, blood in the urine) and nerves and muscles (for example, muscle spasms, weakness, cramps)during or shortly after the infusion of BESPONSA
• you have a history or tendency to prolong the QT interval (a change in the electrical activity of the heart that can produce severe irregular heart rhythms), are taking medications that are known to prolong the QT interval and/or have abnormal levels of electrolytes (for example, calcium, magnesium, potassium)
• you have elevated levels of amylase or lipase enzymes that may be a sign of problems with your pancreas or liver, and the gallbladder or bile ducts.

Inform your doctor, pharmacist or nurse immediatelyif you become pregnant during the treatment period with BESPONSA and until 8months after completing the treatment.

Your doctor will perform periodic blood tests to monitor your blood count during treatment with BESPONSA. See also section 4.

During treatment, especially in the first days after starting treatment, your white blood cell count (leukocytes) may decrease severely (neutropenia) and may be accompanied by fever (febrile neutropenia).

During treatment, especially in the first days after starting treatment, you may have elevated liver enzymes. Your doctor will perform periodic blood tests to monitor your liver enzymes during treatment with BESPONSA.

Treatment with BESPONSA may prolong the QT interval (acchange in the electrical activity of the heart that can cause severe irregular heart rhythms). Your doctor will perform an electrocardiogram (ECG) and blood tests to measure electrolytes (for example, calcium, magnesium, potassium) before the first dose of BESPONSA, and will repeat them during treatment. See also section 4.

Your doctor will also monitor signs and symptoms of tumor lysis syndrome after administration of BESPONSA. See also section 4.

Children and adolescents

BESPONSA should not be used in children and adolescents under 18years of age, as there are no available data in this population.

Other medicines and BESPONSA

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine. This includes medicines obtained without a prescription and herbal remedies.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or nurse before using this medicine.

Contraception

Avoid becoming pregnant or conceiving a child. Women should use effective contraceptive methods during treatment and for at least 8months after the last dose. Men should use effective contraceptive methods during treatment and for at least 5months after the last dose of treatment.

Pregnancy

The effects of BESPONSA on pregnant women are unknown, but according to its mechanism of action, BESPONSA may harm the fetus. Do not use BESPONSA during pregnancy unless your doctor considers it the best medicine for you.

Contact your doctor immediately if you or your partner becomes pregnant during the treatment period with this medicine.

Fertility

Men and women should seek information on fertility preservation before treatment.

Breastfeeding

If you need treatment with BESPONSA, you should stop breastfeeding during treatment and for at least 2months after treatment. Consult your doctor.

Driving and operating machinery

If you feel abnormally tired (this is a very common side effect of BESPONSA), you should not drive or operate machinery.

BESPONSA contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 1 mg of inotuzumab ozogamicin; this is, essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor, pharmacist, or nurse. In case of doubt, consult your doctor, pharmacist, or nurse again.

How BESPONSA is administered

• Your doctor will decide on the correct dose.
• A doctor or nurse will administer BESPONSA through an intravenous infusion that will last for 1 hour.
• Each dose is administered weekly, and each treatment cycle consists of 3 doses.
• If the medication works well and you are to receive a stem cell transplant (see section 2), you may receive 2 cycles or a maximum of 3 treatment cycles.
• If the medication works well, but you are not to receive a stem cell transplant (see section 2), you may receive a maximum of 6 treatment cycles.
• If you do not respond to the medication after 3 cycles, treatment will be suspended.

• Your doctor may change the dose, interrupt, or completely discontinue BESPONSA treatment if you experience certain adverse effects.
• Your doctor may reduce the dose based on your response to treatment.
• Your doctor will perform blood tests during treatment to detect adverse effects and monitor your response to treatment.

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

Medications administered before BESPONSA treatment

Before BESPONSA treatment, you will be administered other medications (premedication) to reduce infusion reactions and other possible adverse effects. These medications may include corticosteroids (e.g., dexamethasone), antipyretics (medications to reduce fever), and antihistamines (medications to reduce allergic reactions).

Before your BESPONSA treatment, you may be administered medications and hydration to prevent tumor lysis syndrome. Tumor lysis syndrome is related to a series of symptoms in the stomach and intestines (e.g., nausea, vomiting, diarrhea), heart (e.g., changes in heart rhythm), kidneys (e.g., decreased urine output, blood in urine), and nerves and muscles (e.g., muscle spasms, weakness, cramps).

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Some of these side effects can be very serious.

Inform your doctor immediatelyif you have signs and symptoms of any of the following serious side effects:

• perfusion-related reactions (see section2); the signs and symptoms include fever and chills during or shortly after perfusion with BESPONSA.
• hepatic veno-occlusive disease (see section2);the signs and symptoms includerapid weight gain, pain in the upper right abdomen, liver enlargement, fluid accumulation causing abdominal swelling, and elevated bilirubin and/or liver enzymes (which can cause yellowing of the skin and eyes).
• low number of white blood cells known as neutrophils (sometimes accompanied by fever), red blood cells, white blood cells, lymphocytes, or a low number of blood components known as platelets (see section2); the signs and symptoms include the development of an infection or fever, easy bruising or frequent nosebleeds.

• tumor lysis syndrome (see section2); which may be related to symptoms in the stomach andintestine (e.g., nausea, vomiting, diarrhea), heart (e.g., changes in heart rhythm), kidneys (e.g., decreased urine output, blood in the urine), and nerves and muscles (e.g., muscle spasms, weakness, cramps).

• prolongation of the QT interval (see section2); the signs and symptoms include a change in the heart's electrical activity that can produce severe irregular heart rhythms. Inform your doctor if you have symptoms such as dizziness, vertigo, or fainting.

Other side effects may include:

Very common: can affect more than 1 in 10people

• infections
• low number of white blood cells that can lead to general weakness and favor the development of infections
• low number of lymphocytes (a type of white blood cell) that can favor the development of infections
• low number of red blood cells that can lead to fatigue and shortness of breath
• decreased appetite
• headache
• bleeding
• abdominal pain
• vomiting
• diarrhea
• nausea
• inflammation of the mouth
• constipation
• increased bilirubin levels that can cause yellowing of the skin, eyes, and other tissues
• fever
• chills
• fatigue
• high levels in the blood of liver enzymes (which can indicate liver damage)

Common: can affect up to 1 in 10people

• reduction in the number of several types of blood cells
• excess uric acid in the blood
• excessive fluid accumulation in the abdomen
• inflammation of the abdomen
• changes in heart rhythm (may appear on the electrocardiogram)
• high levels in the bloodabnormallyhighofamylase(an enzyme necessary for digestion and conversion of starch into sugars)
• high levelsin the bloodabnormally high oflipase (an enzymenecessary for processing fat in the diet)
• hypersensitivity

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on 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 vial label and on the packaging after EXP. The expiration date is the last day of the month indicated.

Unopened vial

-Store in the refrigerator (between 2°C and 8°C).

-Store in the original packaging to protect it from light.

-Do not freeze.

Reconstituted solution

-Use immediately or store in the refrigerator (between 2°C and 8°C) for a maximum of 4hours.

-Protect from light.

-Do not freeze.

Diluted solution

-Use immediately or store at room temperature (between 20°C and 25°C) or in the refrigerator (between 2°C and 8°C). The maximum time elapsed from reconstitution to the end of administration must be ≤ 8hours, with ≤ 4hours between reconstitution and dilution.

-Protect from light.

-Do not freeze.

Inspect this medication for particles or discoloration before administration. Do not use this medication if you observe particles or discoloration.

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

Composition of BESPONSA

• The active ingredient is inotuzumab ozogamicin. Each vial contains 1mg of inotuzumab ozogamicin. After reconstitution, 1ml of solution contains 0.25mg of inotuzumab ozogamicin.
• The other components are sucrose, polisorbate 80, sodium chloride, and tromethamine (see section 2).

Appearance of the product and contents of the pack

BESPONSA is a lyophilized powder for concentrate for solution for infusion (powder for concentrate).

Each pack of BESPONSA contains:

• A glass vial with a white to off-white lyophilized powder.

Marketing authorization holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Brussels

Belgium

Responsible for manufacturing

Pfizer Service Company BV

Hoge Wei 10

B-1930, Zaventem

Belgium

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Spain

Pfizer, S.L.

Phone: +34 91 490 99 00

Last update of the 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/.There are also links to other websites on rare diseases and orphan medicines.

This information is intended for healthcare professionals only. Consult the complete information on dosage and dose modification in the SmPC.

Administration route

BESPONSA is administered by intravenous infusion. The infusion should be administered over 1hour.

Do not administer BESPONSA by rapid intravenous injection or bolus.

BESPONSA should be reconstituted and diluted before administration.

BESPONSA should be administered in cycles of 3 to 4weeks.

For patients who are to undergo hematopoietic stem cell transplantation (HSCT), the recommended duration of treatment is 2cycles. A third cycle may be considered for those patients who do not achieve CR/CRi and EMR negativity after 2cycles. For patients who are not to undergo HSCT, up to a maximum of 6cycles may be administered. Patients who do not achieve CR/CRi after 3cycles should discontinue treatment (see section4.2 of the SmPC).

The following table shows the recommended dosing regimens.

For the first cycle, the total recommended dose for all patients is 1.8mg/m2per cycle, administered in 3 divided doses on days1 (0.8mg/m2), 8 (0.5mg/m2) and 15 (0.5mg/m2). The first cycle has a duration of 3weeks, but may be extended to 4weeks if the patient achieves CR or CRi, and/or to allow recovery from toxicity.

For subsequent cycles, the total recommended dose is 1.5mg/m2per cycle administered in 3doses on days1 (0.5mg/m2), 8 (0.5mg/m2) and 15 (0.5mg/m2) for patients who achieve CR/CRi, or 1.8mg/m2per cycle administered in 3doses on days1 (0.8mg/m2), 8 (0.5mg/m2) and 15 (0.5mg/m2) for patients who do not achieve CR/CRi. Subsequent cycles have a duration of 4weeks.

Instructions for reconstitution, dilution, and administration

Use an appropriate aseptic technique for reconstitution and dilution procedures. Inotuzumab ozogamicin(which has a density of 1.02g/mlat 20 °C)is sensitive to light and should be protected from ultraviolet light during reconstitution, dilution, and administration.

The maximum time elapsed from reconstitution to the end of administration should be ≤8hours, with ≤4hours between reconstitution and dilution.

Reconstitution:

• Calculate the dose (mg) and the number of vials of BESPONSA required.
• Reconstitute each vial of 1mg with 4ml of water for injection, to obtain a single-use solution of 0.25mg/ml of BESPONSA.
• Swirl the vial gently to help dissolve. Do not agitate.
• Inspect the reconstituted solution for particles or discoloration. The reconstituted solution should be transparent or slightly turbid, colorless, and practically free of visible extraneous substances.Do not use if particles or discoloration are observed.
• BESPONSA does not contain bacteriostatic preservatives. The reconstituted solution should be used immediately. If the reconstituted solution cannot be used immediately, it may be stored in the refrigerator (between 2°C and 8°C) for a maximum of 4hours. Protect from light and do not freeze.

Dilution:

• Calculate the required volume of the reconstituted solution needed to obtain the appropriate dose based on the patient's body surface area. Withdraw this amount from the (the) vial(s) using a syringe. Protect from light. Discard any unused reconstituted solution remaining in the vial.
• Add the reconstituted solution to a infusion bag with a sodium chloride 9mg/ml (0.9%) solution, to a total nominal volume of 50ml.The final concentration should be between 0.01 and 0.1mg/ml.Protect from light. It is recommended to use an infusion bag made of polyvinyl chloride (PVC, with or without di(2-ethylhexyl)phthalate [DEHP]), polyolefin (polypropylene and/or polyethylene), or ethylene-vinyl acetate (EVA).
• Invert the infusion bag gently to mix the diluted solution. Do not agitate.
• The diluted solution should be used immediately, or stored at room temperature (between 20°C and 25°C) or in the refrigerator (between 2°C and 8°C). The maximum time elapsed from reconstitution to the end of administration should be ≤8hours, with ≤4hours between reconstitution and dilution. Protect from light and do not freeze.

Administration:

• If the diluted solution is stored in the refrigerator (between 2°C and 8°C), allow it to reach room temperature (between 20°C and 25°C) for approximately 1hour before administration.
• No filtration of the diluted solution is required. However, if the diluted solution is filtered, it is recommended to use filters based on polyethersulfone (PES), polyvinylidene fluoride (PVDF), or hydrophilic polysulfone (HPS). Do not use filters made of nylon or mixed cellulose esters (MCE).
• Protect the infusion bag with a UV light-blocking cover (i.e., amber-colored, dark brown, or green bags, or aluminum foil) during infusion. The infusion line does not need to be protected from light.
• Infuse the diluted solution over 1hour at a rate of 50ml/h at room temperature (between 20°C and 25°C). Protect from light. It is recommended to use infusion lines made of PVC (with or without DEHP), polyolefin (polypropylene and/or polyethylene), or polybutadiene.

Do not mix BESPONSA or administer it in infusion with other medicinal products.

The following table shows the times and storage conditions for the reconstituted and diluted solutions of BESPONSA.

Storage conditions and shelf life

Unopened vials

5years.

Reconstituted solution

BESPONSA does not contain bacteriostatic preservatives. The reconstituted solution should be used immediately. If the reconstituted solution cannot be used immediately, it may be stored in the refrigerator (between 2°C and 8°C)for a maximum of 4 hours. Protect from light and do not freeze.

Diluted solution

The diluted solution should be used immediately or stored at room temperature (between 20°C and 25°C) or in the refrigerator (between 2°C and 8°C). The maximum time elapsed from reconstitution to the end of administration should be ≤8hours, with ≤4hours between reconstitution and dilution. Protect from light and do not freeze.