Besponsa

Основна информация

  • Търговско наименование:
  • Besponsa
  • Използвай за:
  • Хората
  • Вид на лекарството:
  • алопатични наркотици

Документи

Локализация

  • Предлага се в:
  • Besponsa
    Европейски съюз
  • Език:
  • английски

Терапевтична информация

  • Терапевтична група:
  • Antineoplastic agents,
  • Терапевтична област:
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Терапевтични показания:
  • Besponsa is indicated as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL). Adult patients with Philadelphia chromosome positive (Ph+) relapsed or refractory B cell precursor ALL should have failed treatment with at least 1 tyrosine kinase inhibitor (TKI).
  • Каталог на резюме:
  • Revision: 5

Състояние

  • Източник:
  • EMA - European Medicines Agency
  • Статус Оторизация:
  • Authorised
  • Номер на разрешението:
  • EMEA/H/C/004119
  • Дата Оторизация:
  • 27-06-2017
  • EMEA код:
  • EMEA/H/C/004119
  • Последна актуализация:
  • 25-12-2019

Доклад обществена оценка

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© European Medicines Agency, 2017. Reproduction is authorised provided the source is acknowledged.

EMA/269417/2017

EMEA/H/C/004119

EPAR summary for the public

Besponsa

inotuzumab ozogamicin

This is a summary of the European public assessment report (EPAR) for Besponsa. It explains how the

Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is

not intended to provide practical advice on how to use Besponsa.

For practical information about using Besponsa, patients should read the package leaflet or contact

their doctor or pharmacist.

What is Besponsa and what is it used for?

Besponsa is a cancer medicine used to treat a type of blood cancer which affects B cells (a type of

white blood cells) called B-cell precursor acute lymphoblastic leukaemia (ALL). Besponsa is used on its

own in adults whose cancer has come back or did not respond to previous treatment.

Besponsa is only used in patients with ‘CD22-positive B-cell precursor ALL’. This means that patients’

have a particular protein (CD22) on the surface of their white blood cells. In patients who have a type

of chromosome known as Philadelphia-chromosome, treatment with a cancer medicine called a

tyrosine kinase inhibitor should have been tried before starting Besponsa.

Because the number of patients with B-cell precursor ALL is low, the disease is considered ‘rare’, and

Besponsa was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 7 June 2013.

Besponsa contains the active substance inotuzumab ozogamicin.

How is Besponsa used?

Besponsa is given as an infusion (drip) into a vein lasting for at least one hour. The infusions are given

on days 1, 8 and 15 of a 3 or 4 week treatment cycle. The doctor may interrupt treatment or reduce

the dose, if the patient develops certain serious side effects.

Besponsa

EMA/269417/2017

Page 2/3

Patients in whom Besponsa works well should receive 2 or 3 cycles, after which they can have a stem

cell transplant to replace their bone marrow, the only curative treatment. Patients whose treatment

works well, but who are not going to receive a stem cell transplant, may receive up to a maximum of

6 cycles of treatment. In patients who do not respond to treatment, Besponsa should be stopped after

3 cycles.

Besponsa can only be obtained with a prescription, and treatment should be given under the

supervision of a doctor who has experience in the use of cancer treatments.

For further information, see the package leaflet.

How does Besponsa work?

The active substance in Besponsa, inotuzumab ozogamicin, is a monoclonal antibody (a type of

protein) that has been linked to a small molecule, N-acetyl-gamma-calicheamicin dimethylhydrazide.

The monoclonal antibody has been designed to recognise and attach to CD22 on the cancerous B cells.

Once attached, the medicine is taken up by the cell where calicheamicin becomes active, causing

breaks in the cell’s DNA and thereby killing the cancer cell.

What benefits of Besponsa have been shown in studies?

Besponsa was shown to be more effective than other chemotherapy (medicines to treat cancer) in one

main study involving 326 adults with CD22-positive B-cell precursor ALL, which had come back or had

not responded to previous treatment. The main measure of effectiveness was response to treatment.

Patients were considered to have responded if they had no remaining cancerous B cells in their blood

and bone marrow after treatment.

An analysis of the first 218 patients treated showed that after at least 2 cycles of treatment, 81% (88

out of 109) of patients receiving Besponsa responded to treatment compared with 29% (32 out of 109)

of patients receiving other chemotherapy. Patients who responded to treatment could proceed to have

a stem cell transplant.

What are the risks associated with Besponsa?

The most common side effects with Besponsa (which may affect more than 1 in 5 people) are

thrombocytopenia (low blood platelet counts), neutropenia and leucopenia (low white blood cell

counts), infection, anaemia (low red blood cell counts), tiredness, haemorrhage (bleeding), fever,

nausea (feeling sick), headache, febrile neutropenia (low white cell count with fever), abdominal pain

(stomach ache), increased levels of liver enzymes called transaminases and gamma-

glutamyltransferase, and hyperbilirubinaemia (high blood levels of bilirubin, a breakdown product of

red blood cells).

The most serious side effects are infection, febrile neutropenia, haemorrhage, abdominal pain, fever,

tiredness and veno-occlusive liver disease/sinusoidal obstruction syndrome (VOD/SOS, a serious liver

disease).

Besponsa must not be used in patients who have VOD/SOS or have had severe VOD/SOS or have

other serious liver diseases.

For the full list of all side effects and restrictions reported with Besponsa, see the package leaflet.

Besponsa

EMA/269417/2017

Page 3/3

Why is Besponsa approved?

The Agency’s Committee for Medicinal Products for Human Use (CHMP) decided that Besponsa’s

benefits are greater than its risks and recommended that it be approved for use in the EU.

The CHMP considered that although there have been recent advances in the treatment of B-cell

precursor ALL, treatment options for patients remain limited. The main study showed that Besponsa

was better than other commonly used chemotherapy medicines at inducing a response in patients and

allowing them to have a curative stem cell transplant.

With regard to safety, the side effects with Besponsa are similar to those of other chemotherapy

medicines and can usually be managed by dose reduction or treatment interruption.

What measures are being taken to ensure the safe and effective use of

Besponsa?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe

and effective use of Besponsa have been included in the summary of product characteristics and the

package leaflet.

Other information aboutBesponsa

The European Commission granted a marketing authorisation valid throughout the European Union for

Besponsa on 29 June 2017.

The full EPAR for Besponsa can be found on the Agency’s website: ema.europa.eu/Find

medicine/Human medicines/European public assessment reports. For more information about

treatment with Besponsa, read the package leaflet (also part of the EPAR) or contact your doctor or

pharmacist.

The summary of the opinion of the Committee for Orphan Medicinal Products for Besponsa can be

found on the Agency’s website: ema.europa.eu/Find medicine/Human medicines/Rare disease

designation.

This summary was last updated in 06-2017.

Листовка за пациента: състав, показания, Нежелани лекарствени реакции, дозиране, взаимодействия, бременност, кърмене

B. PACKAGE LEAFLET

Package leaflet: Information for the user

BESPONSA 1 mg powder for concentrate for solution for infusion

inotuzumab ozogamicin

This medicine is subject to additional monitoring. This will allow quick identification of new

safety information. You can help by reporting any side effects you may get. See the end of section 4

for how to report side effects.

Read all of this leaflet carefully before you start using this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor, pharmacist or nurse.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

What BESPONSA is and what it is used for

What you need to know before you are given BESPONSA

How BESPONSA is given

Possible side effects

How to store BESPONSA

Contents of the pack and other information

1. What BESPONSA is and what it is used for

The active ingredient in BESPONSA is inotuzumab ozogamicin. This belongs to a group of medicines

that target cancer cells. These medicines are called antineoplastic agents.

BESPONSA is used to treat adults with acute lymphoblastic leukaemia. Acute lymphoblastic

leukaemia is a cancer of blood where you have too many white blood cells. BESPONSA is intended

for the treatment of acute lymphoblastic leukaemia for adult patients who have previously tried other

treatments and for whom those treatments have failed.

BESPONSA acts by attaching to cells with a protein called CD22. Lymphoblastic leukaemia cells

have this protein. Once attached to the lymphoblastic leukaemia cells, the medicine delivers a

substance into the cells that interferes with the cells’ DNA and eventually kills them.

2. What you need to know before you are given BESPONSA

Do not use BESPONSA if you:

are allergic to inotuzumab ozogamicin or any of the other ingredients of this medicine (listed

in section 6).

have previously had severe venoocclusive disease (a condition in which the blood vessels in

the liver become damaged and blocked by blood clots) which was confirmed or have ongoing

venoocclusive disease.

have serious ongoing liver disease, e.g., cirrhosis (a condition in which the liver does not

function properly due to long-term damage), nodular regenerative hyperplasia (a condition

with signs and symptoms of portal hypertension that can be caused by chronic use of

medicines), active hepatitis (a disease characterised by inflammation of the liver).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using BESPONSA if you:

have a history of liver problems or liver diseases or if you have signs and symptoms of a

serious condition called hepatic venoocclusive disease, a condition in which the blood vessels

in the liver become damaged and blocked by blood clots. Venoocclusive disease may be fatal

and is associated with rapid weight gain, pain in the upper right side of your abdomen (belly),

increase in the size of the liver, build-up of fluid causing abdominal swelling, and blood tests

showing increases in bilirubin and/or liver enzymes (that may result in yellowing of the skin

or eyes). This condition may occur during treatment with BESPONSA or after subsequent

treatment with a stem cell transplant. A stem cell transplant is a procedure to transplant

another person’s stem cells (cells which develop into new blood cells) into your bloodstream.

This procedure may take place if your disease responds completely to treatment.

have signs or symptoms of a low number of blood cells known as neutrophils (sometimes

accompanied with fever), red blood cells, white blood cells, lymphocytes, or a low number of

blood components known as platelets; these signs and symptoms include developing an

infection or fever or bruising easily or getting frequent nose bleeds.

have signs and symptoms of an infusion related reaction, such as fever and chills or breathing

problems during or shortly after the BESPONSA infusion.

have signs and symptoms of tumour lysis syndrome, which may be associated with symptoms

in the stomach and intestines (for example, nausea, vomiting, diarrhoea), heart (for example,

changes in the rhythm), kidney (for example, decreased urine, blood in urine), and nerves and

muscles (for example, muscular spasms, weakness, cramps), during or shortly after the

BESPONSA infusion.

have a history of, or tendency to have, QT interval prolongation (a change in electrical activity

of the heart that can cause serious irregular heart rhythms), are taking medicines that are

known to prolong QT interval, and/or have abnormal electrolyte (e.g., calcium, magnesium,

potassium) levels.

have elevations in amylase or lipase enzymes that may be a sign of problems with your

pancreas or liver and gallbladder or bile ducts.

Tell your doctor, pharmacist or nurse immediately

if you became pregnant during the period of

treatment with BESPONSA and for up to 8 months after finishing treatment.

Your doctor will take regular blood tests to monitor your blood counts during treatment with

BESPONSA. See also section 4.

During treatment, especially in the first few days after starting treatment, your white blood cell count

may be severely lowered (neutropenia), which may be accompanied by fever (febrile neutropenia).

During treatment, especially in the first few days after starting treatment, you may have raised liver

enzymes. Your doctor will take regular blood tests to monitor your liver enzymes during treatment

with BESPONSA.

Treatment with BESPONSA may prolong QT interval (a change in electrical activity of the heart that

can cause serious irregular heart rhythms). Your doctor will take an electrocardiogram (ECG) and

blood tests to measure electrolytes (e.g., calcium, magnesium, potassium) before the first dose of

BESPONSA and repeat these tests during treatment. See also section 4.

Your doctor will also monitor for signs and symptoms of tumour lysis syndrome after you receive

BESPONSA. See also section 4.

Children and adolescents

BESPONSA should not to be used in children and adolescents under 18 years of age because no data

are available in this population.

Other medicines and BESPONSA

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines. This includes medicines obtained without a prescription and herbal medicines.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor or nurse for advice before taking this medicine.

Contraception

You must avoid becoming pregnant or fathering a child. Women must use effective contraception

during treatment and for at least 8 months after the last dose of treatment. Men must use effective

contraception during treatment and for at least 5 months after the last dose of treatment.

Pregnancy

The effects of BESPONSA in pregnant women are not known, but based on its mechanism of action

BESPONSA may harm your unborn baby. You should not use BESPONSA during pregnancy, unless

your doctor thinks that it is the best medicine for you.

Contact your doctor immediately if you or your partner becomes pregnant during the period of

treatment with this medicine.

Fertility

Men and women should seek advice regarding fertility preservation before treatment.

Breast-feeding

If you need treatment with BESPONSA, you must stop breast-feeding during treatment and for at least

2 months after treatment. Talk to your doctor.

Driving and using machines

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

use machines.

3. How BESPONSA is given

Always use this medicine exactly as your doctor, pharmacist, or nurse has told you. Check with your

doctor, pharmacist or nurse if you are not sure.

How BESPONSA is given

Your doctor will decide on the correct dose.

A doctor or nurse will give you BESPONSA through a drip in your vein (intravenous

infusion) which will run for 1 hour.

Each dose is given weekly and each treatment cycle is 3 doses.

If the medicine works well and you are going to receive a stem cell transplant (see section 2),

you may receive 2 cycles or a maximum of 3 cycles of treatment.

If the medicine works well, but you are not going to receive a stem cell transplant (see section

2), you may receive up to a maximum of 6 cycles of treatment.

If you do not respond to the medicine within 3 cycles, your treatment will be stopped.

Your doctor may change your dose, interrupt, or completely stop treatment with BESPONSA

if you have certain side effects.

Your doctor may lower your dose based on your response to treatment.

Your doctor will do blood tests during the treatment to check for side effects and for response

to treatment.

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

Medicines given before treatment with BESPONSA

Before your treatment with BESPONSA, you will be given other medicines (pre-medications) to help

reduce infusion reactions and other possible side effects. These may include corticosteroids (e.g.,

dexamethasone), antipyretics (medicines to reduce fever), and antihistamines (medicines to reduce

allergic reactions).

Before your treatment with BESPONSA, you may be given medicines and be hydrated to prevent

tumour lysis syndrome from occurring. Tumour lysis syndrome is associated with a variety of

symptoms in the stomach and intestines (for example, nausea, vomiting, diarrhoea), heart (for

example, changes in the rhythm), kidney (for example, decreased urine, blood in urine), and nerves

and muscles (for example, muscular spasms, weakness, cramps).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of

these side effects may be serious.

Tell your doctor immediately

if you have signs and symptoms of any of the following serious side

effects:

infusion related reaction (see section 2); signs and symptoms include fever and chills or

breathing problems during or shortly after the BESPONSA infusion.

venoocclusive liver disease (see section 2); signs and symptoms include rapid weight gain,

pain in the upper right side of your abdomen, increase in the size of the liver, accumulation of

fluid causing abdominal swelling, and increases in bilirubin and/or liver enzymes (that may

result in yellowing of the skin or eyes).

low number of blood cells known as neutrophils, (sometimes accompanied with fever), red

blood cells, white blood cells, lymphocytes, or low number of blood components known as

platelets (see section 2); signs and symptoms include developing an infection or fever or

bruising easily or getting nose bleeds on a regular basis.

tumour lysis syndrome (see section 2); this may be associated with a variety of symptoms in

the stomach and intestines (for example, nausea, vomiting, diarrhoea), heart (for example,

changes in the rhythm), kidney (for example, decreased urine, blood in urine), and nerves and

muscles (for example, muscular spasms, weakness, cramps).

QT interval prolongation (see section 2); signs and symptoms include a change in electrical

activity of the heart that can cause serious irregular heart rhythms. Tell your doctor if you have

symptoms, such as dizziness, lightheadedness or fainting.

Other side effects may include:

Very common

(may affect more than 1 in 10 people):

Infections

Reduced number of white blood cells which may result in general weakness and a tendency to

develop infections

Reduced number of lymphocytes (a type of white blood cells) which may result in a tendency

to develop infections

Reduced number of red blood cells which may result in fatigue and shortness of breath

Decreased appetite

Headache

Bleeding

Pain in the abdomen

Vomiting

Diarrhoea

Nausea

Mouth inflammation

Constipation

Raised bilirubin level which may result in a yellowish colour in the skin, eyes, and other

tissues

Fever

Chills

Fatigue

High levels of liver enzymes (which can be indicators of liver injury) in the blood

Common

(may affect up to 1 in 10 people):

Reduction in the number of various types of blood cells

Excess of uric acid in the blood

Excessive accumulation of fluid in the abdomen

Swelling of the abdomen

Changes in heart rhythm (may show on electrocardiogram)

Abnormally high levels of amylase (an enzyme needed for digestion and conversion of starch

into sugars) in the blood

Abnormally high levels of lipase (an enzyme needed to process dietary fat) in the blood

Hypersensitivity

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. You can also report side effects directly via 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.

How to store BESPONSA

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

Do not use this medicine after the expiry date which is stated on the vial label and carton after EXP.

The expiry date refers to the last day of that month.

Unopened vial

Store in a refrigerator (2 °C-8 °C).

Store in the original carton in order to protect from light.

Do not freeze.

Reconstituted solution

Use immediately or store in a refrigerator (2 °C-8 °C) for up to 4 hours.

Protect from light.

Do not freeze.

Diluted solution

Use immediately or store at room temperature (20 °C-25 °C) or in a refrigerator (2 °C-8 °C). The

maximum time from reconstitution through the end of administration should be ≤ 8 hours, with ≤

4 hours between reconstitution and dilution.

Protect from light.

Do not freeze.

This medicine should be inspected visually for particulate matter and discolouration prior to

administration. If particles or discolouration are observed, do not use.

Do not throw away any medicines via wastewater or household waste. Ask your doctor how to throw

away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What BESPONSA contains

The active substance is inotuzumab ozogamicin. Each vial contains 1 mg inotuzumab

ozogamicin. After reconstitution, 1 mL of solution contains 0.25 mg inotuzumab ozogamicin.

The other ingredients are sucrose, polysorbate 80, sodium chloride, and tromethamine.

What BESPONSA looks like and contents of the pack

BESPONSA is a powder for concentrate for solution for infusion.

Each pack of BESPONSA contains:

1 glass vial containing a white to off-white lyophilised cake or powder.

Marketing Authorisation Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer

Pfizer Ireland Pharmaceuticals

Grange Castle Business Park

Clondalkin

Dublin 22

Ireland

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder:

Belgique/België/Belgien

Pfizer S.A. / N.V.

Tél/Tel: +32 (0)2 554 62 11

Lietuva

Pfizer Luxembourg SARL filialas Lietuvoje

Tel: + 370 52 51 4000

България

Пфайзер Люксембург САРЛ, Клон

България

Тел.: +359 2 970 4333

Luxembourg/Luxemburg

Pfizer S.A.

Tél/Tel: +32 (0)2 554 62 11

Česká republika

Pfizer PFE, spol. s r.o.

Tel: +420 283 004 111

Magyarország

Pfizer Kft.

Tel: +36-1-488-37-00

Danmark

Pfizer ApS

Tlf: +45 44 20 11 00

Malta

Vivian Corporation Ltd.

Tel: +356 21344610

Deutschland

Pfizer Pharma GmbH

Tel: +49 (0)30 550055 51000

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Norge

Pfizer Norge AS

Tlf: +47 67 52 61 00

Ελλάδα

Pfizer Ελλάς A.E.

Τηλ: +30 210 6785 800

Österreich

Pfizer Corporation Austria Ges.m.b.H.

Tel: +43 (0)1 521 15-0

España

Pfizer, S.L.

Tel: +34 91 490 99 00

Polska

Pfizer Polska Sp. z o.o.

Tel: +48 22 335 61 00

France

Pfizer

Tel: +33 (0)1 58 07 34 40

Portugal

Pfizer Biofarmacêutica, Sociedade Unipessoal Lda

Tel: +351 21 423 5500

Hrvatska

Pfizer Croatia d.o.o.

Tel: + 385 1 3908 777

România

Pfizer Romania S.R.L.

Tel: +40 (0) 21 207 28 00

Ireland

Pfizer Healthcare Ireland

Tel: 1800 633 363 (toll free)

+44 (0)1304 616161

Slovenija

Pfizer Luxembourg SARL

Pfizer, podružnica za svetovanje s področja

farmacevtske dejavnosti, Ljubljana

Tel: + 386 (0)1 52 11 400

Ísland

Icepharma hf.

Sími: +354 540 8000

Slovenská republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: + 421 2 3355 5500

Italia

Pfizer S.r.l.

Tel: +39 06 33 18 21

Suomi/Finland

Pfizer Oy

Puh/Tel: +358 (0)9 43 00 40

Κύπρος

Pfizer Ελλάς Α.Ε. (Cyprus Branch)

Τηλ: +357 22 817690

Sverige

Pfizer Innovations AB

Tel: +46 (0)8 550-520 00

Latvija

Pfizer Luxembourg SARL filiāle Latvijā

Tel: + 371 670 35 775

United Kingdom

Pfizer Limited

Tel: +44 (0) 1304 616161

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

The following information is intended for healthcare professionals only. For full information on

dosage and dose modifications please refer to the Summary of Product Characteristics.

Method of administration

BESPONSA is for intravenous use. The infusion must be administered over 1 hour.

Do not administer BESPONSA as an intravenous push or bolus.

BESPONSA must be reconstituted and diluted before administration.

BESPONSA should be administered in 3- to 4-week cycles.

For patients proceeding to a haematopoietic stem cell transplant (HSCT), the recommended duration

of treatment is 2 cycles. A third cycle may be considered for those patients who do not achieve a

CR/CRi and MRD negativity after 2 cycles. For patients not proceeding to HSCT, a maximum of

6 cycles, may be administered. Any patients who do not achieve a CR/CRi within 3 cycles should

discontinue treatment (see Summary of Product Characteristics section 4.2).

The table below shows the recommended dosing regimens.

For the first cycle, the recommended total dose for all patients is 1.8 mg/m

per cycle, administered as

3 divided doses on Days 1 (0.8 mg/m

), 8 (0.5 mg/m

), and 15 (0.5 mg/m

). Cycle 1 is 3 weeks in

duration, but may be extended to 4 weeks if the patient achieves a CR or CRi, and/or to allow recovery

from toxicity.

For subsequent cycles, the recommended total dose is 1.5 mg/m

per cycle administered as 3 divided

doses on Days 1 (0.5 mg/m

), 8 (0.5 mg/m

), and 15 (0.5 mg/m

) for patients who achieve a CR/CRi or

1.8 mg/m

per cycle given as 3 divided doses on Days 1 (0.8 mg/m

), 8 (0.5 mg/m

), and

15 (0.5 mg/m

) for patients who do not achieve a CR/CRi. Subsequent cycles are 4 weeks in duration.

Dosing regimen for Cycle 1 and subsequent cycles depending on response to treatment

Day 1

Day 8

Day 15

Dosing regimen for Cycle 1

All patients:

Dose (mg/m

Cycle length

21 days

Dosing regimen for subsequent cycles depending on response to treatment

Patients who have achieved a CR

c

or CRi

d

:

Dose (mg/m

Cycle length

28 days

Patients who have not achieved a CR

c

or CRi

d

:

Dose (mg/m

Cycle length

28 days

Abbreviations: ANC=absolute neutrophil counts; CR=complete remission; CRi=complete remission with

incomplete haematological recovery.

+/- 2 days (maintain a minimum of 6 days between doses).

For patients who achieve a CR/CRi, and/or to allow for recovery from toxicity, the cycle length may be

extended up to 28 days (i.e. 7-day treatment-free interval starting on Day 21).

CR is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukaemic blasts, full

recovery of peripheral blood counts (platelets ≥ 100 × 10

/L and ANC ≥ 1 × 10

/L) and resolution of any

extramedullary disease.

Dosing regimen for Cycle 1 and subsequent cycles depending on response to treatment

Day 1

Day 8

Day 15

CRi is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukaemic blasts,

incomplete recovery of peripheral blood counts (platelets < 100 × 10

/L and/or ANC < 1 × 10

/L) and

resolution of any extramedullary disease.

7-day treatment-free interval starting on Day 21.

Instructions for reconstitution, dilution, and administration

Use appropriate aseptic technique for the reconstitution and dilution procedures. Inotuzumab

ozogamicin (which has a density of 1.02 g/mL at 20 °C/68 °F) is light sensitive and should be

protected from ultraviolet light during reconstitution, dilution, and administration.

The maximum time from reconstitution through the end of administration should be ≤ 8 hours, with ≤

4 hours between reconstitution and dilution.

Reconstitution:

Calculate the dose (mg) and number of vials of BESPONSA required.

Reconstitute each 1 mg vial with 4 mL of water for injection, to obtain a single-use solution of

0.25 mg/mL of BESPONSA.

Gently swirl the vial to aid dissolution. Do not shake.

Inspect the reconstituted solution for particulates and discolouration. The reconstituted

solution must be clear to slightly cloudy, colourless, and essentially free of visible foreign

matter. If particles or discolouration are observed, do not use.

BESPONSA contains no bacteriostatic preservatives. The reconstituted solution must be used

immediately. If the reconstituted solution cannot be used immediately, it may be stored in a

refrigerator (2 °C-8 °C) for up to 4 hours. Protect from light and do not freeze.

Dilution:

Calculate the required volume of the reconstituted solution needed to obtain the appropriate

dose according to patient body surface area. Withdraw this amount from the vial(s) using a

syringe. Protect from light. Discard any unused reconstituted solution left in the vial.

Add the reconstituted solution to an infusion container with sodium chloride 9 mg/mL (0.9%)

solution for injection, to a total nominal volume of 50 mL. The final concentration should be

between 0.01 and 0.1 mg/mL. Protect from light. An infusion container made of polyvinyl

chloride (PVC) (di(2-ethylhexyl)phthalate [DEHP]- or non-DEHP-containing), polyolefin

(polypropylene and/or polyethylene), or ethylene vinyl acetate (EVA) is recommended.

Gently invert the infusion container to mix the diluted solution. Do not shake.

The diluted solution must be used immediately, stored at room temperature (20 °C-25 °C) or

in a refrigerator

2 °C-8 °C). The maximum time from reconstitution through the end of

administration should be ≤ 8 hours, with ≤ 4 hours between reconstitution and dilution. Protect

from light and do not freeze.

Administration:

If the diluted solution is stored in a refrigerator (2 °C-8 °C), it must be allowed to equilibrate

at room temperature (20 °C-25 °C) for approximately 1 hour prior to administration.

Filtration of the diluted solution is not required. However, if the diluted solution is filtered,

polyethersulphone (PES)-, polyvinylidene fluoride (PVDF)-, or hydrophilic polysulphone

(HPS)-based filters are recommended. Do not use filters made of nylon or mixed cellulose

ester (MCE).

Protect the intravenous bag from light using an ultraviolet light-blocking cover (i.e., amber,

dark brown, or green bags or aluminium foil) during infusion. The infusion line does not need

to be protected from light.

Infuse the diluted solution for 1 hour at a rate of 50 mL/h at room temperature (20 °C-25 °C).

Protect from light. Infusion lines made of PVC (DEHP or non-DEHP-containing), polyolefin

(polypropylene and/or polyethylene), or polybutadiene are recommended.

Do not mix BESPONSA or administer as an infusion with other medicinal products.

The storage times and conditions for reconstitution, dilution, and administration of BESPONSA are

shown below.

Storage times and conditions for reconstituted and diluted BESPONSA solution

Maximum time from reconstitution through the end of administration ≤ 8 hours

a

Reconstituted solution

Diluted solution

After start of dilution

Administration

Use reconstituted solution

immediately or after being

stored in a refrigerator

(2 °C-8 °C)

for up to 4 hours.

Protect from light. Do not

freeze.

Use diluted solution

immediately or after being

stored at room temperature

(20 °C-25 °C) or in a

refrigerator (2 °C-8 °C). The

maximum time from

reconstitution through the end

of administration should be

≤ 8 hours, with ≤ 4 hours

between reconstitution and

dilution. Protect from light.

Do not freeze.

If the diluted solution is stored

in a refrigerator (2 °C-8 °C),

bring it to room temperature

(20 °C-25 °C) for

approximately 1 hour prior to

administration. Administer

diluted solution as a 1-hour

infusion at a rate of 50 mL/h at

room temperature

(20 °C-25 °C). Protect from

light.

With ≤4 hours between reconstitution and dilution.

Storage conditions and shelf life

Unopened vials

5 years

Reconstituted solution

BESPONSA contains no bacteriostatic preservatives. The reconstituted solution must be used

immediately. If the reconstituted solution cannot be used immediately, it may be stored in a

refrigerator (2 °C-8 °C) for up to 4 hours. Protect from light and do not freeze.

Diluted solution

The diluted solution must be used immediately or stored at room temperature (20 °C-25 °C) or in a

refrigerator (2 °C-8 °C). The maximum time from reconstitution through the end of administration

should be ≤ 8 hours, with ≤ 4 hours between reconstitution and dilution. Protect from light and do not

freeze.