SUMMARY CMI

BESPONSA^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

▼ This medicine is new or being used differently. Please report side effects. See the full CMI for further details.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I being given Besponsa?

Besponsa contains the active ingredient inotuzumab ozogamicin. Besponsa is used to treat adults with acute lymphoblastic leukaemia (ALL). ALL is a cancer of the blood where the cells that help protect your body from infection and foreign materials (white blood cells) grow uncontrollably. For more information, see Section 1. Why am I being given Besponsa? in the full CMI.

2. What should I know before receiving Besponsa?

Do not receive Besponsa if you have ever had an allergic reaction to Besponsa or any of the ingredients listed at the end of the CMI, or have had severe confirmed venoocclusive disease, or have serious ongoing liver disease. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before receiving Besponsa? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Besponsa and affect how it works. Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy with or without a prescription from your pharmacy, supermarket or health food shop. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is Besponsa given?

Besponsa is given in "cycles". One Besponsa treatment cycle is made up of a single Besponsa dose given each week for 3 weeks. A doctor or nurse will give you your Besponsa dose gradually over 1 hour through a drip in your vein. More instructions can be found in Section 4. How is Besponsa given? in the full CMI.

5. What should I know while receiving Besponsa?

For more information, see Section 5. What should I know while receiving Besponsa? in the full CMI.

6. Are there any side effects?

Common side effects may include: nausea, vomiting, diarrhoea, constipation, decreased appetite, headache, general weakness, mouth ulcer, redness or pain.

Serious side effects may include: rapid weight gain, pain in the upper right side of stomach, a yellowish colour of the eyes and skin, changes in heart rhythm, decreased urine, blood in urine, muscle spasms, weakness, cramps, fever, sweating, chills, bruising easily or getting regular nose bleeds, lightheadedness, rash or trouble breathing shortly after receiving the injection. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ 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. You can report side effects to your doctor, or directly at www.tga.gov.au/reporting-problems.

WARNING:

Hepatotoxicity, including fatal and life-threatening hepatic venoocclusive disease has occurred in patients treated with BESPONSA.

An increased risk of post-haematopoietic stem cell transplant (HSCT) non-relapse mortality has been observed in patients treated with BESPONSA.

FULL CMI

BESPONSA^®

Active ingredient: Inotuzumab ozogamicin (rch)

Consumer Medicine Information (CMI)

This leaflet provides important information about Besponsa.

You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about Besponsa.

Where to find information in this leaflet:

1. Why am I being given Besponsa?
2. What should I know before receiving Besponsa?
3. What if I am taking other medicines?
4. How is Besponsa given?
5. What should I know while receiving Besponsa?
6. Are there any side effects?
7. Product details

1. Why am I being given Besponsa?

The active ingredient in Besponsa is inotuzumab ozogamicin. It belongs to a group of medicines called antineoplastic agents that target cancer cells.

Besponsa is used to treat adults with acute lymphoblastic leukaemia (ALL). ALL is a cancer of the blood where the cells that help protect your body from infection and foreign materials (white blood cells) grow uncontrollably.

This medicine works by stopping the abnormal growth of these cells and destroying them.

2. What should I know before receiving Besponsa?

Warnings

Do not receive Besponsa if you:

• have had severe confirmed venoocclusive disease (a condition in which the blood vessels in the liver become damaged and blocked by blood clots) or you currently have this 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])
• are allergic to inotuzumab ozogamicin, or any of the ingredients listed at the end of this leaflet.

Always check the ingredients to make sure you can receive this medicine. See Section 7. Product details for a list of ingredients

Check with your doctor if you:

• have any other medical conditions such as:
  - liver problems
  - heart problems
  - an infection or fever or bruising easily or getting nose bleeds on a regular basis.
• take any medicines for any other condition.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant, are breastfeeding or intend to breastfeed.

It is unlikely that you will be given this medicine if you are pregnant or trying to become pregnant, as it may harm your unborn baby. Your doctor can discuss with you the risks involved.

You must avoid becoming pregnant or fathering a child if you are being treated with Besponsa.

It is not known whether this medicine passes into breast milk.

A risk to the newborn/infant cannot be excluded therefore you should not breastfeed during treatment with Besponsa and for at least 2 months after your last dose.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, vitamins or supplements that you buy with or without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may be affected by Besponsa or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines. Your doctor will advise you.

There are certain periods before, during and after Besponsa treatment where live vaccines are not recommended. Your doctor will advise you.

Check with your doctor or pharmacist if you are not sure if the medicine(s), vitamin(s) or supplement(s) you are taking are affected by Besponsa or may affect how Besponsa works.

4. How is Besponsa given?

Besponsa is given in "cycles". One Besponsa treatment cycle is made up of a single Besponsa dose given each week for 3 weeks.

A doctor or nurse will give you your Besponsa dose gradually over 1 hour through a drip in your vein (intravenous infusion).

How much is given

Your doctor will calculate how much you need to be given.

This will depend on your height and weight and may also depend on your condition and how you have responded to previous treatment.

Medicines given before each cycle

Before each treatment with Besponsa, you will be given other medicines (premedication) to help reduce symptoms such as fever, chills or hot flush, known as infusion reactions, and other possible side effects.

How long it is given

If the medicine works well and you are going to receive a stem cell transplant, 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, 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 will discuss with you how long your treatment will last.

If you forget a treatment

If you miss a treatment, contact your doctor or nurse as soon as possible to make a new appointment.

If you are given too much (overdose)

It is unlikely that you will be given too much Besponsa, as your dose will be calculated and given to you in a specialised setting under the supervision of a doctor.

If you think that you have been given too much Besponsa, you may need urgent medical attention.

If there are no signs of discomfort or poisoning but you still think that you have been given too much Besponsa, and you are in contact with a doctor, you should follow your doctor's advice.

If you are unable to reach your treating doctor, then go to the emergency department at your nearest hospital.

5. What should I know while receiving Besponsa?

Things you must do

If you (or your partner) become pregnant while you are being given this medicine, tell your doctor immediately.

You must avoid becoming pregnant or fathering a child.

Use a proven method of birth control (contraception) during treatment with Besponsa if you can become pregnant or if you can father a child.

You must continue to use effective birth control for at least 8 months (women) or at least 5 months (men) after the last dose of Besponsa.

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are being treated with Besponsa.

Tell all doctors, dentists, and pharmacists who treat you that you are being given this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are being given this medicine.

Keep all of your doctor's appointments so that your progress can be checked.

Your doctor will take regular blood tests to make sure Besponsa is working and to check for side effects.

In particular, your blood counts and liver function will need to be checked before each treatment.

Your doctor will also monitor your heart rhythm, the levels of certain electrolytes (such as calcium, magnesium, potassium) in your blood, and the level of enzymes (known as amylase and lipase) in your blood.

Your doctor may change your dose, interrupt, or completely stop treatment with this medicine if you have certain side effects.

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

Tell your doctor immediately if you have had any of the following symptoms during or shortly after being given Besponsa:

• fever, chills, hot flush, dizziness or lightheadedness, rash or trouble breathing
• nausea, vomiting, diarrhoea, changes in heartbeat, decreased urine or blood in urine, muscle weakness or cramps.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Besponsa affects you.

This medicine may cause fatigue in some people. If you feel tired, do not drive, operate machinery or do anything else that could be dangerous.

Drinking alcohol

No information available.

Tell your doctor if you drink alcohol.

Storage

Besponsa must be kept in the original packaging in a refrigerator, protected from light, before it is time to use it.

Your doctor, nurse or pharmacist will prepare the infusion for you before you are given it. They may give it to you straight away or within 8 hours after the start of preparation.

Your doctor, nurse and pharmacist have more information on how to store Besponsa.

Disposal

Your doctor, nurse or pharmacist will dispose of any left-over medicine.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor if you have any further questions about side effects.

Common side effects

The above list includes the more common side effects of your medicine.

Some side effects (for example, changes in your liver function) can only be found when your doctor does tests from time to time to check your progress.

Serious side effects

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Besponsa contains

Do not take this medicine if you are allergic to any of these ingredients.

What Besponsa looks like

Besponsa is a white or off-white powder or cake supplied in a glass vial (AUST R 288135).

Before Besponsa is given, the powder is mixed with sterile water and diluted with a solution of sodium chloride.

Each Besponsa carton contains 1 vial.

Who distributes Besponsa

Pfizer Australia Pty Ltd
Sydney, NSW
Toll Free Number: 1800 675 229.
www.pfizermedicalinformation.com.au

This leaflet was prepared in November 2024

^® = Registered Trademark

Published by MIMS January 2025

1 Name of Medicine

Inotuzumab ozogamicin (rch).

2 Qualitative and Quantitative Composition

Besponsa (inotuzumab ozogamicin) is a CD22-directed antibody-drug conjugate (ADC) consisting of 3 components:
1) a recombinant humanised immunoglobulin class G subtype 4 (IgG4) kappa antibody inotuzumab, produced in Chinese hamster ovary cells by recombinant deoxyribonucleic acid (DNA) technology, specific for human CD22;
2) a semisynthetic calicheamicin derivative, N-acetyl-gamma-calicheamicin, produced by microbial fermentation followed by synthetic modification, that causes double-stranded DNA breaks; and
3) an acid cleavable linker composed of the condensation product of 4-(4'-acetylphenoxy)-butanoic acid (AcBut) and 3-methyl-3-mercaptobutane hydrazide (known as dimethylhydrazide) that covalently attaches N-acetyl-gamma-calicheamicin to inotuzumab.
Each vial contains 1 mg inotuzumab ozogamicin.
After reconstitution with 4 mL of sterile water for injection, 1 mL of solution contains 0.25 mg inotuzumab ozogamicin. The drug product pH is approximately 8.0.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection.
Besponsa is supplied for intravenous infusion as 1 mg (protein equivalent) of white to off-white lyophilised cake or powder in a single dose vial for reconstitution and dilution.

4 Clinical Particulars

4.1 Therapeutic Indications

Besponsa is indicated for the treatment of adults with relapsed or refractory CD22‐positive B-cell precursor acute lymphoblastic leukaemia (ALL).

4.2 Dose and Method of Administration

Use of Besponsa should be initiated and supervised by a physician experienced in the treatment of haematological malignancies.

Premedication.

Recommended dosage regimen.

Dosage adjustments.

Children and adolescents.

Use in hepatic impairment.

Use in renal impairment.

Use in the elderly.

Instructions for reconstitution, dilution and administration.

Reconstitution.

Dilution.

Administration.

4.3 Contraindications

Hypersensitivity to inotuzumab ozogamicin or to any of the excipients.
Patients who have experienced prior confirmed severe or ongoing venoocclusive liver disease/sinusoidal obstruction syndrome (VOD/SOS).
Patients with serious ongoing hepatic disease (e.g. cirrhosis, nodular regenerative hyperplasia, active hepatitis).

4.4 Special Warnings and Precautions for Use

Hepatotoxicity, including venoocclusive liver disease (VOD)/sinusoidal obstruction syndrome (SOS).

Increased risk of post-transplant non-relapse mortality.

Myelosuppression/cytopenias.

Infusion related reactions.

Tumour lysis syndrome.

QT interval prolongation.

Increased amylase and lipase.

Immunisations.

Paediatric use.

Use in the elderly.

Use in hepatic impairment.

Use in renal impairment.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No clinical drug interaction studies have been performed with Besponsa.
In a randomised clinical study of Besponsa in patients with relapsed or refractory ALL (B1931022), prolonged QT interval was observed with Besponsa (see Section 5.1 Pharmacodynamic Properties, Cardiac electrophysiology). Therefore, the concomitant use of Besponsa with medicinal products known to prolong QT interval or able to induce Torsades de Pointes should be carefully considered. Monitor the QT interval in case of combinations of such medicinal products (see Section 4.4 Special Warnings and Precautions for Use, QT interval prolongation).

Effect of other medicines on inotuzumab ozogamicin.

Effect of inotuzumab ozogamicin on other medicines.

Effect on CYP substrates.

Effect on UGT substrates.

Effect on drug transporter substrates.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

No formal studies have been conducted on effects on the ability to drive and use machines. Patients should be advised that they may experience fatigue during treatment with Besponsa (see Section 4.8 Adverse Effects (Undesirable Effects)). Therefore, caution is recommended when driving or operating machines.

4.8 Adverse Effects (Undesirable Effects)

The adverse effects described in this section reflect exposure to Besponsa in 164 patients with relapsed or refractory ALL who participated in a randomised clinical study of Besponsa versus Investigator's choice of chemotherapy (FLAG, MXN/Ara-C, or HIDAC) (B1931022) (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
In patients who received Besponsa, the median duration of treatment was 8.9 weeks (range: 0.1-26.4 weeks), with a median of 3 treatment cycles started in each patient. In patients who received Investigator's choice of chemotherapy, the median duration of treatment was 0.9 weeks (range: 0.1-15.6 weeks), with a median of 1 treatment cycle started in each patient.
In patients who received Besponsa, the most common (≥ 20%) adverse reactions were thrombocytopenia, neutropenia, infection, anaemia, leukopenia, fatigue, haemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, gamma-glutamyltransferase increased, and hyperbilirubinaemia.
In patients who received Besponsa, the most common (≥ 2%) serious adverse reactions were infection (23%), febrile neutropenia (11%, haemorrhage (5%), abdominal pain (3%), pyrexia (2%), VOD/SOS (2%), and fatigue (2%).
In patients who received Besponsa, the most common (≥ 2%) adverse reactions reported as the reason for permanent discontinuation were infection (6%), thrombocytopenia (2%), hyperbilirubinaemia (2%), transaminases increased (2%), and haemorrhage (2%); the most common (≥ 5%) adverse reactions reported as the reason for dosing interruption were neutropenia (17%), infection (10%), thrombocytopenia (10%), transaminases increased (6%), and febrile neutropenia (5%); the most common (≥ 1%) adverse reactions reported as the reason for dose reduction were neutropenia (1%), thrombocytopenia (1%), and transaminases increased (1%).

Tabular listing of adverse reactions.

Listing of additional adverse reactions.

Blood and lymphatic system disorders.

Metabolism and nutrition disorders.

Gastrointestinal disorders.

Hepatobiliary disorders.

Investigations.

Injury, poisoning, and procedural complications.

Description of selected adverse reactions.

Hepatotoxicity, including venoocclusive liver disease/sinusoidal obstruction syndrome (VOD/SOS).

Increased risk of post-transplant non-relapse mortality.

Myelosuppression/cytopenias.

Complications associated with neutropenia and thrombocytopenia.

Infusion related reactions.

Tumour lysis syndrome.

QT interval prolongation.

Laboratory abnormalities.

Immunogenicity.

Reporting suspected adverse effects.

4.9 Overdose

Overdoses may result in adverse reactions that are consistent with the reactions observed at the recommended therapeutic dose (see Section 4.8 Adverse Effects (Undesirable Effects)). In the event of an overdose, the infusion should be temporarily interrupted and patients should be monitored for liver and haematological toxicities (see Section 4.2 Dose and Method of Administration). Reinitiation of Besponsa at the correct therapeutic dose should be considered when all toxicities have resolved.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Pharmacodynamics.

Pharmacodynamic effects.

Cardiac electrophysiology.

Clinical trials.

Patients with relapsed or refractory ALL who have received 1 or 2 prior treatment regimens for ALL - study B1931022.

5.2 Pharmacokinetic Properties

In patients with relapsed or refractory ALL, steady-state exposure was achieved by Cycle 4. The mean C_max of inotuzumab ozogamicin was 308 nanogram/mL. The mean simulated total area under the concentration-time curve (AUC) per cycle was 100,000 nanogram.h/mL.

Distribution.

Metabolism.

Excretion.

Special populations.

Age, race and gender.

Hepatic impairment.

Renal impairment.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each vial contains the following inactive ingredients: trometamol, sucrose, polysorbate 80, sodium chloride.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
Besponsa contains no bacteriostatic preservatives. The reconstituted solution should be used immediately. If the reconstituted solution cannot be used immediately, it may be refrigerated (2-8°C) for up to 4 hours. Protect from light and do not freeze.
The diluted solution should be used immediately or stored at room temperature (20-25°C) or refrigerated (2-8°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.

6.4 Special Precautions for Storage

Store unopened vials in the original carton at 2-8°C (Refrigerate. Do not freeze) and protect from light until time of use.
Table 9 shows the storage times and conditions for reconstitution, dilution, and administration of Besponsa.

6.5 Nature and Contents of Container

Each carton contains 1 single-use vial containing 1 mg of sterile, preservative free, white to off-white lyophilised cake or powder for injection.
The container is a Type I amber glass vial with chlorobutyl rubber stoppers and crimp seals with a flip off cap.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes