Inotuzumab ozogamicin

What is Inotuzumab ozogamicin?

• Inotuzumab ozogamicin (Besponsa) is a CD22-directed antibody-drug conjugate (ADC) used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

What are the uses of this medicine?

• This medicine is used for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

How does this medicine work?

• Inotuzumab (in" oh tooz' ue mab) ozogamicin (oh" zoe ga mye' sin) is a humanized monoclonal antibody to the human CD24 cell surface marker which is highly expressed on malignant lymphoblastic leukemia cells.
• The monoclonal antibody is conjugated to a cytotoxic agent from a class of calicheamicins called ozogamicin.
• When inotuzumab binds to CD24, it is internalized and the ozogamicin is released by the action of lysosomal enzymes on the linker molecule that joins it to the monoclonal antibody.
• The released intracellular ozogamicin causes breaks in double stranded DNA that leads to apoptotic cell death.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• Concomitant use of Besponsa with drugs known to prolong the QT interval or induce Torsades de Pointes may increase the risk of a clinically significant QTc interval prolongation.

Is this medicine FDA approved?

• It was approved for use in the United States in 2017.

How should this medicine be used?

• Pre-medicate with a corticosteroid, antipyretic, and antihistamine prior to all infusions.

Recommended Dosage:

• For the first cycle, the recommended total dose of Besponsa for all patients is 1.8 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Cycle 1 is 3 weeks in duration, but may be extended to 4 weeks if the patient achieves a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), and/or to allow recovery from toxicity.
• For subsequent cycles:
• In patients who achieve a CR or CRi, the recommended total dose of Besponsa is 1.5 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.5 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Subsequent cycles are 4 weeks in duration.
• OR
• In patients who do not achieve a CR or CRi, the recommended total dose of Besponsa is 1.8 mg/m2 per cycle given as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Subsequent cycles are 4 weeks in duration. Patients who do not achieve a CR or CRi within 3 cycles should discontinue treatment.
• For patients proceeding to hematopoietic stem cell transplant (HSCT), the recommended duration of treatment with Besponsa is 2 cycles. A third cycle may be considered for those patients who do not achieve CR or CRi and minimal residual disease (MRD) negativity after 2 cycles.
• For patients not proceeding to HSCT, additional cycles of treatment, up to a maximum of 6 cycles, may be administered.

Administration

• Besponsa is a cytotoxic drug. Follow applicable special handling and disposal procedures.
• Calculate the dose (mg) and number of vials of Besponsa required.
• Reconstitute each vial with 4 mL of Sterile Water for Injection, USP, to obtain a concentration of 0.25 mg/mL of Besponsa that delivers 3.6 mL (0.9 mg).
• Gently swirl the vial to aid dissolution. DO NOT SHAKE.
• Inspect the reconstituted solution for particulates and discoloration. The reconstituted solution should be clear to opalescent, colorless to slightly yellow, and essentially free of visible foreign matter.
• Calculate the required volume of the reconstituted solution needed to obtain the appropriate dose according to the patient's body surface area. Withdraw this amount from the vial(s) using a syringe. Discard any unused reconstituted Besponsa solution left in the vial.
• Add reconstituted solution to an infusion container with 0.9% Sodium Chloride Injection, USP, to a make a total volume of 50 mL. 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.
• Filtration of the diluted solution is not required. However, if the diluted solution is filtered, polyethersulfone (PES)-, polyvinylidene fluoride (PVDF)-,or hydrophilic polysulfone (HPS)-based filters are recommended. Do not use filters made of nylon or mixed cellulose ester (MCE).
• Infuse the diluted solution for 1 hour at a rate of 50 mL/h at room temperature (20–25°C; 68–77°F). Infusion lines made of PVC (DEHP- or non-DEHP-containing), polyolefin (polypropylene and/or polyethylene), or polybutadiene are recommended.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As injection: 0.9 mg lyophilized powder in a single-dose vial for reconstitution and further dilution.

This medicine is available in fallowing brand namesː

• Besponsa

What side effects can this medication cause?

The most common side effects of this medicine include:

• thrombocytopenia
• neutropenia
• infection
• anemia
• leukopenia
• fatigue
• hemorrhage
• pyrexia
• nausea
• headache
• febrile neutropenia
• transaminases increased
• abdominal pain
• gamma-glutamyltransferase increased
• hyperbilirubinemia

What special precautions should I follow?

• Myelosuppression was observed in patients receiving Besponsa. Monitor complete blood counts; for signs and symptoms of infection; bleeding/hemorrhage; or other effects of myelosuppression during treatment; manage appropriately.
• Infusion related reactions were observed in patients who received Besponsa. Monitor for infusion related reactions during and for at least 1 hour after infusion ends.
• Administer Besponsa with caution in patients who have a history of or predisposition for QTc prolongation, who are taking medicinal products that are known to prolong QT interval. Obtain electrocardiograms (ECGs) and electrolytes at baseline and monitor during treatment. Monitor more frequently when using concomitant mediations known to prolong QT interval.
• Besponsa Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Besponsa can cause embryo-fetal harm when administered to a pregnant woman.
• There are no available data on Besponsa use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage.

Can this medicine be used in children?

• Safety and effectiveness have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

Active ingredients:

• INOTUZUMAB OZOGAMICIN

Inactive ingredients:

• TROMETHAMINE
• SUCROSE
• POLYSORBATE 80
• SODIUM CHLORIDE
• WATER

Who manufactures and distributes this medicine?

• Packager: Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.

What should I know about storage and disposal of this medication?

• Refrigerate (2–8°C; 36–46°F) Besponsa vials and store in the original carton to protect from light.
• Do not freeze.
• Besponsa is a cytotoxic drug.
• Follow applicable special handling and disposal procedures.

• Dailymed label info on Inotuzumab ozogamicin
• FDA Inotuzumab ozogamicin