Inotuzumab ozogamicin parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of inotuzumab.
Drugs List
Therapeutic Indications
Uses
Relapsed/refractory CD22-positive Bcell acute lymphoblastic leukaemia (ALL)
Monotherapy treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL). In adults with Philadelphia chromosome positive (Ph+) when previous treatment with at least 1 tyrosine kinase inhibitor (TKI) has failed.
Dosage
Patients moving to haematopoietic stem cell transplant (HSCT), are recommended to have 2 cycles of treatment. A third cycle may be administered if complete remission (CR) has not been achieved or have complete remission with incomplete haematological recovery (CRi) and minimal residual disease (MRD) negativity after 2 cycles.
Patients not receiving HSCT may be administered up to 6 cycles of treatment, if considered necessary. However, treatment should be discontinued after 3 cycles if CR or CRi is not achieved.
Adults
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Cycle 1
Day 1: 0.8mg per metre squared.
Day 8: 0.5mg per metre squared.
Day 15: 0.5mg per metre squared.
Cycle of 21 days. May be extended to 28 days for patients who achieved CR or CRi and/or to allow for recovery time.
Subsequent Cycles - For patients who achieved CR/CRi
Day 1: 0.5mg per metre squared.
Day 8: 0.5mg per metre squared.
Day 15: 0.5mg per metre squared.
Cycle of 28 days.
Subsequent Cycles - For patients who have not achieved CR/CRi
Day 1: 0.8mg per metre squared.
Day 8: 0.5mg per metre squared.
Day 15: 0.5mg per metre squared.
Cycle of 28 days.
Additional Dosage Information
Dose modifications for haematological toxicities at the start of treatment
Absolute neutrophil count (ANC) equal to or greater than 1 x 10 to the power of 9/L prior to treatment
If the ANC falls below 1 x 10 to the power of 9/L, interrupt the next cycle of treatment until ANC increases back up to, or greater than 1 x 10 to the power of 9/L.
Platelet count equal to or greater than 50 x 10 to the power of 9/L prior to treatment
If platelet count falls below 50 x 10 to the power of 9/L, interrupt the next cycle of treatment until the platelet count increases back up to, or greater than 50 x 10 to the power of 9/L.
ANC less than 1 x 10 to the power of 9/L and/or platelet count less than 50 x 10 to the power of 9/L prior to treatment
If ANC and/or platelet count falls, interrupt the next cycle of treatment until at least one of the following occurs:
- ANC and platelet count recover to at least baseline levels for the next cycle
- ANC recovers to equal to or greater than 1 x 10 to the power of 9/L and platelet count recovers equal to or greater than 50 x 10 to the power of 9/L
- the most recent bone marrow assessment, shows stable or improved disease, and the ANC and platelet count decrease is considered to be due to the underlying disease as opposed to toxicity.
Dose modifications for non-haematological toxicities during treatment
If venoocclusive liver disease/sinusoidal obstruction syndrome (VOD/SOS) or other severe liver toxicities develop, discontinue treatment permanently.
If the total bilirubin is greater than 1.5 x upper limit of normal (ULN) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) is greater than 2.5 x ULN, interrupt treatment until total bilirubin falls equal to or below 1.5 x ULN and AST/ALT falls equal to or below 2.5 x ULN.
If grade 2 toxicity is reached, interrupt treatment until recovery to a grade 1 or to pre-treatment grade, prior to each dose.
Toxicity dose modifications depending on duration
If toxicity occurs less than 7 days within the cycle, interrupt the next dose, maintaining at least 6 days in between doses.
If toxicity occurs within 7 to 14 days of the cycle, omit the next dose.
If toxicity occurs within 14 to 28 days of the cycle, decrease the total dose by 25% for the next cycle, once adequate recovery is achieved. Doses per cycle may be reduced further to only 2 doses for subsequent cycles, if a further modification is required. If the further modification is not tolerated, permanently discontinue treatment.
If toxicity occurs after 28 days of the cycle, consider permanent discontinuation of treatment.
Administration
After dilution, the solution should be administered by slow intravenous infusion over approximately 1 hour.
Contraindications
Children under 18 years
Breastfeeding
Hereditary fructose intolerance
Long QT syndrome
Pregnancy
Severe hepatic disorder
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
History of treatment with anthracyclines
Patients over 55 years
Dehydration
Electrolyte imbalance
Elevated serum bilirubin
Glucose-galactose malabsorption syndrome
History of hepatic disorder
History of torsade de pointes
Administration of live vaccines is not recommended
Consider anti-infective prophylaxis in immunocompromised patients
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Confirm CD22-positive status prior to treatment
Consider premedication with a corticosteroid
Consider premedication with hypouricaemic agent
Exclude hepatitis prior to therapy
Give pre-treatment counselling and consideration of oocyte cryopreservation
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Premedication with antihistamine recommended
Premedication with antipyretic recommended
Preparation contains sucrose
Consult local policy on the safe use of anti-cancer drugs
Interrupt treatment if infusion reaction occurs & monitor until resolution
Monitor throughout infusion and for 1 hour post first infusion
Record name and batch number of administered product
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Treatment to be administered by or under supervision of specialist
Monitor liver function tests at baseline and before each dose
Perform ECG before and during treatment
Monitor bilirubin levels before treatment
Monitor closely patients with pre-existing myelosuppression
Monitor complete blood counts before each dose
Monitor for bleeding during treatment
Monitor for signs and symptoms of veno occlusive disease
Monitor hepatic function in patients with history of hepatic disease
Monitor patients for signs of tumour lysis syndrome
Monitor serum amylase and lipase regularly
Monitor serum electrolytes
Advise patient to report symptoms of infection immediately
Consider discontinuing treatment if hepatotoxicity occurs
If veno-occlusive disorder occurs, discontinue and do not restart therapy
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Discontinue if grade 3 or higher infusion reaction occurs
Interrupt therapy if neutrophil count <1.0x10 to the power 9/L
Interrupt therapy if treatment-related elevations in ALT,AST (>2.5 x ULN)
Interrupt treatment if platelet count <50 x 10 to the power of 9/L
Suspend treatment if grade 2 non-haematological toxicity occurs
May cause impaired fertility
Female: contraception required during and for 8 months after treatment
Male & female: Ensure adequate contraception during treatment
Male: Contraception required during and for 5 months after treatment
Breastfeeding: Do not breastfeed during and for 2 months after treatment
Patients who have already undergone HSCT, prior to starting treatment, require careful consideration.
Monitor patients who develop abnormal live tests and/or show signs of hepatotoxicity, more closely. Patients who undergo HSCT should also have liver tests monitored closely.
In patients with a high tumour burden pre-medicate to reduce uric acid levels and ensure patient is hydrated.
Pregnancy and Lactation
Pregnancy
Inotuzumab ozogamicin is contraindicated during pregnancy.
The manufacturer suggests to avoid the use of inotuzumab ozogamicin in pregnancy unless the potential benefit to the mother outweighs any potential risk to the foetus. At the time of writing there is limited published information regarding the use of inotuzumab ozogamicin during pregnancy. Toxicity has been shown in reproductive studies on animals as well as foetal harm in non-clinical safety findings in pregnant women.
Lactation
Inotuzumab ozogamicin is contraindicated during breastfeeding.
The manufacturer states to avoid breastfeeding for at least 2 months after treatment. At the time of writing there is limited published information regarding the use of inotuzumab ozogamicin during breastfeeding. It is not known whether inotuzumab ozogamicin is excreted in breast milk, however due to its potential adverse effects, the use of inotuzumab ozogamicin is contraindicated in breastfeeding.
Side Effects
Abdominal distension
Abdominal pain
Anaemia
Ascites
Bleeding
Chills
Constipation
Decreased appetite
Diarrhoea
Elevated amylase levels
Elevated serum lipase
Epistaxis
Fatigue
Febrile neutropenia
Gamma glutamyl transferase (GGT) increased
Haemorrhage
Headache
Hepatic veno-occlusive disease
Hyperbilirubinaemia
Hypersensitivity reactions
Hyperuricaemia
Increase in alkaline phosphatase
Increase in serum transaminases
Infections
Infertility
Infusion related reaction
Leukopenia
Lymphopenia
Nausea
Neutropenia
Pancytopenia
Prolongation of QT interval
Pyrexia
Stomatitis
Thrombocytopenia
Tumour lysis syndrome
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: September 2019
Reference Sources
Summary of Product Characteristics: Besponsa 1mg powder for concentrate for solution for infusion. Pfizer Limited. Revised August 2019.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.