Besponsa

/ Pfizer

Inotuzumab ozogamicin should be administered in 3- to 4-week cycles. For patients proceeding to 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 complete remission (CR) or complete remission with incomplete haematological recovery (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. Patients who do not achieve a CR/CRi within 3 cycles should discontinue treatment.
For the first cycle, the recommended total dose: Inotuzumab ozogamicin for all patients is 1.8 mg/m² per cycle, given as 3 divided doses on Days 1 (0.8 mg/m²), 8 (0.5 mg/m²), and 15 (0.5 mg/m²). 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: Inotuzumab ozogamicin is 1.5 mg/m² per cycle given as 3 divided doses on Days 1 (0.5 mg/m²), 8 (0.5 mg/m²), and 15 (0.5 mg/m²) for patients who achieve a CR/CRi or 1.8 mg/m² per cycle given as 3 divided doses on Days 1 (0.8 mg/m²), 8 (0.5 mg/m²), and 15 (0.5 mg/m²) for patients who do not achieve a CR/CRi. Subsequent cycles are 4 weeks in duration.
Dose modifications: Dose modification of Inotuzumab ozogamicin  may be required based on individual safety and tolerability. Management of some adverse drug reactions may require dosing interruptions and/or dose reductions, or permanent discontinuation of Inotuzumab ozogamicin.
If the dose is reduced due to Inotuzumab ozogamicin -related toxicity, the dose should not be re-escalated.
See prescribing information for full details.

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).

Hypersensitivity to the active substance 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).

This drug  is a cytotoxic drug. Follow applicable special handling and disposal procedures.
Hepatotoxicity, including venoocclusive liver disease/sinusoidal obstruction syndrome (VOD/SOS).
Hepatotoxicity, including severe, life-threatening, and sometimes fatal hepatic VOD/SOS, was reported in patients with relapsed or refractory ALL receiving this drug.
Inotuzumab ozogamicin significantly increased the risk of VOD/SOS above that of standard chemotherapy regimens in this patient population. This risk was most marked in patients who underwent subsequent HSCT.
Myelosuppression/cytopenias: In patients receiving inotuzumab ozogamicin, neutropenia, thrombocytopenia, anaemia, leukopenia, febrile neutropenia, lymphopenia, and pancytopenia, some of which were life-threatening, have been reported.
In patients receiving inotuzumab ozogamicin, complications associated with neutropenia and thrombocytopenia (including infections and bleeding/haemorrhagic events, respectively) were reported in some patients.
Complete blood counts should be monitored prior to each dose of BESPONSA and signs and symptoms of infection, during treatment and after HSCT, bleeding/haemorrhage, and other effects of myelosuppression should be monitored during treatment. As appropriate, prophylactic anti-infectives should be administered and surveillance testing should be employed during and after treatment.
Management of severe infection, bleeding/haemorrhage and other effects of myelosuppression, including severe neutropenia or thrombocytopenia, may require a dosing interruption, dose reduction, or discontinuation of treatment.
Infusion related reactions: In patients receiving inotuzumab ozogamicin, infusion related reactions were reported.
Pre-medication with a corticosteroid, antipyretic, and antihistamine is recommended prior to dosing.
Patients should be monitored closely during and for at least 1 hour after the end of infusion for the potential onset of infusion related reactions, including symptoms such as hypotension, hot flush, or breathing problems. If an infusion related reaction occurs, the infusion should be interrupted and appropriate medical management should be instituted. Depending on the severity of the infusion related reaction, discontinuation of the infusion or administration of steroids and antihistamines should be considered. For severe or life-threatening infusion reactions, treatment should be permanently discontinued.
QT interval prolongation: This drug should be administered with caution in patients who have a history of, or predisposition to QT interval prolongation, who are taking medicinal products that are known to prolong QT interval and in patients with electrolyte disturbances. ECG and electrolytes should be obtained prior to the start of treatment and periodically monitored during treatment.
In patients receiving inotuzumab ozogamicin, QT interval prolongation was observed.
Sodium content
This medicinal product contains less than 1 mmol sodium (23 mg) per 1 mg inotuzumab ozogamicin.
Patients on low sodium diets can be informed that this medicinal product is essentially ‘sodium-free’.
This medicinal product may be further prepared for administration with sodium-containing solutions  and this should be considered in relation to the total sodium from all sources
that will be administered to the patient.
See prescribing information for full details.

Most common: Thrombocytopenia, neutropenia, infection, anaemia, leukopenia, fatigue, haemorrhage, pyrexia, nausea, headache, febrile neutropenia, increased transaminases, abdominal pain, increased gamma-glutamyltransferase, and hyperbilirubinaemia.
See prescribing information for full details.

No formal clinical drug interaction studies have been performed.
Based on in vitro data, coadministration of inotuzumab ozogamicin with inhibitors or inducers of cytochrome P450 (CYP) or uridine diphosphate-glucuronosyltransferase (UGT) drug metabolising enzymes are unlikely to alter exposure to N-acetyl-gamma-calicheamicin dimethylhydrazide. In addition, inotuzumab ozogamicin and N-acetyl-gamma-calicheamicin dimethylhydrazide are unlikely to alter the exposure of substrates of CYP enzymes, and N-acetyl-gamma-calicheamicin dimethylhydrazide is unlikely to alter the exposure of substrates of UGT enzymes or major drug transporters.
In patients receiving inotuzumab ozogamicin, prolonged QT interval was observed.
Therefore, the concomitant use of inotuzumab ozogamicin with medicinal products known to prolong QT interval or to induce Torsades de Pointes should be carefully considered. The QT interval should be monitored in case of combinations of such medicinal products.

Pregnancy: Women of childbearing potential should avoid becoming pregnant while receiving this drug. BESPONSA must not be used during pregnancy unless the potential benefit to the mother outweighs the potential risks to the foetus. Pregnant women, or patients becoming pregnant while receiving inotuzumab ozogamicin, or treated male patients as partners of pregnant women, must be apprised of the potential hazard to the fetus.
Lactation: There are no data on the presence of inotuzumab ozogamicin or its metabolites in human milk, the effects on the breast-fed child, or the effects on milk production. Because of the potential for adverse reactions in breast-fed children, women must not breast-feed during treatment with this drug and for at least 2 months after the final dose.
See prescribing information for full details.

In clinical studies in patients with relapsed or refractory ALL, the maximum single and multiple doses of inotuzumab ozogamicin were 0.8 mg/m² and 1.8 mg/m², respectively, per cycle, given as 3 divided doses on Days 1 (0.8 mg/m²), 8 (0.5 mg/m²), and 15 (0.5 mg/m²).
Overdoses may result in adverse reactions that are consistent with the reactions observed at the recommended therapeutic dose.
In the event of an overdose, the infusion should be temporarily interrupted and patients should be monitored for liver and haematological toxicities. Re-initiation of this drug at the correct therapeutic dose should be considered when all toxicities have resolved.  

Storage: Store in a refrigerator (2°C-8°C). Do not freeze. Store in the original carton in order to protect from light.
Compatibility: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section.