IntravenousRefractory CD22-positive B-cell precursor acute lymphoblastic leukaemia, Relapsed CD22-positive B-cell precursor acute lymphoblastic leukaemiaAdult: Premedicate with a corticosteroid, antipyretic, and antihistamine before each dose. Cycle 1: 0.8 mg/m2 on Day 1 and 0.5 mg/m2 on Days 8 and 15 of a 21-day cycle (total dose/cycle 1: 1.8 mg/m2); may be extended to 4 weeks if complete remission (CR) is achieved, or complete remission with incomplete haematologic recovery (CRi) and/or to allow for recovery from toxicity. Subsequent cycles: Patients who achieve CR or CRi: 0.5 mg/m2 on Days 1, 8 and 15 of a 28-day cycle (total dose/cycle: 1.5 mg/m2). Patients who do not achieve CR or CRi: 0.8 mg/m2 on Day 1 and 0.5 mg/m2 on Days 8 and 15 of a 28-day cycle (total dose/cycle: 1.8 mg/m2). Treatment duration: For patients proceeding to haematopoietic stem cell transplant (HSCT): 2 cycles; may consider a 3rd cycle in patients who do not achieve CR or CRi and minimal residual disease (MRD) negativity after 2 cycles. For patients not proceeding to HSCT: Max 6 cycles. Administer the infusion over 1 hour at a rate of 50 mL/hour. Discontinue treatment in patients who do not achieve a CR or CRi within 3 cycles. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guidelines).
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Reconstitute each vial with 4 mL of sterile water for inj to obtain a concentration of 0.25 mg/mL. Gently swirl the vial to mix. Do not shake. Add the required volume of reconstituted solution to obtain the appropriate dose to an infusion container with NaCl 0.9% to a total volume of 50 mL. Gently invert the infusion container to mix. Do not shake.
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Previously confirmed severe or ongoing veno-occlusive liver disease (VOD; also known as sinusoidal obstruction syndromes), current severe hepatic disease (e.g. cirrhosis, nodular regenerative hyperplasia, active hepatitis). Lactation.
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Patient with risk factors for VOD (e.g. ongoing or previous liver disease, previous HSCT, increased age, later salvage lines); history of or predisposition for QTc prolongation (e.g. electrolyte disturbances). Patients with circulating lymphoblasts are recommended to undergo cytoreduction with a combination of hydroxyurea, steroids, and/or vincristine to a peripheral blast count of ≤10,000/mm3 prior to the 1st dose. Patients with a high tumour burden are recommended to receive premedication to reduce uric acid levels and hydration prior to dosing. Pregnancy.
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Significant: Infusion-related reactions, QT interval prolongation; increased LFT, amylase and lipase, hypersensitivity reactions.
Gastrointestinal disorders: Abdominal pain or distension, nausea, vomiting, diarrhoea, constipation, stomatitis.
General disorders and administration site conditions: Pyrexia, chills, fatigue.
Hepatobiliary disorders: Hyperbilirubinaemia.
Investigations: Increased alkaline phosphatase, gamma-glutamyltransferase.
Metabolism and nutrition disorders: Decreased appetite, hyperuricaemia.
Nervous system disorders: Headache.
Potentially Fatal: Hepatotoxicity, including VOD; increased risk of post-HSCT non-relapse mortality; myelosuppression (e.g. neutropenia, thrombocytopenia, anaemia, leucopenia, febrile neutropenia, lymphopenia, and pancytopenia); tumour lysis syndrome, haemorrhagic events, severe infections (e.g. bacterial, fungal, and viral infections; pneumonia, sepsis, neutropenic sepsis, septic shock, and pseudomonal sepsis).
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This drug may cause fatigue, if affected, do not drive or operate machinery. Women of childbearing potential must use proven birth control methods during therapy and for at least 8 months after stopping the treatment. Males with female partners of childbearing potential must use proven birth control methods during treatment and for at least 5 months after the last dose.
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Perform CD22 positivity assay prior to initiation of treatment. Evaluate pregnancy status prior to therapy. Obtain CBC prior to each dose, ECG and electrolytes at baseline and during treatment, LFT (including ALT, AST, total bilirubin, and alkaline phosphatase) prior to and following each dose. Monitor closely for signs and symptoms of VOD (e.g. elevations in total bilirubin, hepatomegaly, rapid weight gain, and ascites); myelosuppression (e.g. bleeding, haemorrhage, infection); toxicities post-HSCT, infection, haemorrhage, tumour lysis syndrome, and increases in amylase and lipase. Monitor for infusion-related reactions during and for at least 1 hour after infusion.
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Concomitant use with drugs known to prolong the QT interval or induce torsades de pointes may increase the risk of a clinically significant QTc interval prolongation. May diminish the effect of live vaccines.
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Description:
Mechanism of Action: Inotuzumab ozogamicin is an antibody-drug conjugate (ADC) composed of a CD22-directed monoclonal antibody that is covalently linked to N-acetyl-gamma-calicheamicin dimethylhydrazide. It binds to CD22-expressing tumour cells, followed by internalisation of the ADC-CD22 complex, and the intracellular release of N-acetyl-gamma-calicheamicin dimethylhydrazide, thereby inducing double-strand DNA cleavage and subsequent cell cycle arrest and apoptosis.
Pharmacokinetics:
Distribution: Volume of distribution: Approx 12 L. Plasma protein binding: Approx 97% (N-acetyl-gamma-calicheamicin dimethylhydrazide).
Metabolism: Primarily metabolised via nonenzymatic reduction (N-acetyl-gamma-calicheamicin dimethylhydrazide).
Excretion: Terminal elimination half-life: Approx 12.3 days.
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Intact vials: Store between 2-8°C. Do not freeze. Protect from light. Reconstituted solution: May be stored between 2-8°C for up to 4 hours if not used immediately. Diluted solution: May be stored between 20-25°C or between 2-8°C if not used immediately. The Max time from reconstitution through administration should be ≤8 hours, with ≤4 hours between reconstitution and dilution. Protect from light. Do not freeze. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
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L01FB01 - inotuzumab ozogamicin ; Belongs to the class of CD22 (Clusters of Differentiation 22) inhibitors. Used in the treatment of cancer.
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Anon. Inotuzumab Ozogamicin. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 19/10/2022. Anon. Inotuzumab Ozogamicin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/10/2022. Besponsa (Pfizer Inc). MIMS Singapore. http://www.mims.com/singapore. Accessed 19/10/2022. Besponsa 1 mg Powder for Concentrate for Solution for Infusion (Pfizer Limited). MHRA. https://products.mhra.gov.uk. Accessed 19/10/2022. Besponsa Injection, Powder, Lyophilized, for Solution (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 19/10/2022. Joint Formulary Committee. Inotuzumab Ozogamicin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/10/2022. Pfizer New Zealand Limited. Besponsa 1 mg Powder for Injection data sheet 23 December 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 19/10/2022.
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