Intramuscular, IntravenousAcute lymphoblastic leukaemiaAdult: As part of a multi-agent combination chemotherapy regimen: ≤21 years 2,500 units/m2 every 14 days; >21 years 2,000 units/m2 every 14 days. Doses are given via IM inj or via IV infusion over 1-2 hours. IM inj is preferred for smaller volume; higher volume must be divided and given at several inj sites. Max volume per IM inj: 3 mL. Premedicate with paracetamol, H1-receptor blocker (e.g. diphenhydramine) and H2-receptor blocker (e.g. famotidine) 30-60 minutes before administration. If asparaginase efficacy fails to reach target levels after trough serum monitoring, consider switching to a different asparaginase preparation. Dose reduction, dosing interruption, or discontinuation may be required according to the severity of adverse reactions (refer to detailed product guidelines).
Child: As part of a multi-agent combination chemotherapy regimen: In patients with a BSA of <0.6 m2: 82.5 units/kg every 14 days; ≥0.6 m2: 2,500 units/m2 every 14 days. Doses are given via IM inj or via IV infusion over 1-2 hours through a running IV infusion of either NaCl 0.9% or dextrose 5%. IM inj is preferred for smaller volume; higher volume must be divided and given at several inj sites. Max volume per IM inj: 2 mL. Premedicate with paracetamol, H1-receptor blocker (e.g. diphenhydramine) and H2-receptor blocker (e.g. famotidine) 30-60 minutes before administration. If asparaginase efficacy fails to reach target levels after trough serum monitoring, consider switching to a different asparaginase preparation. Dose reduction, dosing interruption, or discontinuation may be required according to the severity of adverse reactions (refer to detailed product guidelines).
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Powder for solution for inj or infusion: Reconstitute vial with 5.2 mL sterile water for inj. Gently swirl vial until powder is dissolved. Do not shake. IV infusion: Further dilute the reconstituted solution or solution for inj or infusion in 100 mL NaCl 0.9% or dextrose 5% solution.
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Hypersensitivity. History of serious thrombosis or haemorrhagic events with prior L-asparaginase therapy; history of pancreatitis, including pancreatitis related to previous L-asparaginase therapy. Severe hepatic impairment (bilirubin >3 times ULN; transaminases >10 times ULN). Lactation.
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Philadelphia chromosome-positive patient. Children. Pregnancy.
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Significant: Thrombotic events, including sagittal sinus thrombosis; increased prothrombin time and partial thromboplastin time, hypofibrinogenaemia; CNS toxicity (e.g. encephalopathy), myelosuppression, hyperammonaemia, glucose intolerance; antibody development.
Blood and lymphatic system disorders: Febrile neutropenia.
Gastrointestinal disorders: Diarrhoea, nausea, abdominal pain, vomiting, stomatitis, ascites.
Infections and infestations: Sepsis, infections.
Investigations: Decreased weight; increased AST, ALT, blood bilirubin, blood cholesterol, GGT, and INR.
Metabolism and nutrition disorders: Decreased appetite, hypoalbuminaemia, hypercholesterolaemia, hyperlipidaemia, hypokalaemia.
Musculoskeletal and connective tissue disorders: Pain in extremities.
Nervous system disorders: Peripheral neuropathy, seizure, drowsiness.
Respiratory, thoracic and mediastinal disorders: Hypoxia.
Skin and subcutaneous tissue disorders: Rash.
Vascular disorders: Syncope.
Potentially Fatal: Hypersensitivity reactions (e.g. anaphylaxis); pancreatitis, including haemorrhagic or necrotising pancreatitis; hepatotoxicity, including hepatic veno-occlusive disease.
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This drug may cause drowsiness, dizziness, confusion, seizure, or fainting; if affected, do not drive or operate machinery. Women of childbearing potential and males with female partners of childbearing potential must use effective non-oral birth control methods during treatment and for at least 6 months after treatment discontinuation. Breastfeeding women should not breastfeed during treatment and for 1 month after treatment discontinuation.
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Verify pregnancy status before use in women of childbearing potential. Assess treatment by measuring the trough serum asparaginase activity before the next pegaspargase administration. Monitor serum amylase and lipase levels (regularly); LFTs (at baseline, at least weekly during treatment cycles, and for at least 6 weeks after the last dose); coagulation parameters (at baseline and periodically during and after treatment); CBC with differential, renal function tests, urine and blood glucose (at least weekly during treatment); triglycerides, uric acid; vital signs (during administration). Observe the patient for 1 hour after administration. Monitor for onset of abdominal pain and signs or symptoms of hepatic veno-occlusive disease and thrombosis or bleeding.
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Symptoms: Increased liver enzymes, hyperbilirubinaemia and rash. Management: Symptomatic and supportive treatment. Monitor for signs and symptoms of adverse reactions.
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Increased risk of osteonecrosis (avascular necrosis) with glucocorticoids in children and adolescents, more commonly in girls. May enhance the alterations in coagulation parameters (e.g. decreased fibrinogen and antithrombin III deficiency) with glucocorticoids (e.g. prednisone). May increase the risk of severe hepatotoxicity with other hepatotoxic agents. Prior administration of methotrexate and cytarabine may increase the effect of pegaspargase; conversely, these agents may decrease the effect of pegaspargase when given subsequently. May increase the risk of severe infections with live vaccines. May increase the risk of toxicity with vincristine. Pegaspargase may increase the neurotoxicity of vincristine when administered before vincristine.
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Description:
Mechanism of Action: Pegaspargase is a modified form of L-asparaginase, an asparagine specific enzyme, which is conjugated with monomethoxypolyethylene glycol. L-asparaginase catalyses the conversion of L-asparagine into aspartic acid and ammonia, resulting in the reduction of asparagine, which is necessary for leukaemic cells. Depletion of asparagine in leukaemic cells leads to protein synthesis inhibition and subsequent apoptosis.
Duration: Asparagine depletion: IM: Approx 21 days. IV: 2-4 weeks (in asparaginase-naive adults).
Pharmacokinetics:
Absorption: Bioavailability: IM: 82% (initial dose); 98% (repeated dose).
Metabolism: Degraded systemically.
Excretion: Elimination half-life: IM: Approx 5.8 days (after a single dose of 2,500 units/m2). IV: Approx 5.3 days (after a single dose of 2,500 units/m2); 7 days (in asparaginase-naive adults).
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Intact vial: Store between 2-8°C. Do not freeze. Alternatively, store between 15-25°C for no more than 48 hours. Protect from light. Reconstituted solution: Store below 25°C and use within 24 hours. Diluted solution in NaCl 0.9% or dextrose 5% in water: Store between 2-8°C for up to 48 hours, including administration time. Protect from light.
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L01XX24 - pegaspargase ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
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Buckingham R (ed). Asparaginase. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/05/2024. Joint Formulary Committee. Pegaspargase. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/05/2024. Oncaspar 750 Units/mL Powder for Solution for Injection/Infusion (Les Laboratoires Servier). MHRA. https://products.mhra.gov.uk. Accessed 10/05/2024. Oncaspar 750 Units/mL Powder for Solution for Injection/Infusion (Servier Hong Kong Ltd). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 10/05/2024. Oncaspar 750 Units/mL Powder for Solution for Injection/Infusion (Servier Malaysia Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 10/05/2024. Oncaspar Injection, Solution (Servier Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/05/2024. Pegaspargase. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 10/05/2024. Servier Laboratories NZ Ltd. Oncaspar 750 Units/mL Powder for Solution for Injection/Infusion data sheet 25 August 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 10/05/2024.
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