Acute lymphoblastic leukemia (ALL): Infants, Children, and Adolescents: IM, IV: 2,500 units/m2/dose (as part of a combination chemotherapy regimen); do not administer more frequently than every 14 days
Dosing adjustment for toxicity: Infants, Children, and Adolescents:
Hemorrhage: Grade 3 or 4: Hold therapy, evaluate for coagulopathy, and consider clotting factor replacement as needed; if resolution (ie, bleeding controlled), resume therapy with the next scheduled dose
Hypersensitivity or infusion reactions:
Grade 1: Reduce infusion rate by 50%
Grade 2: Interrupt infusion and treat symptoms; after resolution of symptoms, resume infusion at 50% of previous rate
Grade 3 or 4: Discontinue permanently
Pancreatitis: Grade 3 or 4: If lipase or amylase >3 times ULN, hold therapy until enzyme levels stabilize or are declining. Discontinue permanently if clinical pancreatitis confirmed.
Thromboembolism:
Uncomplicated deep vein thrombosis (DVT): Hold therapy, evaluate and treat DVT with antithrombotic therapy; upon resolution of symptoms, may resume therapy with concomitant antithrombotic agent(s)
Severe or life-threatening thrombosis: Discontinue permanently; treat thrombosis with necessary medical management
The following additional adjustments have been recommended for other asparaginase products (Stock 2011): Older Adolescents:
Hyperammonemia-related fatigue: Continue therapy for grade 2 toxicity. If grade 3 toxicity occurs, reduce dose by 25%; resume full dose when toxicity ≤ grade 2 (make up for missed doses). If grade 4 toxicity occurs, reduce dose by 50%; resume full dose when toxicity ≤ grade 2 (make up for missed doses).
Hyperglycemia: Continue therapy for uncomplicated hyperglycemia. If hyperglycemia requires insulin therapy, hold the asparaginase product (and any concomitant corticosteroids) until blood glucose controlled; resume dosing at prior dose level. For life-threatening hyperglycemia or toxicity requiring urgent intervention, hold the asparaginase product (and corticosteroids) until blood glucose is controlled with insulin; resume the asparaginase product and do not make up for missed doses.
Hypertriglyceridemia: If serum triglyceride level <1 g/dL, continue the asparaginase product but monitor closely for pancreatitis. If triglyceride level >1 g/dL, hold the asparaginase product and monitor; resume therapy at prior dose level after triglyceride level returns to baseline.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Infants, Children, and Adolescents:
Baseline (prior to therapy initiation):
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied)
Severe impairment: Use is contraindicated
Hepatotoxicity during therapy:
Total bilirubin >3 to 10 times ULN: Hold therapy until total bilirubin decreases to ≤1.5 times ULN
Total bilirubin >10 times ULN: Discontinue therapy and do not make up for missed doses
The following adjustments have also been recommended for other asparaginase products (Stock 2011): Older adolescents:
ALT/AST >3 to 5 times ULN: Continue therapy.
ALT/AST >5 to 20 times ULN: Delay next dose until transaminases <3 times ULN.
ALT/AST >20 times ULN: Discontinue therapy if it takes longer than 1 week for transaminases to return to <3 times ULN.
Direct bilirubin <3 mg/dL: Continue therapy.
Direct bilirubin 3.1 to 5 mg/dL: Hold pegaspargase and resume when direct bilirubin <2 mg/dL; consider switching to alternate asparaginase product.
Direct bilirubin >5 mg/dL: Discontinue pegaspargase; do not substitute other asparaginase products; do not make up for missed doses.
(For additional information see "Pegaspargase: Drug information")
Note: To decrease the risk and severity of infusion and hypersensitivity reactions, premedicate 30 to 60 minutes prior to pegaspargase administration with acetaminophen, an H1 antagonist (eg, diphenhydramine), and an H2 antagonist (eg, famotidine). Consider thromboprophylaxis with low molecular weight heparin (LMWH) during induction and intensification phases of asparaginase therapy, particularly in patients at high risk for venous thromboembolism; withhold LMWH for platelet count <30,000/mm3 (ISTH [Zwicker 2020]).
Acute lymphoblastic leukemia, as first-line treatment or in patients with hypersensitivity to native asparaginase: IM, IV:
≤21 years of age: 2,500 units/m2 (as part of a multi-agent combination chemotherapy regimen); do not administer more frequently than every 14 days.
>21 years of age: 2,000 units/m2 (as part of a multi-agent combination chemotherapy regimen); do not administer more frequently than every 14 days.
There are no dosage adjustments provided in the manufacturer’s labeling.
Hepatic impairment prior to treatment initiation:
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling.
Severe impairment: Use is contraindicated.
Hepatotoxicity during treatment:
Total bilirubin >3 to 10 times ULN: Withhold pegaspargase until total bilirubin levels decrease to ≤1.5 times ULN.
Total bilirubin >10 times ULN: Discontinue pegaspargase and do not make up for missed doses.
The following off-label adjustments have also been recommended (Stock 2011):
ALT/AST >3 to 5 times ULN: Continue therapy.
ALT/AST >5 to 20 times ULN: Delay next dose until transaminases <3 times ULN.
ALT/AST >20 times ULN: Discontinue therapy if it takes longer than 1 week for transaminases to return to <3 times ULN.
Direct bilirubin <3 mg/dL: Continue therapy.
Direct bilirubin 3.1 to 5 mg/dL: Hold pegaspargase and resume when direct bilirubin <2 mg/dL; consider switching to alternate asparaginase product.
Direct bilirubin >5 mg/dL: Discontinue pegaspargase; do not substitute other asparaginase products; do not make up for missed doses.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection [preservative free]:
Oncaspar: 750 units/mL (5 mL)
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Oncaspar: 750 units/mL (5 mL)
Note : Have available appropriate agents for maintenance of an adequate airway and treatment of a hypersensitivity reaction (antihistamine, epinephrine, oxygen, IV corticosteroids). Be prepared to treat anaphylaxis at each administration.
Parenteral:
IM: Administer as a deep IM injection into a large muscle. Limit the volume at a single injection site to 2 mL; for IM administration, if the volume to be administered is >2 mL, use multiple injection sites.
IV: Administer dose as an IV infusion over a period of 1 to 2 hours through a running IV infusion line (of either NS or D5W, depending on which fluid was used in preparation of the diluted solution). Do not administer IV push. Use of a 0.2 micron filter may result in some loss of potency. Do not infuse other medications through the same IV line during pegaspargase administration.
Have available appropriate agents for maintenance of an adequate airway and treatment of a hypersensitivity reaction (antihistamine, epinephrine, oxygen, IV corticosteroids). Be prepared to treat anaphylaxis at each administration.
IM: Must only be administered as a deep IM injection into a large muscle. Limit the injection volume to 2 mL per single injection site; use multiple injection sites for IM injection volume >2 mL.
IV: Administer over 1 to 2 hours through a running IV infusion line (of either NS or D5W, depending on which fluid was used in preparation of the diluted solution); do not administer IV push. Do not infuse other medications through the same IV line during pegaspargase administration.
Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Intact vials may be stored at 15°C to 25°C (59°F to 77°F) for no more than 48 hours. Store in original carton to protect from light. Do not shake. Discard if previously frozen, stored at room temperature for >48 hours, excessively shaken/agitated, or if cloudy, discolored, or if precipitate is present. Use immediately after preparation; if not used immediately, solutions diluted for infusion in NS or D5W should be protected from light, refrigerated at 2°C to 8°C (36°F to 46°F) and used within 48 hours (including administration time).
First-line treatment of newly diagnosed acute lymphoblastic leukemia (ALL) as part of a multiple chemotherapeutic drug regimen (FDA approved in pediatric patients [age not specified] and adults); induction treatment of ALL in combination with other chemotherapeutic agents in patients who have developed hypersensitivity to native forms of L-asparaginase derived from Escherichia coli and/or Erwinia chrysanthemi (FDA approved in ages ≥1 year and adults); has been used for the treatment of lymphoma and acute myelogenous leukemia (AML).
Oncaspar may be confused with Asparlas, Elspar
Pegaspargase may be confused with asparaginase (E. coli), asparaginase (Erwinia), asparaginase (Erwinia [recombinant]), calaspargase pegol-mknl, peginesatide
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for pediatric patients.
>10%:
Hypersensitivity: Hypersensitivity reaction (first-line treatment of acute lymphoblastic leukemia [ALL]: 2% to 3%; relapsed ALL with no prior asparaginase hypersensitivity: 10%; relapsed ALL with prior asparaginase hypersensitivity: 32%)
Immunologic: Antibody development (induction: 2%; delayed intensification: 10% to 11%)
1% to 10%:
Cardiovascular: Cerebral thrombosis (grades 3/4: 3%), thromboembolic complications (grades 3/4)
Endocrine & metabolic: Hyperglycemia (grades 3/4: 5%), hypertriglyceridemia (grades 3/4), hypoalbuminemia (grades 3/4)
Gastrointestinal: Pancreatitis (grades 3/4: 2%)
Hematologic & oncologic: Disorder of hemostatic components of blood (grades 3/4: 2%; includes prolonged prothrombin time, partial thromboplastin time, or decreased serum fibrinogen), febrile neutropenia (grades 3/4)
Hepatic: Hyperbilirubinemia (grades 3/4: 2%), increased serum alanine aminotransferase (grades 3/4: ≤3%), increased serum aspartate aminotransferase (grades 3/4: ≤3%)
Postmarketing (all populations):
Cardiovascular: Thrombosis (including sagittal sinus thrombosis)
Endocrine & metabolic: Hyperammonemia, increased serum cholesterol
Gastrointestinal: Hemorrhagic pancreatitis, necrotizing pancreatitis
Hematologic & oncologic: Hemorrhage
Hepatic: Hepatic insufficiency
Hypersensitivity: Anaphylactic shock
Nervous system: Intracranial hemorrhage
Neuromuscular & skeletal: Osteonecrosis
Miscellaneous: Cyst (pancreatic)
History of serious hypersensitivity reactions (including anaphylaxis) to pegaspargase or any component of the formulation; history of serious thrombosis with prior L-asparaginase therapy; history of pancreatitis (including pancreatitis associated with prior L-asparaginase therapy); history of serious hemorrhagic events with prior L-asparaginase therapy; severe hepatic impairment.
Concerns related to adverse effects:
• Glucose intolerance: Pegaspargase may result in glucose intolerance (was irreversible in some cases).
• Hemorrhage: Increased PT, increased PTT, and hypofibrinogenemia may occur in patients receiving pegaspargase. Severe or symptomatic coagulopathy may require appropriate replacement therapy.
• Hepatotoxicity: Hepatotoxicity and abnormal liver function, including elevations of transaminase and bilirubin (direct and indirect) and reduced serum albumin and fibrinogen may occur with pegaspargase.
• Hypersensitivity: Anaphylaxis and serious hypersensitivity reactions may occur with pegaspargase. The risk of serious hypersensitivity reactions is increased in patients with known hypersensitivity to E. coli derived L-asparaginase products. Hypersensitivity reactions may include angioedema, lip swelling, eye swelling, hypotension, bronchospasm, dyspnea, erythema, pruritus, and rash. Premedicate 30 to 60 minutes prior to pegaspargase administration. Observe patients for 1 hour after administration; equipment and immediate treatment for hypersensitivity reactions (eg, epinephrine, oxygen, intravenous steroids, antihistamines) should be available during administration. Discontinue pegaspargase in patients with serious hypersensitivity reactions.
• Pancreatitis: Pancreatitis may occur in patients receiving pegaspargase; hemorrhagic or necrotizing pancreatitis have been reported (sometimes fatal). Avoid alcohol use (Stock 2011). Inform patients of the signs/symptoms of pancreatitis. Untreated pancreatitis may be fatal.
• Thrombotic events: Serious thrombotic events, including sagittal sinus thrombosis may occur with pegaspargase.
Other warnings/precautions:
• Administration route: In a study comparing IV pegaspargase to IM native E. coli asparaginase for post-induction treatment in children with ALL, 5-year disease-free survival did not differ and the overall frequency of asparaginase-related toxicities (including allergy, pancreatitis, and thrombotic or bleeding complications) did not differ between the IV pegaspargase and IM native E. coli asparaginase groups. The median nadir serum asparaginase activity was significantly higher in the IV pegaspargase group. Reported treatment-related anxiety was significantly lower (for both patients and guardians) in the group that received IV pegaspargase (Place 2015).
• Medication error prevention: Do not interchange pegaspargase for asparaginase (E. coli), asparaginase (Erwinia), asparaginase (Erwinia [recombinant]), or calaspargase pegol-mknl; ensure the proper asparaginase formulation, route of administration, and dose prior to administration.
None known.
Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Risk C: Monitor therapy
Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor therapy
Evaluate pregnancy status prior to use in patients who may become pregnant. Effective nonhormonal contraception should be used during therapy and for 3 months after the last pegaspargase dose. Hormonal contraceptives may not be effective and are not recommended as a form of contraception.
Based on animal reproduction studies conducted with L-asparaginase, adverse effects to the fetus may be expected if exposure occurs during pregnancy.
CBC with differential, platelets (at least weekly during treatment), amylase/lipase, liver function tests (bilirubin, transaminases; baseline and at least weekly during treatment), fibrinogen, PT, PTT (coagulation parameters [baseline and periodically during and after treatment]), renal function tests; urine glucose, blood glucose (at least weekly during treatment); triglycerides; uric acid; pregnancy test (prior to treatment in females of reproductive potential); vital signs during administration; monitor for onset of abdominal pain; observe for allergic reaction (for 1 hour after administration); signs/symptoms of thrombosis or bleeding
Pegaspargase is a modified version of L-asparaginase, conjugated with monomethoxypolyethylene glycol (mPEG). In leukemic cells, asparaginase hydrolyzes L-asparagine to ammonia and L-aspartic acid, leading to depletion of asparagine. Leukemia cells require exogenous asparagine; normal cells can synthesize asparagine. Asparagine depletion in leukemic cells leads to inhibition of protein synthesis and apoptosis.
Onset: Mean maximum asparaginase activity: IM: On day 5 (following a single IM dose of 2,500 units/m2)
Duration: Asparagine depletion: IV (in asparaginase naive adults): 2 to 4 weeks (Douer 2007); IM: ~21 days.
Bioavailability: IM: 82% (first dose); 98% (repeat dosing).
Distribution: Vdss: 1.86 L/m2 (following a single IM dose of 2,500 units/m2); ~2 L (following a single IV dose of 2,500 units/m2); Asparaginase-naive adults: IV: 2.4 L/m2 (Douer 2007).
Metabolism: Systemically degraded.
Half-life elimination: ~5.8 days (following a single IM dose of 2,500 units/m2); ~5.3 days (following a single IV dose of 2,500 units/m2); Asparaginase-naive adults: IV: 7 days (Douer 2007).
Excretion: Clearance: 0.17 L/m2/day (following a single IM dose of 2,500 units/m2); 0.2 L/day (following a single IV dose of 2,500 units/m2).
Solution (Oncaspar Injection)
750 units/mL (per mL): $5,338.19
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