ONCASPAR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ONCASPAR (ONCASPAR).

How it works

Pegylated L-asparaginase that depletes asparagine, an essential amino acid for leukemic cell growth, by catalyzing the hydrolysis of asparagine to aspartic acid and ammonia.

What the body does with it

Metabolism	Metabolized by catabolism into small peptides and amino acids via general proteolytic pathways; not primarily hepatic or renal.
Excretion	Primarily cleared by the reticuloendothelial system and proteolysis. Renal excretion is negligible (<1%). Biliary/fecal elimination is not a significant route; metabolism is via catabolism to amino acids.
Half-life	Terminal elimination half-life is approximately 7 days (range 5-10 days). The long half-life supports a 2-week dosing interval. Half-life is prolonged in patients with prior hypersensitivity or those receiving combination therapy.
Protein binding	Minimal to no protein binding. Pegylation does not significantly alter binding; the protein itself may bind non-specifically, but specific binding proteins are not identified. Approximately <5% bound.
Volume of Distribution	Vd approximately 2.5 L/kg (range 2-3 L/kg). This indicates distribution primarily into plasma and extracellular fluid, with limited penetration into tissues.
Bioavailability	Intramuscular: Not established due to lack of absolute bioavailability studies; assumed to be high (near 100%) based on comparable exposure. Subcutaneous: Not recommended. Intravenous: 100%.
Onset of Action	Intravenous: Onset of asparagine depletion within 24 hours. Intramuscular: Onset within 24-48 hours.
Duration of Action	Asparagine depletion persists for 14 days or longer after a single dose. Clinical effect on leukemia cell growth suppression lasts throughout the typical 2-week dosing interval.

Classification & Brands

Dosing & administration

Intravenous or intramuscular: 2,500 IU/m² every 14 days.

Dosage form	VIAL
Renal impairment	No dose adjustment required for renal impairment.
Liver impairment	Contraindicated in patients with severe hepatic impairment (Child-Pugh class C). For moderate impairment (Child-Pugh class B), reduce dose to 2,000 IU/m² every 14 days.
Pediatric use	Weight-based dosing: 2,500 IU/m² intravenously or intramuscularly every 14 days. For patients weighing less than 10 kg, use 82.5 IU/kg every 14 days.
Geriatric use	No specific dose adjustment recommended; use with caution due to increased risk of hepatotoxicity and neurotoxicity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ONCASPAR (ONCASPAR).

Breastfeeding	It is not known whether pegaspargase is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Teratogenic Risk	Pregnancy Category C. In animal studies, pegaspargase was embryotoxic and teratogenic. There are no adequate and well-controlled studies in pregnant women. The risk of fetal harm cannot be ruled out; however, the drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Warnings & precautions

■ FDA Black Box Warning

Risk of serious allergic reactions, including anaphylaxis, and pancreatitis. Treatment should be discontinued in patients with serious thrombotic events or pancreatitis.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reactions to pegaspargase or pre-existing pancreatitis.","History of thrombosis with prior L-asparaginase therapy.","Severe hepatic impairment."]

Clinical Precautions

Precautions

["Hypersensitivity reactions: Severe allergic reactions including anaphylaxis; administer in a setting with resuscitation equipment.","Pancreatitis: Monitor for abdominal pain; discontinue if pancreatitis occurs.","Thrombosis: Venous or arterial thrombosis, including cerebral thrombosis.","Hemorrhage: May cause bleeding, especially in patients with coagulopathy.","Hepatotoxicity: Elevations in liver enzymes; monitor liver function.","Diabetes: Hyperglycemia may occur; monitor blood glucose.","Bone marrow suppression: May cause myelosuppression."]

Clinical Tips & Counseling

Drug interactions

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ONCASPAR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ONCASPAR (ONCASPAR).

How it works

Pegylated L-asparaginase that depletes asparagine, an essential amino acid for leukemic cell growth, by catalyzing the hydrolysis of asparagine to aspartic acid and ammonia.

What the body does with it

Metabolism	Metabolized by catabolism into small peptides and amino acids via general proteolytic pathways; not primarily hepatic or renal.
Excretion	Primarily cleared by the reticuloendothelial system and proteolysis. Renal excretion is negligible (<1%). Biliary/fecal elimination is not a significant route; metabolism is via catabolism to amino acids.
Half-life	Terminal elimination half-life is approximately 7 days (range 5-10 days). The long half-life supports a 2-week dosing interval. Half-life is prolonged in patients with prior hypersensitivity or those receiving combination therapy.
Protein binding	Minimal to no protein binding. Pegylation does not significantly alter binding; the protein itself may bind non-specifically, but specific binding proteins are not identified. Approximately <5% bound.
Volume of Distribution	Vd approximately 2.5 L/kg (range 2-3 L/kg). This indicates distribution primarily into plasma and extracellular fluid, with limited penetration into tissues.
Bioavailability	Intramuscular: Not established due to lack of absolute bioavailability studies; assumed to be high (near 100%) based on comparable exposure. Subcutaneous: Not recommended. Intravenous: 100%.
Onset of Action	Intravenous: Onset of asparagine depletion within 24 hours. Intramuscular: Onset within 24-48 hours.
Duration of Action	Asparagine depletion persists for 14 days or longer after a single dose. Clinical effect on leukemia cell growth suppression lasts throughout the typical 2-week dosing interval.

Classification & Brands

Dosing & administration

Intravenous or intramuscular: 2,500 IU/m² every 14 days.

Dosage form	VIAL
Renal impairment	No dose adjustment required for renal impairment.
Liver impairment	Contraindicated in patients with severe hepatic impairment (Child-Pugh class C). For moderate impairment (Child-Pugh class B), reduce dose to 2,000 IU/m² every 14 days.
Pediatric use	Weight-based dosing: 2,500 IU/m² intravenously or intramuscularly every 14 days. For patients weighing less than 10 kg, use 82.5 IU/kg every 14 days.
Geriatric use	No specific dose adjustment recommended; use with caution due to increased risk of hepatotoxicity and neurotoxicity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ONCASPAR (ONCASPAR).

Breastfeeding	It is not known whether pegaspargase is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Teratogenic Risk	Pregnancy Category C. In animal studies, pegaspargase was embryotoxic and teratogenic. There are no adequate and well-controlled studies in pregnant women. The risk of fetal harm cannot be ruled out; however, the drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Warnings & precautions

■ FDA Black Box Warning

Risk of serious allergic reactions, including anaphylaxis, and pancreatitis. Treatment should be discontinued in patients with serious thrombotic events or pancreatitis.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reactions to pegaspargase or pre-existing pancreatitis.","History of thrombosis with prior L-asparaginase therapy.","Severe hepatic impairment."]