Asparaginase

L01X - Other antineoplastic agents ATC L01XX02 Enzyme approved 1994 Parenteral

JFDA label: Asparaginase Pow for Inj

Mechanism of Action

Hydrolytic Enzyme of Asparagine — Asparagine hydrolytic enzyme

Target	Action	Gene / class
Asparagine efficacy	HYDROLYTIC ENZYME

Indications

Approved

Acute lymphoblastic leukemia

Contraindications

Source: Lexicomp

Additional contraindications (not in the US labeling): Women who are or may become pregnant Absolute
History of serious hypersensitivity reactions, including anaphylaxis to asparaginase (Erwinia) or any component of the formulation Absolute
history of serious pancreatitis, serious thrombosis, or serious hemorrhagic events with prior asparaginase treatment Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Common Thrombosis

Metabolism and nutrition disorders (3)

Common abnormal transaminase · decreased glucose tolerance · Hyperglycemia

Gastrointestinal disorders (3)

Common Nausea · pancreatitis · vomiting

General disorders and administration site conditions (1)

Common Fever

Other (1)

Very Common Hypersensitivity: Hypersensitivity reaction

Dosing

Source: Lexicomp

Note: If administering IV, consider monitoring nadir serum asparaginase activity (NSAA) levels; if desired levels are not achieved, change to IM administration. Acute lymphoblastic leukemia (ALL): IM, IV: As a substitute for pegaspargase: 25,000 units/m2 3 times weekly (Mon, Wed, Fri) for 6 doses for each planned pegaspargase dose As a substitute for asparaginase (E. coli): 25,000 units/m2 for each scheduled asparaginase (E. coli) dose

(For additional information see "Erwinia asparaginase: Pediatric drug information") Note: If administering IV, consider monitoring nadir serum asparaginase activity (NSAA) levels; if desired levels are not achieved, change to IM administration. Acute lymphoblastic leukemia (ALL): Children ≥1 year and Adolescents: IM, IV: Refer to adult dosing. ALL induction: Canadian labeling (not in the US labeling): Children 2 3 times weekly for 9 doses beginning day 4 of week 1 (in combination with vincristine, prednisone, methotrexate, and daunorubicin)

There are no dosage adjustments provided in the manufacturer's labeling.

There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended for other asparaginase products for hepatotoxicity during treatment (Stock 2011): ALT/AST >3 to 5 times ULN: Continue therapy ALT/AST >5 to 20 times ULN: Delay next dose until transaminases ALT/AST >20 times ULN: Discontinue therapy if takes longer than 1 week for transaminases to return to Direct bilirubin Direct bilirubin 3.1 to 5 mg/dL: Hold asparaginase and resume when direct bilirubin Direct bilirubin >5 mg/dL: Discontinue asparaginase; do not substitute other asparaginase products; do not make up for missed doses.

Warnings & Precautions

Source: Lexicomp

Glucose intolerance

In clinical trials, 5% of patients experienced glucose intolerance; may be irreversible. Monitor glucose levels (baseline and periodic) during treatment. May require insulin administration.

Hypersensitivity reactions

Serious hypersensitivity reactions (grade 3 and 4), including anaphylaxis, have occurred in 5% of patients in clinical trials. Immediate treatment for hypersensitivity reactions should be available during treatment. Discontinue for serious hypersensitivity reactions (and administer appropriate treatment).

Pancreatitis

Pancreatitis has been reported in 4% of patients in clinical trials. Promptly evaluate with symptoms suggestive of pancreatitis. For mild pancreatitis, withhold treatment until signs and symptoms subside and amylase levels return to normal; may resume after resolution. Discontinue for severe or hemorrhagic pancreatitis characterized by abdominal pain >72 hours and amylase ≥2 x ULN. Further use is contraindicated if severe pancreatitis is diagnosed.

Thrombosis and hemorrhage

Serious thrombotic events, including sagittal sinus thrombosis and pulmonary embolism, have been reported with asparaginase formulations. Discontinue for thrombotic event, may resume treatment after resolution. Decreases in fibrinogen, protein C activity, protein S activity, and antithrombin III have been noted following a 2-week treatment course administered intramuscularly. Discontinue for hemorrhagic event; may resume treatment after resolution (contraindicated with history of serious thrombosis or hemorrhagic event with prior asparaginase treatment). Other warnings/precautions:

Medication error prevention

Do not interchange Erwinia asparaginase for E. coli asparaginase or pegaspargase; ensure the proper formulation, route of administration, and dose prior to administration.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events were observed in animal reproduction studies.

Lactation

It is not known if asparaginase Erwinia chrysanthemi is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.

Monitoring

Clinical pearl	CBC with differential, amylase, lipase, triglycerides, liver enzymes, blood glucose (baseline and periodically during treatment), coagulation parameters; for IV administration, consider monitoring nadir serum asparaginase activity (NSAA) levels. Monitor for symptoms of hypersensitivity, symptoms of pancreatitis, thrombosis, or hemorrhage.

Biology & Pharmacokinetics

Pharmacokinetics

Half-life	11.75 h

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Asparaginase Pow for Inj	Powder for Injection 10000 IU	1 vial	Pharma Care Drug Store	—