Pegaspargase

Mechanism :

Pegaspargase is a modified version of L-asparaginase, conjugated with polyethylene glycol. Asparagine depletion in leukemic cells leads to inhibition of protein synthesis and apoptosis. Asparaginase is cycle-specific for the G₁ phase of the cell cycle.

Indication :

Acute lymphoblastic leukemia as a first-line agent
Treatment of acute lymphoblastic leukemia (ALL) in patients with hypersensitivity to native forms of L-asparaginase.

Contraindications :

History of serious allergic reactions to pegaspargase or any component of the formulation; Severe hepatic impairment

Dosing :

IM, IV:

2500 units/m². Administer every 14 days.

Adverse Effect :

Increased serum transaminases, Hypersensitivity reaction, thrombosis, hyperglycemia, pancreatitis, blood coagulation disorder.

Interaction :

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib.
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants.
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity.
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants.
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of live vaccines.

Hepatic Dose :

Mild to moderate hepatic impairment: Dose adjustment may not be required.
Severe hepatic impairment: Use is contraindicated.

If hepatotoxicity develops during therapy:
If the ALT or AST level is greater than 3 but less than 5 times the upper limit of normal (ULN): therapy can be continued.
If the ALT or AST level is greater than 5 but less than 20 times ULN: Stop therapy till the ratio is less than 3 times the upper limit of normal, then continue.
If the ALT or AST is greater than 20 ULN: If the levels take longer than 1 week to return to less than 3 times upper limit of normal, stop therapy completely.
If direct bilirubin levels are less than 3 mg/dl: therapy can be continued.
If direct bilirubin levels are between 3.1mg/dl and 5 mg/dl: Stop therapy till bilirubin reaches less than 2 mg/dl and switching to another asparaginase product may need to be considered.
If direct bilirubin levels are greater than 5 mg/dl: Stop pegaspargase therapy, and do not switch to or administer any another asparaginase product.