Pegaspargase

Pronunciation: peg-AS-par-jase
Class: Modified enzyme

Trade Names

Oncaspar
- Injection 750 units/mL

Pharmacology

Leukemic cells are unable to synthesize asparagine because of a lack of asparagine synthetase and are dependent on an exogenous source of asparagine for survival. Rapid depletion of asparagine, which results from treatment with the enzyme L-asparaginase, kills the leukemic cells.

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Pharmacokinetics

Absorption

Levels are detectable for at least 15 days after IV administration.

Distribution

Found in lymph at 20% of the concentration in plasma.

Metabolism

Unknown.

Elimination

Unknown. The t _{1/ 2} is 5.73 days (children), 3.24 days (previously hypersensitive adults), and 5.69 days (nonhypersensitive adults).

Indications and Usage

Combination therapy of acute lymphocytic leukemia (ALL) in adults and children who are hypersensitive to the native form of L-asparaginase; combination therapy of multiagent chemotherapy for first-line treatment of ALL.

Contraindications

History of pancreatitis or serious hemorrhagic events or thrombosis with L-asparaginase therapy; history of serious allergy to any component of the product.

Dosage and Administration

IM or IV 2,500 units/m ² every 14 days.

General Advice

• Avoid excessive agitation; do not shake.
• Discard single-dose vials after a single use. Use solution only if clear.
• Use only 1 dose per vial; do not re-enter the vial. Do not save unused drug for later administration.
• Administer by IV infusion or IM injection.
• IV administration is associated with a higher incidence of adverse reactions than IM administration.
• This drug may be a contact irritant. Gloves are recommended. Avoid inhalation of vapors and contact with skin or mucous membrane. In case of contact, wash with copious amounts of water for at least 15 min.

• Dilute dose in 100 mL of sodium chloride 0.9% or dextrose 5%.
• Infuse diluted solution through a running IV line over 1 to 2 h.

• Use solution for injection as commercially prepared. Syringes prepared for IM administration should contain 2 mL or less; prepare multiple syringes for larger doses.
• The volume of a single IM injection should not exceed 2 mL.

Storage/Stability

Refrigerate (36° to 46°F) solution for injection, but do not freeze. Do not administer if there is any indication that the drug has been frozen; freezing destroys activity of product. Do not use solution stored at room temperature for longer than 48 h or if it has been shaken or vigorously agitated.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

CNS thrombosis (3%).

GI

Pancreatitis (2%).

Hematologic-Lymphatic

Coagulopathy including prolonged PT or PTT, or hypofibrinogenemia (2%).

Lab Tests

Elevated transaminases (3%); hyperbilirubinemia (2%).

Metabolic-Nutritional

Hyperglycemia (5%).

Miscellaneous

Allergic reactions to asparaginase (2%); serious allergic reactions including anaphylaxis.

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 1 yr of age.

Thrombosis

Serious thrombotic events, including sagittal sinus thrombosis, can occur.

Overdosage

Symptoms

Rash, slight increase in liver enzymes.

Patient Information

• Inform patient of the possibility of hypersensitivity reactions.
• May predispose the patient to infection. Patient should notify health care provider of any adverse reactions that occur.
• Advise patient to immediately report any of the following to health care provider: acute shortness of breath, chest pain, arm or leg swelling, excessive thirst or increase in volume or frequency of urination, severe abdominal pain, severe headache.

Copyright © 2009 Wolters Kluwer Health.