Pegaspargase

A to Z Drug Facts

Actions 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.

 Indications

Adult and Pediatric

Combination therapy of acute lymphocytic leukemia in patients who are hypersensitive to the native form of L-asparaginase; may be used for single agent therapy in these patients when combination therapy is inappropriate.

 Contraindications Pancreatitis or history of pancreatitis; significant hemorrhagic events associated with prior L-asparaginase therapy; previous serious allergic reactions.

 Route/Dosage

Combination or Single Agent Therapy of Acute Lymphocytic Leukemia

ADULTS: IM or IV 2500 IU/m² every 14 days.

PEDIATRIC: IM or IV Dose may be determined by body surface area or body weight. Administer dose every 14 days. The recommended dose for children with a body surface area ³ 0.6 m² is 2500 IU/m². The recommended dose for children with a body surface area < 0.6 m² is 82.5 IU/kg.

Interactions

Methotrexate

Pegaspargase may interfere with drugs such as methotrexate which require cell replication for their lethal effects.

Protein-bound drugs

Depletion of serum proteins by pegaspargase may increase the toxicity of other drugs which are protein bound.

Warfarin, heparin, dipyridamole, aspirin, or nonsteroidal anti-inflammatory agents

Pegaspargase may increase or decrease the anticoagulant effects of warfarin, heparin, dipyridamole, aspirin, or nonsteroidal anti-inflammatory agents. Patients may be at increased risk for bleeding or thrombosis.

Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Superficial, deep vein, catheter or atrial thrombosis. CNS: Malaise, headache, seizures, paresthesias, confusion, emotional lability, Parkinson-like syndrome. DERMATOLOGIC: Rashes, urticaria. ENDOCRINE: Hyperglycemia, hypoglycemia, hyperuricemia. GI: Nausea and vomiting, abdominal pain, diarrhea, anorexia, jaundice, elevation of LFTs, fatty changes in the liver, fatal hemorrhagic pancreatitis (rare). HEMATOLOGIC: Hypofibrinogenemia, leukopenia, thrombocytopenia, hemolytic anemia, disseminated intravascular coagulation, prolonged prothrombin time and partial thromboplastin time. HYPERSENSITIVITY: Acute anaphylactoid reactions are common, discontinuation of therapy and administration of fluids, corticosteroids, antihistamines, or pressors may be required. MUSCULOSKELETAL: Arthralgia, myalgia. RENAL: Prerenal azotemia, transient proteinuria. OTHER: Fever, chills, night sweats.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Bleeding: Patients taking pegaspargase are at higher than usual risk for bleeding problems, especially with simultaneous use of other drugs that have anticoagulant properties, such as aspirin and NSAIDs. Infection: Pegaspargase may have immunosuppressive activity. Therefore, it is possible that use of the drug may predispose patients to infection. Hepatic/CNS toxicity: Severe hepatic and CNS toxicity following multi-agent chemotherapy that includes pegaspargase may occur. Caution appears warranted when treating patients with pegaspargase in combination with hepatotoxic agents, particularly when liver dysfunction is present.

 Administration/Storage

• Refrigerate 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 > 48 hr or if it has been frozen.
• Avoid excessive agitation; do not shake.
• Single-dose vials should be discarded 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 alter administration.
• Administer by IV infusion or IM injection.
• IV administration is associated with a higher incidence of adverse effects than IM administration.
• This drug may be a contact irritant. Gloves are recommended. Inhalation of vapors and contact with skin or mucous membranes must be avoided. In case of contact, wash with copious amounts of water for at least 15 min.

IV

• Dilute dose in 100 mL of 0.9% Sodium Chloride or 5% Dextrose.
• Infuse diluted solution through a running IV line over 1 to 2 hr.

IM

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

 Assessment/Interventions

• Hypersensitivity reactions to pegaspargase, including life-threatening anaphylaxis, may occur during therapy. As a routine precaution, keep patient under observation for 1 hr with resuscitation equipment and other agents necessary to treat anaphylaxis.
• Monitor peripheral blood count and bone marrow, serum amylase determinations to detect early evidence of pancreatitis, glucose because hyperglycemia may occur, LFTs, and ammonia. Blood ammonia may increase during therapy. Monitoring of fibrinogen, PT, and PTT may be indicated.

 Patient/Family Education

• Inform patients of the possibility of hypersensitivity reactions.
• Instruct patients that the simultaneous use of pegaspargase with other drugs that may increase the risk of bleeding should be avoided.
• May predispose the patient to infection. Patients should notify the health care provider of any adverse reactions that occur.

Books@Ovid
Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts