Dosing and uses of Elspar, L Asparaginase (asparaginase)
Adult dosage forms and strengths
powder for injection
- 10,000 International Units
Acute Lymphocytic Leukemia
Asparaginase is discontinued as of 8/3/2012 and supply is expected to be exhausted by approximately 12/31/2012
Discontinued worldwide because manufacturer unable to guarantee supply
Single agent treatment
- 200 International Units/kg/day IV x 28 days
Combo treatment with prednisone, vincristine
- 1000 International Units/m²/day IV for 10 days OR
- 6000 International Units/m² IV/IM q3Days x 9 doses
- High dose (Off-label): 10,000 units/m²/day for 3-12 doses
Acute Myeloid Leukemia (Orphan)
Orphan designation for the treatment of acute myeloid leukemia
Orphan sponsor
- ERYTECH Pharma S.A; Batiment Adenine 60, avenue Rockefeller; Lyon 69008 France
Monitor
CBC, serum amylase, LFTs
Administration
IV infuse >30 minutes
Discontinue at first sign of pancreatitis
See also pegaspargase
Pediatric dosage forms and strengths
powder for injection
- 10,000 International Units
Acute Lymphocytic Leukemia
Asparaginase is discontinued as of 8/3/2012 and supply is expected to be exhausted by approximately 12/31/2012
Discontinued worldwide because manufacturer unable to guarantee supply
Single agent treatment: 200 International Units/kd/day IV x 28 days
Elspar, L Asparaginase (asparaginase) adverse (side) effects
>10%
Abdominal cramps (70%)
Anorexia (70%)
Azotemia (66%)
Nausea (50-60%)
Vomiting (50-60%)
Agitation (10-60%)
Depression (10-60%)
Fatigue (10-60%)
Fever (10-60%)
Chills (10-60%)
Anaphylaxis (15-35%)
Coma (25%)
Confusion (25%)
Somnolence (25%)
Stupor (25%)
Pancreatitis, acute (15%)
1-10%
Hyperglycemia
Stomatitis
Hyperuricemia
<1%
Disorientation
Drowsiness
Hallucination
Headache
Hyperthermia
Parkinsonian symptoms
Venous thrombosis
Hypotension
Intracranial hemorrhage
Cerebrovascular hemorrhage
Peripheral edema
Thrombosis
Cough
Hypofibrinogenemia
Depression of clotting factors
Severe protein C deficiency
Decrease antithrombin III
Glucosuria
Hemorrhagic pancreatitis
Ketoacidosis
Hepatotoxicity
Urticaria
Weight loss
Acute renal failure
Warnings
Contraindications
Hypersensitivity
History of pancreatitis, thrombosis, or serious pancreatitis events with prior L-asparaginase treatment
Cautions
Anaphylaxis and other serious allergic reactions can occur; observe patients for 1 hr after administration
Serious thrombotic events, including sagittal sinus thrombosis, can occur
Pancreatitis, in some cases fulminant or fatal, can occur
Glucose intolerance, in some cases irreversible, can occur
Coagulopathy can occur
Hepatotoxicity including hepatic failure can occur
Posterior Reversible Encephalopathy Syndrome (PRES) reported
Do not interchange with Erwinia asparaginase or pegylated E. coli asparaginase
Pregnancy and lactation
Pregnancy category: C
Lactation: It is not known whether this drug is excreted in milk. Because of the potential for serious adverse reactions in nursing infants from Elspar, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Elspar, L Asparaginase (asparaginase)
Mechanism of action
Depletes asparagine, which is needed by leukemic cells for DNA synthesis; cycle specific for G1 phase
Pharmacokinetics
Vd: 4-5 L/kg
Half-life: 39-49 hr (IM); 8-30 hr (IV)
Peak plasma time: 14-24 hr (IM)
Administration
IM administration greatly reduces incidence of anaphylaxis
IV Compatibilities
Y-site: methotrexate, Na-bicarB
IV Preparation
IV: reconstitute with SWI or NS to obtain 2000 IU/mL solution
IM: reconstitute with 2 mL Ns
Refrigerate & use within 8 hr
IV/IM Administration
IV: Administered over no less than 30 min through the sidearm of a running infusion of NS or D5W
IM: Administered in volume no greater than 2 mL; larger volumes require 2 injection sites
