Dosing and uses of Erwinaze (asparaginase Erwinia chrysanthemi)
Adult dosage forms and strengths
injection, powder for reconstitution
- 10,000 IU/vial
Acute Lymphoblastic Leukemia
Asparagine specific enzyme indicated as part of a multiagent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase
Substitution for pegaspargase: 25,000 IU/m² IM/IV 3 times/week (Monday/Wednesday/Friday) for 6 doses (for each planned dose of pegaspargase)
Substitution for native E. coli asparaginase: 25,000 IU/m² IM/IV for each scheduled dose of native E. coli asparaginase
Pediatric dosage forms and strengths
injection, powder for reconstitution
- 10,000 IU/vial
Acute Lymphoblastic Leukemia
Asparagine specific enzyme indicated as part of a multiagent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase
Use in children: A single-arm, multi-center, open-label, safety and clinical pharmacology trial of 58 patients was conducted during the clinical trials; median age was 10 years (2-18 years)
Substitution for pegaspargase: 25,000 IU/m² IM/IV 3 times/week (Monday/Wednesday/Friday) for 6 doses (for each planned dose of pegaspargase)
Substitution for native E. coli asparaginase: 25,000 IU/m² IM/IV for each scheduled dose of native E. coli asparaginase
Erwinaze (asparaginase Erwinia chrysanthemi) adverse (side) effects
>10%
Hypersensitivity reactions, including anaphylaxis (17%)
1-10%
Hypersensitivity, grades 3/4 (5%)
Glucose intolerance (5%)
Pancreatitis (4%)
Fever (3%)
Coagulation abnormalities (3%)
Thrombosis (2%)
Hyperglycemia (2%)
Headache (1%)
Hyperbilirubinemia (1%)
Abnormal transaminases (>1%)
Coagulation abnormalities including thrombosis and hemorrhage (>1%)
Nausea (>1%)
Vomiting (>1%)
Postmarketing reports
Abdominal pain/discomfort
Diarrhea
Local reactions
Warnings
Contraindications
History of serious hypersensitivity reactions to asparaginase Erwinia chrysanthemi, including anaphylaxis
History of serious pancreatitis with prior L-asparaginase therapy
History of serious thrombosis with prior L-asparaginase therapy
History of serious hemorrhagic events with prior L-asparaginase therapy
Cautions
Serious hypersensitivity reactions, including anaphylaxis have occurred; administer in setting with resuscitation equipment; discontinue drug if hypersensitivity reaction occurs
Glucose intolerance reported and in some cases, may be irreversible; monitor serum glucose levels at baseline and periodically during treatment
Serious thrombotic events, including sagittal sinus thrombosis reported with both E. coli and Erwinia-derived L-asparaginase therapy; coagulation proteins were decreased in the majority of patients after a 2-week course (eg, fibrinogen, protein C activity, protein S activity, and anti-thrombin III); discontinue for a thrombotic or hemorrhagic event until symptoms resolve; after resolution, treatment may resume
Pancreatitis
- Pancreatitis reported during clinical trials
- Discontinue drug for severe or hemorrhagic pancreatitis manifested by abdominal pain >72 hr and amylase elevation 2.0 x ULN or more
- Mild pancreatitis: hold drug until signs and symptoms subside, and amylase levels return to normal; after resolution, treatment may resume
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown whether distributed in breast milk
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 Erwinaze (asparaginase Erwinia chrysanthemi)
Mechanism of action
Catalyzes deamidation of asparagine to aspartic acid and ammonia, thereby reducing circulating levels of asparagine
The mechanism of action is thought to be based on the inability of leukemic cells to synthesize asparagine due to lack of asparagine synthetase activity
The lack of asparagine synthetase activity results in cytotoxicity specific for leukemic cells that depend on an exogenous source of the amino acid asparagine for their protein metabolism and survivaL
Pharmacokinetics
Serum trough concentration: 0.1 IU/mL or greater at 48-72 hr
Serum activity levels 0.4 IU/mL or greater shown in 80% at 48 hr and in 38% at 72 hr
Half-life: 16 hr (IM)
Administration
IM Preparation
Visually inspect the powder for foreign particulate matter and discoloration prior to reconstitution; do use vial if present
Reconstitute vial contents by slowly injecting 1 or 2 mL of preservative free sterile sodium chloride (0.9%) injection against the inner vial walL
Do not forcefully inject solution for reconstitution directly onto or into the powder
When reconstituted with 1 mL the resultant concentration is 10,000 IU/mL
When reconstituted with 2 mL the resultant concentration is 5,000 IU/mL
Dissolve contents by gentle mixing or swirling; do not shake or invert vial When reconstituted, solution should be a clear and colorless
Do not use the reconstituted solution if any visible particles or protein aggregates are present
Calculate the dose needed and the volume needed to obtain the calculated dose
Withdraw the volume containing the calculated dose from the vial into a polypropylene syringe within 15 minutes of reconstitution
Administer within 4 hr or discard
IM Administration
Limit volume of single injection site to 2 mL; if volume of dose exceeds 2 mL, use multiple injection sites
If a partial vial is used, do not save or reuse the unused drug for later administration; discard unused portions
IV Preparation
Slowly inject the reconstituted asparaginase into an IV infusion bag containing 100 mL of 0.9%NaCl acclimatized to room temperature
Do not shake or squeeze IV bag
If partial vial is used, do not save or reuse the unused drug for later administration; discard unused portions
IV Administration
Infuse asparaginase in 100 mL of normal saline over 1-2 hr
Do not infuse other drugs through same IV line while administering asparaginase
Storage
Store unused or unopened vials and cartons at 36-46°F (2-8°C) and protect from light
Do not freeze or refrigerate reconstituted solution
