asparaginase Erwinia chrysanthemi
High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.
Part of combination chemotherapy in the treatment of acute lymphocytic leukemia (ALL) in patients who developed hypersensitivity to E. coli-derived asparaginase.
- Catalyst in the conversion of asparagine (an amino acid) to aspartic acid and ammonia.
- Depletes asparagine in leukemic cells.
Death of leukemic cells.
Absorption: Bioavailability after IM administration unknown; IV administration results in complete bioavailability.
Distribution: Remains in the intravascular space. Poor penetration into the CSF.
Metabolism and Excretion: Slowly sequestered in the reticuloendothelial system.
Half-life: IV: 8–30 hr; IM: 39–49 hr.
- Previous hypersensitivity;
- History of pancreatitis with prior L-asparaginase;
- History of serious thrombosis or hemorrhagic events with prior L-asparaginase;
- OB: Pregnancy (may cause fetal harm);
Use Cautiously in:
Rep: Women of reproductive potential.
Adverse Reactions/Side Effects
GI: PANCREATITIS, ↑ liver function tests, nausea, vomiting
Hemat: hemorrhage, thromboembolic events
Misc: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS, fever
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
IM IV (Adults and Children): Substitution for E.coli-derived asparaginase– 25,000 International Units/m2 substituted for each dose of E.coli-derived asparaginase; Substitution for pegasparagase– 25,000 International Units/m2 3 times a wk (Mon/Wed/Fri) for 6 doses substituted for each dose of pegasparagase.
Powder for injection: 10,000 International Units/vial
- Monitor vital signs before and periodically during therapy; may cause fever.
- Monitor for signs and symptoms of pancreatitis (abdominal pain, nausea, vomiting, ↑ serum amylase) during therapy. If abdominal pain >72 hrs and serum amylase ↑ ≥2.0 x upper limit of normal occur, discontinue therapy. If mild pancreatitis occurs, withhold asparaginase Erwinia chrysanthemi until symptoms and serum amylase return to normal; then restart.
- Monitor for hypersensitivity reaction (urticaria, diaphoresis, facial swelling, joint pain, hypotension, bronchospasm). Epinephrine and resuscitation equipment should be readily available.
Lab Test Considerations:
Verify a negative pregnancy test before starting therapy.
- Monitor CBC and coagulation studies before and periodically throughout therapy. May ↓ fibrinogen, protein C activity, protein S activity, and anti-thrombin III. If thrombotic or hemorrhagic event occurs, withhold asparaginase Erwinia chrysanthemi until symptoms resolve; then resume therapy.
- Hepatotoxicity may be manifested by ↑ AST, ALT, bilirubin, or cholesterol. Liver function test results usually return to normal after therapy. May cause pancreatitis; monitor frequently for ↑ amylase or glucose.
- Monitor blood glucose prior to and periodically during therapy. May cause hyperglycemia treatable with fluids and insulin.
- For IV doses, monitoring pre-dose nadir serum asparaginase activity (NSAA) levels and switch to IM administration if desired NSAA levels are not achieved.
- Deficient knowledge, related to medication regimen (Patient/Family/Teaching)
- High Alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order and dose calculations.
- Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in specially designated containers.
- Reconstitute by adding 1 or 2 mL of 0.9% NaCl for injection (without preservatives) against inner wall of the 10,000-International Unit vial. Swirl vial gently; do not shake or invert. Administer no more than 2 mL per injection site. Concentration: Reconstitution with 1 mL = 10,000 International Units/mL; with 2 mL = 5,000 International Units/mL. Solution is clear and colorless; do not administer solutions that are discolored or contain a precipitate. Withdraw dose needed into a polypropylene syringe and administer within 15 min of reconstitution. Do not refrigerate or freeze; administer within 4 hrs or discard. Inject IM with no >2 mL/site. Do not save unused portions; discard.
- IM Limit volume to 2 mL at each injection site. If volume >2 mL, use multiple injection sites.
- Intermittent Infusion: For IV use, slowly inject reconstituted solution into 100 mL 0.9% NaCl at room temperature; do not shake or squeeze IV bag.
- Rate: Infuse over 1–2 hr.
- Y-Site Incompatibility: Do not infuse other IV drugs through same IV line.
- Explain purpose of medication to patient.
- Instruct patient to notify health care professional if signs and symptoms of hypersensitivity reaction, pancreatitis, thrombosis or hemorrhage (headache, arm or leg swelling, shortness of breath, chest pain) or hyperglycemia (excess thirst or increase in frequency or volume of urination), occur.
- Rep: May be teratogenic. Advise females of reproductive potential to use effective nonhormonal contraception and avoid breastfeeding during and for 3 mos after last dose. Advise female patients to notify health care professional promptly if pregnancy is planned or suspected, or if breast feeding.
- Emphasize need for periodic lab tests to monitor for side effects.
Improvement of hematologic status in patients with leukemia.
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