asparaginase Erwinia chrysanthemi

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
a-spare-a-ji-nase


Trade Name(s)

  • Erwinaze
  • Rylaze

Ther. Class.

antineoplastics

Pharm. Class.

enzymes

Indications

Part of combination chemotherapy in the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma in patients who developed hypersensitivity to E. coli–derived asparaginase.

Action

  • Catalyst in the conversion of asparagine (an amino acid) to aspartic acid and ammonia.
  • Depletes asparagine in leukemic cells.

Therapeutic Effect(s):

Death of leukemic and lymphoma cells.

Pharmacokinetics

Absorption: 37% absorbed following IM administration unknown.

Distribution: Remains in the intravascular space. Poor penetration into the CSF.

Metabolism and Excretion: Slowly sequestered in the reticuloendothelial system.

Half-life: 15–18 hr.

TIME/ACTION PROFILE

ROUTEONSETPEAKDURATION
IMunknownunknownunknown

Contraindication/Precautions

Contraindicated in:

  • Previous hypersensitivity;
  • History of pancreatitis with prior asparaginase therapy;
  • History of serious thrombosis or hemorrhagic events with prior asparaginase therapy;
  • Severe hepatic impairment
  • OB:  Pregnancy;
  • Lactation: Lactation.

Use Cautiously in:

  • Rep:   Women of reproductive potential.
  • Pedi:   Children <1 mo (safety and effectiveness not established).

Adverse Reactions/Side Effects

CV: tachycardia

Endo: hyperglycemia

F and E: dehydration

GI: ↓ appetite, ↑ liver enzymes, abdominal pain, constipation, diarrhea, hyperbilirubinemia, nausea, PANCREATITIS, stomatitis, HEPATOTOXICITY (including hepatic veno-occlusive disease [VOD]), vomiting

Hemat: bleeding, thrombotic events

MS: pain

Neuro: headache, insomnia, peripheral neuropathy

Resp: cough

Misc: fatigue, fever, HYPERSENSITIVITY REACTIONS(including anaphylaxis and angioedema) , infection

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

IM (Adults and Children ≥1 mo): Substitution for calaspargase pegol: 25 mg/m2  every 48 hr for 11 doses substituted for each dose of calaspargase pegol  or  25 mg/m2  on Monday morning and Wednesday morning, then 50 mg/m2  on Friday afternoon (administer 9 doses to substitute for each dose of calaspargase pegol.  Substitution for pegaspargase: 25 mg/m2  every 48 hr for 7 doses substituted for each dose of pegaspargase or  25 mg/m2  on Monday morning and Wednesday morning, then 50 mg/m2  on Friday afternoon (administer 6 doses to substitute for each dose of pegaspargase.

Availability

Solution for injection: 10 mg/0.5 mL

Assessment

  • 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.
  • Monitor for hypersensitivity reaction (urticaria, diaphoresis, facial swelling, joint pain, hypotension, bronchospasm). Epinephrine and resuscitation equipment should be readily available.  If Grade 2 hypersensitivity reactions occur,  treat the symptoms.  If Grades 3 or 4 occur,  discontinue therapy permanently.
  • Monitor for hepatic VOD (rapid weight gain, fluid retention with ascites, hepatomegaly, and rapid ↑ in bilirubin levels). If hepatic VOD occurs, discontinue therapy permanently and provide supportive care.

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 antithrombin III.  If uncomplicated thrombosis occurs,  treat with appropriate antithrombotic therapy and withhold asparaginase  Erwinia chrysanthemi  until symptoms resolve; then resume therapy while continuing antithrombotic therapy.  If severe or life-threatening thrombosis occurs,  discontinue therapy permanently and treat with appropriate antithrombotic therapy.  If Grade 3–4 hemorrhage occurs,  hold medication. Evaluate for coagulopathy and consider clotting factor replacement as needed. Resume therapy with the next scheduled dose if bleeding is controlled.
  • Monitor serum bilirubin, AST, and ALT prior to each cycle of therapy and at least weekly during each cycle that includes asparaginase  Erwinia chrysanthemi  through 4 wk after the last dose.  If total bilirubin > 3 times to ≤ 10 times the upper limit of normal (ULN),  hold medication until total bilirubin levels decrease to ≤ 1.5 times the ULN.  If total bilirubin > 10 times the ULN,  discontinue therapy and do not make up missed doses. Liver function test results usually return to normal after therapy.
  • May cause pancreatitis; monitor frequently for ↑ amylase or glucose. If  Grades 2–4 pancreatitis occur,  hold medication for elevations in lipase or amylase > 2 times the ULN, or for symptomatic pancreatitis. Resume treatment when lipase and amylase are < 1.5 times the ULN and symptoms are resolved. Discontinue therapy permanently if clinical necrotizing or hemorrhagic pancreatitis is confirmed.
  • Monitor blood glucose prior to and periodically during therapy. May cause hyperglycemia treatable with fluids and insulin.

Implementation

  • 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.
  • Before administration, premedicate with acetaminophen, an H1  receptor blocker (such as diphenhydramine), and an H2  receptor blocker (such as famotidine) 30–60 min before administration to decrease risk and severity of hypersensitivity reactions.
  • Rylaze  does not require reconstitution. Solution is opalescent, colorless to slightly yellow. Do not use solutions that are cloudy, discolored, or contain particulate matter. Solution is stable for up to 4 hr at room temperature.
  • IM Limit volume to 2 mL at each injection site. If volume >2 mL, use multiple injection sites. Rotate injection sites. Do not inject into scar tissue or areas that are reddened, inflamed, or swollen.

Patient/Family Teaching

  • 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), hyperglycemia (excess thirst or increase in frequency or volume of urination), or hepatic VOD (jaundice, severe nausea/vomiting, bleeding, or bruising) occur.
  • Rep:  May cause fetal harm. Advise females of reproductive potential to use effective nonhormonal contraception during and for 3 mo after last dose and to avoid breastfeeding during and for 1 wk after last dose. Advise female patients to notify health care professional promptly if pregnancy is planned or suspected or if breastfeeding.
  • Emphasize need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

Improvement of hematologic status in patients with ALL and lymphoblastic lymphoma.