calaspargase

General

Pronunciation:
kal-as-par-jase


Trade Name(s)

  • Asparlas

Ther. Class.
antineoplastics

Pharm. Class.
enzymes

Indications

Acute lymphoblastic leukemia (ALL) (in combination with other chemotherapy agents).

Action

Consists of l-asparaginase bound to monomethoxypolyethylene glycol (mPEG). This compound depletes asparagine (by converting it to aspartic acid and ammonia), which leukemic cells cannot synthesize. Normal cells are able to produce their own asparagine and are less susceptible to the effects of asparaginase. Binding to PEG renders asparaginase less antigenic and therefore less likely to induce hypersensitivity reactions.

Therapeutic Effect(s):

Death of leukemic cells.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Not distributed well to tissues.

Metabolism and Excretion: Unknown.

Half-life: 16.1 days.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
IVunknown1.2 hrunknown

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity to pegylated L-asparinginase
  • History of serious thrombosis during previous L-asparaginase therapy
  • History of serious pancreatitis during previous L-asparaginase therapy
  • History of serious hemorrhagic events during previous L-asparaginase therapy;
  • Severe hepatic impairment
  • OB:   Pregnancy (may cause fetal harm)
  • Lactation: Lactation.

Use Cautiously in:

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

Adverse Reactions/Side Effects

CV: arrhythmias

GI: PANCREATITIS, HEPATOTOXICITY, ↑ bilirubin, ↑ liver enzymes, diarrhea

Hemat: THROMBOSIS, HEMORRHAGE

Resp: dyspnea

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), INFECTION

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

Interactions

Drug-Drug

None reported

Route/Dosage

IV (Adults and Children 1 mo-21 yr): 2500 units/m2  every 21 days.

Availability

Solution for injection (requires dilution): 750 units/mL

Assessment

  • Monitor for signs and symptoms of hypersensitivity reactions (angioedema, lip swelling, eye swelling, erythema, blood pressure decreased, bronchospasm, dyspnea, pruritus, rash) during therapy. Administer only in clinical settings with resuscitation equipment and other agents to treat anaphylaxis (epinephrine, oxygen, intravenous steroids, antihistamines) and observe patients for 1 hr after administration.  If Grade 1 reactions occur,  reduce infusion rate by 50%.  If Grade 2 reactions occur,  hold infusion, treat symptoms, when symptoms resolve, resume infusion at 50% rate.  If Grade 3 or 4 reactions occur,  discontinue calaspargase permanently.
  • Assess for signs and symptoms of pancreatitis (severe abdominal pain, nausea, vomiting) during therapy.  If Grade 3 or 4 symptoms occur,  hold infusion for ↑ lipase or amylase >3 times ULN until levels stabilize or are declining. Discontinue calaspargase permanently if clinical pancreatitis is confirmed.
  • Monitor for signs and symptoms of thromboembolism (severe headache, arm or leg swelling, shortness of breath, chest pain) in extremity during therapy.  If uncomplicated deep vein thrombosis occurs,  hold infusion. Treat with antithrombotic therapy. When symptoms resolve consider continuing therapy while continuing antithrombotic therapy.  If severe or life-threatening thrombosis occurs,  discontinue permanently. Treat with antithrombotic therapy
  • Assess for signs and symptoms of hemorrhage (bleeding, bruising, blood in stool or vomit, black or tarry stools).  If Grade 3 or 4 hemorrhage occurs,  hold infusion. Evaluate for coagulopathy and consider clotting factor replacement as needed. If bleeding is controlled, resume with next scheduled dose.

Lab Test Considerations: Obtain a negative pregnancy test before starting therapy.

  • Monitor serum amylase and/or lipase levels to identify early signs of pancreatic inflammation.
  • Monitor PT, aPTT, fibrinogen in patients with signs and symptoms of hemorrhage.
  • Monitor bilirubin, AST, and ALT at least weekly, during cycles of calasparagase through 6 wks after last dose.  If total bilirubin >3 x to ≤10 x ULN,  hold therapy until total bilirubin levels ↓ to ≤ 1.5 x ULN.  If total bilirubin >10 x ULN,  discontinue calaspargase and do not make up for missed doses. May also cause ↓ serum albumin and plasma fibrinogen.
  • May cause hyperglycemia and glucose intolerance.

Potential Diagnoses

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, dose calculations and infusion pump settings.
  • Intermittent Infusion:  Solution is clear and colorless; do not administer solutions that are discolored, cloudy, or contain particulate matter. Stable at room temperature up to 4 hrs or refrigerated up to 48 hrs; do not administer solutions that have been shaken or vigorously agitated, frozen, or stored at room temperature for more than 48 hours. Protect from light; do not freeze. Diluent:   100 mL of 0.9% NaCl or D5W.
  • Rate: Administer immediately after dilution into running infusion of 0.9% NaCl or D5W over 1 hr.

Patient/Family Teaching

  • Explain purpose of medication to patient.
  • Advise patient to notify health care professional immediately if signs and symptoms of hypersensitivity, pancreatitis, thromboembolism, hemorrhage, or hepatotoxicity (jaundice, severe nausea or vomiting, easy bruising or bleeding) occur.
  • Advise patient to notify health care professional if excessive thirst or any increase in the volume or frequency of urination occurs.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Rep:  Advise women of reproductive potential to use effective contraception, including a barrier method, and avoid breastfeeding during therapy and for at least 3 months after last dose. Notify health care professional if pregnancy is planned or suspected or if breastfeeding. Oral contraceptives interact with calasparagase; use non-oral contraceptive methods.

Evaluation/Desired Outcomes

Improvement of hematologic status in patients with leukemia.

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