calaspargase pegol

kal-AS-par-jase

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzymes

High Alert

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

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 effects:

Death of leukemic cells.

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 16.1 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	1.2 hr	unknown

Contraindicated in:

Hypersensitivity to pegylated L-asparaginase;
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;
Lactation: Lactation.

Use Cautiously in:

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

CV: arrhythmias

GI: ↑bilirubin, ↑liver enzymes, pancreatitis, diarrhea, HEPATOTOXICITY(INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE)

Hemat: thrombosis, HEMORRHAGE

Resp: dyspnea

Misc: hypersensitivity reactions (including anaphylaxis and angioedema), INFECTION

Drug-drug:

May ↓ effectiveness of hormonal contraceptives.

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

Solution for injection : 750 units/mL

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,↓ infusion rate by 50%. If Grade 2 reactions occur, hold infusion, and treat symptoms; when symptoms resolve, resume infusion at 50% rate. If Grade 3 or 4 reactions occur, discontinue calaspargase pegol 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 upper limit of normal (ULN) until levels stabilize or are declining. Discontinue calaspargase pegol 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 calaspargase pegol 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:

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

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.
Premedicate with acetaminophen, an antihistamine (e.g., diphenhydramine), and an H₂ receptor antagonist (e.g., famotidine) 30–60 min prior to each course of therapy.
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 hr or refrigerated up to 48 hr; do not administer solutions that have been shaken or vigorously agitated, frozen, or stored at room temperature for more than 48 hr. 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.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

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: May cause fetal harm. Advise females of reproductive potential to use effective contraception, including a barrier method, and avoid breastfeeding during therapy and for at least 3 mo after last dose. Notify health care professional if pregnancy is planned or suspected or if breastfeeding. Calasparagase pegol can render hormonal contraceptives ineffective; use nonhormonal contraceptive methods.

Improvement of hematologic status in patients with leukemia.

Asparlas

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Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆