pegaspargase

peg-ass-PAR-jase

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzymes

High Alert

First-line treatment of acute lymphoblastic leukemia (ALL) (in combination with other chemotherapy agents).
ALL in patients who have had a previous hypersensitivity reaction to native l-asparaginase (in combination with other chemotherapy agents).

Consists of l-asparaginase bound to polyethylene glycol (PEG). This compound depletes asparagine, 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: Unknown.

Metabolism/Excretion: Metabolized by serum proteases and in the reticuloendothelial system.

Half-Life: 5.7 days (less in patients with previous hypersensitivity to native l-asparaginase).

(hematologic effects)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	unknown	14 days

Contraindicated in:

Hypersensitivity to pegaspargase;
History of serious thrombosis with previous l-asparaginase therapy;
History of pancreatitis, including pancreatitis association with previous l-asparaginase therapy;
History of serious hemorrhagic events to previous l-asparaginase therapy;
Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

History of previous hypersensitivity reaction to l-asparaginase (↑ risk of hypersensitivity reaction);
Rep: Women of reproductive potential.

CV: DEEP VEIN THROMBOSIS (DVT), peripheral edema

Endo: hyperglycemia

GI: abdominal pain, anorexia, diarrhea, HEPATOTOXICITY(INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE), nausea, PANCREATITIS, vomiting

Hemat: HEMORRHAGE, neutropenia

Local: injection site reactions

Metab: hypercholesterolemia, hypertriglyceridemia

MS: arthralgia, myalgia

Neuro: headache, malaise, paresthesia, SEIZURES

Resp: PULMONARY EMBOLISM

Misc: chills, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), night sweats

Drug-drug:

May alter response to anticoagulants or antiplatelet agents.
May ↑ risk of toxicity of dexamethasone.

IM IV (Adults >21 yr): 2500 units/m² no more frequently than every 14 days.
IM IV (Adults and Children ≤21 yr): 2000 units/m² no more frequently than every 14 days.

Solution for injection: 750 units/mL

Assess patient for previous hypersensitivity reactions to native l-asparaginase. Monitor for hypersensitivity reaction (urticaria, diaphoresis, facial swelling, joint pain, hypotension, bronchospasm) for ≥1 hr following administration. If Grade 1 reaction occurs,↓ infusion rate by 50%. If Grade 2 reaction occurs, hold infusion and treat symptoms. When symptoms resolve, resume infusion at 50% reduced rate. If Grade 3 to 4 reaction occurs, permanently discontinue infusion. Epinephrine and resuscitation equipment should be readily available. Reaction may occur up to 2 hr after administration.
Monitor for development of bone marrow depression. Assess for fever, sore throat, and signs of infection. Monitor platelet count throughout therapy. Assess for bleeding. Avoid IM injections and rectal temperatures. Apply pressure to venipuncture sites for 10 min. If Grade 3 to 4 hemorrhage occurs, hold infusion. Evaluate for coagulopathy and consider clotting factor replacement as needed. Resume pegaspargase with next scheduled dose if bleeding is controlled. Anemia may occur. Monitor for ↑ fatigue, dyspnea, and orthostatic hypotension.
Monitor patient frequently for signs of pancreatitis (nausea, vomiting, abdominal pain). If Grade 3 to 4 pancreatitis occurs, hold pegaspargase for elevations in lipase or amylase >3 times upper limit of normal (ULN) until enzyme levels stabilize or are ↓. Discontinue pegaspargase permanently if pancreatitis is confirmed.
Monitor for signs and symptoms of thromboembolism (headache, arm or leg swelling, shortness of breath, chest pain) during therapy. If uncomplicated DVT occurs, hold infusion and treat with antithrombotic therapy. On resolution of symptoms, consider resuming pegaspargase while continuing antithrombotic therapy. If severe or life-threatening thrombosis occurs, discontinue pegaspargase permanently. Treat with antithrombotic therapy.
Assess nausea, vomiting, and appetite. Weigh patient weekly. Prophylactic antiemetics may be used prior to administration.

Lab Test Considerations:

Obtain negative pregnancy test before starting therapy.Monitor CBC prior to and periodically throughout therapy. May alter coagulation studies. May ↓ fibrinogen and ↑ PT and aPTT.
- Monitor serum amylase frequently to detect pancreatitis.
- Monitor blood glucose; may cause hyperglycemia.
- May cause ↑ BUN and serum creatinine.
- Hepatotoxicity, including life-threatening veno-occlusive disease, may occur. Evaluate bilirubin and transaminases prior to each dose, at least weekly during therapy, and through 6 wk after last dose of pegaspargase. Monitor for rapid weight gain, ascites, hepatomegaly, and rapid bilirubin ↑. If total bilirubin >3 times to <10 times ULN, hold infusion until total bilirubin is ≤1.5 times ULN. If total bilirubin >10 times ULN, permanently discontinue pegaspargase.
- May cause ↓ serum calcium.
- May cause ↑ serum and urine uric acid and hyponatremia.
- May cause hypercholesterolemia and hypertriglyceridemia.

Premedicate with acetaminophen, an H₁ receptor blocker (e.g., diphenhydramine), and an H₂ receptor blocker (e.g., famotidine) 30–60 min before administration to ↓ risk and severity of hypersensitivity reactions.
IM is preferred route because of a lower incidence of adverse reactions.
- Solutions should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in specially designated containers.
IM: Limit single injection volume to 2 mL. If volume of injection is >2 mL, use multiple injection sites.

IV Administration:

Intermittent Infusion: Diluent: Dilute each dose in 100 mL of 0.9% NaCl or D5W. Do not shake or agitate. Do not use if solution is cloudy or has formed a precipitate.
- Use only one dose per vial; do not re-enter the vial. Discard unused portions.
- Keep refrigerated. Do not freeze.
Rate: Administer over 1–2 hr.

Inform patient of the possibility of hypersensitivity reactions, including anaphylaxis.
Advise patient that concurrent use of other medications may ↑ the risk of bleeding and the toxicity of pegaspargase. Consult health care professional before taking any other medications, including OTC drugs.
Instruct patient to notify health care professional if abdominal pain, severe nausea and vomiting, jaundice, fever, chills, sore throat, bleeding or bruising, excess thirst or urination, or mouth sores occur. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to be especially careful to avoid falls. Advise patient not to drink alcoholic beverages or take medications containing aspirin or NSAIDs because these may precipitate gastric bleeding.
Instruct patient not to receive any vaccinations without advice of health care professional. Advise parents that this may alter child’s immunization schedule.
Rep: May cause fetal harm. Advise females of reproductive potential to use two methods of effective contraception, including a barrier method, for 3 mo after last dose. Advise females to avoid breastfeeding during therapy and for 1 mo after last dose. Pegaspargase may effectiveness of hormonal contraceptives; hormonal contraceptives are not recommended.
Emphasize the need for periodic lab tests to monitor for side effects.

Improvement of hematologic status in patients with leukemia.

Oncaspar

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Indications ⬆ ⬇

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 ⬆