peg-ass-PAR-jase

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzymes

• First-line treatment of acute lymphoblastic leukemia (ALL) (in combination with other chemotherapy agents).
• Treatment of 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.

• 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)

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 (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

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

Endo: hypercholesterolemia, hyperglycemia, hypertriglyceridemia.

CV: peripheral edema.

GI: HEPATOTOXICITY, PANCREATITIS, abdominal pain, anorexia, diarrhea, nausea, vomiting.

Hemat: HEMORRHAGE, THROMBOSIS, neutropenia.

Local: injection site reactions.

MS: arthralgia, myalgia.

Neuro: paresthesia , SEIZURES, headache, malaise.

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

Drug-Drug:

• May alter response to anticoagulants or antiplatelet agents.

• 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 infusion and hypersensitivity reaction (urticaria, diaphoresis, facial swelling, joint pain, hypotension, bronchospasm) for at least 1 hr following administration. If Grade 1 reaction occurs, reduce infusion rate by 50%. If Grade 2 reaction occurs, hold infusion and treat symptoms. When symptoms resolve, resume infusion and reduce infusion rate by 50%. 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 (bleeding gums, bruising, petechiae, guaiac test stools, urine, and emesis). Avoid giving IM injections and taking 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 increased 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 x upper limit of normal (ULN) until enzyme levels stabilize or are declining, 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 deep vein thrombosis occurs, hold infusion and treat with antithrombotic therapy. Upon 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.

• Obtain negative pregnancy test before starting therapy.Monitor CBC prior to and periodically throughout therapy. May alter coagulation studies. Fibrinogen may be decreased; PT and partial thromboplastin time (PTT) may be ↑.
  • Monitor serum amylase frequently to detect pancreatitis.
  • Monitor blood glucose; may cause hyperglycemia.
  • May cause elevated BUN and serum creatinine.
  • Hepatotoxicity may be manifested by increased AST, ALT, alkaline phosphatase, or bilirubin. Liver function tests usually return to normal after therapy. If total bilirubin >3 times to <10 times UNL, hold infusion until total bilirubin is 1.5 times ULN. If total bilirubin >10 times ULN, discontinue pegaspargase and do not make up for missed doses.
  • May cause ↓ serum calcium.
  • May cause elevated serum and urine uric acid and hyponatremia.
  • May cause hypercholesterolemia and hypertriglyceridemia.

• IM is the 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 1 dose per vial; do not re-enter the vial. Discard unused portions.
  • Keep refrigerated but do not freeze. Freezing destroys activity but does not change the appearance of pegaspargase.
• Rate: Administer over 1–2 hr via Y-site through an infusion that is already running.
• Additive Incompatibility: Information unavailable. Do not admix with other medications or solutions.

• Inform patient of the possibility of hypersensitivity reactions, including anaphylaxis.
• Advise patient that concurrent use of other medications may increase 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, electric razor, and to be especially careful to avoid falls. Patients should also be cautioned 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: Advise females of reproductive potential to use 2 methods of effective contraception, including a barrier method, and avoid breast feeding during therapy and for at least 3 mo after last dose. Pegaspargase may decrease effectiveness of oral contraceptives, oral 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

• Risk for infection (Adverse Reactions).

NDC Code^*

• 0944- Baxalta US Inc.
  • 0944-3810- ONCASPAR
    • 0944-3810-01- 1 VIAL, SINGLE-USE in 1 CARTON (0944-3810-01) > 5 mL in 1 VIAL, SINGLE-USE