Oncaspar (Pegaspargase) is a modified version of L-asparaginase that causes the depletion of asparagine in leukemic cells.

Indications of Pegaspargase:

• Acute lymphoblastic leukemia and hypersensitivity to asparaginase:

  • It is indicated for the treatment of acute lymphoblastic leukemia in pediatric and adult patients with hypersensitivity to native forms of L-asparaginase (as a component of a multiagent chemotherapy regimen).

• Acute lymphoblastic leukemia, first-line treatment:

  • It is prescribed as a first-line treatment of ALL (as a component of a multiagent chemotherapy regimen) in pediatric and adult patients.

Oncaspar (Pegaspargase) Dose in Adults

Oncaspar dose in the treatment of patients with hypersensitivity to native asparaginase Acute lymphoblastic leukemia (ALL): 

• ≤21 years:

  • 2,500 units/m² (as part of a multi-agent combination chemotherapy regimen);
  • do not administer more frequently than every 14 days.

• >21 years:

  • 2,000 units/m² (as part of a multi-agent combination chemotherapy regimen);
  • do not administer more frequently than every 14 days.

Oncaspar (Pegaspargase) Dose in Childrens

Oncaspar dose in the treatment of Acute lymphoblastic leukemia:

• IM, IV:
  • 2,500 units/m² /dose (as part of a combination chemotherapy regimen);
  • Do not administer more frequently than every 14 days.

Oncaspar Dosing adjustment for toxicity:

• Hemorrhage:

  • Grade 3 or 4: Hold therapy, evaluate for coagulopathy, and consider clotting factor replacement as needed.
  • Therapy should be resumed with the next scheduled dose if bleeding is controlled.

• Hypersensitivity or infusion reactions:

  • Grade 1: 50% dose reduction.
  • Grade 2: Interrupt infusion and treat symptoms; after the resolution of symptoms, resume infusion at 50% of the previous rate
  • Grade 3 or 4: Discontinue permanently

• Pancreatitis:

  • Grade 3 or 4: If lipase or amylase >3 times upper normal limit, hold therapy until enzyme levels stabilize or are declining. Discontinue permanently if clinical pancreatitis confirmed.

  • Thromboembolism:

  • Uncomplicated deep vein thrombosis:

    • Hold therapy, evaluate and treat DVT with antithrombotic therapy;
    • upon resolution of symptoms, may resume therapy with concomitant antithrombotic agents.

  • Severe or life-threatening thrombosis:

    • Discontinue permanently; treat thrombosis with necessary medical management.

• Additional adjustments recommended for other asparaginase products:

  • Older Adolescents:

    • Hyperammonemia-related fatigue:

      • Continue therapy for grade 2 toxicity.
      • Dose reduction by 25% should be done with grade 3 toxicity.
      • A full dose should be resumed when toxicity ≤ grade 2 (make up for missed doses).
      • Dose reduction by 50% for grade 4 toxicity and resume full dose when toxicity ≤ grade 2 (make up for missed doses).

    • Hyperglycemia:

      • Continue therapy for uncomplicated hyperglycemia.
      • If hyperglycemia requires insulin therapy, asparaginase product and concomitant corticosteroids should be held until blood glucose is controlled;
      • resume dosing at the prior dose level.
      • It should also be stopped in case of life-threatening hyperglycemia or toxicity requiring urgent intervention until blood glucose is controlled with insulin and is resumed without makeup for missed doses.

    • Hypertriglyceridemia:

      • If serum triglyceride level <1 g/dL, continue the asparaginase product but monitor closely for pancreatitis.
      • It should be withheld if triglyceride level >1 g/dL. It should be resumed at the prior dose level after triglyceride level returns to baseline.

Oncaspar (Pegaaspargase) pregnancy Risk Category: C

• Studies on animal reproduction revealed that the foetus experienced adverse effects.
• Before starting therapy, it is important to get rid of any pregnant women.
• Effective contraception, which includes a barrier method, should be used during and for at most 3 months following the pegaspargase treatment.
• In this instance, oral contraception is ineffective.

Pegaspargase can be used during breastfeeding

• Breast milk contains no pegaspargase excretion..
• The manufacturer does not recommend breastfeeding during therapy or for three months after the last dose of pegaspargase.

Oncaspar dose adjustment in renal disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

Oncaspar Dose adjustment in liver disease:

• • Mild to moderate impairment:

    • There are no dosage adjustments provided in the manufacturer’s labeling.

  • Severe impairment:

    • Use is contraindicated.

• Hepatotoxicity during treatment:

  • Total bilirubin >3 to 10 times ULN:

    • Withhold pegaspargase until total bilirubin levels decrease to ≤1.5 times ULN.

  • Total bilirubin >10 times ULN:

    • Discontinue pegaspargase and do not make up for missed doses.

• The following off-label adjustments have also been recommended (Stock 2011):

  • ALT/AST >3 to 5 times ULN:

    • Continue therapy.

  • ALT/AST >5 to 20 times ULN:

    • Delay the next dose until transaminases <3 times ULN.

  • ALT/AST >20 times ULN:

    • Discontinue therapy if it takes longer than 1 week for transaminases to return to <3 times ULN.

  • Direct bilirubin <3 mg/dL:

    • Continue therapy.

  • Direct bilirubin 3.1 to 5 mg/dL:

    • Hold pegaspargase and resume when direct bilirubin <2 mg/dL; consider switching to alternate asparaginase product.

  • Direct bilirubin >5 mg/dL:

    • • Discontinue pegaspargase;
      • Do not substitute other asparaginase products;
      • Do not make up for missed doses.

Common Side Effects of Oncaspar (Pegaspargase):

• Hepatic:

  • Increased Serum Transaminases

• Hypersensitivity:

  • Hypersensitivity Reaction

Rare Side Effects Of Oncaspar (Pegaspargase):

• Cardiovascular:

  • Thrombosis

• Central Nervous System:

  • Cerebral Thrombosis

• Endocrine & Metabolic:

  • Hyperglycemia

• Gastrointestinal:

  • Pancreatitis

• Hematologic:

  • Blood Coagulation Disorder

• Hepatic:

  • Abnormal Hepatic Function Tests
  • Hyperbilirubinemia

• Immunologic:

  • Hypersensitivity To L-Asparaginase

Contraindication to Oncaspar (Pegaspargase):

• History of severe hypersensitivity reactions, including anaphylaxis of pegaspargase and any component of the formulation
• Liver dysfunction severe
• History of hemorhagic, thrombotic or pancreatitis with L-asparaginase treatment.

Warnings and precautions

• Glucose intolerance

  • Monitoring serum glucose is important to avoid glucose intolerance.

• Hemorrhage

  • It can lead to coagulopathies, such as increased prothrombin times (PT), increased partial-thromboplastin times (PTT), or hypofibrinogenemia.
  • It is important to evaluate the coagulation profile.
  • In severe cases of coagulation disorders, alternate therapy should be considered.

• Hepatotoxicity

  • Transaminitis can lead to reduced serum albumin or fibrinogen, which can cause hepatic impairment. Therefore, it is important to monitor liver function during and after treatment.
  • With severe hepatotoxicity, it is important to discontinue pegaspargase treatment and receive supportive treatment.

• Hypersensitivity

  • Hypersensitivity reactions like angioedema and lip/eye swelling, hypotension or dyspnea can occur.
  • You should stop all drug treatment immediately. This includes intravenous steroids, oxygen, epinephrine, and antihistamines in severe reactions.
  • Patients with hypersensitivity to L-asparaginase products derived from E.coli are at greater risk for serious hypersensitivity reactions.

• Pancreatitis

  • Patients who receive pegaspargase may develop pancreatitis. This could be hemorhagic, necrotizing or both.
  • In the event of symptoms, serum amylase and lipase should be tested.
  • You can continue the therapy for symptomatic chemical pancreatitis (amylase/lipase >3x ULN) and only radiologic abnormalities.
  • If diagnosed with pancreatitis, the drug should be kept under suspicion.

• Thrombotic events

  • It is important to monitor the levels of antithrombin III regularly.
  • If there are any serious thrombotic events, such as sagittal thrombosis or sagittal sinusthrombosis then it is important to stop all treatment immediately
  • Some patients may need anticoagulation prophylaxis while on therapy.

Pegaspargase: Drug Interaction

Monitoring parameters:

• Vital signs
• Pregnancy status before treatment
• CBC
• Liver function tests,amylase/lipase
• Renal function tests
• Blood and urine glucose
• Lipid profile
• Uric acid levels
• Clotting profile PT,APTT,fibrinogen, antithrombin III acitivity
• Signs /symptoms for allergic reaction
• Signs/symptoms of thrombosis or bleeding.

How to administer Oncaspar (Pegaspargase)?

IM:

• You must inject it intramuscularly into a large muscle.
• The injection volume should not exceed 2 mL at a single site.
• Multiple injection sites are required for IM volumes greater than 2 mL.

IV:

• You can administer the fluid over 60 to 120 minutes using an IV line. The fluid used in preparation of the solution may have been normal saline, dextrose or other liquids.
• It should not be used as an IV push.

To manage any reaction, it is important to have the equipment for treating hypersensitivity reactions and securing the airway available at all times. This includes antihistamine, Epinephrine, oxygen, and IV corticosteroids.

Mechanism of action of Pegaspargase (Oncaspar):

• Pegaspargase (a modified L-asparaginase) is conjugated with monomethoxypolyethylenegl (mPEG). Hydrolyzing L'asparagine into ammonia or L-aspartic acids causes depletion in asparagine-deficient cells.
• While normal cells can produce asparagine from their own bodies, leukemia cells need to be supplied with exogenous asparagine.
• Asparagine depletion occurs in leukemia cells and inhibits protein synthesis and apoptosis.

Onset:

• Mean maximum asparaginase activity: IM: On day 5 (following a single IM dose of 2,500 units/m )

Duration: Asparagine depletion:

• IV (in asparaginase naive adults): 2 to 4 weeks
• IM: ~21 days

Bioavailability:

• IM: 82% (first dose); 98% (repeat dosing)

Distribution:

• V : 1.86 L/m (following a single IM dose of 2,500 units/m ); 2 L (following a single IV dose of 2,500 units/m ); Asparaginase-naive adults: IV: 2.4 L/m (Douer 2007)

Metabolism:

• Systemically degraded

Half-life elimination:

• 5.8 days (following a single IM dose of 2,500 units/m )
• ~5.3 days (following a single IV dose of 2,500 units/m )
• Asparaginase-naive adults: IV: 7 days.

Excretion:

• Clearance: 0.17 L/m /day (following a single IM dose of 2,500 units/m² ); 0.2 L/day (following a single IV dose of 2,500 units/m² )

International Brands of Pegaspargase:

• Oncaspar
• Ai Yang

Pegaspargase Brands in Pakistan:

No Brands Available in Pakistan.