Pegaspargase, also known by its brand name Oncaspar, is a medication used in the treatment of acute lymphoblastic leukemia (ALL), a type of cancer that affects the white blood cells. It belongs to a class of drugs called asparagine-specific enzymes.

Pegaspargase is a modified form of the enzyme called L-asparaginase. It works by breaking down the amino acid called asparagine, which is necessary for the growth and survival of leukemia cells. By depleting the levels of asparagine, pegaspargase helps to inhibit the growth of cancer cells and ultimately leads to their death.

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): 

Pegaspargase is a medicine used to treat a type of cancer called acute lymphoblastic leukemia (ALL). It is given to patients who are receiving their first treatment or to those who are allergic to another similar medicine called native asparaginase.

For patients who are 21 years old or younger:

• The usual dose of pegaspargase is 2,500 units per square meter of body surface area.
• It is given either through an injection into the muscle or through a vein.
• This is done as part of a combination chemotherapy treatment, where multiple drugs are used together.
• The pegaspargase dose should not be given more often than every 14 days.

For patients who are over 21 years old:

• The usual dose of pegaspargase is 2,000 units per square meter of body surface area.
• It is also given as part of a combination chemotherapy treatment and should not be given more frequently than every 14 days.

Oncaspar (Pegaspargase) Dose in Childrens

Oncaspar dose in the treatment of Acute lymphoblastic leukemia:

• In the treatment of Acute lymphoblastic leukemia (ALL) in infants, children, and adolescents, pegaspargase is given as part of a combination chemotherapy regimen.
• The usual dose of pegaspargase is 2,500 units per square meter of body surface area per dose.
• It can be administered either through an injection into the muscle (IM) or through a vein (IV).
• It's important to note that pegaspargase should not be given more frequently than every 14 days.

Oncaspar Dosing adjustment for toxicity:

Hemorrhage:

• Grade 3 or 4: Stop the therapy, check for blood clotting problems, and consider using clotting factors if needed.
• If bleeding is controlled and resolved, resume therapy with the next scheduled dose.

Hypersensitivity or Infusion Reactions:

• Grade 1: Slow down the infusion rate by 50%.
• Grade 2: Pause the infusion and treat the symptoms. Once the symptoms are resolved, resume the infusion at 50% of the previous rate.
• Grade 3 or 4: Stop the infusion permanently.

Pancreatitis:

• Grade 3 or 4: If the levels of lipase or amylase are more than three times the upper limit of normal (ULN), pause the therapy until the enzyme levels stabilize or start to decrease.
• If clinical pancreatitis is confirmed, discontinue the therapy permanently.

Thromboembolism (Blood Clots):

• Uncomplicated deep vein thrombosis (DVT): Pause the therapy, evaluate and treat the DVT with antithrombotic therapy. Once the symptoms are resolved, therapy may be resumed with the use of antithrombotic medications.
• Severe or life-threatening thrombosis: Stop the therapy permanently and manage the thrombosis with appropriate medical treatment.

Additional Adjustments for Other Asparaginase Products:

• Older Adolescents:
  • Hyperammonemia-related fatigue:
    • Grade 2 toxicity: Continue therapy. If grade 3 toxicity occurs, reduce the dose by 25% and resume full dose when toxicity improves to grade 2.
    • Grade 4 toxicity: Reduce the dose by 50% and resume full dose when toxicity improves to grade 2.
  • Hyperglycemia:
    • Uncomplicated hyperglycemia: Continue therapy. If insulin therapy is required, pause the asparaginase product until blood glucose is controlled and then resume at the previous dose level.
    • Life-threatening hyperglycemia: Pause the asparaginase product until blood glucose is controlled with insulin. Resume therapy without making up for missed doses.
  • Hypertriglyceridemia:
    • Triglyceride level <1 g/dL: Continue therapy but monitor closely for pancreatitis.
    • Triglyceride level >1 g/dL: Pause therapy and monitor. Resume at the previous dose level after triglyceride level returns to baseline.

Oncaspar (Pegaaspargase) pregnancy Risk Category: C

• Before using pegaspargase, it is important to assess the pregnancy status of females who can become pregnant, as studies in animals suggest potential harm to the fetus if exposed during pregnancy.
• During treatment and for at least three months after the last dose of pegaspargase, effective contraception should be used.
• It is recommended to use a barrier method of contraception, as oral contraceptives may not be reliable and are not recommended for this purpose.

Pegaspargase can be used during breastfeeding

• The presence of pegaspargase in breast milk is not known, and there is a possibility of adverse reactions in breastfed infants.
• Therefore, the manufacturer does not recommend breastfeeding during pegaspargase therapy and 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:

Hepatic Impairment Prior to Treatment Initiation:

• Mild to moderate impairment: No specific dosage adjustments are provided in the manufacturer's labeling.
• Severe impairment: The use of pegaspargase is not recommended.

Hepatotoxicity During Treatment:

• Total bilirubin >3 to 10 times the upper limit of normal (ULN): Hold 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.

Additional Off-Label Adjustments (as recommended):

• ALT/AST >3 to 5 times ULN: Continue therapy.
• ALT/AST >5 to 20 times ULN: Delay the next dose until transaminase levels are below 3 times ULN.
• ALT/AST >20 times ULN: Discontinue therapy if it takes longer than 1 week for transaminase levels to return to below 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 is below 2 mg/dL. Consider switching to an alternate asparaginase product.
• Direct bilirubin >5 mg/dL: Discontinue pegaspargase. Do not substitute with other asparaginase products and do not make up for missed doses.

These dosing adjustments are based on the presence of hepatic impairment and hepatotoxicity.

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):

• Pegaspargase should not be used if there is a history of serious hypersensitivity reactions (including anaphylaxis) to pegaspargase or any ingredient in the formulation.
• It is also contraindicated in individuals with a history of serious thrombosis (blood clotting) associated with previous L-asparaginase therapy, as well as those with a history of pancreatitis (including pancreatitis linked to previous L-asparaginase therapy), serious hemorrhagic events related to previous L-asparaginase therapy, or severe hepatic impairment.
• These contraindications are important to ensure the safety and well-being of the patient, as using pegaspargase in these circumstances may lead to severe adverse reactions or complications.

Warnings and precautions

Glucose intolerance

• Pegaspargase can potentially cause glucose intolerance, and in some cases, this condition may be irreversible.
• It is important to monitor the levels of serum glucose during treatment with pegaspargase.
• Regular monitoring helps to detect any changes in glucose levels and allows for appropriate management of glucose intolerance if it occurs.

Hemorrhage

• In patients receiving pegaspargase, there is a possibility of experiencing hemorrhage, which can be indicated by increased prothrombin time (PT), increased partial thromboplastin time (PTT), and low levels of fibrinogen in the blood (hypofibrinogenemia).
• If severe or symptomatic coagulopathy (abnormal blood clotting) occurs, appropriate replacement therapy may be necessary.
• It is important to evaluate coagulation parameters, including PT, PTT, and fibrinogen levels, in patients who show signs or symptoms of hemorrhage.
• Regular monitoring of these parameters helps in detecting any abnormalities and allows healthcare providers to take appropriate measures to manage and treat any coagulation issues that may arise during pegaspargase treatment.

Hepatotoxicity

• Pegaspargase can cause hepatotoxicity, which refers to liver damage and abnormal liver function.
• This may result in elevated levels of transaminases (liver enzymes) and bilirubin (both direct and indirect), as well as reduced levels of serum albumin and fibrinogen.
• To monitor for potential hepatotoxicity, it is recommended to regularly check bilirubin and transaminase levels at least once a week during treatment cycles that include pegaspargase.
• Monitoring should continue for at least 6 weeks after the last dose of pegaspargase.
• If serious liver toxicity occurs, pegaspargase should be discontinued, and supportive care should be provided to manage the condition and promote liver health.
• It is essential to closely monitor liver function to ensure the safety and well-being of patients receiving pegaspargase treatment.

Hypersensitivity

• Pegaspargase can potentially cause anaphylaxis and serious hypersensitivity reactions.
• Patients who have a known hypersensitivity to E.
• coli derived L-asparaginase products are at an increased risk of experiencing these reactions.
• Hypersensitivity reactions can manifest as angioedema (swelling), lip swelling, eye swelling, low blood pressure (hypotension), bronchospasm, difficulty breathing (dyspnea), redness (erythema), itching (pruritus), and rash.
• It is important to closely observe patients for one hour after administering pegaspargase.
• During administration, it is crucial to have equipment and immediate treatment options available to address hypersensitivity reactions promptly.
• This may include items such as epinephrine, oxygen, intravenous steroids, and antihistamines.
• If a patient experiences a serious hypersensitivity reaction, pegaspargase should be discontinued.
• Prompt recognition and appropriate management of hypersensitivity reactions are necessary to ensure patient safety.

Pancreatitis

• Pancreatitis, inflammation of the pancreas, can occur in patients receiving pegaspargase.
• It is important to note that hemorrhagic or necrotizing pancreatitis, which can be fatal, have been reported in some cases.
• To reduce the risk of pancreatitis, patients should avoid alcohol use.
• Patients should also be informed about the signs and symptoms of pancreatitis, as untreated pancreatitis can be life-threatening.
• Regular assessment of serum amylase and/or lipase levels is recommended to detect early signs of pancreatic inflammation.
• If pancreatitis is suspected, pegaspargase should be discontinued.
• If pancreatitis is confirmed, pegaspargase should not be resumed.
• However, in cases of asymptomatic chemical pancreatitis (elevated amylase or lipase levels) or only radiologic abnormalities, consideration may be given to continuing therapy.
• Close monitoring of amylase and/or lipase levels is necessary in such cases.
• These precautions are crucial in managing and preventing complications related to pancreatitis in patients receiving pegaspargase treatment.

Thrombotic events

• Pegaspargase treatment can potentially lead to serious thrombotic events, including sagittal sinus thrombosis.
• If a patient experiences a serious thrombotic event, pegaspargase should be discontinued.
• It may be necessary to monitor antithrombin III activity and consider repletion if indicated, as recommended by Barreto in 2017.
• In certain patients, anticoagulation prophylaxis during therapy may be considered, as suggested by Farge in 2013.
• These measures are important to address and manage the risk of thrombotic events associated with pegaspargase treatment.
• Close monitoring, appropriate interventions, and individualized management strategies can help reduce the occurrence and severity of thrombotic complications in patients receiving pegaspargase.

Pegaspargase: Drug Interaction

Risk Factor C (Monitor therapy)
Pegloticase	May diminish the therapeutic effect of PEGylated Drug Products.
Pegvaliase	PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased.

Monitoring parameters:

Complete blood count (CBC) with differential and platelet count:

• Weekly monitoring is recommended to assess blood cell counts and platelet levels.

Amylase and lipase levels:

• These pancreatic enzymes should be monitored to detect any signs of pancreatic inflammation.

Liver function tests:

• Monitor bilirubin and transaminases (liver enzymes) to evaluate liver function. Baseline tests should be conducted, followed by weekly monitoring during treatment.

Fibrinogen, prothrombin time (PT), and partial thromboplastin time (PTT):

• Regular monitoring of these coagulation parameters helps assess blood clotting function. Baseline testing is advised, along with periodic checks during and after treatment.

Renal function tests:

• Monitoring kidney function through tests such as serum creatinine helps ensure proper kidney health during treatment.

Urine glucose and blood glucose:

• Weekly monitoring of glucose levels is recommended to assess for glucose intolerance or changes in blood sugar levels.

Triglycerides and uric acid:

• Regular monitoring of these parameters helps identify any abnormalities or potential metabolic changes.

Pregnancy test:

• It is important to perform a pregnancy test before initiating treatment in females of reproductive potential.
• Consider monitoring antithrombin III activity, as suggested by Barreto in 2017.

Vital signs during administration:

• Regularly monitor vital signs such as blood pressure, heart rate, and temperature during pegaspargase administration.

Abdominal pain:

• Observe for the onset of abdominal pain, as it can be a potential symptom of pancreatitis.

Allergic reaction:

• Patients should be observed for allergic reactions for at least one hour after administration.

Signs/symptoms of thrombosis or bleeding:

• Monitor for any signs or symptoms of blood clotting or bleeding issues throughout the treatment period.

Regular monitoring of these parameters and careful observation of symptoms helps ensure the safe and effective use of pegaspargase and allow for timely intervention if any complications arise.

How to administer Oncaspar (Pegaspargase)?

During pegaspargase administration, it is crucial to have appropriate agents readily available for maintaining an adequate airway and treating hypersensitivity reactions. These agents include antihistamines, epinephrine, oxygen, and intravenous corticosteroids. It is important to be prepared to manage anaphylaxis, a severe allergic reaction, at each administration.

IM:

• For intramuscular (IM) administration, pegaspargase should be injected deeply into a large muscle.
• The injection volume should not exceed 2 mL per single injection site.
• If a larger IM injection volume is required, multiple injection sites should be used.

IV:

• For intravenous (IV) administration, pegaspargase should be administered over 1 to 2 hours using a running IV infusion line.
• The diluted solution should be infused through either normal saline (NS) or dextrose 5% in water (D5W), depending on the fluid used in the preparation.
• It is important to note that pegaspargase should not be administered as an IV push.

Following these administration guidelines ensures the proper delivery and safety of pegaspargase therapy.

Mechanism of action of Pegaspargase (Oncaspar):

• Pegaspargase is a modified form of L-asparaginase that has been attached to a substance called monomethoxypolyethylene glycol (mPEG).
• It works by breaking down L-asparagine, an amino acid, into ammonia and L-aspartic acid in leukemic cells.
• This depletion of asparagine is crucial because leukemia cells rely on external sources of asparagine, while normal cells can produce it on their own.
• By depriving leukemic cells of asparagine, pegaspargase inhibits their ability to synthesize proteins and triggers a process called apoptosis, which leads to cell death.

Onset:

• The maximum activity of asparaginase is reached on day 5 after a single intramuscular (IM) dose of 2,500 units/m.

Duration:

• Asparagine depletion lasts for approximately 2 to 4 weeks in asparaginase-naive adults when administered intravenously (IV), and around 21 days with IM administration.

Bioavailability:

• The bioavailability of pegaspargase is 82% for the first dose and 98% for repeat dosing when given via the IM route.

Distribution:

• The volume of distribution is 1.86 L/m following a single IM dose of 2,500 units/m and 2 L after a single IV dose of the same strength.
• In asparaginase-naive adults, the volume of distribution with IV administration is 2.4 L/m.

Metabolism:

• Pegaspargase is systemically degraded in the body.

Half-life elimination:

• The half-life of elimination is approximately 5.8 days after a single IM dose of 2,500 units/m and 5.3 days after a single IV dose of the same strength.
• In asparaginase-naive adults receiving IV administration, the half-life is 7 days.

Excretion:

• The clearance of pegaspargase is 0.17 L/m/day after a single IM dose of 2,500 units/m and 0.2 L/day after a single IV dose of the same strength.

International Brands of Pegaspargase:

• Oncaspar
• Ai Yang

Pegaspargase Brands in Pakistan:

No Brands Available in Pakistan.