Pegaspargase

Pegaspargase
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

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Overview

Pegaspargase is an asparginase that is FDA approved for the treatment of acute lymphoblastic leukemia (ALL) and acute lymphoblastic leukemia and hypersensitivity to asparaginase. Common adverse reactions include allergic reactions (including anaphylaxis), central nervous system thrombosis, coagulopathy, elevated transaminases, hyperbilirubinemia, hyperglycemia, and pancreatitis.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

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Off-Label Use and Dosage (Adult)

Guideline-Supported Use

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Pediatric Indications and Dosage

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Off-Label Use and Dosage (Pediatric)

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Contraindications

• History of serious allergic reactions to Oncaspar.
• History of serious thrombosis with prior L-asparaginase therapy.
• History of pancreatitis with prior L-asparaginase therapy.
• History of serious hemorrhagic events with prior L-asparaginase therapy.

Warnings

Anaphylaxis and Serious Allergic Reactions

• Anaphylaxis and serious allergic reactions can occur in patients receiving Oncaspar®. The risk of serious allergic reactions is higher in patients with known hypersensitivity to other forms of L-asparaginase. Observe patients for 1 hour after administration of Oncaspar® in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (for example, epinephrine, oxygen, intravenous steroids, antihistamines). Discontinue Oncaspar® in patients with serious allergic reactions.

Thrombosis

• Serious thrombotic events, including sagittal sinus thrombosis can occur in patients receiving Oncaspar®. Discontinue Oncaspar® in patients with serious thrombotic events.

Pancreatitis

• Pancreatitis can occur in patients receiving Oncaspar®. Evaluate patients with abdominal pain for evidence of pancreatitis. Discontinue Oncaspar® in patients with pancreatitis.

Glucose Intolerance

• Glucose intolerance can occur in patients receiving Oncaspar®. In some cases, glucose intolerance is irreversible. Monitor serum glucose.

Coagulopathy

• Increased prothrombin time, increased partial thromboplastin time, and hypofibrinogenemia can occur in patients receiving Oncaspar®. Monitor coagulation parameters at baseline and periodically during and after treatment. Initiate treatment with fresh-frozen plasma to replace coagulation factors in patients with severe or symptomatic coagulopathy.

Hepatotoxicity and Abnormal Liver Function

• Hepatotoxicity and abnormal liver function, including elevations of AST (SGOT), ALT (SGPT), alkaline phosphatase, bilirubin (direct and indirect), and depression of serum albumin, and plasma fibrinogen can occur. Perform appropriate monitoring.

Adverse Reactions

Clinical Trials Experience

The following serious adverse reactions are described in greater detail in other sections of the label:

• Anaphylaxis and serious allergic reactions.
• Serious thrombosis.
• Pancreatitis.
• Glucose intolerance.
• Coagulopathy.
• Hepatotoxicity and abnormal liver function.

The most common adverse reactions with Oncaspar® are allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system (CNS) thrombosis, coagulopathy, hyperbilirubinemia, and elevated transaminases. Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) has been reported in patients exposed to Oncaspar®.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.

First-Line ALL

• The data presented below are derived from 2 studies in patients with standard-risk ALL who received Oncaspar® as a component of first-line multi-agent chemotherapy. Study 1 was a randomized (1:1), active-controlled study that enrolled 118 patients, with a median age of 4.7 years (1.1-9.9 years), of whom 54% were males and 65% White, 14% Hispanic, 8% Black, 8% Asian, and 6% other. Of the 59 patients in Study 1 who were randomized to Oncaspar®, 48 patients (81%) received all 3 planned doses of Oncaspar®, 6 (10%) received 2 doses, 4 (7%) received 1 dose, and 1 patient (2%) did not receive the assigned treatment. Study 2 is an ongoing, multi-factorial design study in which all patients received Oncaspar® as a component of various multi-agent chemotherapy regimens; interim safety data are available for 2,770 patients. Study participants had a median age of 4 years (1-10 years), and were 55% male, 68% White, 18% Hispanic, 4% Black, 3% Asian, and 7% other. Per protocol, the schedule of Oncaspar® varied by treatment arm, with intermittent doses of Oncaspar® for up to 10 months.
• In Study 1, detailed safety information was collected for pre-specified adverse reactions identified as asparaginase-induced adverse reactions and for grade 3 and 4 non-hematologic adverse reactions according to the Children’s Cancer Group (CCG) Toxicity and Complication Criteria. The per-patient incidence, by treatment arm, for these selected adverse reactions occurring at a severity of grade 3 or 4 are presented in TABLE 1 below:

• Safety data were collected in Study 2 only for National Cancer Institute Common Toxicity Criteria (NCI CTC) version 2.0, grade 3 and 4 non-hematologic toxicities. In this study, the per-patient incidence for the following adverse reactions occurring during treatment courses in which patients received Oncaspar® were: elevated transaminases, 11%; coagulopathy, 7%; hyperglycemia, 5%; CNS thrombosis/hemorrhage, 2%; pancreatitis, 2%; clinical allergic reaction, 1%; and hyperbilirubinemia, 1%. There were 3 deaths due to pancreatitis.

Previously Treated ALL

• Adverse reaction information was obtained from 5 clinical trials that enrolled a total of 174 patients with relapsed ALL who received Oncaspar® as a single agent or in combination with multi-agent chemotherapy. The toxicity profile of Oncaspar® in patients with previously treated relapsed ALL is similar to that reported above with the exception of clinical allergic reactions (see TABLE 2). The most common adverse reactions of Oncaspar® were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies. The most common serious adverse events due to Oncaspar® treatment were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%).

Allergic Reactions

Allergic reactions include the following: bronchospasm, hypotension, laryngeal edema, local erythema or swelling, systemic rash, and urticaria.

First-Line ALL

• Among 58 Oncaspar®-treated patients enrolled in Study 1, clinical allergic reactions were reported in 2 patients (3%). One patient experienced a grade 1 allergic reaction and the other grade 3 hives; both occurred during the first delayed intensification phase of the study (see TABLE 2).

Previously Treated ALL

• Among 62 patients with relapsed ALL and prior hypersensitivity reactions to asparaginase, 35 patients (56%) had a history of clinical allergic reactions to native Escherichia (E.) coli L-asparaginase, and 27 patients (44%) had history of clinical allergic reactions to both native E. coli and native Erwinia L-asparaginase. Twenty (32%) of these 62 patients experienced clinical allergic reactions to Oncaspar® (see TABLE 2).
• Among 112 patients with relapsed ALL with no prior hypersensitivity reactions to asparaginase, 11 patients (10%) experienced clinical allergic reactions to Oncaspar® (see TABLE 2).

Immunogenicity

• As with all therapeutic proteins, there is a potential for immunogenicity, defined as development of binding and/or neutralizing antibodies to the product.
• In Study 1, Oncaspar®-treated patients were assessed for evidence of binding antibodies using an enzyme-linked immunosorbent assay (ELISA) method. The incidence of protocol-specified “high-titer” antibody formation was 2% in Induction (n=48), 10% in Delayed Intensification 1 (n=50), and 11% in Delayed Intensification 2 (n=44). There is insufficient information to determine whether the development of antibodies is associated with an increased risk of clinical allergic reactions, altered pharmacokinetics, or loss of anti-leukemic efficacy.
• The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to Oncaspar® with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

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Drug Interactions

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Use in Specific Populations

Pregnancy

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Administration and Monitoring

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Monitoring

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IV Compatibility

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Y-Site

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Overdosage

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Chronic Overdose

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Pharmacology

Pegaspargase
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Nonclinical Toxicology

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Clinical Studies

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How Supplied

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Storage

There is limited information regarding Pegaspargase Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

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Precautions with Alcohol

Alcohol-Pegaspargase interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Pegaspargase Brand Names in the drug label.

Look-Alike Drug Names

• (Paired Confused Name 1a) — (Paired Confused Name 1b)
• (Paired Confused Name 2a) — (Paired Confused Name 2b)
• (Paired Confused Name 3a) — (Paired Confused Name 3b)

Drug Shortage Status

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References

The contents of this FDA label are provided by the National Library of Medicine.