Pegaspargase
FDA Drug Information • Also known as: Oncaspar
- Brand Names
- Oncaspar
- Drug Class
- Asparagine-specific Enzyme [EPC]
- Route
- INTRAMUSCULAR, INTRAVENOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Pegaspargase is a conjugate of monomethoxypolyethylene glycol (mPEG) and L-asparaginase (L-asparagine amidohydrolase), an asparagine specific enzyme. L-asparaginase is a tetrameric enzyme that is produced endogenously by E. coli and consists of identical 34.5 kDa subunits. Approximately 69 to 82 molecules of mPEG are linked to L-asparaginase; the molecular weight of each mPEG molecule is about 5 kDa. ONCASPAR activity is expressed in International Units. ONCASPAR (pegaspargase) injection is supplied as a clear, colorless, preservative-free, isotonic sterile solution in phosphate-buffered saline, pH 7.3, for intramuscular use or for dilution prior to intravenous infusion. Each vial of ONCASPAR contains 3,750 International Units of pegaspargase in 5 mL of solution. Each milliliter contains 750 International Units of pegaspargase, dibasic sodium phosphate, USP (5.58 mg), monobasic sodium phosphate, USP (1.20 mg), and Sodium Chloride, USP (8.50 mg) in Water for Injection, USP.
What Is Pegaspargase Used For?
1 INDICATIONS AND USAGE ONCASPAR is an asparagine specific enzyme indicated as a component of a multi-agent chemotherapeutic regimen for treatment of pediatric and adult patients with: First-line acute lymphoblastic leukemia ( 1.1 ) Acute lymphoblastic leukemia and hypersensitivity to asparaginase ( 1.2 ) 1.1 First Line Acute Lymphoblastic Leukemia (ALL) ONCASPAR ® is indicated as a component of a multi-agent chemotherapeutic regimen for the first-line treatment of pediatric and adult patients with ALL. 1.2 Acute Lymphoblastic Leukemia and Hypersensitivity to Asparaginase ONCASPAR is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of pediatric and adult patients with ALL and hypersensitivity to native forms of L-asparaginase.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Administered intramuscularly or intravenously no more frequently than every 14 days. ( 2.1 ) Patients ages 21 years and younger: 2,500 International Units/m 2 . ( 2.1 ) Patients ages over 21 years: 2,000 International Units/m 2 . ( 2.1 ) For intramuscular administration, limit the volume at a single injection site to 2 mL; if greater than 2 mL, use multiple injection sites. ( 2.3 ) For intravenous administration, give over a period of 1 to 2 hours in 100 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP through an infusion that is already running. ( 2.3 ) Do not administer ONCASPAR if drug has been frozen, stored at room temperature for more than 48 hours, or shaken or vigorously agitated. ( 16 ) 2.1 Recommended Dosage Patients 21 Years of Age or Younger The recommended dose of ONCASPAR for patients up to and including 21 years of age is 2,500 International Units/m 2 intramuscularly or intravenously no more frequently than every 14 days. Patients More Than 21 Years of Age The recommended dose of ONCASPAR for adult patients more than 21 years of age is 2,000 International Units/m 2 intramuscularly or intravenously no more frequently than every 14 days. 2.2 Recommended Premedication Premedicate patients with acetaminophen, an H-1 receptor blocker (such as diphenhydramine), and an H-2 receptor blocker (such as famotidine) 30-60 minutes prior to administration of ONCASPAR to decrease the risk and severity of both infusion and hypersensitivity reactions [see Warnings and Precautions (5.1) ] . 2.3 Recommended Monitoring and Dosage Modifications for Adverse Reactions Monitor patients at least weekly, with bilirubin, transaminases, glucose and clinical examinations until recovery from the cycle of therapy. If an adverse reaction should occur, modify treatment according to Table 1. Table 1. Dosage Modifications Adverse Reaction Severity Grade 1 is mild, grade 2 is moderate, grade 3 is severe, and grade 4 is life-threatening. Action Infusion Reaction/Hypersensitivity Reaction [see Warnings and Precautions (5.1) ] Grade 1 Reduce the infusion rate by 50% Grade 2 Interrupt the infusion of ONCASPAR Treat the symptoms When symptoms resolve, resume the infusion and reduce the infusion rate by 50% Grade 3 to 4 Discontinue ONCASPAR permanently Thrombosis [see Warnings and Precautions (5.2) ] Uncomplicated deep vein thrombosis Hold ONCASPAR Treat with appropriate antithrombotic therapy Upon resolution of symptoms consider resuming ONCASPAR, while continuing antithrombotic therapy Severe or life-threatening thrombosis Discontinue ONCASPAR permanently Treat with appropriate antithrombotic therapy Pancreatitis [see Warnings and Precautions (5.3) ] Grades 3 to 4 Hold ONCASPAR for elevations in lipase or amylase >3 × ULN until enzyme levels stabilize or are declining Discontinue ONCASPAR permanently if clinical pancreatitis is confirmed Hemorrhage [see Warnings and Precautions (5.5) ] Grade 3 to 4 Hold ONCASPAR Evaluate...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Anaphylaxis and serious hypersensitivity reactions [see Warnings and Precautions (5.1) ] Thrombosis [see Warnings and Precautions (5.2) ] Pancreatitis [see Warnings and Precautions (5.3) ] Glucose intolerance [see Warnings and Precautions (5.4) ] Hemorrhage [see Warnings and Precautions (5.5) ] Hepatotoxicity, including VOD [see Warnings and Precautions (5.6) ] The most common (>5%) grade > 3 adverse reactions with ONCASPAR are hypoalbuminemia, elevated transaminase, febrile neutropenia, hypertriglyceridemia, hyperglycemia, bilirubin increased, pancreatitis, abnormal clotting studies, embolic and thrombotic events, hypersensitivity, sepsis, and infections. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Servier Pharmaceuticals, at 1-800-807-6124 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. The most common grade 3 and 4 adverse reactions (>5%) included: hypoalbuminemia, elevated transaminase, febrile neutropenia, hypertriglyceridemia, hyperglycemia, bilirubin increased, pancreatitis, abnormal clotting studies, embolic and thrombotic events, hypersensitivity, sepsis, and infections. First-Line Treatment of Acute Lymphoblastic Leukemia (ALL) Study CCG-1962 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 race. 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. In Study CCG-1962, detailed safety information was collected for pre-specified adverse reactions identified as asparaginase induced adverse reactions and for grade 3 and 4 nonhematologic 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 2: Table 2. Incidence of Selected Grades 3 and 4 Adverse Reactions in Study CCG-1962 ONCASPAR (n=58) Native E. coli L-Asparaginase (n=59) Infection 3 (5%) 3 (5%) Abnormal Liver Tests 3 (5%) 5 (8%) Elevated Transaminases Aspartate aminotransferase, alanine aminotransferase. 2 (3%) 4 (7%) Hyperbilirubinemia 1 (2%) 1 (2%) Hyperglycemia 3 (5%) 2 (3%) Central Nervous System Thrombosis 2 (3%) 2 (3%) Coagulopathy Prolonged prothrombin time or partial thromboplastin time; or hypofibrinogenemia. 1 (2%) 3 (5%) Pancreatitis 1 (2%) 1 (2%) Allergic Reactions to Asparaginase 1 (2%) 0 The safety of ONCASPAR was investigated in Study DFCI 11-001, an open label, randomized, active-controlled multicenter clinical trial that included 119 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma treated with ONCASPAR in combination with the Dana Farber Cancer Institute (DFCI) ALL Consortium backbone therapy. The median age on enrollment was 4 years (range, 1-18 years). The majority of patients were male (60%) and white (75%). Most patients were considered standard risk ALL (59%) and had B-cell lineage ALL (87%). The median number of doses of ONCASPAR during the study was 16 doses (one dose during induction therapy then administered every two weeks during post induction therapy). The median duration of exposure to ONCASPAR was 8 months. Table 3 summarizes the incidence of selected Grades ≥3 adverse reactions that occurred in 2 or more patients receiving ONCASPAR. Because not all grade 1 and 2 adverse reactions were collected...
Drug Interactions
7 DRUG INTERACTIONS 7.1 Glucocorticoids Pegaspargase may increase the risk of glucocorticoid-induced toxicities, including osteonecrosis through a potential increase in exposure of dexamethasone [see Adverse Reactions (6.3) ] .
Contraindications
4 CONTRAINDICATIONS ONCASPAR is contraindicated in patients with a: History of serious hypersensitivity reactions, including anaphylaxis, to ONCASPAR or to any of the excipients [see Warnings and Precautions (5.1) ] . History of serious thrombosis with prior L-asparaginase therapy [see Warnings and Precautions (5.2) ] . History of pancreatitis, including pancreatitis related to prior L-asparaginase therapy [see Warnings and Precautions (5.3) ] . History of serious hemorrhagic events with prior L-asparaginase therapy [see Warnings and Precautions (5.5) ] . Severe hepatic impairment [see Warnings and Precautions (5.6) ] . History of serious hypersensitivity reactions to ONCASPAR. ( 4 ) History of serious thrombosis with prior L-asparaginase therapy. ( 4 ) History of pancreatitis with prior L-asparaginase therapy. ( 4 ) History of serious hemorrhagic events with prior L-asparaginase therapy. ( 4 ) Severe hepatic impairment. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk summary Based on published literature studies with L-asparaginase in pregnant animals, ONCASPAR can cause fetal harm when administered to a pregnant woman. There are no available data on ONCASPAR use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Published literature studies in pregnant animals suggest asparagine depletion may cause harm to the animal offspring (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Animal Data Animal reproduction studies have not been conducted with ONCASPAR to evaluate its effect on reproduction and fetal development. Published literature studies in which pregnant rabbits were administered L-asparaginase or pregnant rats were deprived of dietary asparagine suggested harm to the animal offspring.
Overdosage
10 OVERDOSAGE Three patients received 10,000 International Units/m 2 of ONCASPAR as an intravenous infusion. One patient experienced a slight increase in liver enzymes. A second patient developed a rash 10 minutes after the start of the infusion, which was controlled with the administration of an antihistamine and by slowing down the infusion rate. A third patient did not experience any adverse reactions. There is no specific antidote for ONCASPAR overdosage. In case of overdose, monitor patients closely for signs and symptoms of adverse reactions, and appropriately manage with symptomatic and supportive treatment.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING ONCASPAR (pegaspargase) injection is supplied as a sterile, clear, colorless, preservative-free solution in Type I single-dose vial containing 3,750 International Units of pegaspargase per 5 mL (750 International Units per mL) solution (NDC 72694-954-01). Store ONCASPAR refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not shake or freeze product . Unopened vials may be stored at room temperature (15°C to 25°C [59°F to 77°F]) for no more than 48 hours.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.