Calaspargase Pegol
FDA Drug Information • Also known as: Asparlas
- Brand Names
- Asparlas
- Drug Class
- Asparagine-specific Enzyme [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Calaspargase pegol-mknl contains an asparagine specific enzyme derived from Escherichia coli , as a conjugate of L-asparaginase (L-asparagine amidohydrolase) and monomethoxypolyethylene glycol (mPEG) with a succinimidyl carbonate (SC) linker. The SC linker is a chemically stable carbamate bond between the mPEG moiety and the lysine groups of L-asparaginase. L-asparaginase is a tetrameric enzyme that is produced endogenously by E. coli and consists of identical 34.5 kDa subunits. Approximately 31 to 39 molecules of SC-PEG are linked to L-asparaginase; the molecular weight of each SC-PEG molecule is about 5 kDa. The activity of ASPARLAS is expressed in units (U). ASPARLAS injection is supplied as a clear, colorless, preservative-free, isotonic sterile solution in phosphate-buffered saline, pH 7.3 that requires dilution prior to intravenous infusion. Each vial of ASPARLAS contains 3,750 units in 5 mL of solution. Each milliliter contains 750 units of calaspargase pegol-mknl; 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 Calaspargase Pegol Used For?
1 INDICATIONS AND USAGE ASPARLAS is an asparagine specific enzyme indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia in pediatric and young adult patients age 1 month to 21 years. ( 1.1 ) 1.1 Acute Lymphoblastic Leukemia ASPARLAS is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia in pediatric and young adult patients age 1 month to 21 years.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Recommended Dosage: 2,500 units/m 2 intravenously no more frequently than every 21 days. ( 2.1 ) See Full Prescribing Information for important details regarding dosing modifications and preparation and administration. ( 2.2 , 2.3 , 2.4 ) 2.1 Recommended Dosage The recommended dose of ASPARLAS is 2,500 units/m 2 given intravenously no more frequently than every 21 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 ASPARLAS 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 ASPARLAS Treat the symptoms When symptoms resolve, resume the infusion and reduce the infusion rate by 50% Grade 3 to 4 Discontinue ASPARLAS permanently Pancreatitis [see Warnings and Precautions (5.2) ] Grades 3 to 4 Hold ASPARLAS for elevations in lipase or amylase >3 × upper limit of normal (ULN) until enzyme levels stabilize or are declining Discontinue ASPARLAS permanently if clinical pancreatitis is confirmed Thrombosis [see Warnings and Precautions (5.3) ] Uncomplicated deep vein thrombosis Hold ASPARLAS Treat with appropriate antithrombotic therapy Upon resolution of symptoms consider resuming ASPARLAS, while continuing antithrombotic therapy Severe or life-threatening thrombosis Discontinue ASPARLAS permanently Treat with appropriate antithrombotic therapy Hemorrhage [see Warnings and Precautions (5.4) ] Grade 3 to 4 Hold ASPARLAS Evaluate for coagulopathy and consider clotting factor replacement as needed Resume ASPARLAS with the next scheduled dose if bleeding is controlled Hepatotoxicity [see Warnings and Precautions (5.5) ] Total bilirubin more than 3 times to no more than 10 times the ULN Hold ASPARLAS until total bilirubin is ≤1.5 times the ULN Total bilirubin more than 10 times the ULN Discontinue ASPARLAS and do not make up for missed doses 2.4 Preparation and Administration ASPARLAS is a clear and colorless solution. Visually inspect parenteral drug products for particulate matter, cloudiness, or discoloration prior to administration. If any of these are present, discard the vial. Do not administer if ASPARLAS has been shaken or vigorously agitated, frozen, or stored at room temperature for more than 48...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Warnings and Precautions (5.1) ] Pancreatitis [see Warnings and Precautions (5.2) ] Thrombosis [see Warnings and Precautions (5.3) ] Hemorrhage [see Warnings and Precautions (5.4) ] Hepatotoxicity, including VOD [see Warnings and Precautions (5.5) ] The most common (incidence ≥10%) grade ≥3 adverse reactions were elevated transaminase, bilirubin increased, pancreatitis, and abnormal clotting studies. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Servier Pharmaceuticals LLC 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, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Study DFCI 11-001 The safety of ASPARLAS was investigated in Study DFCI 11-001, an open-label, randomized, active-controlled multicenter clinical trial that treated 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma, with ASPARLAS 2,500 U/m 2 (n=118) or pegaspargase 2,500 U/m 2 (n=119) as part of a Dana-Farber Cancer Institute (DFCI) ALL Consortium backbone therapy. The median age on enrollment was 5 years (range, 1-20 years). The majority of patients were male (62%) and white (70%). Most patients were considered standard risk (SR, 59%) and had B-cell lineage ALL (87%). The median number of doses during the study was 11 doses for ASPARLAS (administered every three weeks) and 16 doses for pegaspargase (administered every two weeks). The median duration of exposure was 8 months for both ASPARLAS and pegaspargase. There was 1 fatal adverse reaction (multi-organ failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst). Table 2 summarizes the incidence of selected grades ≥3 adverse reactions that occurred in 2 or more patients receiving ASPARLAS. Because not all grade 1 and 2 adverse reactions were collected prospectively, only grade 3 and 4 adverse events are presented in Table 2. Table 2: Selected Grades ≥3 Adverse Reactions in Patients Receiving ASPARLAS with Multi-Agent Chemotherapy (Study DFCI 11-001) ASPARLAS or pegaspargase were administered as a component of multi-agent chemotherapy regimens. Adverse Reaction Grouped terms: Elevated transaminase : Alanine aminotransferase increased, Aspartate aminotransferase increased, Transaminases increased; Bilirubin increased : Bilirubin conjugated increased, Blood bilirubin increased; Pancreatitis : Amylase increased, Lipase increased, Pancreatic necrosis, Pancreatitis, Pancreatitis relapsing; Abnormal clotting studies : Activated partial thromboplastin time prolonged, Blood fibrinogen decreased; Diarrhea : Colitis, Diarrhea, Enterocolitis, Neutropenic colitis; Hypersensitivity : Anaphylactic reaction, Drug hypersensitivity, Hypersensitivity; Embolic and thrombotic events SMQ : Device related thrombosis, Disseminated intravascular coagulation, Embolism, Intracardiac thrombus, Intracranial venous sinus thrombosis, Pulmonary embolism, Superior sagittal sinus thrombosis, Thrombosis in device, Venous thrombosis, Venous thrombosis limb; Sepsis : Bacterial sepsis, Sepsis; Dyspnea : Hypoxia, Respiratory failure; Hemorrhages SMQ (excludes laboratory terms): Disseminated intravascular coagulation, Epistaxis, Hematoma, Hemorrhage intracranial, Melena, Esophageal ulcer hemorrhage, Small intestinal hemorrhage, Upper gastrointestinal hemorrhage; Fungal infection : Fungal infection, Hepatic infection fungal, Respiratory tract infection fungal, Splenic infection fungal, Systemic candida; Pneumonia : Lung infection, Pneumonia, Pneumonitis; Arrhythmia : Atrioventricular block complete, Sinus tachycardia, Ventricular arrhythmia; Cardiac failure : Ejection fraction...
Contraindications
4 CONTRAINDICATIONS ASPARLAS is contraindicated in patients with: History of serious hypersensitivity reactions, including anaphylaxis, to pegylated L-asparaginase therapy [see Warnings and Precautions (5.1) ] History of serious pancreatitis during previous L-asparaginase therapy [see Warnings and Precautions (5.2) ] History of serious thrombosis during previous L-asparaginase therapy [see Warnings and Precautions (5.3) ] History of serious hemorrhagic events during previous L-asparaginase therapy [see Warnings and Precautions (5.4) ] Severe hepatic impairment [see Warnings and Precautions (5.5) ] History of serious hypersensitivity reactions to pegylated L-asparaginase. ( 4 ) History of serious thrombosis during L-asparaginase therapy. ( 4 ) History of serious pancreatitis related to previous L-asparaginase treatment. ( 4 ) History of serious hemorrhagic events during previous 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, ASPARLAS can cause fetal harm when administered to a pregnant woman. There are no available data on ASPARLAS use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, intravenous administration of calaspargase pegol-mknl to pregnant rats during organogenesis at doses 0.2 to 1 times the maximum recommended human doses did not result in adverse developmental outcomes. Published literature studies in pregnant rabbits, however, 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 risk of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Animal Data In an embryo-fetal development study, calaspargase pegol-mknl was administered intravenously at doses of 75, 150, and 300 U/kg (0.2, 0.6 and 1 times the maximum recommended human dose, respectively, based on AUC) to pregnant rats during the period of organogenesis. Maternal toxicity of decreased body weight and food consumption was seen at all dose levels resulting in reductions in gravid uterine and placental weights, and slight reductions in fetal body weights. No evidence of structural abnormalities or embryo-fetal mortality were observed in this study at any of the doses tested. Published literature studies in which pregnant rabbits were administered L-asparaginase suggested harm to the animal offspring.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING ASPARLAS (calaspargase pegol-mknl) injection is supplied as a clear, colorless, preservative-free sterile solution in a single-dose vial containing 3,750 units of calaspargase pegol-mknl per 5 mL solution (NDC 72694-515-01). Store ASPARLAS 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.