Pegaspargase is an asparagine specific enzyme that is indicated for the first-line treatment of acute lymphoblastic leukemia (ALL) in adults and pediatric patients and ALL in adults and pediatric patients who experienced hypersensitivity to native forms of L-asparaginase. It is used in combination with multi-agent chemotherapy. Use of pegaspargase is contraindicated in patients with severe hepatic impairment, a history of pancreatitis, or who have had a serious thrombosis or hemorrhagic event related to prior L-asparaginase therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Pegaspargase is available as a 3,750 units/5 mL (750 units/mL) solution in a single-dose vial.
-Do not administer if the vial has been shaken or vigorously agitated, frozen, or stored at room temperature for more than 48 hours.
-Premedication with acetaminophen, an H1-receptor blocker (e.g., diphenhydramine), and an H2-receptor blocker (e.g., famotidine) is recommended prior to each dose.
Intravenous Administration
Dilution:
-Dilute the calculated dose of pegaspargase in 100 mL of 0.9% sodium chloride injection or 5% dextrose injection; discard any unused portion left in a vial.
-Storage after dilution: Use immediately or store up to 48 hours in the refrigerator (2 to 8 degrees C; 36 to 46 degrees F). Protect from light; do not shake or freeze.
Intravenous (IV) Infusion:
-After dilution, immediately administer the diluted admixture IV over 1 to 2 hours into a running infusion of 0.9% sodium chloride injection or 5% dextrose injection, respectively.
-Do not infuse other drugs through the same IV line during the pegaspargase infusion.
-For 1 hour after administration, monitor patients for signs or symptoms of infusion or hypersensitivity reactions; therapy interruption, infusion rate reduction, or permanent discontinuation may be necessary in patients who develop a reaction.
Intramuscular Administration
Intramuscular injection:
-No vial reconstitution or dilution is necessary.
-Administer intramuscularly.
-Do not administer more than 2 mL at a single injection site. If the volume is greater than 2 mL, administer in multiple injection sites.
-For 1 hour after administration, monitor patients for signs or symptoms of hypersensitivity reactions; therapy interruption or permanent discontinuation may be necessary in patients who develop a reaction.
Severe pancreatitis occurred in 1% to 24% of patients who received pegaspargase in clinical studies; fatal cases of hemorrhagic or necrotizing pancreatitis have been reported. Advise patients to report symptoms of pancreatitis. Hold pegaspargase and obtain serum amylase and/or lipase levels if pancreatitis is suspected; permanently discontinue pegaspargase if pancreatitis is confirmed. Grade 3 and 4 pancreatitis was reported in 2% of patients (age range, 1 to 9 years) with previously untreated, standard-risk ALL who received pegaspargase as part of multi-agent chemotherapy (n = 58) in a randomized study. Grade 3 or higher pancreatitis, increased amylase (hyperamylasemia), and/or lipase levels occurred in 24% of patients (age range, 1 to 18 years) with newly diagnosed ALL or lymphoblastic lymphoma who received pegaspargase in combination with multi-agent chemotherapy (n = 119) in another randomized trial. Incidences of grade 1 and 2 adverse reactions were not collected prospectively in these trials. In pooled results from 5 clinical trials, pancreatitis was reported in 1% of patients with relapsed ALL who received pegaspargase as a single-agent or in combination with chemotherapy (n = 174). Additionally, pancreatitis and pancreatic cyst were reported in postmarketing surveillance of pegaspargase. In one series of 50 children with ALL treated with pegaspargase, 9 patients (18%) were diagnosed with pancreatitis; all had prior therapy with native L-asparaginase. Symptoms associated with pancreatitis appeared within a median 15 days from pegaspargase administration; grade 3 or 4 toxicities included hyperamylasemia and hyperlipasemia, pancreatic inflammation, and pseudocyst. One patient also developed an increased ammonia level and encephalopathy. Six patients became symptomatic after their initial dose. Hyperammonemia was reported in postmarketing surveillance of pegaspargase.
Severe hyperglycemia has been reported in 3% to 24% of patients who received pegaspargase therapy in clinical trials. Advise patients to report symptoms of hyperglycemia (e.g., excessive thirst). Monitor blood glucose in all patients receiving pegaspargase at least weekly until recovery from the cycle of therapy. Grade 3 and 4 hyperglycemia occurred in 5% of patients (age range, 1 to 9 years) with previously untreated, standard-risk ALL who received pegaspargase intramuscularly as part of multi-agent chemotherapy (n = 58) in a randomized study. Grade 3 or higher hyperglycemia was reported in 24% of patients (age range, 1 to 18 years) with newly diagnosed ALL or lymphoblastic lymphoma who received pegaspargase in combination with multi-agent chemotherapy (n = 119) in another randomized trial. Incidences of grade 1 and 2 adverse reactions were not collected prospectively in these trials. In pooled results from 5 clinical trials, hyperglycemia requiring insulin therapy was reported in 3% of patients with relapsed ALL who received pegaspargase as a single-agent or in combination with chemotherapy (n = 174). Additionally, hyperglycemia was reported in postmarketing surveillance of pegaspargase.
Antibody formation occurred in 2% to 19% of patients who received pegaspargase in 2 clinical trials. High-titer antibody formation occurred in 2%, 10%, and 11% of patients (age range, 1.1 to 9.9 years) with previously untreated ALL who received pegaspargase with multi-agent chemotherapy during induction (n = 48), delayed intensification 1 (n = 50) and delayed intensification 2 (n = 44) therapy, respectively, in a randomized trial. Antibody formation occurred in 19% of patients (age range, 1 to 18 years) with previously untreated ALL or lymphoblastic lymphoma who received pegaspargase in combination with chemotherapy (n = 100) in another randomized trial; anti-PEG antibodies were found in all but one of these patients. The presence of anti-drug antibodies correlated with cases of hypersensitivity reactions.
Severe, life-threatening hepatotoxicity, including potentially fatal cases of sinusoidal obstruction syndrome (SOS), previously termed veno-occlusive disease (VOD), was reported in patients treated with pegaspargase in combination with standard chemotherapy. Additionally, SOS/VOD and hepatic impairment were reported in postmarketing surveillance of pegaspargase. Obtain liver function tests (LFTs) prior to each dose and then at least weekly during cycles of therapy that include pegaspargase and for 6 weeks after the last pegaspargase dose; increased monitoring is recommended in patients who develop abnormal LFTs. Frequently monitor for signs and symptoms of SOS/VOD (e.g., rapid weight gain, fluid retention with ascites, hepatomegaly, and rapid increase of bilirubin level). Therapy interruption or discontinuation may be necessary in patients who develop severe hepatotoxicity; provide supportive care as indicated. Grade 3 and 4 abnormal liver function tests (5%) including elevated hepatic enzymes (3%) and hyperbilirubinemia (2%) occurred in patients (age range, 1 to 9 years) with previously untreated, standard-risk ALL who received pegaspargase intramuscularly as part of multi-agent chemotherapy (n = 58) in a randomized study. Grade 3 or higher elevated hepatic enzymes (e.g., ALT and AST levels) (66%), hypoalbuminemia (28%), and increased bilirubin level/hyperbilirubinemia (25%) were reported in patients (age range, 1 to 18 years) with newly diagnosed ALL or lymphoblastic lymphoma who received pegaspargase in combination with multi-agent chemotherapy (n = 119) in another randomized trial. Incidences of grade 1 and 2 adverse reactions were not collected prospectively in these trials. In pooled results from 5 clinical trials, elevated hepatic enzymes and hyperbilirubinemia were reported commonly in patients with relapsed ALL who received pegaspargase as a single-agent or in combination with chemotherapy (n = 174).
Thrombotic events including severe thrombosis (4% or less) have been reported in patients who received pegaspargase therapy in clinical trials. In patients who develop an uncomplicated deep vein thrombosis, hold pegaspargase until symptoms resolve; treat with appropriate antithrombotic therapy. Permanently discontinue pegaspargase and treat with appropriate antithrombotic therapy in patients who have a severe or life-threatening thrombosis. Grade 3 and 4 central nervous system thrombosis was reported in 3% of patients (age range, 1 to 9 years) with previously untreated, standard-risk ALL who received pegaspargase intramuscularly as part of multi-agent chemotherapy (n = 58) in a randomized study. Grade 3 or higher embolism or thromboembolism occurred in 8% of patients (age range, 1 to 18 years) with newly diagnosed ALL or lymphoblastic lymphoma who received pegaspargase in combination with multi-agent chemotherapy (n = 119) in another randomized trial. Incidences of grade 1 and 2 adverse reactions were not collected prospectively in these trials. In pooled results from 5 clinical trials, thrombosis was reported in 4% of patients with relapsed ALL who received pegaspargase as a single-agent or in combination with chemotherapy (n = 174). Additionally, thrombosis including superior sagittal sinus thrombosis was reported in postmarketing surveillance of pegaspargase.
Prolonged bleeding time (e.g., increased prothrombin time (PT), increased partial thromboplastin time (PTT), and hypofibrinogenemia) has been reported in patients who received pegaspargase therapy in clinical trials. Evaluate coagulation parameters (e.g., PT/PTT and fibrinogen levels) in patients who have signs or symptoms of bleeding. Consider replacement therapy in patients who develop severe or symptomatic coagulopathy. Discontinue pegaspargase in patients who develop severe or life-threatening bleeding. Grade 3 and 4 coagulopathies occurred in 2% of patients (age range, 1 to 9 years) with previously untreated, standard-risk ALL who received pegaspargase intramuscularly as part of multi-agent chemotherapy (n = 58) in a randomized study. Grade 3 or higher abnormal clotting studies/prolonged bleeding time (e.g., increased active PTT and hypofibrinogenemia) (21%) and bleeding (4%) were reported in patients (age range, 1 to 18 years) with newly diagnosed ALL or lymphoblastic lymphoma who received pegaspargase in combination with multi-agent chemotherapy (n = 119) in another randomized trial. The term bleeding included disseminated intravascular coagulation (DIC), epistaxis, hematoma, intracranial bleeding, melena, esophageal ulcer hemorrhage, small intestine and upper GI bleeding. Incidences of grade 1 and 2 adverse reactions were not collected prospectively in these trials. In pooled results from 5 clinical trials, coagulopathies were reported commonly in patients with relapsed ALL who received pegaspargase as a single-agent or in combination with chemotherapy (n = 174). Additionally, coagulopathy and bleeding including central nervous system/intracranial bleeding were reported in postmarketing surveillance of pegaspargase. Administration of antithrombin III concentrates has been associated with a normalization of the hypercoagulable state.
Severe hypersensitivity reactions have been reported in 2% to 32% of patients who received pegaspargase therapy in clinical trials. Allergic reactions may include bronchospasm, hypotension, laryngeal edema, local erythema or swelling, rash, and urticaria. Premedicate patients with acetaminophen, an H1 receptor blocker (e.g., diphenhydramine), and an H2 receptor blocker (e.g., famotidine) 30 to 60 minutes prior to each dose. Monitor patients for signs or symptoms of allergic reactions for 1 hour after drug administration. Therapy interruption, an infusion rate reduction (when administered IV), or permanent discontinuation may be necessary in patients who develop hypersensitivity or infusion-related reactions. Grade 3 and 4 allergic reaction occurred in 2% of patients (age range, 1 to 9 years) with previously untreated, standard-risk ALL who received pegaspargase intramuscularly as part of multi-agent chemotherapy (n = 58) in a randomized study. Grade 3 or higher hypersensitivity (e.g., anaphylactoid reactions) was reported in 7% of patients (age range, 1 to 18 years) with newly diagnosed ALL or lymphoblastic lymphoma who received pegaspargase in combination with multi-agent chemotherapy (n = 119) in another randomized trial. Incidences of grade 1 and 2 adverse reactions were not collected prospectively in these trials. In pooled results from 5 clinical trials, allergic reactions occurred in 32% of patients who had previously had an allergic reaction to E. coli L-asparaginase (n = 62) and 10% of patients who had not previously had an allergic reaction to E. coli L-asparaginase (n = 112) in patients with relapsed ALL who received pegaspargase as a single agent or in combination with multi-agent chemotherapy. Additionally, anaphylactic shock and hypersensitivity reactions were reported in postmarketing surveillance of pegaspargase.
Febrile neutropenia was reported in 40% of patients (age range, 1 to 18 years) with newly diagnosed ALL or lymphoblastic lymphoma who received pegaspargase in combination with multi-agent chemotherapy (n = 119) in another randomized trial.
Grade 3 or higher hypertriglyceridemia was reported in 30% of patients (age range, 1 to 18 years) with newly diagnosed ALL or lymphoblastic lymphoma who received pegaspargase in combination with multi-agent chemotherapy (n = 119) in a randomized trial. Increased blood cholesterol level/hypercholesterolemia was reported in postmarketing surveillance of pegaspargase.
Osteonecrosis was reported in postmarketing surveillance of pegaspargase.
Infection has been reported in patients who received pegaspargase therapy in clinical trials. Grade 3 and 4 infection occurred in 5% of patients (age range, 1 to 9 years) with previously untreated, standard-risk ALL who received pegaspargase intramuscularly as part of multi-agent chemotherapy (n = 58) in a randomized study. Grade 3 or higher pneumonia (7%) including pneumonitis, sepsis (6%), and fungal infection (3%) were reported in patients (age range, 1 to 18 years) with newly diagnosed ALL or lymphoblastic lymphoma who received pegaspargase in combination with multi-agent chemotherapy (n = 119) in another randomized trial.
Grade 3 or higher diarrhea was reported in 5% of patients (age range, 1 to 18 years) with newly diagnosed ALL or lymphoblastic lymphoma who received pegaspargase in combination with multi-agent chemotherapy (n = 119) in a randomized trial. The term diarrhea included colitis, neutropenic colitis, and enterocolitis.
Use of pegaspargase is contraindicated in patients who have had a serious hypersensitivity reaction to the product or any of its excipients. Administer pegaspargase in a clinical setting that has resuscitation equipment and other treatment necessary to treat anaphylaxis (e.g., epinephrine, oxygen, IV steroids, and antihistamines). Premedicate patients with acetaminophen, an H1 receptor blocker (e.g., diphenhydramine), and an H2 receptor blocker (e.g., famotidine) 30 to 60 minutes prior to each dose. Monitor patients for signs or symptoms of hypersensitivity or infusion-related reactions for 1 hour after drug administration. Therapy interruption, an infusion rate reduction (when administered IV), or permanent discontinuation may be necessary in patients who develop hypersensitivity or infusion-related reaction.
Use of pegaspargase is contraindicated in patients who have a history of pancreatitis. Advise patients to report symptoms of pancreatitis (e.g., severe abdominal pain). Hold pegaspargase and obtain serum amylase and/or lipase levels if pancreatitis is suspected; permanently discontinue pegaspargase if pancreatitis is confirmed.
Use of pegaspargase is contraindicated in patients who have a history of serious bleeding during previous L-asparaginase therapy. Evaluate coagulation parameters (e.g., prothrombin time/partial thromboplastin time and fibrinogen level) in patients who have signs or symptoms of bleeding. Consider replacement therapy in patients who develop severe or symptomatic coagulopathy. Discontinue pegaspargase in patients who develop severe or life-threatening bleeding.
Use of pegaspargase is contraindicated in patients who have a history of serious thrombosis during previous L-asparaginase therapy. Thromboembolism including sagittal sinus thrombosis has been reported with pegaspargase therapy. In patients who develop an uncomplicated deep vein thrombosis, hold pegaspargase until symptoms resolve; treat with appropriate antithrombotic therapy. Permanently discontinue pegaspargase and treat with appropriate antithrombotic therapy in patients who have a severe or life-threatening thrombosis.
Advise patients to report symptoms of hyperglycemia (e.g., excessive thirst). Monitor blood glucose in all patients receiving pegaspargase at least weekly until recovery from the cycle of therapy.
Use of pegaspargase is contraindicated in patients who have a history of severe hepatic disease/impairment. Obtain liver function tests (LFTs) prior to each dose and then at least weekly during cycles of therapy that include pegaspargase and for 6 weeks after the last pegaspargase dose; increased monitoring is recommended in patients who develop abnormal LFTs. Frequently monitor for signs and symptoms of hepatic veno-occlusive disease (e.g., rapid weight gain, fluid retention with ascites, hepatomegaly, and rapid increase of bilirubin level). Therapy interruption or discontinuation may be necessary in patients who develop severe hepatotoxicity; provide supportive care as indicated.
Pegaspargase may cause fetal harm when administered during pregnancy, based on published literature reports in animals. Females of reproductive potential should avoid becoming pregnant while taking pegaspargase. Advise pregnant women of the potential risk to the fetus. There are published literature reports of fetal toxicity when pregnant rabbits received L-asparaginase or were deprived of dietary asparagine.
Counsel patients about the reproductive risk and contraception requirements during pegaspargase therapy. Pregnancy testing should be performed in women of reproductive potential prior to initiating therapy. These women should use effective non-hormonal contraception during therapy and for 3 months after the final pegaspargase dose. The concomitant use of pegaspargase and hormonal contraceptives is not recommended due to a potential for reduced contraceptive efficacy. Discuss the potential hazard to the fetus if a patient becomes pregnant while taking this drug.
It is not known if pegaspargase is secreted in human milk or if it has effects on the breastfed child or on milk production. Because there is a potential for adverse reactions in a breastfed child from pegaspargase, women should be advised against breast-feeding during pegaspargase therapy and for 1 month after the last dose.
For the treatment of acute lymphocytic leukemia (ALL):
NOTE: The FDA has designated pegaspargase as an orphan drug for the treatment of ALL.
-for the treatment of newly diagnosed ALL, in combination with multi-agent chemotherapy:
Intravenous or Intramuscular Dosage:
Adults older than 21 years: 2,000 units/m2 IV or IM in combination with multi-agent chemotherapy; repeat a single dose no more frequently than every 14 days. Premedicate patients with acetaminophen, an H1 receptor blocker (e.g., diphenhydramine), and an H2 receptor blocker (e.g., famotidine) 30 to 60 minutes prior to each dose. Therapy interruption or discontinuation may be necessary in patients who develop severe toxicity.
Adults 21 years and younger: 2,500 units/m2 IV or IM in combination with multi-agent chemotherapy; repeat a single dose no more frequently than every 14 days. Premedicate patients with acetaminophen, an H1 receptor blocker (e.g., diphenhydramine), and an H2 receptor blocker (e.g., famotidine) 30 to 60 minutes prior to each dose. Therapy interruption or discontinuation may be necessary in patients who develop severe toxicity.
Infants, Children, and Adolescents: 2,500 units/m2 IV or IM in combination with multi-agent chemotherapy; repeat a single dose no more frequently than every 14 days. Premedicate patients with acetaminophen, an H1 receptor blocker (e.g., diphenhydramine), and an H2 receptor blocker (e.g., famotidine) 30 to 60 minutes prior to each dose. Therapy interruption or discontinuation may be necessary in patients who develop severe toxicity. The rate of depleted serum asparagine concentrations to 1 micromol or less and 3-year event-free survival rates were similar in pediatric patients aged 1 to 9 years with previously untreated, standard-risk ALL who received pegaspargase or native E. coli L-asparaginase intramuscularly as part of multi-agent chemotherapy in a multicenter, randomized study (n = 118; Study CCG-1962). Pegaspargase has been evaluated in pediatric patients aged 1 month to 17 years in clinical trials.
-for the treatment of ALL in patients who had hypersensitivity to native forms of L-asparaginase, in combination with multi-agent chemotherapy:
Intravenous or Intramuscular Dosage:
Adults older than 21 years: 2,000 units/m2 IV or IM in combination with multi-agent chemotherapy; repeat a single dose no more frequently than every 14 days. Premedicate patients with acetaminophen, an H1 receptor blocker (e.g., diphenhydramine), and an H2 receptor blocker (e.g., famotidine) 30 to 60 minutes prior to each dose. Therapy interruption or discontinuation may be necessary in patients who develop severe toxicity. The re-induction response rate was 50% in patients with relapsed acute leukemia (n = 42; ALL, n = 39) and a prior hypersensitivity to native E. coli L-asparaginase who received pegaspargase as a single-agent or in combination with multi-agent chemotherapy in 4 studies. The complete response rate was 36%.
Adults 21 years and younger: 2,500 units/m2 IV or IM in combination with multi-agent chemotherapy; repeat a single dose no more frequently than every 14 days. Premedicate patients with acetaminophen, an H1 receptor blocker (e.g., diphenhydramine), and an H2 receptor blocker (e.g., famotidine) 30 to 60 minutes prior to each dose. Therapy interruption or discontinuation may be necessary in patients who develop severe toxicity. The re-induction response rate was 50% in patients with relapsed acute leukemia (n = 42; ALL, n = 39) and a prior hypersensitivity to native E. coli L-asparaginase who received pegaspargase as a single-agent or in combination with multi-agent chemotherapy in 4 studies. The complete response rate was 36%.
Infants, Children, and Adolescents: 2,500 units/m2 IV or IM in combination with multi-agent chemotherapy; repeat a single dose no more frequently than every 14 days. Premedicate patients with acetaminophen, an H1 receptor blocker (e.g., diphenhydramine), and an H2 receptor blocker (e.g., famotidine) 30 to 60 minutes prior to each dose. Therapy interruption or discontinuation may be necessary in patients who develop severe toxicity. The re-induction response rate was 50% in patients with relapsed acute leukemia (n = 42; ALL, n = 39) and a prior hypersensitivity to native E. coli L-asparaginase who received pegaspargase as a single-agent or in combination with multi-agent chemotherapy in 4 studies. The complete response rate was 36%. Pegaspargase has been evaluated in pediatric patients aged 1 month to 17 years in clinical trials.
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Infusion Reaction or Hypersensitivity Reaction
Grade 1 toxicity: If pegaspargase is administered via the IV route, reduce the infusion rate by 50%.
Grade 2 toxicity: Hold therapy and treat symptoms. If pegaspargase is administered via the IV route, resume the infusion at a 50% reduced infusion rate when symptoms resolve.
Grade 3 or 4 toxicity: Permanently discontinue pegaspargase.
Bleeding
Grade 3 or 4 toxicity: Hold therapy and evaluate the patient for coagulopathy; consider clotting factor replacement as necessary. Resume pegaspargase at the next scheduled dose if bleeding is controlled.
Pancreatitis
Grade 3 or 4 toxicity: Hold therapy if increased lipase or amylase levels greater than 3-times the ULN occur; resume therapy when enzyme levels stabilize or decline. Permanently discontinue pegaspargase if clinical pancreatitis is confirmed.
Thromboembolism
Uncomplicated deep vein thrombosis: Hold pegaspargase and treat with appropriate antithrombotic therapy. Consider resuming therapy when symptoms resolve; continue antithrombotic therapy.
Severe or life-threatening thrombosis: Permanently discontinue pegaspargase; treat with appropriate antithrombotic therapy.
Maximum Dosage Limits:
-Adults
Older than 21 years: 2,000 units/m2 IV or IM repeated no sooner than every 14 days.
21 years and younger: 2,500 units/m2 IV or IM repeated no sooner than every 14 days.
-Geriatric
2,000 units/m2 IV or IM repeated no sooner than every 14 days.
-Adolescents
2,500 units/m2 IV or IM repeated no sooner than every 14 days.
-Children
2,500 units/m2 IV or IM repeated no sooner than every 14 days.
-Infants
2,500 units/m2 IV or IM repeated no sooner than every 14 days.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in baseline mild or moderate hepatic impairment are not available; it appears that no dosage adjustments are needed. Use of pegaspargase in patients with a history of severe hepatic impairment is contraindicated.
Treatment-Related Hepatotoxicity
Total bilirubin level greater than 3- to 10-times the upper limit of normal (ULN): Hold pegaspargase; resume therapy when the total bilirubin levels decrease to 1.5-times the ULN or less.
Total bilirubin level greater than 10-times the ULN: Discontinue pegaspargase; do not make up for missed doses.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Albuterol; Budesonide: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Azelastine; Fluticasone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Beclomethasone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Betamethasone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Budesonide: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Budesonide; Formoterol: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciclesonide: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Corticosteroids: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Cortisone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Cytarabine, ARA-C: (Major) Acute pancreatitis has been reported in patients being treated with cytarabine who have had prior treatment with L-asparaginase. This may be schedule dependent. L-asparaginase may have schedule-dependent synergy and antagonism with high-dose cytarabine. Similar reactions may occur with pegaspargase.
Deflazacort: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Desogestrel; Ethinyl Estradiol: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Dexamethasone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Dienogest; Estradiol valerate: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Drospirenone: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Drospirenone; Estetrol: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Drospirenone; Estradiol: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Drospirenone; Ethinyl Estradiol: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Estradiol; Levonorgestrel: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Estradiol; Norethindrone: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Estradiol; Norgestimate: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Ethinyl Estradiol; Norelgestromin: (Major) Avoid the concomitant use of pegaspargase and hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose. (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Ethinyl Estradiol; Norgestrel: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Etonogestrel: (Major) Avoid the concomitant use of pegaspargase and hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Etonogestrel; Ethinyl Estradiol: (Major) Avoid the concomitant use of pegaspargase and hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose. (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Fludrocortisone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Flunisolide: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Fluticasone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Fluticasone; Salmeterol: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Fluticasone; Vilanterol: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Formoterol; Mometasone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Hydrocortisone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Leuprolide; Norethindrone: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Levonorgestrel: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Levonorgestrel; Ethinyl Estradiol: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Methotrexate: (Major) L-Asparaginase with methotrexate has shown both therapeutic synergistic and antagonistic effects depending upon the schedule of administration of these agents. When methotrexate is given 3-24 hours prior to L-Asparaginase Escherichia coli, the L-asparaginase blocks the antifolate effects of methotrexate and decreases methotrexate toxicity. If L-asparaginase is given prior to methotrexate, the efficacy of methotrexate is decreased. This could be due to inhibition of protein synthesis preventing progression to the S-phase of the cell cycle. Alternatively, L-asparaginase pretreatment may inhibit methotrexate polyglutamation, which is required for intracellular retention of methotrexate. Cells are refractory to methotrexate for up to 10 days following a single dose of L-asparaginase. During the period following L-asparaginase protein inhibition, there is a period of increased DNA synthesis that leads to increased sensitivity to methotrexate. Since the active component of pegaspargase is L-asparaginase, the same drug-drug interactions reported with L-asparaginase would be expected with pegaspargase. It is recommended to give L-asparaginase or pegaspargase at least 10-14 days prior to methotrexate or shortly after methotrexate administration.
Methylprednisolone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Mometasone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Non-oral combination contraceptives: (Major) Avoid the concomitant use of pegaspargase and hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Norethindrone: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Norethindrone; Ethinyl Estradiol: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Norgestimate; Ethinyl Estradiol: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Norgestrel: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Olopatadine; Mometasone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Oral Contraceptives: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Prednisolone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Prednisone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Segesterone Acetate; Ethinyl Estradiol: (Major) Avoid the concomitant use of pegaspargase and hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose. (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose.
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Triamcinolone: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Vincristine Liposomal: (Major) Administration of pegaspargase concurrently or prior to vincristine may result in decreased hepatic metabolism of vincristine and cause additive neurotoxicity. Administration of L-asparaginase after vincristine may lessen this effect; vincristine should be given 12 to 24 hours prior to L-asparaginase or pegaspargase.
Vincristine: (Major) Administration of pegaspargase concurrently or prior to vincristine may result in decreased hepatic metabolism of vincristine and cause additive neurotoxicity. Administration of L-asparaginase after vincristine may lessen this effect; vincristine should be given 12 to 24 hours prior to L-asparaginase or pegaspargase.
Zonisamide: (Moderate) Concomitant use of zonisamide with pegaspargase may increase the risks of hyperammonemia and encephalopathy. Monitor serum ammonia concentrations if signs or symptoms of encephalopathy occur. Hyperammonemia resulting from zonisamide resolves when zonisamide is discontinued and may resolve or decrease in severity with a decrease of the daily dose.
Pegaspargase contains an Escherichia (E.) coli-derived asparagine specific enzyme as a conjugate of L-asparaginase (L-asparagine amidohydrolase) and monomethoxypolyethylene glycol (mPEG). L-asparaginase is a tetrameric enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. The depletion of plasma L-asparagine causes selective killing of leukemic cells that are deficient in asparagine synthetase and depend on exogenous L-asparagine for survival.
Pegaspargase is given intramuscularly (IM) or intravenously (IV). Following a single IM dose of pegaspargase 2,500 units/m2, the mean steady-state volume of distribution was 1.86 L/m2, the mean elimination half-life was 5.8 days, and the clearance was 0.17 L/m2/day in pediatric patients with newly diagnosed standard-risk acute lymphoblastic leukemia (ALL) (n = 57). Following a single IV infusion of pegaspargase 2,500 units/m2, the mean steady-state volume of distribution was 2 L, the mean elimination half-life was 5.3 days, and the clearance was 0.2 L/day in patients with newly diagnosed high-risk B-precursor ALL (n = 47). Additionally, the mean cerebral spinal fluid asparagine concentrations decreased from a pretreatment concentration of 0.6 micrograms (mcg)/mL (n = 20) to 0.2 mcg/mL on day 4 (n = 41) and remained decreased after 25 days following IV pegaspargase administration.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
The mean Cmax and AUC values were 1.6 units/mL and 16.6 units x day/mL, respectively, following a single IV infusion of pegaspargase 2,500 units/m2 in patients with newly diagnosed high-risk B-precursor ALL (n = 47).
Intramuscular Route
The relative bioavailability of pegaspargase was 82% after the first IM dose and 98% after repeat dosing. The mean Cmax of approximately 1 unit/mL occurred at 5 days (Tmax) following a single IM dose of pegaspargase 2,500 units/m2 in pediatric patients with newly diagnosed standard-risk acute lymphoblastic leukemia (n = 45 to 52). The mean half-life of absorption from the IM site was 1.7 days.