Calaspargase pegol-mknl is an asparagine specific enzyme that is indicated in combination with multi-agent chemotherapy for the treatment of acute lymphoblastic leukemia in patients 1 month to 21 years of age. Use of calaspargase pegol is contraindicated in patients with severe liver impairment, serious hypersensitivity reactions to pegylated L-asparaginase, serious thrombosis during L-asparaginase therapy, or serious pancreatitis related to previous L-asparaginase treatment.
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.
Intravenous Administration
-Calaspargase pegol 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.
Dilution:
-Dilute the calculated dose of calaspargase pegol in 100 mL of 0.9% sodium chloride injection or 5% dextrose injection; discard any unused portion left in a vial.
-Storage after dilution: Store up to 4 hours at room temperature (15 to 25 degrees C; 59 to 77 degrees F) or up to 24 hours when refrigerated (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 hour 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 calaspargase pegol 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.
Pancreatitis occurred in 12% to 16% of patients who received calaspargase pegol in clinical studies. Hemorrhagic or necrotizing pancreatitis has been reported with other asparaginase therapy. Advise patients to report symptoms of pancreatitis. Assess serum amylase and/or lipase levels to identify early signs of pancreatic inflammation. Hold calaspargase pegol therapy if pancreatitis is suspected; permanently discontinue therapy if pancreatitis is confirmed. Grade 3 or higher pancreatitis (including hyperamylasemia and increased lipase level) was reported in 18% of patients (age range, 1 to 20 years) with B-cell lineage acute lymphoblastic leukemia who received calaspargase pegol in combination with multi-agent chemotherapy (n = 118) in a randomized trial. One patient died due to multi-organ failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst. The incidence of grade 1 and 2 adverse reactions was not collected prospectively in this trial.
Serious thromboembolism including sagittal sinus thrombosis occurred in 9% to 12% of patients who received calaspargase pegol in clinical studies. In patients who develop an uncomplicated deep vein thrombosis, hold calaspargase pegol until symptoms resolve; treat with appropriate antithrombotic therapy. Permanently discontinue calaspargase pegol and treat with appropriate antithrombotic therapy in patients who have a severe or life-threatening thrombosis. Grade 3 or 4 embolic/thrombotic events were reported in 8% of patients (age range, 1 to 20 years) with B-cell lineage acute lymphoblastic leukemia who received calaspargase pegol in combination with multi-agent chemotherapy (n = 118) in a randomized trial. The incidence of grade 1 and 2 adverse reactions was not collected prospectively in this trial. The term embolic/thrombotic events included device-related thrombosis, disseminated intravascular coagulation (DIC), embolism, intracardiac thrombus, intracranial venous sinus thrombosis, pulmonary embolism, superior sagittal sinus thrombosis, and venous thrombosis.
Bleeding associated with prolonged bleeding time (e.g., increased prothrombin time (PT), increased partial thromboplastin time (PTT), and hypofibrinogenemia) occurred with calaspargase pegol therapy in clinical trials. Evaluate coagulation parameters (e.g., PT/PTT and fibrinogen level) in patients who have signs or symptoms of bleeding. Consider replacement therapy in patients who develop severe or symptomatic coagulopathy. Grade 3 or 4 bleeding (4%) and abnormal clotting studies (14%) were reported in patients (age range, 1 to 20 years) with B-cell lineage acute lymphoblastic leukemia who received calaspargase pegol in combination with multi-agent chemotherapy (n = 118) in a randomized trial. The incidence of grade 1 and 2 adverse reactions was not collected prospectively in this trial. The term bleeding included disseminated intravascular coagulation, epistaxis, hematoma, intracranial bleeding, melena, bleeding esophageal ulcer, small intestinal hemorrhage, and upper GI bleeding. The term abnormal clotting studies included prolonged activated partial thromboplastin time and decreased fibrinogen level.
Hepatotoxicity including hypoalbuminemia occurred with calaspargase pegol therapy in clinical trials. Additionally, veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) was reported in postmarketing surveillance. Obtain liver function tests (LFTs) prior to each dose, at least weekly during cycles of therapy that include calaspargase pegol, and through 6 weeks after the last calaspargase pegol dose. Monitor patients for signs and symptoms of hepatic VOD/SOS such as rapid weight gain, fluid retention with ascites, hepatomegaly, and a rapid increase in bilirubin levels. Increase the frequency of LFT and VOD/SOS monitoring in patients who develop abnormal LFTs. Therapy interruption or discontinuation may be necessary in patients who develop severe hepatotoxicity; provide supportive care as indicated. Grade 3 or 4 elevated hepatic enzymes/transaminase levels (52%) and increased bilirubin level/hyperbilirubinemia (20%) were reported in patients (age range, 1 to 20 years) with B-cell lineage acute lymphoblastic leukemia who received calaspargase pegol in combination with multi-agent chemotherapy (n = 118) in a randomized trial. The term elevated transaminase levels included increased AST and ALT levels.
Infection including grade 3 or 4 sepsis (5%), fungal infection/systemic candidiasis (3%), and pneumonia/pneumonitis (3%) were reported in patients (age range, 1 to 20 years) with B-cell lineage acute lymphoblastic leukemia who received calaspargase pegol in combination with multi-agent chemotherapy (n = 118) in a randomized trial. The incidence of grade 1 and 2 adverse reactions was not collected prospectively in this trial.
Grade 3 or 4 diarrhea was reported in 9% of patients (age range, 1 to 20 years) with B-cell lineage acute lymphoblastic leukemia who received calaspargase pegol in combination with multi-agent chemotherapy (n = 118) in a randomized trial. The incidence of grade 1 and 2 adverse reactions was not collected prospectively in this trial. The term diarrhea included colitis, enterocolitis, and neutropenic colitis.
Grade 3 or 4 dyspnea was reported in 4% of patients (age range, 1 to 20 years) with B-cell lineage acute lymphoblastic leukemia who received calaspargase pegol in combination with multi-agent chemotherapy (n = 118) in a randomized trial. The incidence of grade 1 and 2 adverse reactions was not collected prospectively in this trial. The term dyspnea included hypoxia and respiratory failure.
Grade 3 or 4 arrhythmias and heart failure were each reported in 2% of patients (age range, 1 to 20 years) with B-cell lineage acute lymphoblastic leukemia who received calaspargase pegol in combination with multi-agent chemotherapy (n = 118) in a randomized trial. The incidence of grade 1 and 2 adverse reactions was not collected prospectively in this trial. The term arrhythmia included complete AV block, sinus tachycardia, and ventricular arrhythmias; the term heart failure (cardiac failure) included decreased ejection fraction and left ventricular dysfunction.
Severe hypersensitivity reactions including anaphylactoid reactions occurred in 7% to 21% of patients who received calaspargase pegol in clinical studies. Monitor patients for signs or symptoms of hypersensitivity or infusion-related reactions for 1 hour after drug administration. Therapy interruption, an infusion rate reduction, or permanent discontinuation may be necessary in patients who develop a hypersensitivity or infusion-related reaction; administer appropriate treatment or supportive care as required (e.g., epinephrine, oxygen, IV steroids, and antihistamines). Grade 3 or 4 hypersensitivity/anaphylactoid reaction was reported in 8% of patients (age range, 1 to 20 years) with B-cell lineage acute lymphoblastic leukemia who received calaspargase pegol in combination with multi-agent chemotherapy (n = 118) in a randomized trial. The incidence of grade 1 and 2 adverse reactions was not collected prospectively in this trial.
Antibody formation including new or an increased titer of anti-drug antibodies (ADA) occurred in 15% of patients with B-cell lineage acute lymphoblastic leukemia who received calaspargase pegol in combination with multi-agent chemotherapy (n = 98) in a randomized trial. Most (93%) of patients who developed antibody formation also tested positive for anti-PEG antibodies. ADA formation correlated with the development of hypersensitivity reactions in an immunogenicity study. In this study, hypersensitivity reactions occurred in 80% and 6% of calaspargase pegol-treated patients who had new/increased titer of ADA and no evidence of ADA, respectively; 2 patients with ADA experienced anaphylaxis.
Use of calaspargase pegol is contraindicated in patients who have had a serious pegylated L-asparaginase hypersensitivity reaction. Administer calaspargase pegol 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, or permanent discontinuation may be necessary in patients who develop a hypersensitivity or infusion-related reaction.
Use of calaspargase pegol is contraindicated in patients who have a history of serious pancreatitis during previous L-asparaginase therapy. Pancreatitis has been reported with calaspargase pegol therapy. Monitor blood glucose in all patients at least weekly until recovery from the cycle of therapy; assess serum amylase and/or lipase levels to identify early signs of pancreatic inflammation. Advise patients to report symptoms of pancreatitis (e.g., severe abdominal pain) or hyperglycemia (e.g., excessive thirst). Hold calaspargase pegol therapy if pancreatitis is suspected; permanently discontinue therapy if pancreatitis is confirmed.
Use of calaspargase pegol 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 calaspargase pegol therapy. In patients who develop an uncomplicated deep vein thrombosis, hold calaspargase pegol until symptoms resolve; treat with appropriate antithrombotic therapy. Permanently discontinue calaspargase pegol and treat with appropriate antithrombotic therapy in patients who have a severe or life-threatening thrombosis.
Use of calaspargase pegol is contraindicated in patients with severe hepatic disease/impairment. Obtain liver function tests (LFTs) prior to each dose, at least weekly during cycles of therapy that include calaspargase pegol, and through 6 weeks after the last calaspargase pegol dose. Monitor patients for signs and symptoms of hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) such as rapid weight gain, fluid retention with ascites, hepatomegaly, and a rapid increase in bilirubin levels. Increase the frequency of LFT and VOD/SOS monitoring in patients who develop abnormal LFTs. Therapy interruption or discontinuation may be necessary in patients who develop severe hepatotoxicity; provide supportive care as indicated.
Use of calaspargase pegol is contraindicated in patients who have a history of serious hemorrhagic events during previous L-asparaginase therapy. Bleeding associated with prolonged bleeding time (e.g., increased prothrombin time (PT), increased partial thromboplastin time (PTT), and hypofibrinogenemia) has been reported with calaspargase pegol therapy. Evaluate coagulation parameters (e.g., PT/PTT and fibrinogen level) in patients who have signs or symptoms of bleeding. Consider replacement therapy in patients who develop severe or symptomatic coagulopathy.
Calaspargase pegol may cause fetal harm when administered during pregnancy, based on data from published literature reports in pregnant rabbits who received L-asparaginase. Females of reproductive potential should avoid becoming pregnant while taking calaspargase pegol. Discuss the potential hazard to the fetus if a patient becomes pregnant while taking this drug. Calaspargase pegol has not been evaluated in pregnant women; no evidence of structural abnormalities or embryo-fetal death was observed when calaspargase pegol was administered IV in pregnant rats during organogenesis at doses from 0.2- to 1-times the maximum recommended human dose.
Counsel patients about the reproductive risk and contraception requirements during calaspargase pegol 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 at least 3 months after the final calaspargase pegol dose. The concomitant use of calaspargase pegol and hormonal contraceptives may reduce the effectiveness of the hormonal contraceptives.
It is not known if calaspargase pegol is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because there is a potential for adverse reactions in nursing infants from calaspargase pegol, women should be advised against breast-feeding during calaspargase pegol therapy and for 3 months after the last dose.
For the treatment of acute lymphocytic leukemia (ALL):
NOTE: The FDA has designated calaspargase pegol as an orphan drug for the treatment of ALL.
-for the treatment of ALL, in combination with multi-agent chemotherapy:
Intravenous dosage:
Adults 21 years or younger, Adolescents, Children, and Infants: 2,500 units/m2 IV in combination with multi-agent chemotherapy; repeat a single dose no more frequently than every 21 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. Monitor patients for signs and symptoms of infusion or hypersensitivity reactions. Therapy interruption or discontinuation may be necessary in patients who develop severe toxicity. Depleted serum asparaginase activity has been demonstrated following calaspargase pegol therapy. The nadir of serum asparaginase activity was greater than 0.1 units/mL at weeks 6, 12, 18, 24, and 30 in 99% of patients with B-cell ALL who received calaspargase pegol 2,500 units/m2 IV every 3 weeks in combination with multi-agent chemotherapy (n = 124; median age, 11.5 years; range, 1 to 26 years).
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Infusion Reaction or Hypersensitivity Reaction
Grade 1 toxicity: Reduce the infusion rate by 50%.
Grade 2 toxicity: Hold the infusion and treat symptoms; resume the infusion at a 50% reduced infusion rate when symptoms resolve.
Grade 3 or 4 toxicity: Permanently discontinue calaspargase pegol.
Bleeding
Grade 3 or 4 toxicity: Hold therapy and evaluate the patient for coagulopathy; consider clotting factor replacement as necessary. Resume calaspargase pegol 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 calaspargase pegol if clinical pancreatitis is confirmed.
Thromboembolism
Uncomplicated deep vein thrombosis: Hold calaspargase pegol and treat with appropriate antithrombotic therapy. Consider resuming therapy when symptoms resolve; continue antithrombotic therapy.
Severe or life-threatening thrombosis: Permanently discontinue calaspargase pegol; treat with appropriate antithrombotic therapy.
Maximum Dosage Limits:
-Adults
Older than 21 years: Safety and efficacy have not been established.
21 years or younger: 2,500 units/m2 IV repeated no sooner than every 21 days.
-Geriatric
Safety and efficacy have not been established.
-Adolescents
2,500 units/m2 IV repeated no sooner than every 21 days.
-Children
2,500 units/m2 IV repeated no sooner than every 21 days.
-Infants
2,500 units/m2 IV repeated no sooner than every 21 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 calaspargase in patients with severe hepatic impairment is contraindicated.
Treatment-Related Hepatotoxicity
Total bilirubin level greater than 3- to 10-times the upper limit of normal (ULN): Hold calaspargase pegol; 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 calaspargase pegol; 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
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.
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) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Dienogest; Estradiol valerate: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Drospirenone: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Drospirenone; Estetrol: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Drospirenone; Estradiol: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Drospirenone; Ethinyl Estradiol: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Elagolix; Estradiol; Norethindrone acetate: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Estradiol; Levonorgestrel: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Estradiol; Norethindrone: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Estradiol; Norgestimate: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Ethinyl Estradiol; Norelgestromin: (Major) The concomitant use of calaspargase pegol and hormonal contraceptives may reduce the efficacy of hormonal contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm. (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Ethinyl Estradiol; Norethindrone Acetate: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Ethinyl Estradiol; Norgestrel: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Etonogestrel: (Major) The concomitant use of calaspargase pegol and hormonal contraceptives may reduce the efficacy of hormonal contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Etonogestrel; Ethinyl Estradiol: (Major) The concomitant use of calaspargase pegol and hormonal contraceptives may reduce the efficacy of hormonal contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm. (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Leuprolide; Norethindrone: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Levonorgestrel: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Levonorgestrel; Ethinyl Estradiol: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Non-oral combination contraceptives: (Major) The concomitant use of calaspargase pegol and hormonal contraceptives may reduce the efficacy of hormonal contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Norethindrone: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Norethindrone; Ethinyl Estradiol: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Norgestimate; Ethinyl Estradiol: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Norgestrel: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Oral Contraceptives: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
Relugolix; Estradiol; Norethindrone acetate: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
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) The concomitant use of calaspargase pegol and hormonal contraceptives may reduce the efficacy of hormonal contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm. (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm.
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.
Calaspargase pegol contains an Escherichia (E.) coli-derived asparagine specific enzyme as a conjugate of L-asparaginase (L-asparagine amidohydrolase) and monomethoxypolyethylene glycol (mPEG) with a succinimidyl carbonate (SC) linker. L-asparaginase is a tetrameric enzyme that deaminates asparagine and glutamine resulting in the cell death of lymphoblasts that are deficient in asparagine synthetase and depend on exogenous L-asparagine for survival. Calaspargase pegol uses the identical enzyme and polyethylene glycol moiety as pegaspargase, another pegylated form of E.coli L-asparaginase. However, it differs from pegaspargase by replacing the succinimidyl succinate linker with a SC linker which creates a more stable drug.
Calaspargase pegol is administered intravenously. The volume of distribution was 2.96 L (coefficient of variation (CV), 84.3%), the elimination half-life was 16.1 days (CV, 51.9%), and the clearance was 0.147 L/day (CV, 76.1%) in patients with newly diagnosed high-risk B-precursor acute lymphoblastic leukemia who received a single dose of calaspargase pegol 2,500 units/m2 in combination with a multidrug backbone therapy as induction therapy (n = 43; age range, 1 to 26 years). Additionally, the mean cerebral spinal fluid asparagine concentrations decreased from a pretreatment concentration of 0.8 micrograms (mcg)/mL (n = 10) to 0.2 mcg/mL on day 4 (n = 37) and remained decreased after 25 days.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
The pharmacokinetics of plasma asparaginase are nonlinear following calaspargase pegol administration. The Cmax value was 1.62 L (coefficient of variation (CV), 23%), the median Tmax occurred at 1.17 hours, and the AUC(0 to inf) value was 25.5 days X units/mL (CV, 30.4%) in patients with newly diagnosed high-risk B-precursor acute lymphoblastic leukemia who received a single dose of calaspargase pegol 2,500 units/m2 in combination with a multidrug backbone therapy as induction therapy (n = 43; age range, 1 to 26 years).