Oncaspar

Other Antineoplastic Plant Alkaloids and Natural Agents

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.

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 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.[61310]

elevated hepatic enzymes / Delayed / 0-66.0
hypertriglyceridemia / Delayed / 0-30.0
hypoalbuminemia / Delayed / 0-28.0
hyperbilirubinemia / Delayed / 0-25.0
pancreatitis / Delayed / 1.0-24.0
hyperamylasemia / Delayed / 0-24.0
hyperglycemia / Delayed / 3.0-24.0
prolonged bleeding time / Delayed / 0-21.0
coagulopathy / Delayed / 0-21.0
thromboembolism / Delayed / 0-8.0
anaphylactoid reactions / Rapid / 0-7.0
infection / Delayed / 0-7.0
diarrhea / Early / 0-5.0
thrombosis / Delayed / 0-4.0
bleeding / Early / 0-4.0
GI bleeding / Delayed / Incidence not known
disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
intracranial bleeding / Delayed / Incidence not known
laryngeal edema / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
osteonecrosis / Delayed / Incidence not known
colitis / Delayed / Incidence not known
enterocolitis / Delayed / Incidence not known

neutropenia / Delayed / 0-40.0
antibody formation / Delayed / 2.0-19.0
encephalopathy / Delayed / Incidence not known
hyperammonemia / Delayed / Incidence not known
melena / Delayed / Incidence not known
hematoma / Early / Incidence not known
erythema / Early / Incidence not known
hypotension / Rapid / Incidence not known
infusion-related reactions / Rapid / Incidence not known
hypercholesterolemia / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known

epistaxis / Delayed / Incidence not known
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known

Oncaspar

Rx

Asparagine specific enzyme
Used in combination with multi-agent chemotherapy for the treatment of acute lymphoblastic leukemia in pediatric patients and adults
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

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.[61310]

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.

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.

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%.

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%.[61310]

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.[61310]

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 HepatotoxicityTotal 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.[61310]

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

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.
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.
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.

Oncaspar Intramuscular Inj Sol: 1mL, 750IU
Oncaspar Intravenous Inj Sol: 1mL, 750IU

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.

2,000 units/m2 IV or IM repeated no sooner than every 14 days.

2,500 units/m2 IV or IM repeated no sooner than every 14 days.

2,500 units/m2 IV or IM repeated no sooner than every 14 days.

2,500 units/m2 IV or IM repeated no sooner than every 14 days.

Safety and efficacy have not been established.

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.[61310]

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.[61310]
Affected cytochrome P450 isoenzymes and drug transporters: none

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).[61310]

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.[61310]

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.[61310]

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.[61310]