Erwinaze

Other Antineoplastic Plant Alkaloids and Natural Agents

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Erwinase
Reconstitution:
Slowly inject 1 or 2 mL of preservative free sterile 0.9% Sodium Chloride injection against the inner vial wall. Do not forcefully inject solution directly onto or into the powder.
If 1 mL of 0.9% Sodium Chloride is used, the resultant concentration is 10,000 International Units per mL.
If 2 mL of 0.9% Sodium Chloride is used, the resultant concentration is 5,000 International Units per mL.
Dissolve contents by gentle mixing or swirling; do not shake or invert the vial.
The reconstituted solution should be clear and colorless; discard if any visible particles or protein aggregates are present.
Storage: Do not freeze or refrigerate the reconstituted solution. Withdraw the calculated dose within 15 minutes of reconstitution; discard any unused portion of the vial(s).
Dilution:
Withdraw the calculated dose/volume from the reconstituted vial using a polypropylene syringe.
Slowly inject the dose into an IV infusion bag containing 100 mL of 0.9% Sodium Chloride injection that has been acclimatized to room temperature; do not shake or squeeze the IV bag.
Intravenous infusion:
Infuse the diluted solution over 1 to 2 hours; administer within 4 hours from vial reconstitution.
Do not infuse other IV drugs through the same line.

Limit the volume to 2 mL per injection site; multiple injection sites may be needed.
Discard any unused portion of the vial(s).
Divide the doses equally into multiple syringes if the volume to be administered is greater than 2 mL.
Rotate injection sites and do not inject into scar tissue or areas that are reddened, inflamed, or swollen.
Erwinase
Erwinase is available as a 10,000 International Units lyophilized powder that requires vial reconstitution prior to administration.
Reconstitution:
Slowly inject 1 or 2 mL of preservative free sterile 0.9% Sodium Chloride injection against the inner vial wall. Do not forcefully inject solution directly onto or into the powder.
If 1 mL of 0.9% Sodium Chloride is used, the resultant concentration is 10,000 International Units per mL.
If 2 mL of 0.9% Sodium Chloride is used, the resultant concentration is 5,000 International Units per mL.
Dissolve contents by gentle mixing or swirling; do not shake or invert the vial.
The reconstituted solution should be clear and colorless; discard if any visible particles or protein aggregates are present.
Storage: Do not freeze or refrigerate the reconstituted solution. Withdraw the calculated dose within 15 minutes of reconstitution; discard any unused portion of the vial(s).
Intramuscular injection:
Withdraw the calculated dose/volume from the reconstituted vial using a polypropylene syringe.
Inject the dose intramuscularly; administer within 4 hours from vial reconstitution.
Rylaze
Rylaze is available as a 10 mg per 0.5 mL single-dose solution vial; do not shake the vial.
Intramuscular injection:
Withdraw the calculated dose/volume from the solution vial(s) into a syringe.
Storage: Use immediately or store the syringe at room temperature (15 to 25 degrees C; 59 to 77 degrees F) for up to 8 hours or refrigerated (2 to 8 degrees C; 36 to 46 degrees F) for up to 24 hours.
Inject the dose intramuscularly.

elevated hepatic enzymes / Delayed / 0-25.0
fatigue / Early / 0-18.0
infection / Delayed / 0-17.0
acute respiratory distress syndrome (ARDS) / Early / 0-15.0
pulmonary edema / Early / 0-15.0
stomatitis / Delayed / 0-12.0
nausea / Early / 0.3-9.0
dehydration / Delayed / 0-9.0
pancreatitis / Delayed / 0-8.0
hypokalemia / Delayed / 0-8.0
anorexia / Delayed / 0-6.0
diarrhea / Early / 0-6.0
fever / Early / 0-6.0
musculoskeletal pain / Early / 0-6.0
hyperglycemia / Delayed / 3.0-4.0
abdominal pain / Early / 0-2.0
bleeding / Early / 0-2.0
hyperbilirubinemia / Delayed / 0.1-2.0
sinus tachycardia / Rapid / 0-2.0
anaphylactoid reactions / Rapid / 0-2.0
thrombosis / Delayed / 0-1.0
rash / Early / 0-1.0
vomiting / Early / 0-0.3
GI bleeding / Delayed / Incidence not known
coagulopathy / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
stroke / Early / Incidence not known
clotting factor deficiency / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known
enterocolitis / Delayed / Incidence not known
necrotizing fasciitis / Delayed / Incidence not known
nephrotoxicity / Delayed / Incidence not known

antibody formation / Delayed / 11.0-47.0
gastritis / Delayed / 0-15.0
constipation / Delayed / 0-15.0
hypoglycemia / Early / 0-15.0
hypofibrinogenemia / Delayed / 0-15.0
hyperammonemia / Delayed / 0-15.0
peripheral neuropathy / Delayed / 0-15.0
encephalopathy / Delayed / 0-15.0
bone pain / Delayed / 0-15.0
hypertension / Early / 0-15.0
hypotension / Rapid / 0-15.0
metabolic acidosis / Delayed / 0-15.0
infusion-related reactions / Rapid / 0-15.0
hyperphosphatemia / Delayed / 0-15.0
hypertriglyceridemia / Delayed / 0-15.0
hypercholesterolemia / Delayed / 0-15.0
colitis / Delayed / Incidence not known
prolonged bleeding time / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known
erythema / Early / Incidence not known

headache / Early / 0-36.0
gait disturbance / Delayed / 0-15.0
dizziness / Early / 0-15.0
paresthesias / Delayed / 0-15.0
weakness / Early / 0-15.0
muscle cramps / Delayed / 0-15.0
insomnia / Early / 0-15.0
agitation / Early / 0-15.0
anxiety / Delayed / 0-15.0
irritability / Delayed / 0-15.0
cough / Delayed / 0-15.0
injection site reaction / Rapid / 0-15.0
pruritus / Rapid / 0-15.0
epistaxis / Delayed / 0-9.0
menorrhagia / Delayed / Incidence not known
petechiae / Delayed / Incidence not known
folliculitis / Delayed / Incidence not known
sinusitis / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
myalgia / Early / Incidence not known
back pain / Delayed / Incidence not known
asthenia / Delayed / Incidence not known
throat irritation / Early / Incidence not known
xerosis / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
urticaria / Rapid / Incidence not known

Erwinase, RYLAZE

Rx

Asparagine specific enzyme
Used in combination with multi-agent chemotherapy in adult and pediatric patients with acute lymphoblastic leukemia or lymphoblastic lymphoma who have developed hypersensitivity to E. coli-derived asparaginase
Contraindicated in patients who have had serious pancreatitis, thrombosis, or bleeding events with prior asparaginase therapy

NOTE: Consider monitoring nadir serum asparaginase activity (NSAA) concentrations when administering asparaginase Erwinia chrysanthemi IV and switching to IM administration if desired NSAA concentrations are not achieved.

To substitute for a dose of pegaspargase: 25,000 International Units/m2 IV or IM 3 times a week (Monday/Wednesday/Friday) for 6 doses. To substitute for native E. coli asparaginase: 25,000 International Units/m2 IV or IM for each scheduled dose of native E. coli asparaginase within a treatment.

To substitute for a dose of pegaspargase: 25,000 International Units/m2 IV or IM 3 times a week (Monday/Wednesday/Friday) for 6 doses. To substitute for native E. coli asparaginase: 25,000 International Units/m2 IV or IM for each scheduled dose of native E. coli asparaginase within a treatment.

25 mg/m2 intramuscularly (IM) every 48 hours to replace a long-acting asparaginase product. Premedicate patients with acetaminophen, an H-1 receptor blocker (e.g., diphenhydramine), and an H-2 receptor blocker (e.g., famotidine) at 30 to 60 minutes prior to the IM injection to decrease the risk and severity of hypersensitivity reactions. Replace a single dose of calaspargase pegol with 11 doses of recombinant asparaginase Erwinia chrysanthemi; replace a single dose of pegaspargase with 7 doses of recombinant asparaginase Erwinia chrysanthemi. Continue therapy based on the duration of therapy for the replaced long-acting asparaginase product. Intramuscular administration of different dosing regimens of recombinant asparaginase Erwinia chrysanthemi on Monday, Wednesday, and Friday for 6 doses to replace a single dose of pegaspargase were evaluated in patients (median age, 10 [range, 1 to 25] years) with acute lymphoblastic leukemia or lymphoblastic lymphoma in a multi-cohort, open-label (JZP458-201) trial (n = 225). Based on simulation using 2,000 virtual subjects, 96% (95% CI, 94.4% to 97.2%) of patients who receive recombinant asparaginase Erwinia chrysanthemi 25 mg/m2 IM every 48 hours would achieve a nadir serum asparaginase activity (NSAA) level of at least 0.1 units/mL at 48 hours after the dose. In this trial, 83% of patients had developed a grade 3 or higher allergic reaction to and 7% of patients had silent inactivation after receiving a pegylated E. coli-derived asparaginase product.

25 mg/m2 intramuscularly (IM) every 48 hours to replace a long-acting asparaginase product. Premedicate patients with acetaminophen, an H-1 receptor blocker (e.g., diphenhydramine), and an H-2 receptor blocker (e.g., famotidine) at 30 to 60 minutes prior to the IM injection to decrease the risk and severity of hypersensitivity reactions. Replace a single dose of calaspargase pegol with 11 doses of recombinant asparaginase Erwinia chrysanthemi; replace a single dose of pegaspargase with 7 doses of recombinant asparaginase Erwinia chrysanthemi. Continue therapy based on the duration of therapy for the replaced long-acting asparaginase product. Intramuscular administration of different dosing regimens of recombinant asparaginase Erwinia chrysanthemi on Monday, Wednesday, and Friday for 6 doses to replace a single dose of pegaspargase were evaluated in patients (median age, 10 [range, 1 to 25] years) with acute lymphoblastic leukemia or lymphoblastic lymphoma in a multi-cohort, open-label (JZP458-201) trial (n = 225). Based on simulation using 2,000 virtual subjects, 96% (95% CI, 94.4% to 97.2%) of patients who receive recombinant asparaginase Erwinia chrysanthemi 25 mg/m2 IM every 48 hours would achieve a nadir serum asparaginase activity (NSAA) level of at least 0.1 units/mL at 48 hours after the dose. In this trial, 83% of patients had developed a grade 3 or higher allergic reaction to and 7% of patients had silent inactivation after receiving a pegylated E. coli-derived asparaginase product.

25 mg/m2 intramuscularly (IM) on Monday (in the morning) and Wednesday (in the morning), and then 50 mg/m2 IM on Friday (in the afternoon) to replace a long-acting asparaginase product. Administer the Friday afternoon dose at 53 to 58 hours after the Wednesday morning dose (e.g., 8 am on Monday and Wednesday, and 1 pm to 6 pm on Friday). Premedicate patients with acetaminophen, an H-1 receptor blocker (e.g., diphenhydramine), and an H-2 receptor blocker (e.g., famotidine) at 30 to 60 minutes prior to the IM injection to decrease the risk and severity of hypersensitivity reactions. Replace a single dose of calaspargase pegol with 9 doses of recombinant asparaginase Erwinia chrysanthemi; replace a single dose of pegaspargase with 6 doses of recombinant asparaginase Erwinia chrysanthemi. Continue therapy based on the duration of therapy for the replaced long-acting asparaginase product. Intramuscular administration of 3 different dosing regimens of recombinant asparaginase Erwinia chrysanthemi on Monday, Wednesday, and Friday for 6 doses to replace a single dose of pegaspargase were evaluated in patients (median age, 10 [range, 1 to 25] years) with acute lymphoblastic leukemia or lymphoblastic lymphoma in a multi-cohort, open-label (JZP458-201) trial (n = 225). In patients who receive recombinant asparaginase Erwinia chrysanthemi 25 mg/m2 IM on Monday and Wednesday and 50 mg/m2 IM on Friday, a nadir serum asparaginase activity (NSAA) level of at least 0.1 units/mL is expected in 91.6% (95% CI, 90.4% to 92.8%) of patients at 58 hours after the Wednesday morning dose and 91.4% (95% CI, 90.1% to 92.6%) of patients at 67 hours after the Friday afternoon dose based on simulation using 2,000 virtual subjects. In this trial, 83% of patients had developed a grade 3 or higher allergic reaction to and 7% of patients had silent inactivation after receiving a pegylated E. coli-derived asparaginase product.[66764]

25 mg/m2 intramuscularly (IM) on Monday (in the morning) and Wednesday (in the morning), and then 50 mg/m2 IM on Friday (in the afternoon) to replace a long-acting asparaginase product. Administer the Friday afternoon dose at 53 to 58 hours after the Wednesday morning dose (e.g., 8 am on Monday and Wednesday, and 1 pm to 6 pm on Friday). Premedicate patients with acetaminophen, an H-1 receptor blocker (e.g., diphenhydramine), and an H-2 receptor blocker (e.g., famotidine) at 30 to 60 minutes prior to the IM injection to decrease the risk and severity of hypersensitivity reactions. Replace a single dose of calaspargase pegol with 9 doses of recombinant asparaginase Erwinia chrysanthemi; replace a single dose of pegaspargase with 6 doses of recombinant asparaginase Erwinia chrysanthemi. Continue therapy based on the duration of therapy for the replaced long-acting asparaginase product. Intramuscular administration of 3 different dosing regimens of recombinant asparaginase Erwinia chrysanthemi on Monday, Wednesday, and Friday for 6 doses to replace a single dose of pegaspargase were evaluated in patients (median age, 10 [range, 1 to 25] years) with acute lymphoblastic leukemia or lymphoblastic lymphoma in a multi-cohort, open-label (JZP458-201) trial (n = 225). In patients who receive recombinant asparaginase Erwinia chrysanthemi 25 mg/m2 IM on Monday and Wednesday and 50 mg/m2 IM on Friday, a nadir serum asparaginase activity (NSAA) level of at least 0.1 units/mL is expected in 91.6% (95% CI, 90.4% to 92.8%) of patients at 58 hours after the Wednesday morning dose and 91.4% (95% CI, 90.1% to 92.6%) of patients at 67 hours after the Friday afternoon dose based on simulation using 2,000 virtual subjects. In this trial, 83% of patients had developed a grade 3 or higher allergic reaction to and 7% of patients had silent inactivation after receiving a pegylated E. coli-derived asparaginase product.

25 mg/m2 intramuscularly (IM) every 48 hours to replace a long-acting asparaginase product. Premedicate patients with acetaminophen, an H-1 receptor blocker (e.g., diphenhydramine), and an H-2 receptor blocker (e.g., famotidine) at 30 to 60 minutes prior to the IM injection to decrease the risk and severity of hypersensitivity reactions. Replace a single dose of calaspargase pegol with 11 doses of recombinant asparaginase Erwinia chrysanthemi; replace a single dose of pegaspargase with 7 doses of recombinant asparaginase Erwinia chrysanthemi. Continue therapy based on the duration of therapy for the replaced long-acting asparaginase product. Intramuscular administration of different dosing regimens of recombinant asparaginase Erwinia chrysanthemi on Monday, Wednesday, and Friday for 6 doses to replace a single dose of pegaspargase were evaluated in patients (median age, 10 [range, 1 to 25] years) with acute lymphoblastic leukemia or lymphoblastic lymphoma in a multi-cohort, open-label (JZP458-201) trial (n = 225). Based on simulation using 2,000 virtual subjects, 96% (95% CI, 94.4% to 97.2%) of patients who receive recombinant asparaginase Erwinia chrysanthemi 25 mg/m2 IM every 48 hours would achieve a nadir serum asparaginase activity (NSAA) level of at least 0.1 units/mL at 48 hours after the dose. In this trial, 83% of patients had developed a grade 3 or higher allergic reaction to and 7% of patients had silent inactivation after receiving a pegylated E. coli-derived asparaginase product.

25 mg/m2 intramuscularly (IM) every 48 hours to replace a long-acting asparaginase product. Premedicate patients with acetaminophen, an H-1 receptor blocker (e.g., diphenhydramine), and an H-2 receptor blocker (e.g., famotidine) at 30 to 60 minutes prior to the IM injection to decrease the risk and severity of hypersensitivity reactions. Replace a single dose of calaspargase pegol with 11 doses of recombinant asparaginase Erwinia chrysanthemi; replace a single dose of pegaspargase with 7 doses of recombinant asparaginase Erwinia chrysanthemi. Continue therapy based on the duration of therapy for the replaced long-acting asparaginase product. Intramuscular administration of different dosing regimens of recombinant asparaginase Erwinia chrysanthemi on Monday, Wednesday, and Friday for 6 doses to replace a single dose of pegaspargase were evaluated in patients (median age, 10 [range, 1 to 25] years) with acute lymphoblastic leukemia or lymphoblastic lymphoma in a multi-cohort, open-label (JZP458-201) trial (n = 225). Based on simulation using 2,000 virtual subjects, 96% (95% CI, 94.4% to 97.2%) of patients who receive recombinant asparaginase Erwinia chrysanthemi 25 mg/m2 IM every 48 hours would achieve a nadir serum asparaginase activity (NSAA) level of at least 0.1 units/mL at 48 hours after the dose. In this trial, 83% of patients had developed a grade 3 or higher allergic reaction to and 7% of patients had silent inactivation after receiving a pegylated E. coli-derived asparaginase product.

25 mg/m2 intramuscularly (IM) on Monday (in the morning) and Wednesday (in the morning), and then 50 mg/m2 IM on Friday (in the afternoon) to replace a long-acting asparaginase product. Administer the Friday afternoon dose at 53 to 58 hours after the Wednesday morning dose (e.g., 8 am on Monday and Wednesday, and 1 pm to 6 pm on Friday). Premedicate patients with acetaminophen, an H-1 receptor blocker (e.g., diphenhydramine), and an H-2 receptor blocker (e.g., famotidine) at 30 to 60 minutes prior to the IM injection to decrease the risk and severity of hypersensitivity reactions. Replace a single dose of calaspargase pegol with 9 doses of recombinant asparaginase Erwinia chrysanthemi; replace a single dose of pegaspargase with 6 doses of recombinant asparaginase Erwinia chrysanthemi. Continue therapy based on the duration of therapy for the replaced long-acting asparaginase product. Intramuscular administration of 3 different dosing regimens of recombinant asparaginase Erwinia chrysanthemi on Monday, Wednesday, and Friday for 6 doses to replace a single dose of pegaspargase were evaluated in patients (median age, 10 [range, 1 to 25] years) with acute lymphoblastic leukemia or lymphoblastic lymphoma in a multi-cohort, open-label (JZP458-201) trial (n = 225). In patients who receive recombinant asparaginase Erwinia chrysanthemi 25 mg/m2 IM on Monday and Wednesday and 50 mg/m2 IM on Friday, a nadir serum asparaginase activity (NSAA) level of at least 0.1 units/mL is expected in 91.6% (95% CI, 90.4% to 92.8%) of patients at 58 hours after the Wednesday morning dose and 91.4% (95% CI, 90.1% to 92.6%) of patients at 67 hours after the Friday afternoon dose based on simulation using 2,000 virtual subjects. In this trial, 83% of patients had developed a grade 3 or higher allergic reaction to and 7% of patients had silent inactivation after receiving a pegylated E. coli-derived asparaginase product.

25 mg/m2 intramuscularly (IM) on Monday (in the morning) and Wednesday (in the morning), and then 50 mg/m2 IM on Friday (in the afternoon) to replace a long-acting asparaginase product. Administer the Friday afternoon dose at 53 to 58 hours after the Wednesday morning dose (e.g., 8 am on Monday and Wednesday, and 1 pm to 6 pm on Friday). Premedicate patients with acetaminophen, an H-1 receptor blocker (e.g., diphenhydramine), and an H-2 receptor blocker (e.g., famotidine) at 30 to 60 minutes prior to the IM injection to decrease the risk and severity of hypersensitivity reactions. Replace a single dose of calaspargase pegol with 9 doses of recombinant asparaginase Erwinia chrysanthemi; replace a single dose of pegaspargase with 6 doses of recombinant asparaginase Erwinia chrysanthemi. Continue therapy based on the duration of therapy for the replaced long-acting asparaginase product. Intramuscular administration of 3 different dosing regimens of recombinant asparaginase Erwinia chrysanthemi on Monday, Wednesday, and Friday for 6 doses to replace a single dose of pegaspargase were evaluated in patients (median age, 10 [range, 1 to 25] years) with acute lymphoblastic leukemia or lymphoblastic lymphoma in a multi-cohort, open-label (JZP458-201) trial (n = 225). In patients who receive recombinant asparaginase Erwinia chrysanthemi 25 mg/m2 IM on Monday and Wednesday and 50 mg/m2 IM on Friday, a nadir serum asparaginase activity (NSAA) level of at least 0.1 units/mL is expected in 91.6% (95% CI, 90.4% to 92.8%) of patients at 58 hours after the Wednesday morning dose and 91.4% (95% CI, 90.1% to 92.6%) of patients at 67 hours after the Friday afternoon dose based on simulation using 2,000 virtual subjects. In this trial, 83% of patients had developed a grade 3 or higher allergic reaction to and 7% of patients had silent inactivation after receiving a pegylated E. coli-derived asparaginase product.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no initial dosage adjustments are needed.
Treatment-Related Hepatotoxicity (Rylaze)Total bilirubin level greater than 3 to 10 times the ULN: Hold Rylaze; 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 Rylaze; do not make up for missed doses.

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

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.
Corticosteroids: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions.
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. In addition, L-asparaginase may have schedule-dependent synergy and antagonism with high-dose cytarabine.
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 to 24 hours prior to L-asparaginase, 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.
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.
Thyroid hormones: (Moderate) Some hypothyroid patients receiving asparaginase may require reduced doses of thyroid hormone. Other patients may remain euthyroid during combined treatment. Monitor TSH levels and monitor for symptoms of hyperthyroidism; a free-T4 concentration may be useful to assess euthyroidism. Asparaginase may decrease the serum TBG (thyroxine-binding globulin) concentration. Decreased amounts of TBG may result in an increased clinical response to thyroid hormones.
Vincristine Liposomal: (Moderate) Use L-asparaginase and vincristine together with caution; increased vincristine-related toxicity may occur. L-asparaginase administered before or concurrently with vincristine may reduce the hepatic clearance of vincristine. If these drugs are used together, administer vincristine 12 to 24 hours before L-asparaginase to minimize toxicity.
Vincristine: (Moderate) Use L-asparaginase and vincristine together with caution; increased vincristine-related toxicity may occur. L-asparaginase administered before or concurrently with vincristine may reduce the hepatic clearance of vincristine. If these drugs are used together, administer vincristine 12 to 24 hours before L-asparaginase to minimize toxicity.
Zonisamide: (Moderate) Concomitant use of zonisamide with asparaginase 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.

Erwinase Intramuscular Inj Pwd F/Sol: 10000IU
Erwinase Intravenous Inj Pwd F/Sol: 10000IU
RYLAZE Intramuscular Inj Sol: 0.5mL, 10mg

Erwinaze: 25,000 International Units/m2 IV or IM.Rylaze: 50 mg/m2 IM.

Erwinaze: 25,000 International Units/m2 IV or IM.Rylaze: 50 mg/m2 IM.

Erwinaze: 25,000 International Units/m2 IV or IM.Rylaze: 50 mg/m2 IM.

Erwinaze: 25,000 International Units/m2 IV or IM.Rylaze: 50 mg/m2 IM.

Erwinaze: Safety and efficacy not established.Rylaze: 50 mg/m2 IM.

Safety and efficacy not established.

Asparaginase Erwinia chrysanthemi is an asparagine specific enzyme derived from Erwinia chrysanthemi. This enzyme catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia, resulting in a reduced circulating asparagine levels. Leukemic cells have an inability to synthesize asparagine due to a lack of asparagine synthetase activity. Asparaginase Erwinia chrysanthemi therapy deprives leukemic cells of an exogenous source of asparagine which eventually leading to cell death. Asparaginase erwinia chrysanthemi (recombinant)-rywn is produced by fermentation of a genetically engineered Pseudomonas fluorescens bacterium containing the DNA which encodes for asparaginase Erwinia chrysanthemi. It's amino acid sequence is identical to native asparaginase Erwinia chrysanthemi, also known as crisantaspase.

Asparaginase Erwinia chrysanthemi (Erwinaze) is administered intravenously (IV) and intramuscularly (IM). Nadir serum asparaginase activity (NSAA) of 0.1 units/mL or more correlates with asparagine depletion and serum concentrations that predict clinical efficacy.
Recombinant asparaginase Erwinia chrysanthemi (Rylaze) is administered IM. Achieving and maintaining a NSAA greater than 0.1 unit/mL predicts clinical efficacy. The geometric mean volume of distribution was 1.37 L/m2 (coefficient of variation (CV), 47%), apparent half-life was 15.9 hours (CV, 11%), and geometric mean clearance was 0.17 L/hour/m2 (CV, 42%) in pediatric and young adult patients with acute lymphocytic leukemia or lymphoblastic lymphoma who received recombinant asparaginase Erwinia chrysanthemi. Metabolism into small peptides occurs via catabolic pathways.

Based on a population pharmacokinetic model in patients aged 1 to 17 years, the mean half-life of asparaginase Erwinia chrysanthemi after IV administration was 7.51 hours (coefficient of variation (CV), 23.9%). Following asparaginase Erwinia chrysanthemi 25,000 International Units/m2 IV 3 days per week for 6 doses, a nadir serum asparaginase activity (NSAA) concentration of 0.1 International Units/mL or more was achieved in 83% of patients at 48 hours post dose 5 (n = 20 of 24) and 43% of patients at 72 hours post dose 6 (n = 9 of 21); a NSAA concentration of 0.4 International Units/mL or more was achieved in 29% and 0% of patients, respectively.

Based on a population pharmacokinetic (PK) model in patients aged 1 to 18 years, the mean half-life of asparaginase Erwinia chrysanthemi after IM administration was 15.6 hours (coefficient of variation (CV), 20%). Following asparaginase Erwinia chrysanthemi 25,000 International Units/m2 IM 3 days per week for 6 doses, a nadir serum asparaginase activity (NSAA) concentration of 0.1 International Units/mL or more was achieved in 100% of patients at 48 hours (n = 35) or 72 hours (n = 13) post dose 3; a NSAA concentration of 0.4 International Units/mL or more was achieved in 80% and 38% of patients, respectively.
In a virtual population, the simulated geometric mean Ctrough value was 0.46 units/mL (coefficient of variation (CV), 75%), based on serum asparaginase activity (SAA), after the last dose of recombinant asparaginase Erwinia chrysanthemi 25 mg/m2 IM every 48 hours. Following the administration of recombinant asparaginase Erwinia chrysanthemi 25 mg/m2 IM on Monday and Wednesday and 50 mg/m2 IM on Friday, the simulated geometric mean Ctrough values were 0.3 units/mL (CV, 75%) at a maximum interval of 58 hours after the last Wednesday morning dose and 0.39 units/mL (CV, 87%) at a maximum interval of 67 hours after the last Friday afternoon dose in a virtual population. The median Tmax is 12 (range, 8 to 24) hours.

Asparaginase Erwinia chrysanthemi may cause fetal harm if used during pregnancy, based on data from animal studies. Females of reproductive potential should avoid pregnancy during asparaginase Erwinia chrysanthemi therapy. Advise pregnant women of the potential risk to the fetus. An increased incidence of partially undescended thymic tissue was observed in the offspring of pregnant rats who received IM asparaginase Erwinia chrysanthemi at doses that were 0.5 times the maximum recommended human dose. Additionally, fetal malformation (i.e., absent kidney, absent accessory lung lobe, additional subclavian artery, and delayed ossification) occurred in the offspring of pregnant rabbits who received IM asparaginase Erwinia chrysanthemi at doses that were 0.005 times the maximum recommended human dose.

Breast-feeding is not recommended during asparaginase Erwinia chrysanthemi (Erwinaze) or recombinant asparaginase Erwinia chrysanthemi (Rylaze) treatment and for 3 months (Erwinaze) or 1 week (Rylaze) after the last dose due to the potential for serious adverse reactions in the breast-fed child. There are no data on the presence of asparaginase Erwinia chrysanthemi in human milk, the effects on the breast-fed child, or the effects on milk production.