asparaginase Erwinia chrysanthemi recombinant (Rx)

Brand and Other Names:Rylaze, asparaginase Erwinia chrysanthemi recombinant-rywn
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, solution

  • 10mg/0.5mL

Acute Lymphoblastic Leukemia

Indicated as part of a chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in patients who have developed hypersensitivity or silent inactivation to Escherichia coli–derived asparaginase

25 mg/m2 IM q48hr; duration-dependent regimen

Lymphoblastic Lymphoma

Indicated as part of a chemotherapeutic regimen for lymphoblastic lymphoma (LBL) in patients who have developed hypersensitivity or silent inactivation to E coli–derived asparaginase

25 mg/m2 IM q48hr; duration-dependent regimen

Dosage Modifications

Renal or hepatic impairment

  • Not studied

Hypersensitivity

  • Grade 2: Treat symptoms
  • Grade 3-4: Discontinue permanently

Pancreatitis, grade ≥2

  • Hold if lipase or amylase >2x ULN, or for symptomatic pancreatitis
  • Resume treatment when lipase and amylase <1.5x ULN and symptoms resolve
  • Discontinue permanently if clinical necrotizing or hemorrhagic pancreatitis confirmed

Thrombosis

  • Uncomplicated: Hold and treat with antithrombotic therapy; consider resuming upon symptom resolution while continuing antithrombotic therapy
  • Severe or life-threatening: Discontinue permanently; treat with antithrombotic therapy

Hemorrhage, grade ≥3

  • Hold asparaginase
  • Evaluate for coagulopathy and consider clotting factor replacement as needed
  • Resume with next scheduled dose if bleeding controlled

Hepatotoxicity

  • Total bilirubin (TB) >3 x to ≤10x ULN: Hold until TB ≤1.5x ULN
  • TB >10x ULN: Discontinue and do not make up missed doses

Dosing Considerations

Test females of reproductive potential for pregnancy before initiating

Treatment duration

  • When replacing a long-acting asparaginase product, refer to prescribing information of product being replaced to determine treatment duration with asparaginase Erwinia chrysanthemi recombinant

Monitoring

  • Monitor bilirubin, transaminases, glucose, and clinical examinations before treatment and q2-3 weeks and as indicated clinically
  • If results are abnormal, monitor until recovery from the cycle of therapy
  • If an adverse reaction occurs, modify treatment

Dosage Forms & Strengths

injection, solution

  • 10mg/0.5mL

Acute Lymphoblastic Leukemia

Indicated as part of a chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in children aged ≥1 month who have developed hypersensitivity or silent inactivation to Escherichia coli–derived asparaginase

<1 month: Safety and efficacy not established

25 mg/m2 IM q48hr; duration-dependent regimen

Lymphoblastic Lymphoma

Indicated as part of a chemotherapeutic regimen for lymphoblastic lymphoma (LBL) in children aged ≥1 month who have developed hypersensitivity or silent inactivation to E coli–derived asparaginase

<1 month: Safety and efficacy not established

25 mg/m2 IM q48hr; duration-dependent regimen

Dosage Modifications

Renal or hepatic impairment

  • Not studied

Hypersensitivity

  • Grade 2: Treat symptoms
  • Grade 3-4: Discontinue permanently

Pancreatitis, grade ≥2

  • Hold if lipase or amylase >2x ULN, or for symptomatic pancreatitis
  • Resume treatment when lipase and amylase <1.5x ULN and symptoms resolve
  • Discontinue permanently if clinical necrotizing or hemorrhagic pancreatitis confirmed

Thrombosis

  • Uncomplicated: Hold and treat with antithrombotic therapy; consider resuming upon symptom resolution while continuing antithrombotic therapy
  • Severe or life-threatening: Discontinue permanently; treat with antithrombotic therapy

Hemorrhage, grade ≥3

  • Hold asparaginase
  • Evaluate for coagulopathy and consider clotting factor replacement as needed
  • Resume with next scheduled dose if bleeding controlled

Hepatotoxicity

  • Total bilirubin (TB) >3 x to ≤10x ULN: Hold until TB ≤1.5x ULN
  • TB >10x ULN: Discontinue and do not make up missed doses

Dosing Considerations

Test females of reproductive potential for pregnancy before initiating

Treatment duration

  • When replacing a long-acting asparaginase product, refer to prescribing information of product being replaced to determine treatment duration with asparaginase Erwinia chrysanthemi recombinant

Monitoring

  • Monitor bilirubin, transaminases, glucose, and clinical examinations before treatment and q2-3 weeks and as indicated clinically
  • If results are abnormal, monitor until recovery from the cycle of therapy
  • If an adverse reaction occurs, modify treatment
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Adverse Effects

>10%

All grades

  • Abnormal liver test (70%)
  • Nausea (46%)
  • Musculoskeletal pain (39%)
  • Fatigue (36%)
  • Infection (30%)
  • Headache (30%)
  • Pyrexia (27%)
  • Hypersensitivity (24%)
  • Febrile neutropenia (24%)
  • Decreased appetite (21%)
  • Stomatitis (21%)
  • Bleeding (21%)
  • Hyperglycemia (21%)
  • Abdominal pain (18%)
  • Tachycardia (18%)
  • Diarrhea (18%)
  • Constipation (15%)
  • Dehydration (15%)
  • Neuropathy peripheral (15%)
  • Cough (15%)
  • Insomnia (15%)

Grades ≥3

  • Febrile neutropenia (24%)
  • Abnormal liver test (12%)
  • Infection (12%)

Other clinically relevant adverse reactions <15%

  • Gastrointestinal disorders: Abdominal discomfort, abdominal distension, pancreatitis
  • General disorders and administration site conditions: Infusion site reaction, pain
  • Infections and infestations: Viral infection, bacterial infection, fungal infection
  • Investigations: Blood fibrinogen decreased, activated partial thromboplastin time prolonged
  • Metabolism and nutrition disorders: Acidosis
  • Musculoskeletal and connective-tissue disorders: Bone pain, muscular weakness, muscle spasms
  • Nervous system disorders: Paresthesia
  • Psychiatric disorders: Agitation, anxiety, irritability
  • Renal and urinary disorders: Acute kidney injury
  • Skin and subcutaneous disorders: Pruritus
  • Vascular disorders: Hypotension

1-10%

Grades ≥3

  • Nausea (9%)
  • Stomatitis (9%)
  • Dehydration (9%)
  • Musculoskeletal pain (6%)
  • Pyrexia (6%)
  • Hypersensitivity (6%)
  • Decreased appetite (6%)
  • Diarrhea (6%)
  • Fatigue (3%)
  • Hyperglycemia (3%)
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Warnings

Contraindications

History of serious hypersensitivity reactions to E asparaginase, including anaphylaxis

Serious pancreatitis during previous asparaginase therapy

Serious thrombosis during previous asparaginase therapy

Serious hemorrhagic events during previous asparaginase therapy

Cautions

Pancreatitis reported; monitor for signs and symptoms; withhold or discontinue depending on severity

Serious thrombotic events reported, including sagittal sinus thrombosis and pulmonary embolism; discontinue if thrombotic event occurs and administer antithrombotic therapy; consider resumption only if event was an uncomplicated thrombosis

Bleeding reported; monitor for bruising, nose bleeds, hematuria, rectal bleeding, and gingival bleeding; monitor PT, PTT, and hypofibrinogenemia

Hepatotoxicity reported; evaluate bilirubin and transaminases before initiating and q2-3 weeks as clinically indicated during treatment

Hypersensitivity

  • Hypersensitivity reactions observed with L-asparaginase class products include angioedema, urticaria, lip swelling, eye swelling, rash or erythema, blood pressure decreased, bronchospasm, dyspnea, and pruritus
  • Owing to risk for serious allergic reactions (eg, life-threatening anaphylaxis), administer in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis
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Pregnancy & Lactation

Pregnancy

Based on findings from animal reproduction studies, can cause fetal harm when administered to pregnant females

Advise pregnant females of potential fetal risk

Pregnancy testing recommended in females of reproductive potential before initiating

Animal data

  • In embryofetal development studies, asparaginase E chrysanthemi was administered IM every other day during organogenesis to pregnant rats (at 3, 6, or 12 mg/m2) and rabbits (at 0.12, 0.30, or 0.48 mg/m2)
  • In rats given 12 mg/m2 (~0.48 times the maximum recommended human dose [MRHD]), maternal toxicity of decreased body weight gain was observed, as was a fetal finding of increased incidence of partially undescended thymic tissue
  • In rabbits, maternal toxicity consisting of decreased body weight was observed at 0.48 mg/m2 (~0.02 times the MRHD), increased postimplantation loss, decreased number of live fetuses, and gross abnormalities (eg, absent kidney, absent accessory lung lobe, additional subclavian artery, and delayed ossification) observed at doses ≥0.12 mg/m2 (~0.005 times the MRHD)

Contraception

  • Females of reproductive potential: Use effective nonhormonal contraceptive methods during treatment and for 3 months after last dose

Lactation

Data are unavailable regarding presence in human milk, effects on breastfed children, or effects on milk production

Advise women not to breastfeed during treatment and for 1 week after last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

Enzyme that catalyzes conversion of the amino acid L-asparagine into aspartic acid and ammonia

Pharmacological effect based on the killing of leukemic cells owing to depletion of plasma asparagine

Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival

Absorption

Bioavailability: 37%

Peak plasma time: 10 hr

AUC: 37.9 hr⋅U/mL (dose 1); 48.5 hr⋅U/mL (dose 7)

Peak plasma concentration

  • Dose 1: 1.8 U/mL
  • Dose 7: 2.24 U/mL
  • 48 hr after most recent dose
    • Dose 1: 0.33 U/mL
    • Dose 7: 0.4 U/mL

Distribution

Vd: 1.48 L/m2

Metabolism

Via catabolic pathways into small peptides

Elimination

Half-life: 18.2 hr

Clearance: 0.31 L/hr/m2

Pharmacogenomics

Black and Asian patients had 29% lower clearance which may increase serum asparaginase activity exposure compared with White patients

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Administration

IM Preparation

Visually inspect for particulate matter, cloudiness, or discoloration; if any of these observed, discard vial

Determine dose, total volume of solution required, and the number of vials needed; >1 vial may be needed to obtain full dose

Do not shake vial

Withdraw required volume into syringe; if >2 mL required, divide doses equally into multiple syringes (1 syringe for each injection site)

Discard remaining unused drug in vial

Administer within 4 hr of preparation

IM Administration

Rotate injection sites

Do not inject into scar tissues or areas that are reddened, inflamed, or swollen

Storage

Does not contain a preservative

Unopened vials

  • Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
  • Do not shake or freeze

Prepared syringes

  • Store at room temperature at 15-25ºC (59-77ºF) OR
  • Refrigerate at 2-8ºC (36-46ºF) for up to 4 hr
  • No need to protect from light
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Images

No images available for this drug.
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Patient Handout

A Patient Handout is not currently available for this monograph.
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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.