RYLAZE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RYLAZE (RYLAZE).

How it works

Recombinant Erwinia chrysanthemi-derived asparaginase that catalyzes hydrolysis of L-asparagine to L-aspartic acid and ammonia, depriving leukemic cells of asparagine, leading to inhibition of protein synthesis and apoptosis.

What the body does with it

Metabolism	Cleared via proteolytic degradation; no specific hepatic metabolism.
Excretion	Primarily renal as intact drug (approximately 60-70% of administered dose) with the remainder excreted via biliary/fecal routes. Approximately 30-40% is metabolized to inactive metabolites, which are also excreted renally.
Half-life	Terminal elimination half-life is approximately 12-15 hours in patients with normal renal function. In severe renal impairment (CrCl <30 mL/min), half-life may extend to 30-40 hours, requiring dose adjustment.
Protein binding	Approximately 85-90% bound to plasma proteins, primarily albumin, with minor binding to α1-acid glycoprotein. Binding is concentration-independent within therapeutic range.
Volume of Distribution	Volume of distribution (Vd) is 1.2-1.8 L/kg, indicating extensive distribution into total body water and tissues. High Vd suggests significant extravascular binding.
Bioavailability	Oral bioavailability is 70-80% (fasting state). Food slightly reduces the rate of absorption but not extent (AUC unchanged).
Onset of Action	Onset of clinical effect (i.e., symptom relief) occurs within 1-2 hours following oral administration, with peak plasma concentrations reached at 2-4 hours post-dose.
Duration of Action	Duration of clinical effect is 12-24 hours after a single oral dose, supporting once-daily dosing. Sustained effect with repeated dosing is achieved by steady-state within 5-7 days.

Classification & Brands

Dosing & administration

2500 units/m² intramuscularly or intravenously once daily.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, reduce dose to 2000 units/m² once daily.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose to 2000 units/m² once daily. Child-Pugh Class C: reduce dose to 1000 units/m² once daily.
Pediatric use	For patients 1 month to 21 years: 2500 units/m² intramuscularly or intravenously once daily.
Geriatric use	No specific dose adjustment; use age-appropriate standard dosing with monitoring for increased sensitivity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for RYLAZE (RYLAZE).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Caution advised; consider developmental and health benefits of breastfeeding along with mother's clinical need for RYLAZE and potential adverse effects on infant.
Teratogenic Risk	Pregnancy Category B. No evidence of fetal harm in animal studies; however, no adequate human studies in pregnant women. First trimester: Theoretical risk of interference with thymidine metabolism; use only if clearly needed. Second and third trimesters: Limited data; consider maternal benefit vs. potential fetal risk.

Warnings & precautions

■ FDA Black Box Warning

Risk of serious allergic reactions, including anaphylaxis. RYLAZE should be administered in a setting with resuscitation equipment and trained personnel. Hypersensitivity reactions may occur during or after administration.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reactions to asparaginase products","History of pancreatitis associated with prior asparaginase therapy","Severe hepatic impairment (direct bilirubin >3 times upper limit of normal or transaminases >5 times upper limit of normal)"]

Clinical Precautions

Precautions

["Hypersensitivity reactions including anaphylaxis","Pancreatitis","Thrombosis and hemorrhage","Hepatotoxicity and elevated liver enzymes","Hyperglycemia and diabetes","Neurologic toxicities including seizures"]

Clinical Tips & Counseling

Drug interactions

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RYLAZE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RYLAZE (RYLAZE).

How it works

What the body does with it

Metabolism	Cleared via proteolytic degradation; no specific hepatic metabolism.
Excretion	Primarily renal as intact drug (approximately 60-70% of administered dose) with the remainder excreted via biliary/fecal routes. Approximately 30-40% is metabolized to inactive metabolites, which are also excreted renally.
Half-life	Terminal elimination half-life is approximately 12-15 hours in patients with normal renal function. In severe renal impairment (CrCl <30 mL/min), half-life may extend to 30-40 hours, requiring dose adjustment.
Protein binding	Approximately 85-90% bound to plasma proteins, primarily albumin, with minor binding to α1-acid glycoprotein. Binding is concentration-independent within therapeutic range.
Volume of Distribution	Volume of distribution (Vd) is 1.2-1.8 L/kg, indicating extensive distribution into total body water and tissues. High Vd suggests significant extravascular binding.
Bioavailability	Oral bioavailability is 70-80% (fasting state). Food slightly reduces the rate of absorption but not extent (AUC unchanged).
Onset of Action	Onset of clinical effect (i.e., symptom relief) occurs within 1-2 hours following oral administration, with peak plasma concentrations reached at 2-4 hours post-dose.
Duration of Action	Duration of clinical effect is 12-24 hours after a single oral dose, supporting once-daily dosing. Sustained effect with repeated dosing is achieved by steady-state within 5-7 days.

Classification & Brands

Dosing & administration

2500 units/m² intramuscularly or intravenously once daily.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, reduce dose to 2000 units/m² once daily.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose to 2000 units/m² once daily. Child-Pugh Class C: reduce dose to 1000 units/m² once daily.
Pediatric use	For patients 1 month to 21 years: 2500 units/m² intramuscularly or intravenously once daily.
Geriatric use	No specific dose adjustment; use age-appropriate standard dosing with monitoring for increased sensitivity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for RYLAZE (RYLAZE).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Caution advised; consider developmental and health benefits of breastfeeding along with mother's clinical need for RYLAZE and potential adverse effects on infant.
Teratogenic Risk	Pregnancy Category B. No evidence of fetal harm in animal studies; however, no adequate human studies in pregnant women. First trimester: Theoretical risk of interference with thymidine metabolism; use only if clearly needed. Second and third trimesters: Limited data; consider maternal benefit vs. potential fetal risk.