Asparaginase erwinia chysanthemi- (RYLAZE) -(Jun 2021)- To Treat Lymphoblastic leukemiaDrug Name:
Asparaginase erwinia chysanthemi- (RYLAZE) -(Jun 2021)- To Treat Lymphoblastic leukemia
List Of Brands:
Indication Type Description:
Dosages/ Overdosage Etc
Pregnancy and lactation
U.S. FDA APPROVED DRUGS SURING 2021
Serial No 27
Name of the Drug- RYLAZE
Active Ingredient - Asaparginase erwina chrysanthem (recombinant)-rywn
Pharmacological Classification- To treat acute lymphoblastic leukemia in patients who are allergic to E.Coli derived asparginase products, as a component of a chemotherapy regimen
Date of Approval- 6/30/2021
HIGHLIGHTS OF PRESCRIBING INFORMATION -
These highlights do not include all the information needed to use RYLAZE safely and effectively.
See full prescribing information for RYLAZE. RYLAZETM (asparaginase erwinia chrysanthemi (recombinant)- rywn) injection, for intramuscular use
Initial U.S. Approval: 2021
INDICATIONS AND USAGE
RYLAZE is an asparagine specific enzyme indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase.
Most common adverse reactions (incidence > 20%) are abnormal liver test, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensi
RYLAZE is contraindicated in patients with a history of: • Serious hypersensitivity reactions to RYLAZE, including anaphylaxis.
• Serious pancreatitis during previous L-asparaginase therapy. • Serious thrombosis during previous L-asparaginase therapy. • Serious hemorrhagic events during previous L-asparaginase therapy.
WARNINGS AND PRECAUTIONS-
• Hypersensitivity: Monitor for signs or symptoms. Discontinue RYLAZE for serious reaction. • Pancreatitis: Monitor for symptoms. Discontinue if pancreatitis occurs • Thrombosis: Discontinue RYLAZE for severe or life-threatening thrombosis. Provide anticoagulation therapy as indicated. • Hemorrhage: Discontinue RYLAZE for severe or life-threatening hemorrhage. • Hepatotoxicity: Discontinue RYLAZE for grade 4 increases of bilirubin.
Dosages/ Overdosage Etc:
DOSAGE AND ADMINISTRATION
When replacing a long-acting asparaginase product, the recommended dosage of RYLAZE is 25 mg/m2 administered intramuscularly every 48 hours.
DOSAGE FORMS AND STRENGTHS
Injection: 10 mg/0.5 mL solution in a single-dose vial.
PATIENT COUNSELING INFORMATION
Inform patients of the risk of allergic reactions, including anaphylaxis. Instruct the patient on the symptoms of allergic reactions and to seek medical advice immediately if they experience such symptoms
. • Pancreatitis- Instruct patients on signs and symptoms of pancreatitis and to seek medical attention if they experience severe abdominal pain
• Thrombosis- Instruct patients on the risk of thrombosis and to seek medical advice immediat
• Hemorrhage - Advise patients to report any unusual bleeding or bruising to their healthcare provider .
• Hepatotoxicity- Advise patients to report any jaundice, severe nausea or vomiting, or easy bleeding or bruising to their healthcare provider
• Pregnancy - Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy
Advise females of reproductive potential to use effective non-hormonal contraception during treatment with RYLAZE and for 3 months after the last dose
• Lactation - Advise women not to breastfeed during treatment with RYLAZE and for 1 week after the last dose
Manufactured by: Jazz Pharmaceuticals Ireland Limited Leinster, Ireland U.S. License No. 2167 Distributed by: Jazz Pharmaceuticals, Inc. 3170 Porter Drive, Palo Alto, CA 94304
1. Mechanism of Action - Asparaginase erwinia chrysanthemi (recombinant)-rywn is an enzyme that ca
The pharmacological effect of RYLAZE is based on the killing of leukemic cells due 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.
2. Pharmacodynamics Asparaginase erwinia chrysanthemi (recombinant)-rywn exposure-response relationships and the time course of pharmacodynamic response are unknown.
3. Pharmacokinetics The pharmacokinetic parameters of asparaginase erwinia chrysanthemi (recombinant)-rywn are presented based on serum asparaginase activity (SAA) following administration of the approved recommended dosage in pediatric and young adult patients (1 to 24 years), unless otherwise specified.
Absorption-The median tmax of asparaginase erwinia chrysanthemi (recombinant)-rywn is 10 hours. The mean absolute bioavailability for IM administration is 37% in healthy subjects.
Distribution- The geometric mean (%CV) apparent volume of distribution of asparaginase erwinia chrysanthemi (recombinant)-rywn is 1.48 L/m2 (49%).
Elimination -The geometric mean (%CV) apparent clearance of asparaginase erwinia chrysanthemi (recombinant)-rywn is 0.31 L/hour/m2 (36%) and the apparent half-life is 18.2 hours (16%).
Metabolism -Asparaginase erwinia chrysanthemi (recom
Specific Populations- There were no clinically significant differences in the pharmacokinetics of asparaginase erwinia chrysanthemi (recombinant)-rywn based on age (1 to 52 years), weight (9 to 131 kg), or sex after the dose was adjusted by body surface area (BSA).
The effect of renal and hepatic impairment on the pharmacokinetics of asparaginase erwinia chrysanthemi (recombinant)-rywn has not been studied.
Body Surface Area The apparent volume of distribution and apparent clearance of asparaginase erwinia chrysanthemi (recombinant)-rywn increase with increasing BSA (0.44 to 2.53 m2 )
Race and Ethnicity Black (n=10) and Asian (n=5) patients had 29% lower clearance which may increase SAA exposure compared to White (n=61) patients. There were no clinically significant differences in clearance between Hispanic (n=28) and Non-Hispanic (n=53) patients.
13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity, and impairment of fertility studies have not been conducted with asparaginase erwinia chrysanthemi (recombinant)-rywn.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy Risk Summary Based on findings from animal reproduction studies, RYLAZE can cause fetal harm when administered to a pregnant woman.
There are no available data on RYLAZE use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively.
2. Lactation Risk Summary- There are no data on the presence of asparaginase erwinia chrysanthemi (recombinant)-rywn in human milk, the effects on the breastfed child, or the effects on milk production.
Because of the potential for adverse reactions in the breastfed child, advise women not to breastfeed during treatment with RYLAZE and for 1 week after the last dose.
3. Females and Males of Reproductive Potential RYLAZE can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy Testing- Pregnancy testing is recommended in females of reproductive potential prior to initiating RYLAZE.
Contraception -Advise females of reproductive potential to use effective non-hormonal contraceptive methods during treatment with RYLAZE and for 3 months after the last dose.
4. Pediatric Use - The safety and effectiveness of RYLAZE in the treatment of ALL and LBL have been established in pediatric patients 1 month to < 17 years who have developed hypersensitivity to a long-acting E. coliderived asparaginase.
Use of RYLAZE in these age groups is supported by evidence from an adequate and well-controlled study in adults and pediatric patients. The trial included 84 pediatric patients, including 2 infants (1 month to < 2 years), 62 children (2 years to < 12 years old), and 20 adolescents (12 years to < 17 years old). There were no clinically meaningful differences in safety or nadir serum asparaginase activity across age groups. The safety and effectiveness of RYLAZE have not been established in pediatric patients younger than 1 month of age.
5. Geriatric Use- Clinical studies of RYLAZE did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients.