Rylaze asparaginase erwinia chrysanthemi (recombinant)-rywn 20 mg/mL Injection, 3 vials
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Asparagine-specific Enzyme class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Asparaginase erwinia chrysanthemi is used with other chemotherapy medications to treat acute lymphocytic leukemia (ALL; a type of cancer of the white blood cells). It is used in patients who have had some types of allergic reactions to medications similar to asparaginase erwinia chrysanthemi such as (asparaginase [Elspar] or pegaspargase [Oncaspar]). Asparaginase erwinia chrysanthemi is an enzyme that interferes with natural substances necessary for cancer cell growth. It works by killing or stopping the growth of cancer cells.
Read the full MedlinePlus article ↗- Rylaze is specifically designed for patients who have developed an allergic reaction to asparaginase products made from E. coli bacteria — the type most commonly used first in leuk...
- Why am I getting Rylaze instead of the asparaginase I was on before?
- The most important things to watch for are signs of a serious allergic reaction — things like hives, swelling, trouble breathing, or feeling faint — which can happen during or afte...
- What should I watch out for after getting my injection?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Asparaginase Erwinia Chrysanthemi (Recombinant)-Rywn — tap one for details:
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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0.2 mg / 1 mL
UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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50 mmol / 1 mL
UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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11.6 mmol / 1 mL
UNII 22ADO53M6F
A mineral salt derived from phosphoric acid, used as a buffer to maintain the pH balance of the medication and help stabilize the active ingredients.
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8.5 mmol / 1 mL
UNII 593YOG76RN
A salt made from sodium and phosphate that helps regulate acidity and maintain proper pH balance in the medicine. It also acts as a buffer to keep the product stable.
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170 mmol / 1 mL
UNII 7YIN7J07X4
A natural sugar derived from plants and microorganisms. It acts as a filler to give the medication bulk and stability, and helps preserve the active ingredient during storage and manufacturing.
5 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $11,149.46 | $33,448.37 / 3 vials |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9021 | $58.698 / J9021 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Rylaze 20 mg/mLthis 68727-0900-03 | Jazz | 3 vials | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Jun 30, 2033 |
Is there a biosimilar for RYLAZE 10 MG/0.5 ML VIAL?
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🗺️ Medicaid utilization & spend
🔬 Reported adverse events (FAERS)
Top reported reactions
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 68727-0900-03 You're viewing this | 3 VIAL, SINGLE-DOSE in 1 CARTON (68727-900-03) / .5 mL in 1 VIAL, SINGLE-DOSE (68727-900-01) | 2021-06-30 | Active |
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE RYLAZE is 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. 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.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION There are two RYLAZE regimens that can be used to replace a long-acting asparaginase product. The recommended dosages of RYLAZE are: When administered every 48 hours • 25 mg/m 2 intramuscularly every 48 hours; When administered Monday/Wednesday/Friday • 25 mg/m 2 intramuscularly on Monday morning and Wednesday morning and 50 mg/m 2 intramuscularly on Friday afternoon. ( 2.1 )
2.1Recommended Dosage There are two RYLAZE regimens that can be used to replace a long-acting asparaginase product. The recommended dosages of RYLAZE are: When administered every 48 hours: • 25 mg/m 2 administered intramuscularly every 48 hours; When administered on a Monday/Wednesday/Friday schedule: • 25 mg/m 2 intramuscularly on Monday morning and Wednesday morning, and 50 mg/m 2 intramuscularly on Friday afternoon. Administer the Friday afternoon dose 53 to 58 hours after the Wednesday morning dose (e.g., 8:00 am on Monday and Wednesday, and 1:00 pm to 6:00 pm on Friday) [see Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14 )] .
Table 1 shows the number of RYLAZE dosages recommended for the intended duration of treatment for replacement of one dose of calaspargase pegol products (3 weeks of asparaginase coverage) or one dose of pegaspargase products (2 weeks of asparaginase coverage). See the full prescribing information for the long-acting asparaginase product to determine the total duration of administration of RYLAZE as replacement therapy. Table 1: Recommended Duration of RYLAZE Dosing to Replace One Long-Acting Asparaginase Dose When RYLAZE is Administered: Recommended Duration of RYLAZE to Replace Calaspargase Pegol Products Recommended Duration of RYLAZE to Replace Pegaspargase Products 25 mg/m 2 intramuscular every 48 hours Replace one dose of calaspargase pegol products with 11 doses of RYLAZE Replace one dose of pegaspargase products with 7 doses of RYLAZE 25 mg/m 2 intramuscular on Monday morning and Wednesday morning, and 50 mg/m 2 intramuscular on Friday afternoon* Replace one dose of calaspargase pegol products with 9 doses of RYLAZE Replace one dose of pegaspargase products with 6 doses of RYLAZE *See bullet above for timing of 25/25/50 mg/m 2 dosing of RYLAZE.
2.2Recommended Premedication Premedicate patients with acetaminophen, an H-1 receptor blocker (such as diphenhydramine), and an H-2 receptor blocker (such as famotidine) 30-60 minutes prior to administration of RYLAZE to decrease the risk and severity of hypersensitivity reactions [see Warnings and Precautions ( 5.1 )] .
2.3Recommended Monitoring and Dosage Modifications for Adverse Reactions Monitor patient’s bilirubin, transaminases, glucose, and clinical examinations prior to treatment every 2-3 weeks and as indicated clinically. If results are abnormal, monitor patients until recovery from the cycle of therapy. If an adverse reaction occurs, modify treatment according to Table 2.
Table 2: Dosage Modifications Adverse Reaction Severity* Action Hypersensitivity Reaction [see Warnings and Precautions ( 5.1 )] Grade 2 • Treat the symptoms. Grade 3 to 4 • Discontinue RYLAZE permanently. Pancreatitis [see Warnings and Precautions ( 5.2 )] Grade 2 to 4 • Hold RYLAZE for elevations in lipase or amylase > 2 times the ULN**, or for symptomatic pancreatitis. • Resume treatment when lipase and amylase are < 1.5 times the ULN and symptoms are resolved. • Discontinue RYLAZE permanently if clinical necrotizing or hemorrhagic pancreatitis is confirmed.
Thrombosis [see Warnings and Precautions ( 5.3 )] Uncomplicated thrombosis • Hold RYLAZE. • Treat with appropriate antithrombotic therapy. • Upon resolution of symptoms, consider resuming RYLAZE, while continuing antithrombotic therapy. Severe or life-threatening thrombosis • Discontinue RYLAZE permanently. • Treat with appropriate antithrombotic therapy. Hemorrhage [see Warnings and Precautions ( 5.4 )] Grade 3 to 4 • Hold RYLAZE. • Evaluate for coagulopathy and consider clotting factor replacement as neede…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 10 mg/0.5 mL clear to opalescent, colorless to slightly yellow solution in a single-dose vial. Injection: 10 mg/0.5 mL solution in a single-dose vial. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS RYLAZE is contraindicated in patients with: • History of serious hypersensitivity reactions to Erwinia asparaginase , including anaphylaxis [see Warnings and Precautions ( 5.1 )] ; • History of serious pancreatitis during previous asparaginase therapy [see Warnings and Precautions ( 5.2 )] ; • History of serious thrombosis during previous asparaginase therapy [see Warnings and Precautions ( 5.3 )] ; • History of serious hemorrhagic events during previous asparaginase therapy [see Warnings and Precautions ( 5.4 )] ; • Severe hepatic impairment [ see Warnings and Precautions ( 5.5 ) ].
RYLAZE is contraindicated in patients with: • History of serious hypersensitivity reactions to RYLAZE, including anaphylaxis. ( 4 ) • History of serious pancreatitis during previous L-asparaginase therapy. ( 4 ) • History of serious thrombosis during previous L-asparaginase therapy.
( 4 ) • History of serious hemorrhagic events during previous L-asparaginase therapy. ( 4 ) • Severe hepatic impairment. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Hypersensitivity: Monitor for signs or symptoms. Discontinue RYLAZE for serious reaction. ( 5.1 ) • Pancreatitis: Monitor for symptoms.
Discontinue if pancreatitis occurs. ( 5.2 ) • Thrombosis: Discontinue RYLAZE for severe or life-threatening thrombosis. Provide anticoagulation therapy as indicated.
( 5.3 ) • Hemorrhage: Discontinue RYLAZE for severe or life-threatening hemorrhage. ( 5.4 ) • Hepatotoxicity, including hepatic veno-occlusive disease: Discontinue RYLAZE for grade 4 increases of bilirubin. ( 5.5 )
5.1Hypersensitivity Reactions Hypersensitivity reactions after the use of RYLAZE occurred in 29% of patients in clinical trials, and it was severe in 6% of patients [see Adverse Reactions ( 6.1 )] . Anaphylaxis was observed in 2% of patients after intramuscular administration. Discontinuation of RYLAZE due to hypersensitivity reactions occurred in 5% of patients.
Hypersensitivity reactions were higher in patients who received intravenous asparaginase erwinia chrysanthemi (recombinant)-rywn. The intravenous route of administration is not approved. In patients administered RYLAZE intramuscularly in clinical trials, the median number of doses of RYLAZE that patients received prior to the onset of the first hypersensitivity reaction was 12 doses (range: 1-64 doses).
The most commonly observed reaction was rash (19%), and 1 patient (1%) experienced a severe rash. 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. Premedicate patients prior to administration of RYLAZE as recommended [see Dosage and Administration ( 2.2 )] .
Because of the risk of serious allergic reactions (e.g., life-threatening anaphylaxis), administer RYLAZE in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g., epinephrine, oxygen, intravenous steroids, antihistamines) [see Dosage and Administration ( 2.3 )] . Discontinue RYLAZE in patients with serious hypersensitivity reactions [see Dosage and Administration ( 2.3 )] .
5.2Pancreatitis Pancreatitis, including elevated amylase or lipase, was reported in 20% of patients in clinical trials of RYLAZE and was severe in 8% [see Adverse Reactions ( 6.1 )] . Symptomatic pancreatitis occurred in 7% of patients, and it was severe in 6% of patients. Elevated amylase or lipase without symptomatic pancreatitis was observed in 13% of patients treated with RYLAZE.
Hemorrhagic or necrotizing pancreatitis have been reported with L-asparaginase class products. Inform patients of the signs and symptoms of pancreatitis, which, if left untreated, could be fatal. Evaluate patients with symptoms compatible with pancreatitis to establish a diagnosis.
Assess serum amylase and lipase levels in patients with any signs or symptoms of pancreatitis. Discontinue RYLAZE in patients with severe or hemorrhagic pancreatitis. In the case of mild pancreatitis, withhold RYLAZE until the signs and symptoms subside and amylase and/or lipase levels return to 1.5 times the ULN [see Dosage and Administration ( 2.3 )] .
After resolution of mild pancreatitis, treatment with RYLAZE may be resumed.
5.3Thrombosis Serious thrombotic events, including sagittal sinus thrombosis and pulmonary embolism, have been reported in 1% of patients following treatment with RYLAZE. Discontinue RYLAZE for a thrombotic event, and administer appropriate antithrombotic therapy. Consider resumption of treatment with RYLAZE only if the patient had an uncomplicated thrombosis [see Dosage and Administration ( 2.3 )] .
5.4Hemorrhage Bleeding was reported in 25% of patients treated with RYLAZE, and it was severe in 2%. Most commonly observed reactions were bruising (12%) and nose bleed (9%) [see Adverse Reactions ( 6.1 )] . In patients treated with L-asparaginase class products, hemorrhage may be associated with increased prothrombin time (PT),…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in greater detail in other sections of the labeling: • Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] • Pancreatic Toxicity [see Warnings and Precautions ( 5.2 )] • Thrombosis [see Warnings and Precautions ( 5.3 )] • Hemorrhage [see Warnings and Precautions ( 5.4 )] • Hepatotoxicity, including VOD [see Warnings and Precautions ( 5.5 )] Most common adverse reactions (incidence > 20%) are abnormal liver test, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage, stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Jazz Pharmaceuticals Ireland Limited at 1-800-520-5568 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of RYLAZE described in the WARNINGS AND PRECAUTIONS reflect exposure in 167 patients administered RYLAZE intramuscularly at various dosages when used in combination with chemotherapy in study JZP458-201 [see Clinical Studies ( 14 )] .
These patients received a median of 4 courses of RYLAZE (range: 1-15 courses); 65% of patients received at least four courses. The safety of RYLAZE described below and in Table 3 was evaluated in study JZP458-201, a multi-cohort study. Patients received RYLAZE administered intramuscularly at dosages of 25 mg/m 2 on Monday, Wednesday, and Friday or 25 mg/m 2 on Monday and Wednesday, and 50 mg/m 2 on Friday, for 6 doses as a replacement for a single dose of pegaspargase as a component of multi-agent chemotherapy [see Clinical Studies ( 14 )] .
The patients had a median age of 11 years (range: 1‑25 years); the majority of patients were male (57%) and White (68%). The patients received a median of 4 courses of RYLAZE (range: 1-14 courses); 65% of patients received at least four courses. A fatal adverse reaction (infection) occurred in 1 patient treated with the RYLAZE 25/25/25 mg/m 2 dosage.
Serious adverse reactions occurred in 60% of patients who received the recommended dosages of RYLAZE. The most frequent nonhematological serious adverse reactions (in ≥ 5% of patients) were febrile neutropenia, infection, drug hypersensitivity, pyrexia, nausea, dehydration, stomatitis, acute kidney injury, pancreatitis, diarrhea, and viral infection. Permanent discontinuation due to an adverse reaction occurred in 10% of patients who received RYLAZE intramuscularly at the recommended dosages.
Adverse reactions resulting in permanent discontinuation included pancreatitis (5%), drug hypersensitivity (4%), and infection (1%). All patients treated with the recommended dosages of RYLAZE as a component of multi-agent chemotherapy experienced neutropenia, anemia, or thrombocytopenia. The most common nonhematological adverse reactions (incidence > 20%) in patients were abnormal liver test, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage, stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia.
Table 3 shows the common adverse reactions occurring in at least 15% of the patients. Table 3: Adverse Reactions (≥ 15% Incidence) in Patients Receiving RYLAZE as a Component of Multi-Agent Chemotherapy in Study JZP458-201 Adverse Reaction RYLAZE 25/25/25 mg/m 2 Intramuscular Dosage a (N = 33) RYLAZE 25/25/50 mg/m 2 Intramuscular Dosage a (N = 51) All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%) Abnormal liver test* # 70 18 75 27 Musculoskeletal pain* 45 6 35 4 Nausea* 45 9 47 8 Fatigue* 36 18 22 18 Headache 3…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Lactation: Advise not to breastfeed. ( 8.2 )
8.1Pregnancy 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. In animal reproductive and developmental toxicity studies, intramuscular administration of asparaginase Erwinia chrysanthemi to pregnant rats and rabbits during organogenesis resulted in structural abnormalities and embryo-fetal mortality ( see Data ) at exposures below those in patients at the recommended human dose.
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. Data Animal Data Animal reproductive and developmental toxicity studies have not been conducted with RYLAZE.
In embryofetal development studies, asparaginase Erwinia chrysanthemi was administered intramuscularly every other day during the period of organogenesis to pregnant rats (at 3, 6, or 12 mg/m 2 ) and rabbits (at 0.12, 0.30, or 0.48 mg/m 2 ). In rats given 12 mg/m 2 (approximately 0.48 times the maximum recommended human dose), 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/m 2 (approximately 0.02 times the maximum recommended human dose).
Increased post-implantation loss, a decrease in the number of live fetuses, and gross abnormalities (e.g., absent kidney, absent accessory lung lobe, additional subclavian artery, and delayed ossification) were observed at doses of ≥ 0.12 mg/m 2 (approximately 0.005 times the maximum recommended human dose).
8.2Lactation 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.
8.3Females 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.
8.4Pediatric 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. coli -derived 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 139 pediatric patients, including 2 infants (1 month to < 2 years), 99 children (2 years to < 12 years old), and 38 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.
8.5Geriatric 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.
🤰 Pregnancy ▾
8.1Pregnancy 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. In animal reproductive and developmental toxicity studies, intramuscular administration of asparaginase Erwinia chrysanthemi to pregnant rats and rabbits during organogenesis resulted in structural abnormalities and embryo-fetal mortality ( see Data ) at exposures below those in patients at the recommended human dose.
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. Data Animal Data Animal reproductive and developmental toxicity studies have not been conducted with RYLAZE.
In embryofetal development studies, asparaginase Erwinia chrysanthemi was administered intramuscularly every other day during the period of organogenesis to pregnant rats (at 3, 6, or 12 mg/m 2 ) and rabbits (at 0.12, 0.30, or 0.48 mg/m 2 ). In rats given 12 mg/m 2 (approximately 0.48 times the maximum recommended human dose), 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/m 2 (approximately 0.02 times the maximum recommended human dose).
Increased post-implantation loss, a decrease in the number of live fetuses, and gross abnormalities (e.g., absent kidney, absent accessory lung lobe, additional subclavian artery, and delayed ossification) were observed at doses of ≥ 0.12 mg/m 2 (approximately 0.005 times the maximum recommended human dose).
🧒 Pediatric Use ▾
8.4Pediatric 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. coli -derived 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 139 pediatric patients, including 2 infants (1 month to < 2 years), 99 children (2 years to < 12 years old), and 38 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.
🧓 Geriatric Use ▾
8.5Geriatric 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Asparaginase erwinia chrysanthemi (recombinant)-rywn is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. 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.
12.2Pharmacodynamics Asparaginase erwinia chrysanthemi (recombinant)-rywn exposure-response relationships and the time course of pharmacodynamic response are unknown.
12.3Pharmacokinetics The pharmacokinetic parameters of asparaginase erwinia chrysanthemi (recombinant)-rywn are presented based on serum asparaginase activity (SAA) after administration of RYLAZE in pediatric and young adult patients with ALL or LBL, unless otherwise specified. Asparaginase erwinia chrysanthemi (recombinant)-rywn maximum SAA (C max ) and area under the SAA-time curve (AUC) increase proportionally over a dosage range from 12.5 to 50 mg/m 2 (0.25 to 1 times the maximum approved recommended dose of 50 mg/m 2 ).
The simulated exposures for asparaginase erwinia chrysanthemi (recombinant)-rywn after administration of the approved recommended dosages in a virtual population are summarized in Table 4. Table 4: Simulated RYLAZE Pharmacokinetic Parameters Based on SAA PK Parameter Geometric Mean (%CV) After Last Dose 25 mg/m 2 Intramuscularly Every 48 Hours 25/25/50 mg/m 2 Intramuscularly Monday, Wednesday, Friday Last 25 mg/m 2 Wednesday morning dose Last 50 mg/m 2 Friday afternoon dose C max (U/mL) 2.3 (55%) 2.3 (54%) 4.1 (57%) C trough (U/mL) 0.46 (75%) 0.3 (75%) a 0.39 (87%) b a C trough at maximum interval of 58 hours after the last 25 mg/m 2 Wednesday morning dose. b C trough at maximum interval of 67 hours after the last 50 mg/m 2 Friday afternoon dose.
Absorption The median (min, max) T max of asparaginase erwinia chrysanthemi (recombinant)-rywn after intramuscular administration is 12 (8, 24) hours. The mean absolute bioavailability after intramuscular administration is 37% in healthy subjects. Distribution The geometric mean (%CV) volume of distribution of asparaginase erwinia chrysanthemi (recombinant)-rywn is
1.37L/m 2 (47%). Elimination The geometric mean (%CV) clearance of asparaginase erwinia chrysanthemi (recombinant)-rywn is
0.17L/hour/m 2 (42%) and the apparent half-life is 15.9 (11%) hours. Metabolism Asparaginase erwinia chrysanthemi (recombinant)-rywn is expected to be metabolized into small peptides by catabolic pathways. Specific Populations There were no clinically significant differences in the pharmacokinetics of asparaginase erwinia chrysanthemi (recombinant)-rywn based on age (1.4 to 25 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 volume of distribution and clearance of asparaginase erwinia chrysanthemi (recombinant)-rywn increase with increasing BSA (0.44 to 2.53 m 2 ). Racial and Ethnic Groups Black or African American patients had 29% lower clearance which may increase SAA exposure compared to White and Asian patients.
There were no clinically significant differences in clearance between Hispanic and Non-Hispanic patients.
12.6Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti‑drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of RYLAZE or of other asparaginase erwinia chrysanthemi (recombinant) products. During treatment in Study JZP458-201 (range 1 to 15 courses), 78/166 (47%…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Asparaginase erwinia chrysanthemi (recombinant)-rywn is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING RYLAZE (asparaginase erwinia chrysanthemi (recombinant)-rywn) injection is supplied as a sterile, clear to opalescent, colorless to slightly yellow, preservative-free solution in single-dose vials. Each single-dose vial (NDC 68727-900-01) contains 10 mg/0.5 mL asparaginase erwinia chrysanthemi (recombinant)-rywn. Each carton of RYLAZE (NDC 68727-900-03) contains 3 single-dose vials.
Store RYLAZE vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not shake or freeze.
📋 Description ▾
11 DESCRIPTION Asparaginase erwinia chrysanthemi (recombinant)-rywn contains an asparagine specific bacterial enzyme (L-asparaginase). L-asparaginase is a tetrameric enzyme that consists of four identical 35 kDa subunits with a combined molecular weight of 140 kDa. The amino acid sequence is identical to native asparaginase Erwinia chrysanthemi (also known as crisantaspase).
The activity of asparaginase erwinia chrysanthemi (recombinant)-rywn is expressed in units, defined as the amount of enzyme that catalyzes the conversion of 1μmol of L-asparagine per reaction minute, per mg of protein. 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 . RYLAZE (asparaginase erwinia chrysanthemi (recombinant)-rywn) injection is supplied as a sterile, clear to opalescent, colorless to slightly yellow, preservative-free solution for intramuscular injection.
Each 0.5 mL contains 10 mg asparaginase erwinia chrysanthemi (recombinant)-rywn and the inactive ingredients: polysorbate 80 (0.1 mg), sodium chloride (1.5 mg), sodium phosphate dibasic anhydrous (0.8 mg), sodium phosphate monobasic monohydrate (0.6 mg), and trehalose dihydrate (32.1 mg). Sodium hydroxide may be added during manufacture to adjust the pH. The pH is approximately 7.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION • Hypersensitivity 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 [see Warnings and Precautions ( 5.1 )] . • Pancreatitis Instruct patients on signs and symptoms of pancreatitis and to seek medical attention if they experience severe abdominal pain [see Warnings and Precautions ( 5.2 )] . • Thrombosis Instruct patients on the risk of thrombosis and to seek medical advice immediately if they experience headache, arm or leg swelling, shortness of breath, and chest pain [see Warnings and Precautions ( 5.3 )] . • Hemorrhage Advise patients to report any unusual bleeding or bruising to their healthcare provider [see Warnings and Precautions ( 5.4 )] . • Hepatotoxicity, including Veno-Occlusive Liver Disease Inform patients that liver problems, including severe, life-threatening, or fatal VOD and abnormalities in liver tests, may develop during RYLAZE treatment.
Advise patients to report any jaundice, severe nausea or vomiting, or easy bleeding or bruising to their healthcare provider [see Warnings and Precautions ( 5.5 )] . • 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 [see Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective non-hormonal contraception during treatment with RYLAZE and for 3 months after the last dose [see Use in Specific Populations ( 8.3 )] . • Lactation Advise women not to breastfeed during treatment with RYLAZE and for 1 week after the last dose [see Use in Specific Populations ( 8.2 )] .
Manufactured by: Jazz Pharmaceuticals Ireland Limited Dublin, Ireland U.S. License No. 2167 Distributed by: Jazz Pharmaceuticals, Inc.
Palo Alto, CA 94306 Protected by U.S. Patent nos. 8,288,127 and 10,787,671 RYLAZE ® is a trademark of Jazz Pharmaceuticals plc or its subsidiaries. ©2024 Jazz Pharmaceuticals