Ryzneuta
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kosar Doraghi, M.D.[2]]
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Black Box Warning
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RYZNEUTA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation
See full prescribing information for complete Boxed Warning.
Fatal Splenic Rupture
Permanently discontinue RYZNEUTA in patients experiencing serious allergic reactions, including anaphylaxis.
Monitor patients with symptoms; consider intensive care.
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Overview
Ryzneuta is a leukocyte growth factor that is FDA approved for the treatment of and decrease the incidence of infection, as manifested by [febrile neutropenia], in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. There is a Black Box Warning for this drug as shown here. Common adverse reactions include [nausea], [anemia], and [thrombocytopenia].
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
20 mg administered subcutaneously once per chemotherapy cycle. Administer approximately 24 hours after cytotoxic chemotherapy. Do not administer between 14 days before and 24 hours after administration of cytotoxic chemotherapy.
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Ryzneuta FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Contraindications
Patients with a history of serious allergic reactions to granulocyte stimulating factors such as efbemalenograstim alfa-vuxw, pegfilgrastim, or filgrastim products
Warnings
|
RYZNEUTA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation
See full prescribing information for complete Boxed Warning.
Fatal Splenic Rupture
Permanently discontinue RYZNEUTA in patients experiencing serious allergic reactions, including anaphylaxis.
Monitor patients with symptoms; consider intensive care.
|
- Fatal Splenic Rupture:
Evaluate patients reporting left upper abdominal or shoulder pain for enlarged spleen or splenic rupture.
- Acute Respiratory Distress Syndrome (ARDS):
Evaluate patients showing fever, lung infiltrates, or respiratory distress. Discontinue RYZNEUTA in patients diagnosed with ARDS.
- Serious Allergic Reactions:
Permanently discontinue RYZNEUTA in patients experiencing serious allergic reactions, including anaphylaxis.
- Sickle Cell Crises in Patients with Sickle Cell Disorders:
Discontinue RYZNEUTA if sickle cell crisis occurs.
- Glomerulonephritis:
Evaluate and consider dose-reduction or interruption of RYZNEUTA if causality is likely.
- Thrombocytopenia:
Monitor platelet counts.
- Capillary Leak Syndrome:
Monitor patients with symptoms; consider intensive care.
- Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer:
Monitor breast and lung cancer patients using RYZNEUTA with chemotherapy and/or radiotherapy for signs and symptoms of MDS/AML.
Adverse Reactions
Clinical Trials Experience
- Splenic Rupture
- Acute Respiratory Distress Syndrome
- Serious Allergic Reactions
- Sickle Cell Crisis in Patients with Sickle Cell Disorders
- Glomerulonephritis
- Leukocytosis
- Thrombocytopenia
- Capillary Leak Syndrome
- Potential for Tumor Growth Stimulatory Effects on Malignant Cells
- Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer
- Aortitis
Postmarketing Experience
There is limited information regarding Ryzneuta Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Ryzneuta Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Ryzneuta in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ryzneuta in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Ryzneuta during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Ryzneuta in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Ryzneuta in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Ryzneuta in geriatric settings.
Gender
There is no FDA guidance on the use of Ryzneuta with respect to specific gender populations.
Race
There is no FDA guidance on the use of Ryzneuta with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Ryzneuta in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Ryzneuta in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Ryzneuta in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Ryzneuta in patients who are immunocompromised.
Administration and Monitoring
Administration
The recommended dosage of RYZNEUTA is a single subcutaneous injection of 20 mg administered once per chemotherapy cycle at least 24 hours after cytotoxic chemotherapy. Do not administer RYZNEUTA within 14 days before and <24 hours after administration of cytotoxic chemotherapy.
- Administration:
RYZNEUTA is administered subcutaneously via a single-dose prefilled syringe by a healthcare professional. Prior to use, remove the carton from the refrigerator for a minimum of 30 minutes to allow the product to reach room temperature. Discard any product left at room temperature for greater than 48 hours. Inspect visually for particulate matter and discoloration prior to administration. Do not administer RYZNEUTA if discoloration or particulates are observed. Caution: This product contains natural rubber latex which may cause allergic reactions. The needle cap on the prefilled syringe contains natural rubber; people with latex allergies should not administer this product. The RYZNEUTA prefilled syringe does not bear graduation marks and is intended only to deliver the entire contents of the syringe (20 mg/mL) for direct administration to adult patients. Administer injection by pinching the skin and holding. Inject into the abdomen, the back or side of the upper arms, or the thighs. Rotate injection sites. Do not inject into scar tissue or areas that are reddened, inflamed, or swollen. If injecting into the abdomen, avoid a 2-inch diameter circle around the navel. Once the entire dose has been injected, the needle safety device will be triggered, pulling the needle automatically from the skin, and into the barrel; the entire needle will be covered by the needle guard.
Monitoring
There is limited information regarding Ryzneuta Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Ryzneuta and IV administrations.
Overdosage
Overdosage of RYZNEUTA may lead to leukocytosis and bone pain. In case of overdose, administer general supportive measures as necessary. Monitor the patient for adverse reactions
Pharmacology
There is limited information regarding Ryzneuta Pharmacology in the drug label.
Mechanism of Action
Efbemalenograstim alfa-vuxw is a colony-stimulating factor that acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end-cell functional activation.
Structure
Efbemalenograstim alfa-vuxw is a leukocyte growth factor, comprised of a 413 amino acid recombinant fusion protein. It consists of human G-CSF, a 16 amino-acid linker, and the Fc portion of human IgG2. In solution, efbemalenograstim alfa-vuxw forms covalently-linked dimers due to disulfide bonds between Fc moieties, resembling an immunoglobulin-like structure. The dimer is a water-soluble, glycosylated protein with a molecular weight of approximately 93.4 kilodaltons (kDa), with 89.5 kDa attributed to amino acids and the rest from glycosylation. Efbemalenograstim alfa-vuxw is derived from a genetically-engineered strain of Chinese hamster ovary (CHO) cells grown in a serum-free medium. RYZNEUTA (Efbemalenograstim alfa-vuxw) Injection:
Supplied in 1 mL prefilled single-dose syringes for manual subcutaneous injection. The prefilled syringe does not have graduation marks and is intended to deliver the entire contents (20 mg/mL). Each syringe contains 20 mg efbemalenograstim alfa-vuxw in a sterile, clear, colorless, preservative-free solution with pH 5.2. The solution contains acetate (0.6 mg), EDTA (0.29 mg), polysorbate 20 (0.1 mg), sodium (0.23 mg), and sorbitol (50 mg) in Water for Injection, USP.
Pharmacodynamics
Over the tested dose range of 30 to 360 μg/kg in healthy adult males, neutrophils generally increased in a dose-dependent manner; however, the effect on neutrophils plateaued at the top two doses of 240 and 360 μg/kg
Pharmacokinetics
Absorption The median tmax of efbemalenograstim alfa-vuxw administered as 80 to 320 μg/kg in female patients with breast cancer receiving EC chemotherapy ranged from 24 hours to 48 hours in Cycle 1 and 9 to 30 hours in Cycle 3. The median tmax of efbemalenograstim alfa-vuxw administered as 240 to 320 μg/kg in female participants with breast cancer receiving TAC chemotherapy was 36 hours in Cycle 1 and ranged from 24 to 30 hours in Cycle 3
Nonclinical Toxicology
Efbemalenograstim alfa did not affect reproductive performance or fertility in male or female rats at cumulative weekly doses approximately 2.2 times higher than the recommended human dose (based on body surface area
Clinical Studies
Study GC-627-04 (NCT02872103): Randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer. Chemotherapy regimen: Doxorubicin 60 mg/m2 and docetaxel 75 mg/m2 every 21 days for up to 4 cycles. 122 patients received RYZNEUTA (20 mg) or placebo on day 2 of chemotherapy cycle 1. All received RYZNEUTA on day 2 of cycles 2 – 4. Efficacy: Mean duration of severe neutropenia in cycle 1 was significantly lower for RYZNEUTA-treated patients compared to placebo (1.4 days vs. 4.3 days, p<0.001). Incidence of febrile neutropenia was lower in RYZNEUTA-treated patients compared to placebo in cycle 1 (4.8% vs. 25.6%, p=0.0016). Study GC-627-05 (NCT03252431):
Randomized, active-controlled study in patients with non-metastatic breast cancer. Chemotherapy regimen: Docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days for up to 4 cycles. 393 patients received RYZNEUTA (20 mg) or pegfilgrastim (6 mg) on day 2 of each chemotherapy cycle. No significant difference observed in mean days of severe neutropenia between RYZNEUTA and pegfilgrastim arms in cycle 1 (0.2 days in both arms).
How Supplied
RYZNEUTA (efbemalenograstim alfa-vuxw) injection is a clear, colorless, preservative-free solution supplied in a prefilled single-dose syringe with a 27-gauge, 1/2-inch needle and an UltraSafe Passive™ Needle Guard, containing 20 mg of efbemalenograstim alfa-vuxw.
Storage
Store refrigerated at 2° to 8°C (36° to 46°F) in the carton to protect from light. Do not shake. Discard syringes stored at room temperature for more than 48 hours. Do not freeze. Discard syringe if frozen.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
- Recommended Dosage:
The recommended dosage of RYZNEUTA is a single subcutaneous injection of 20 mg administered once per chemotherapy cycle at least 24 hours after cytotoxic chemotherapy. Do not administer RYZNEUTA within 14 days before and <24 hours after administration of cytotoxic chemotherapy.
- Administration:
RYZNEUTA is administered subcutaneously via a single-dose prefilled syringe by a healthcare professional. Prior to use, remove the carton from the refrigerator for a minimum of 30 minutes to allow the product to reach room temperature. Discard any product left at room temperature for greater than 48 hours. Inspect visually for particulate matter and discoloration prior to administration. Do not administer RYZNEUTA if discoloration or particulates are observed. Caution: This product contains natural rubber latex which may cause allergic reactions. The needle cap on the prefilled syringe contains natural rubber; people with latex allergies should not administer this product. The RYZNEUTA prefilled syringe does not bear graduation marks and is intended only to deliver the entire contents of the syringe (20 mg/mL) for direct administration to adult patients. Administer injection by pinching the skin and holding. Inject into the abdomen, the back or side of the upper arms, or the thighs. Rotate injection sites. Do not inject into scar tissue or areas that are reddened, inflamed, or swollen. If injecting into the abdomen, avoid a 2-inch diameter circle around the navel. Once the entire dose has been injected, the needle safety device will be triggered, pulling the needle automatically from the skin, and into the barrel; the entire needle will be covered by the needle guard.
Precautions with Alcohol
Alcohol-Ryzneuta interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Ryzneuta Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Ryzneuta Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.