BRIEF SUMMARY

EFLAPEGRASTIM- (Sep 2022)

Indn-  decrease the incidence of of infection  in  patients with non-myeloid malignancies             receiving non-myelosuppressive anti-cancer  drugs  

Comp-  Injection: 13.2 mg/0.6 mL solution in a single-dose prefilled syringe                                    recoommended Dose: 13.2 mg administered subcutaneously once per                            chemotherapyapy cycle.

             Administer approximately 24 hours after cytotoxic chemotherapy. Do not                          administer within the period from 14 days before to 24 hours after administration                of cytotoxic chemotherapy

ADR-  The most common adverse reactions  are fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, and back pain.

CI- Patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as eflapegrastim, pegfilgrastim or filgrastim products. 

WARNINGS -

 Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.

 Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue Rolvedon in patients with ARDS.

Serious allergic reactions, including anaphylaxis: Permanently discontinue Rolvedon 

Pat inform-

Advise patients of the following risks and potential risks with Rolvedon:

 Splenic rupture and splenomegaly

 Acute respiratory distress syndrome

 Serious allergic reactions 

 Sickle cell crisis

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U.S.  APPROVED DRUGS SURING 2022                                        

Serial No 21

Name-                        ROLVEDON

Active Ingredient -   Eflapegrastim

Pharmacological Classification- To decrease the incidence of of infection  in                                                                 patients with non-myeloid malignancies                                                                          receiving non-myelosuppressive anti-cancer                                                               drugs  associted with clinically significant                                                                    incidence of febrile neutropenia

                                                                                                                                             Date of Approval-         9/9/2022   

  HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                         ROLVEDON™ safely and effectively.                                                                           See full prescribing information for ROLVEDON. ROLVEDON™ (eflapegrastim-xnst) injection, for subcutaneous use.

Initial U.S. Approval: 2022

INDICATIONS AND USAGE-

 Rolvedon is a leukocyte growth factor indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia.

 Limitations of Use Rolvedon is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

DOSAGE AND ADMINISTRATION-

• Recommended Dose: 13.2 mg administered subcutaneously once per chemotherapy cycle.

 • Administer approximately 24 hours after cytotoxic chemotherapy. Do not administer within the period from 14 days before to 24 hours after administration of cytotoxic chemotherapy

DOSAGE FORMS AND STRENGTHS--

 Injection: 13.2 mg/0.6 mL solution in a single-dose prefilled syringe.

CONTRAINDICATIONS-

 Patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as eflapegrastim, pegfilgrastim or filgrastim products. 

WARNINGS AND PRECAUTIONS-

 • Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.

 • Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue Rolvedon in patients with ARDS.

• Serious allergic reactions, including anaphylaxis: Permanently discontinue Rolvedon in patients with serious allergic reactions.

 • Sickle Cell Crisis in Patients with Sickle Cell Disorders: Discontinue Rolvedon if sickle cell crisis occurs.

 • Glomerulonephritis: Evaluate and consider dose-reduction or interruption of Rolvedon if causality is likely.

 • Leukocytosis: Monitor complete blood count (CBC) during Rolvedon therapy.

 • Thrombocytopenia: Monitor platelet counts.

 • Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML): Monitor patients with breast and lung cancer using Rolvedon in conjunction with chemotherapy and/or radiotherapy for signs and symptoms of MDS/AML.

ADVERSE REACTIONS-

 The most common adverse reactions (=20%) are fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, and back pain.

PATIENT COUNSELING INFORMATION-

 Advise the patient to read the FDA-approved patient labeling (Patient Information). Rolvedon should only be given by a healthcare professional. Inform patients to contact their healthcare provider with any questions.

Advise patients of the following risks and potential risks with Rolvedon:

• Splenic rupture and splenomegaly [see Warnings and Precautions

 • Acute respiratory distress syndrome [see Warnings and Precautions

 • Serious allergic reactions [see Warnings and Precautions

 • Sickle cell crisis [see Warnings and Precautions

 • Glomerulonephritis [see Warnings and Precautions

 • Leukocytosis [see Warnings and Precautions

 • Thrombocytopenia [see Warnings and Precautions

 • Capillary leak syndrome [see Warnings and Precautions

 • Potential for tumor growth stimulatory effects on malignant cells [see Warnings and Precautions

 • Increased risk of myelodysplastic syndrome and/or acute myeloid leukemia in patients with breast and lung cancer who receive Rolvedon in conjunction with chemotherapy and/or radiation therapy [see Warnings and Precautions

 • Aortitis [see Warnings and Precautions 

Manufactured by: Spectrum Pharmaceuticals, Inc. 9 Reference ID: 5044179 18200 Von Karman Avenue, Suite 700 Irvine, CA 92612 USA U.S. License No. 2312

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                        Eflapegrastim-xnst is a recombinant human granulocyte growth factor that binds to G-CSF receptors on myeloid progenitor cells and neutrophils, triggering signaling pathways that control cell differentiation, proliferation, migration and survival.

2. Pharmacodynamics Eflapegrastim-xnst has been shown to elevate neutrophil counts in healthy subjects and in cancer patients.

Absolute neutrophil count (ANC), Cmax and area under the effect curve (AUEClast) increased with increasing doses of eflapegrastim-xnst in a linear, but less than dose-proportional, manner over a dose range of 45 to 350 mcg/kg.

3. Pharmacokinetics-                                                                                                         The pharmacokinetics of eflapegrastim-xnst was studied in healthy subjects and patients with breast cancer.

After subcutaneous (SC) dosing, the pharmacokinetics of eflapegrastim-xnst was nonlinear and exposure increases were not dose-proportional over the dose range of 45 to 350 mcg/kg.

Absorption-                                                                                                                   The median Tmax of eflapegrastim-xnst is 25 hours (6 to 144 hours) in patients with breast cancer following administration of the recommended dosage.

Distribution-                                                                                                                  The volume of distribution of eflapegrastim-xnst is 1.44 L. Elimination The geometric mean half-life of eflapegrastim-xnst in patients with breast cancer is 36.4 hours (Range: 16.1 to 115 hours) during Cycle 1.

Eflapegrastim-xnst clearance decreased with increasing doses following single dose administration, suggesting target-mediated clearance of eflapegrastim-xnst by neutrophils.

Metabolism-                                                                                                            Eflapegrastim-xnst is expected to be metabolized by endogenous degradation following receptor-mediated internalization by cells bearing the G-CSF receptor. Excretion

Eflapegrastim-xnst was not detected in urine.

Drug Interaction Studies-                                                                                              No studies evaluating the drug interaction potential of eflapegrastim-xnst have been conducted.

 Immunogenicity-                                                                                                         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 eflapegrastim-xnst or of other eflapegrastim products.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-

There are no available data on Rolvedon use in pregnant women; however, data from published studies with use of other recombinant human granulocyte colony-stimulating factor (rhG-CSF) products in pregnant women have not identified any drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

2. Lactation Risk Summary-

There are no data on the presence of eflapegrastim-xnst in human milk, the effects on the breastfed child, or the effects on milk production. Endogenous granulocyte colony-stimulating factor (G-CSF) is present in human milk. Other recombinant human granulocyte colony-stimulating factor (rhG-CSF) products are present in human milk at low levels and are not orally absorbed by infants.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Rolvedon and any potential adverse effects on the breastfed child from Rolvedon or from the underlying maternal condition.

3. Pediatric Use-                                                                                                        Safety and effectiveness in pediatric patients have not been established.

4.Geriatric Use -                                                                                                              Of the 314 patients in clinical studies of Rolvedon, 39% were 65 and over, while 6% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

 OVERDOSAGE-

Overdose of Rolvedon may result in leukocytosis and bone pain. In the event of overdose, general supportive measures should be instituted as necessary. Monitor the patient for adverse reactions.