Leukocyte Growth Factor

Rolvedon

Approved 9 Sept 2022SubcutaneousInjectable

Indications

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

( 1 ) Limitations of Use Rolvedon is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. ( 1 )

Contraindications

Rolvedon is contraindicated in patients with a history of serious allergic reactions to eflapegrastim, pegfilgrastim, or filgrastim products. Reactions may include anaphylaxis [see Warnings and Precautions ( 5.3 )] . Patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as eflapegrastim, pegfilgrastim or filgrastim products. ( 4 )

Warnings and precautions

Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture. ( 5.1 )
Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue Rolvedon in patients with ARDS. ( 5.2 )
Serious allergic reactions, including anaphylaxis: Permanently discontinue Rolvedon in patients with serious allergic reactions. ( 5.3 )
Sickle Cell Crisis in Patients with Sickle Cell Disorders: Discontinue Rolvedon if sickle cell crisis occurs. ( 5.4 )
Glomerulonephritis: Evaluate and consider dose-reduction or interruption of Rolvedon if causality is likely. ( 5.5 )
Leukocytosis: Monitor complete blood count (CBC) during Rolvedon therapy. ( 5.6 )

Indications

( 1 ) Limitations of Use Rolvedon is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. ( 1 )

Contraindications

Warnings and precautions

Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture. ( 5.1 )
Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue Rolvedon in patients with ARDS. ( 5.2 )
Serious allergic reactions, including anaphylaxis: Permanently discontinue Rolvedon in patients with serious allergic reactions. ( 5.3 )
Sickle Cell Crisis in Patients with Sickle Cell Disorders: Discontinue Rolvedon if sickle cell crisis occurs. ( 5.4 )
Glomerulonephritis: Evaluate and consider dose-reduction or interruption of Rolvedon if causality is likely. ( 5.5 )
Leukocytosis: Monitor complete blood count (CBC) during Rolvedon therapy. ( 5.6 )

Pregnancy and breastfeeding

8.1Pregnancy 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. Animal reproduction studies were conducted in rats and rabbits. In rats, eflapegrastim-xnst did not adversely affect embryofetal and/or postnatal development when administered from organogenesis throughout lactation at doses that produced maternal exposures up to 7 times the exposure at the recommended clinical dose.

In rabbits, eflapegrastim-xnst caused embryofetal lethality and reduced fetal weight when administered during the organogenesis period at approximately 6 times the exposure at the clinical dose (see Data) . 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.

Data Animal Data In an embryofetal developmental study in rabbits, eflapegrastim-xnst was administered subcutaneously every other day during the period of organogenesis at doses up to 10 times the clinical exposure at the maximum recommended dose of 13.2 mg. Increased post-implantation loss, reduced number of live fetuses, and reduced fetal body weights were observed at 6 times the clinical exposure, based on AUC. No malformations were observed up to 10 times the clinical exposure, based on AUC.

In an embryofetal developmental study in rats, eflapegrastim-xnst administered subcutaneously every other day during the period of organogenesis did not adversely affect embryofetal development at doses up to 7 times clinical exposure, based on AUC. In a pre- and post-natal development study in rats, eflapegrastim-xnst administered subcutaneously once weekly from organogenesis through lactation did not adversely affect behavioral, developmental, or reproductive parameters at doses up to 7 times the clinical exposure, based on AUC.

Adverse reactions

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

Splenic rupture [see Warnings and Precautions ( 5.1 )]
Acute respiratory distress syndrome [see Warnings and Precautions ( 5.2 )]
Serious allergic reactions [see Warnings and Precautions ( 5.3 )]
Sickle cell crisis in patients with sickle cell disorders [see Warnings and Precautions ( 5.4 )]
Glomerulonephritis [see Warnings and Precautions ( 5.5 )]
Leukocytosis [see Warnings and Precautions ( 5.6 )]
Thrombocytopenia [see Warnings and Precautions ( 5.7 )]
Capillary leak syndrome [see Warnings and Precautions ( 5.8 )]
Potential for tumor growth stimulatory effects on malignant cells [see Warnings and Precautions ( 5.9 )]
Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer [see Warnings and Precautions ( 5.10 )]
Aortitis [see Warnings and Precautions ( 5.11 )]
Nuclear Imaging [see Warnings and Precautions ( 5.12 )] The most common adverse reactions (≥20%) are fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, and back pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact 1-800-518-1084 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 clinical practice. The safety of Rolvedon was evaluated in Study 1 and Study 2 [see Clinical Studies ( 14 )]. Patients with early-stage breast cancer received Rolvedon 13.2 mg by subcutaneous injection (n=314) or pegfilgrastim 6 mg by subcutaneous injection (n=326) on Day 2 of each cycle after docetaxel 75 mg/m 2 and cyclophosphamide 600 mg/m 2 (TC) chemotherapy.

Among patients receiving Rolvedon, a total of 272 patients received four 21-day treatment cycles. The most common adverse reactions (≥20%) were fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, and back pain. Table 1 summarizes the adverse reactions that occurred in Studies 1 and 2. Table 1. Common Adverse Reactions with a Frequency of ≥10% Through Week 14 in Patients with Early-Stage Breast Cancer in Study 1 and Study 2 Adverse Reaction Rolvedon (N = 314) % Pegfilgrastim** (N=326) % *Grouped Terms **Study 1 and Study 2 were not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the Rolvedon and the pegfilgrastim treatment groups.

Fatigue * 181 (58%) 192 (59%) Nausea 162 (52%) 166 (51%) Diarrhea 125 (40%) 126 (39%) Bone pain 119 (38%) 121 (37%) Headache * 92 (29%) 90 (28%) Pyrexia * 87 (28%) 84 (26%) Anemia * 77 (25%) 52 (16%) Rash * 77 (25%) 99 (30%) Myalgia 69 (22%) 49 (15%) Arthralgia 66 (21%) 48 (15%) Back pain * 63 (20%) 55 (17%) Decreased appetite 61 (19%) 50 (15%) Peripheral edema * 57 (18%) 53 (16%) Abdominal pain * 53 (17%) 67 (21%) Dizziness * 50 (16%) 38 (12%) Dyspnea * 49 (16%) 44 (13%) Cough * 48 (15%) 51 (16%) Thrombocytopenia * 44 (14%) 17 (5%) Pain 37 (12%) 42 (13%) Pain in extremity 36 (11%) 42 (13%) Local administration reactions * 34 (11%) 27 (8%) Flushing 32 (10%) 27 (8%) Permanent discontinuation due to an adverse reaction occurred in 4% of patients who received Rolvedon.

The adverse reaction requiring permanent discontinuation in 3 patients who received Rolvedon was rash.

Rolvedon

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Rolvedon

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Splenic Rupture

5.2Acute Respiratory Distress Syndrome

5.3Serious Allergic Reactions

5.4Sickle Cell Crisis in Patients with Sickle Cell Disorders Severe

5.5Glomerulonephritis

5.6Leukocytosis

5.7Thrombocytopenia

5.8Capillary Leak Syndrome

5.9Potential for Tumor Growth Stimulatory Effects on Malignant Cells

5.11Aortitis

5.12Nuclear Imaging

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

Composition

Official product information

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