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Eflapegrastim: Drug information

Eflapegrastim: Drug information
(For additional information see "Eflapegrastim: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Rolvedon
Pharmacologic Category
  • Colony Stimulating Factor;
  • Hematopoietic Agent
Dosing: Adult
Chemotherapy-induced neutropenia, prevention

Chemotherapy-induced neutropenia, prevention: SUBQ: 13.2 mg once per chemotherapy cycle (Ref). Administer ~24 hours after cytotoxic chemotherapy. Do not administer within the period from 14 days before to 24 hours after administration of cytotoxic chemotherapy.

Dosing: Kidney Impairment: Adult

Altered kidney function prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling.

Nephrotoxicity during treatment: Glomerulonephritis (suspected): If glomerulonephritis is suspected, evaluate for cause; if likely due to eflapegrastim, consider dose reduction or treatment interruption.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Adjustment for Toxicity: Adult

Acute respiratory distress syndrome: Discontinue eflapegrastim.

Allergic reactions, serious: Permanently discontinue eflapegrastim.

Aortitis (suspected): Discontinue eflapegrastim if aortitis is suspected.

Capillary leak syndrome: Monitor closely and manage symptomatically if capillary leak syndrome develops (may require intensive care).

Sickle cell crisis: Discontinue eflapegrastim if sickle cell crisis occurs.

WBC ≥100,000/mm3: Discontinue eflapegrastim.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions (Significant): Considerations
Acute myeloid leukemia and myelodysplastic syndrome

Acute myeloid leukemia and myelodysplastic syndrome have been reported with filgrastim, another granulocyte-colony stimulating factor product, when used in conjunction with chemotherapy and/or radiotherapy (Ref).

Aortitis

Aortitis has been rarely reported in patients receiving other granulocyte-colony stimulating factor (G-CSF) products (eg, filgrastim, pegfilgrastim), commonly presenting with systemic symptoms (eg, high fever, abdominal pain, malaise, back pain, and increased inflammatory markers (eg, c-reactive protein, white blood cell count) rather than peripheral vasculitis (Ref). Aortitis recurrence with re-administration of G-CSF following aortitis resolution has also been reported (Ref).

Mechanism: Not fully elucidated; may be related to cytokines and complex immune reactions between anti-cancer agents and G-CSF (Ref).

Onset: Varied; median time to onset of 8 days and mean time to onset of 12.3 days (range: 0 to 180 days) has been reported (Ref).

Capillary leak syndrome

Capillary leak syndrome (CLS), characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration, have been reported in patients who received granulocyte-colony stimulating factor (G-CSF) products. CLS episodes may vary in frequency and severity and may be life-threatening if treatment is delayed (Ref).

Mechanism: Not fully elucidated; one study suggests G-CSF may trigger neutrophil activation and the release of inflammatory mediators, resulting in tissue damage and systemic manifestations of increased capillary permeability (Ref).

Onset: Varied; has been reported within a few hours of administration (Ref) or over the course of 3 weeks (Ref).

Pulmonary toxicity

Acute respiratory distress syndrome, respiratory status deterioration (including acute respiratory failure), and exacerbation of preexisting pulmonary disease have been reported with granulocyte-colony stimulating factor (G-CSF) products and may be life-threatening (Ref).

Mechanism: Not fully elucidated; G-CSF enhancement of cytokine production (eg, TNF-α, IL-1β, and IL-8) increases alveolar permeability and neutrophil influx by activation of the oxidative burst within circulating or resident alveolar neutrophils and macrophages (Ref).

Onset: Rapid; has been reported within 1 day (range: 0.5 to 2 days) (Ref).

Risk factors:

• ≥3 courses of cancer chemotherapy (Ref)

• Neutropenia recovery period (including early or steep neutrophil recovery period) (Ref)

• Recent history of pulmonary infiltrates or pneumonia (Ref)

• Pulmonary infection (Ref)

Splenic enlargement and rupture

Spleen enlargement and splenic rupture, including fatal cases, have been reported with other granulocyte-colony stimulating factor (G-CSF) products (eg, filgrastim, pegfilgrastim) (Ref).

Mechanism: Not fully elucidated; it has been speculated that large increase of immature myeloid cell density (mainly granulocyte precursors) in the spleen through extra medullar hematopoiesis may cause splenic rupture (Ref).

Onset: Varied; onset has been reported <2 weeks after G-CSF initiation (range: 3 to 13 days) (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Cardiovascular: Peripheral edema (18%), skin rash (25%)

Gastrointestinal: Abdominal pain (17%), decreased appetite (19%), diarrhea (40%), nausea (52%)

Hematologic & oncologic: Anemia (25%), thrombocytopenia (14%)

Local: Injection-site reaction (11%)

Nervous system: Dizziness (16%), fatigue (58%), headache (29%), pain (12%)

Neuromuscular & skeletal: Arthralgia (21%), back pain (20%), lower leg pain (11%), myalgia (22%), ostealgia (38%)

Respiratory: Cough (15%), dyspnea (16%)

Miscellaneous: Fever (28%)

1% to 10%: Cardiovascular: Flushing (10%)

Contraindications

History of serious allergic reactions (eg, anaphylaxis) to eflapegrastim, pegfilgrastim, filgrastim, or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Allergic reactions: Serious allergic reactions (including anaphylaxis) may occur with granulocyte colony-stimulating factor (G-CSF) products, such as eflapegrastim.

• Hematologic effects: WBC counts of ≥100,000/mm3 have been reported with G-CSF products. Thrombocytopenia has also been reported with G-CFS products.

• Nephrotoxicity: Based on findings of azotemia, hematuria (micro- and macroscopic), proteinuria, and renal biopsy, glomerulonephritis has occurred in patients receiving G-CSF products. Evaluate for cause if glomerulonephritis is suspected. Glomerulonephritis usually resolved after eflapegrastim dose reduction or discontinuation.

Disease-related concerns:

• Sickle cell disorders: Severe and sometimes fatal sickle cell crises may occur in patients with sickle cell disorders receiving G-CSF products.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Tumor growth effects: The G-CSF receptor through which G-CSF products act has been found on tumor cell lines. G-CSF products may possibly act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Rolvedon: Eflapegrastim-xnst 13.2 mg/0.6 mL (0.6 mL) [contains polysorbate 80]

Generic Equivalent Available: US

No

Pricing: US

Solution Prefilled Syringe (Rolvedon Subcutaneous)

13.2 mg/0.6 mL (per 0.6 mL): $5,400.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

SUBQ: Administer the entire contents of the prefilled syringe SUBQ. The syringe does not have graduation marks and is intended to deliver the entire contents upon administration. Place sealed blister pack tray on a clean, flat surface and allow tray to reach room temperature for at least 30 minutes prior to use; do not warm syringe any other way. Do not shake. Do not use prefilled syringe if it is dropped onto a hard surface (use a new syringe for the dose).

Use: Labeled Indications

Prevention of chemotherapy-induced neutropenia: To decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with clinically significant incidence of febrile neutropenia.

Limitations of use: Eflapegrastim is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic cell transplantation.

Medication Safety Issues
Sound-alike/look-alike issues:

Eflapegrastim may be confused with filgrastim, pegfilgrastim, sargramostim, tbo-filgrastim.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Belotecan: Granulocyte Colony-Stimulating Factors may enhance the neutropenic effect of Belotecan. Management: Do not administer granulocyte colony-stimulating factor (G-CSF) until at least 24 hours after completion of belotecan administration. Monitor neutrophil counts and signs/symptoms of neutropenic fever in patients receiving this combination. Risk D: Consider therapy modification

Betibeglogene Autotemcel: Granulocyte Colony-Stimulating Factors may interact via an unknown mechanism with Betibeglogene Autotemcel. Management: Granulocyte-colony stimulating factor is not recommended for 21 days after betibeglogene autotemcel infusion. Risk X: Avoid combination

Bleomycin: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of bleomycin. Risk D: Consider therapy modification

Exagamglogene Autotemcel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Exagamglogene Autotemcel. Risk X: Avoid combination

Lovotibeglogene Autotemcel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination

Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Risk C: Monitor therapy

Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor therapy

Tisagenlecleucel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Tisagenlecleucel. Risk X: Avoid combination

Topotecan: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Topotecan. Specifically, the risk for the development of interstitial lung disease may be increased. Granulocyte Colony-Stimulating Factors may enhance the myelosuppressive effect of Topotecan. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of topotecan. Additionally, monitor patients closely for the development of interstitial lung disease with this combination. Risk D: Consider therapy modification

Pregnancy Considerations

Adverse events were not observed in reproduction studies conducted in rabbits and rats at doses up to 10 and 7 times the maximum human dose, respectively, based on AUC.

Breastfeeding Considerations

It is not known if eflapegrastim is present in breast milk.

Eflapegrastim is a recombinant granulocyte colony-stimulating factor (G-CSF). Endogenous G-CSF and other recombinant G-CSFs are present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Monitor CBC (including platelets) during therapy. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain. Evaluate for acute respiratory distress syndrome in patients who develop fever and lung infiltrates or respiratory distress. Monitor for signs/symptoms of allergic reactions, glomerulonephritis, aortitis, and capillary leak syndrome. Monitor for signs/symptoms of myelodysplastic syndromes and acute myeloid leukemia.

Mechanism of Action

Eflapegrastim is a long-acting recombinant human granulocyte growth factor conjugated with a recombinant human IgG Fc fragment with the Fc fragment allowing for an extended half-life (Cobb 2020; Schwartzberg 2020). Eflapegrastim binds to granulocyte colony-stimulating factor receptors on myeloid progenitor cells and neutrophils, triggering signaling pathways to cell differentiation, proliferations, migration, and survival.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vd: 1.44 L.

Metabolism: Eflapegrastim is internalized by cells bearing the granulocyte-colony stimulating factor receptor and expected to be metabolized via endogenous degradation.

Half-life elimination: Mean: 36.4 hours (range: 16.1 to 115 hours).

Time to peak: 25 hours (range: 6 to 144 hours).

Excretion: Not detected in urine.

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