Filgrastim

Serious allergic reactions (including anaphylaxis) have been reported, usually with the initial exposure; may be managed symptomatically with administration of antihistamines, steroids, bronchodilators, and/or epinephrine. Allergic reactions may recur within days after the initial allergy management has been stopped. Do not administer filgrastim products to patients who have experienced serious allergic reaction to filgrastim or pegfilgrastim. Permanently discontinue filgrastim products in patients with serious allergic reactions.

Reports of alveolar hemorrhage, manifested as pulmonary infiltrates and hemoptysis (requiring hospitalization), have occurred in healthy donors undergoing PBPC mobilization (off-label for use in healthy donors); hemoptysis resolved upon discontinuation.

Capillary leak syndrome (CLS), characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration, may occur in patients receiving human granulocyte colony-stimulating factors (G-CSF). CLS episodes may vary in frequency and severity. If CLS develops, monitor closely and manage symptomatically (may require intensive care). CLS may be life-threatening if treatment is delayed.

Moderate or severe cutaneous vasculitis has been reported, generally occurring in patients with severe chronic neutropenia on chronic therapy. Withhold treatment if cutaneous vasculitis occurs; may be restarted with a dose reduction once symptoms resolve and the ANC has decreased.

White blood cell counts of ≥100,000/mm3 have been reported with filgrastim doses >5 mcg/kg/day. When filgrastim products are used as an adjunct to myelosuppressive chemotherapy, discontinue when absolute neutrophil count (ANC) exceeds 10,000/mm3 after the ANC nadir has occurred (to avoid potential excessive leukocytosis). Doses that increase the ANC beyond 10,000/mm3 may not result in additional clinical benefit. Monitor complete blood cell count (CBC) twice weekly during therapy. In patients receiving myelosuppressive chemotherapy, filgrastim discontinuation generally resulted in a 50% decrease in circulating neutrophils within 1 to 2 days, and a return to pretreatment levels in 1 to 7 days. When used for peripheral blood progenitor cell collection, discontinue filgrastim products if leukocytes >100,000/mm3. Thrombocytopenia has also been reported with filgrastim products; monitor platelet counts.

Based on findings of azotemia, hematuria (micro- and macroscopic), proteinuria, and renal biopsy, glomerulonephritis has occurred in patients receiving filgrastim. Glomerulonephritis usually resolved after filgrastim dose reduction or discontinuation. If glomerulonephritis is suspected, evaluate for cause; if likely due to filgrastim, consider dose reduction or treatment interruption.

Acute respiratory distress syndrome (ARDS) has been reported. Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS; discontinue in patients with ARDS.

Rare cases of splenic rupture have been reported (may be fatal); in patients with upper abdominal pain, left upper quadrant pain, or shoulder tip pain, withhold treatment and evaluate for enlarged spleen or splenic rupture. Disease-related concerns:

Establish diagnosis of severe chronic neutropenia (SCN) prior to initiation; use prior to appropriate diagnosis of SCN may impair or delay proper evaluation and treatment for neutropenia due to conditions other than SCN. Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been reported to occur in the natural history of congenital neutropenia (without cytokine therapy). Cytogenetic abnormalities and transformation to MDS and AML have been observed with filgrastim when used to manage SCN, although the risk for MDS and AML appears to be in patients with congenital neutropenia. Abnormal cytogenetics and MDS are associated with the development of AML. The effects of continuing filgrastim products in patients who have developed abnormal cytogenetics or MDS are unknown; consider risk versus benefits of continuing treatment.

May precipitate severe sickle cell crises, sometimes resulting in fatalities, in patients with sickle cell disorders (sickle cell trait or sickle cell disease); carefully evaluate potential risks and benefits. Discontinue in patients undergoing sickle cell crisis. Concurrent drug therapy issues:

Do not use filgrastim products in the period 24 hours before to 24 hours after administration of cytotoxic chemotherapy because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy. Transient increase in neutrophil count is seen 1 to 2 days after filgrastim initiation; however, for sustained neutrophil response, continue until post-nadir ANC reaches 10,000/mm3.

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

The American Society of Clinical Oncology (ASCO) Recommendations for the Use of WBC Growth Factors Clinical Practice Guideline Update recommend that prophylactic colony-stimulating factors be used in patients ≥65 years with diffuse aggressive lymphoma treated with curative chemotherapy (eg, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), especially if patients have comorbid conditions (Smith 2015).

Colony-stimulating factor (CSF) use in pediatric patients is typically directed by clinical pediatric protocols. The American Society of Clinical Oncology (ASCO) Recommendations for the Use of WBC Growth Factors Clinical Practice Guideline Update states that CSFs may be reasonable as primary prophylaxis in pediatric patients when chemotherapy regimens with a high likelihood of febrile neutropenia are employed. Likewise, secondary CSF prophylaxis should be limited to high-risk patients. In pediatric cancers in which dose-intense chemotherapy (with a survival benefit) is used, CSFs should be given to facilitate chemotherapy administration. CSFs should not be used in the pediatric population for non-relapsed acute lymphoblastic or myeloid leukemia when no infection is present (Smith 2015).

Avoid concurrent radiation therapy with filgrastim products; safety and efficacy have not been established with patients receiving radiation therapy. Dosage form specific issues:

The packaging of some dosage forms may contain latex. Granix (tbo-filgrastim), including all components, is not made with natural rubber latex.

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:

Filgrastim products should not be routinely used in the treatment of established neutropenic fever. CSFs may be considered in cancer patients with febrile neutropenia who are at high risk for infection-associated complications or who have prognostic factors indicative of a poor clinical outcome (eg, prolonged and severe neutropenia, age >65 years, hypotension, pneumonia, sepsis syndrome, presence of invasive fungal infection, uncontrolled primary disease, hospitalization at the time of fever development) (Freifeld 2011; Smith 2006). CSFs should not be routinely used for patients with neutropenia who are afebrile. Dose-dense regimens that require CSFs should only be used within the context of a clinical trial or if supported by convincing evidence (Smith 2015).

Some products available internationally may have vial strength and dosing expressed as units (instead of as micrograms). Refer to prescribing information for specific strength and dosing information.

Increased bone marrow hematopoietic activity due to colony-stimulating factor use has been associated with transient bone-imaging changes; interpret results accordingly.

The G-CSF receptor through which filgrastim products act has been found on tumor cell lines. May potentially act as a growth factor for any tumor type (including myeloid malignancies and myelodysplasia). When used for stem cell mobilization, may release tumor cells from marrow, which could be collected in leukapheresis product; potential effect of tumor cell reinfusion is unknown.