Pegfilgrastim

Capillary leak syndrome (CLS), characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration, may occur in patients receiving human granulocyte colony-stimulating factors (G-CSF), including pegfilgrastim. CLS episodes 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.

Hypersensitivity, including serious allergic reactions or anaphylaxis may occur, usually with the initial dose; may recur within days after discontinuation of initial antiallergic treatment. Permanently discontinue for severe reactions. Do not administer in patients with a history of serious allergic reaction to pegfilgrastim or filgrastim. Skin rash, urticaria, generalized erythema, and flushing have been reported.

Glomerulonephritis has occurred, and generally resolved after pegfilgrastim dose reduction or discontinuation. Diagnosis was made by the presence of azotemia, microscopic and macroscopic hematuria, proteinuria, and renal biopsy. Evaluate if glomerulonephritis is suspected; if felt due to pegfilgrastim, consider dose reduction or therapy interruption.

Leukocytosis (WBC ≥100,000/mm3) has been reported in patients receiving pegfilgrastim. Monitor complete blood counts during therapy.

Acute respiratory distress syndrome (ARDS) has been reported with use; evaluate patients with pulmonary symptoms such as fever, pulmonary infiltrates, or respiratory distress for ARDS. Discontinue pegfilgrastim if ARDS occurs.

Rare cases of splenic rupture have been reported (some fatal); patients must be instructed to report left upper abdominal pain or shoulder pain. Disease-related concerns:

May precipitate sickle cell crises in patients with sickle cell disorders (severe and sometimes fatal sickle cell crises have occurred with filgrastim). Concurrent drug therapy issues:

Do not use pegfilgrastim in the period 14 days before to 24 hours after administration of cytotoxic chemotherapy because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy. Safety and efficacy have not been established with dose-dense chemotherapy regimens (Smith 2006). 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).

The 6 mg fixed dose should not be used in infants, children, and adolescents weighing • Stem cell mobilization: Not indicated for peripheral blood progenitor cell (PBPC) mobilization for hematopoietic stem cell transplantation. Dosage form specific issues:

Some products may contain acrylic adhesive; patients sensitive to acrylic adhesives may experience a significant reaction.

The packaging (needle cover) contains latex.

The On-body injector (OBI) is not recommended for use in patients with acute hematopoietic radiation injury syndrome. The OBI contains an acrylic adhesive; may result in a significant reaction in patients who react to acrylic adhesives. A health care provider must fill the OBI prior to applying to the patient's skin. The OBI delivery system may be applied on the same day as chemotherapy administration as long as pegfilgrastim is delivered no less than 24 hours after chemotherapy is administered. The prefilled syringe provided in the OBI kit contains overfill to compensate for loss during delivery; do not use for manual subcutaneous injection (will result in higher than recommended dose). Do not use prefilled syringe intended for manual injection to fill the OBI; may result in lower than intended dose. The OBI is only for use with pegfilgrastim; do not use to deliver other medications. Do not expose the OBI to oxygen-rich environments (eg, hyperbaric chambers); MRI; x-ray (including airport x-ray); CT scan; or ultrasound (may damage injector system). Keep the OBI at least 4 inches away from electrical equipment, including cell phones, cordless phones, microwaves, and other common appliances (injector may not work properly). Missed or partial doses have been reported; the risk for neutropenia, neutropenic fever, and/or infection is increased if a dose is not correctly delivered. Provide patient training and instruct patients to notify health care provider immediately if OBI mal

Colony-stimulating factors 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). Colony-stimulating factors should not be routinely used for patients with neutropenia who are afebrile. Dose-dense regimens that require colony-stimulating factors should only be used within the context of a clinical trial or if supported by convincing evidence. The safety/efficacy of pegfilgrastim in the setting of dose-dense therapy has not been fully established (Smith 2015).

The granulocyte-colony stimulating factor (G-CSF) receptor through which pegfilgrastim (and filgrastim) work has been located on tumor cell lines. May potentially act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia (pegfilgrastim is not approved for myeloid malignancies).