filgrastim (Rx)

>10%

Nausea (57%)

Vomiting (57%)

Bone pain (22%-33%)

Alopecia (18%)

Diarrhea (14%)

Fever (12%)

Fatigue (11%)

1-10%

Headache

Anorexia

Chest pain

Cough

Dyspnea

Constipation

Stomatitis

Sore throat

Rash

Frequency Not Defined

Elevated uric acid

Elevated lactate dehydrogenase

Elevated alkaline phosphatase

Postmarketing Reports

Splenic rupture

ARDS

Asthenia

Glomerulonephritis

Alveolar hemorrhage and hemoptysis

Sickle cell crisis

Cutaneous vasculitis

Sweet syndrome (acute febrile neutrophilic dermatosis)

Decreased bone density and osteoporosis in children with severe chronic neutropenia receiving long-term treatment

Aortitis

Respiratory distress syndrome

Myelodysplastic syndrome

Acute myeloid leukemia

Capillary leak syndrome

Extramedullary hematopoiesis

Contraindications

History of serious allergic reactions to filgrastim or pegfilgrastim products

Cautions

Allergic reactions reported (angioneurotic edema, dermatitis-allergic, hypersensitivity, rash, pruritic rash, and urticaria); allergic reactions can recur within days after discontinuation of initial antiallergic treatment; permanently discontinue therapy in patients with serious allergic reactions

Associated with rare cases of potentially fatal splenic rupture; evaluate if patient experiences left upper abdominal and/or shoulder tip pain

Rare cases of ARDS reported; evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS; discontinue therapy in patients with ARDS

Monitor for thrombocytopenia

Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders; discontinue therapy if sickle cell crisis occurs

Glomerulonephritis reported; if suspected, evaluate for cause; if causality likely, consider dose-reduction or interruption

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging changes; this should be considered when interpreting bone-imaging results

WBC counts ≥100‚000/mm³ were observed in ~2% of patients receiving filgrastim at dosages >5 mcg/kg/day

Off-label use for PBPC mobilization has resulted in alveolar hemorrhage, resulting in pulmonary infiltrates and hemoptysis

Cutaneous vasculitis has been reported; hold therapy in patients with cutaneous vasculitis; therapy may be started at a reduced dose when the symptoms resolve and the ANC has decreased

Capillary leak syndrome (CLS) can occur in patients receiving filgrastim products and is characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration; patients who develop symptoms of CLS should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care

In patients with cancer receiving the drug as an adjunct to myelosuppressive chemotherapy‚ to avoid the potential risks of excessive leukocytosis‚ recommended that therapy be discontinued if the ANC surpasses 10‚000/mm³ after the chemotherapy-induced ANC nadir has occurred; monitor CBC counts at least twice weekly during therapy; dosages that increase the ANC beyond 10‚000/mm³ may not result in any additional clinical benefit

During period of administration of therapy for PBPC mobilization in patients with cancer, discontinue therapy if leukocyte count rises to >10‚000/mm³

Simultaneous use with chemotherapy and radiation therapy not recommended

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging changes; consider when interpreting bone-imaging results

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes; this should be considered when interpreting bone-imaging results

Aortitis

• Aortitis has been reported; may occur as early as the first week after start of therapy
• Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (eg, C-reactive protein and WBC)
• Consider aortitis in patients who develop these signs and symptoms without known etiology
• Discontinue if aortitis is suspected

Severe chronic neutropenia

• Confirm if patients have severe chronic neutropenia (SCN)
• Myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) have been reported to occur in the natural history of congenital neutropenia without cytokine therapy
• MDS and AML reported in patients with breast and lung cancer receiving chemotherapy and/or radiotherapy; monitor patients for signs and symptoms of MDS/AML in these settings
• Effect of filgrastim on the development of abnormal cytogenetics and the effect of continued administration in patients with abnormal cytogenetics or MDS are unknown
• If a patient with SCN develops abnormal cytogenetics or myelodysplasia‚ the risks and benefits should be carefully considered before continuing treatment

Drug interaction overview

• Drugs that may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution
• Safety and efficacy of concomitantly using filgrastim with cytotoxic chemotherapy or radiation therapy have not been established; because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy‚ do not use in the period 24 hr before through 24 hr after the administration of cytotoxic chemotherapy

Pregnancy

Available data from published studies, including several observational studies of pregnancy outcomes in women exposed to filgrastim products and those who were unexposed, have not established an association with use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes

Reports in scientific literature have described transplacental passage of drug in pregnant women when administered less than or equal to 30 hours prior to preterm delivery (less than or equal to 30 weeks' gestation)

In animal reproduction studies, effects of filgrastim on prenatal development have been studied in rats and rabbits; no malformations were observed in either species; no maternal or fetal effects were observed in pregnant rats at doses up to 58 times the human doses; drug has been shown to have adverse effects in pregnant rabbits at doses 2 -10 times higher than the human doses

Lactation

There is published literature documenting transfer of filgrastim into human milk; there are a few case reports describing use of filgrastim in breastfeeding mothers with no adverse effects noted in the infants; there are no data on effects of filgrastim on milk production; other filgrastim products are secreted poorly into breast milk, and filgrastim products are not absorbed orally by neonates; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on the breastfed child from the drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant human G-CSF; acts on hematopoietic cells to stimulate production, maturation, and activation of neutrophils; increases migration and cytotoxicity of neutrophils.

Absorption

100% (SC)

Peak Plasma Time: 2-8 hr

Distribution

Vd: 0.15 L/kg

Metabolism

Degraded systemically

Elimination

Duration: Neutrophil counts decrease to baseline in approximately 4 days

Half-life elimination: 1.8-3.5 hr

Clearance: 0.5-0.7 mL/min/kg

IV Incompatibilities

Y-site: amphotericin B, cefepime, cefoperazone, cefotaxime, cefoxitin, ceftizoxime, ceftriaxone, cefuroxime, clindamycin, dactinomycin, etoposide, fluorouracil, furosemide, heparin, mannitol, methylprednisolone sodium succinate, metronidazole, mitomycin, piperacillin, prochlorperazine, thiotepa

IV Compatibilities

Y-site (partial list): acyclovir, ampicillin, bleomycin, carboplatin, carmustine, cyclophosphamide, diphenhydramine, daunorubicin, doxorubicin, fluconazole, metoclopramide, morphine SO4, KCl, Na-bicarb

IV Preparation

Vials may be diluted in D5W to >15 mcg/mL for infusion

5-15 mcg/mL dilution: Protect from adsorption to plastic materials by the addition of human albumin to a final concentration of 2 mg/mL

Do not dilute with saline at any time, because the product may precipitate

IV Administration

Short IV infusion over 15-30 min, OR

Continuous IV infusion

SC Administration

SC injection may be administered by healthcare professional, caregiver, or patient

See specific instructions in prescribing information for Zarxio or Releuko prefilled syringes with BD UltraSafe Plus Passive Needle Guard; syringes are not designed to allow for direct administration of doses of <0.3 mL (180 mcg)

Prior to use‚ remove vial or prefilled syringe from refrigerator and allow to reach room temperature for a minimum of 30 minutes and a maximum of 24 hr; discard any vial or prefilled syringe left at room temperature for >24 hr; visually inspect for particulate matter and discoloration prior to administration (the solution is clear and colorless); do not administer dose if particulates or discoloration are observed

Discard unused portion in vials or prefilled syringes; do not reenter the vial; do not save unused drug for later administration

If the patient or caregiver misses a dose, instruct them to contact their healthcare provider

Administer undiluted by SC in the outer area of upper arms, abdomen (except for the 2-inch area around the navel), thighs, or upper outer areas of the buttock

Rotate injection site daily

Do not inject into an area that is tender, red, bruised or hard, or that has scars or stretch marks

Storage

Visually inspected before use; only clear solutions without particles should be used

Avoid shaking

Neupogen, Nivestym

• Refrigerate at 2-8°C (36-46°F) in the original pack to protect from light
• Protect from freezing; if frozen, thaw in the refrigerator before administration; discard if frozen more than once

Zarxio

• Refrigerate at 2-8°C (36-46°F) in the original pack to protect from light
• Protect from freezing; if frozen, thaw in the refrigerator before administration; discard if frozen more than once
• Prior to injection‚ may be allowed to reach room temperature for a maximum of 24 hr; discard if left at >25°C (77°F) for >24 hr

Granix

• Refrigerate at 2-8°C (36-46°F) in the original pack to protect from light
• Within its shelf life, product may be removed from refrigeration for a single period of up to 5 days between 73-81°F (23-27°C); if not used within 5 days, the product may be returned to refrigerator up to the expiration date; dispose if stored at room temperature >5 days
• Exposure to -1° to 5°C (23-30°F) for up to 72 hr and temperatures as low as -15° to -25°C (5° to -13°F) for up to 24 hr do not adversely affect the stability