filgrastim (Rx)

Brand and Other Names:G-CSF, Neupogen, more...tbo-filgrastim, Granix, Zarxio, filgrastim-sndz, Nivestym, filgrastim-aafi
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution, single-dose vials

  • Neupogen, Granix, Nivestym
  • 300mcg/mL
  • 480mcg/1.6mL

injectable solution, prefilled syringe for SC

  • Neupogen, Granix, Nivestym, Zarxio
  • 300mcg/0.5mL
  • 480mcg/0.8mL

Biosimilars to Neupogen

  • Zarxio (filgrastim-sndz)
  • Granix (tbo-filgrastim)
  • Nivestym (filgrastim-aafi)

Myelosuppressive Chemotherapy Treatment

Neupogen, Granix, Zarxio, Nivestym

Indicated to decrease infection incidence‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever

Neupogen, Zarxio, Nivestym: 5 mcg/kg/day SC or IV infusion (short 15-30 min or continuous); may increase by 5 mcg/kg increments according to duration and severity of ANC

Granix: 5 mcg/kg/day SC

Do not administer within the 24-hr period prior to chemotherapy

Induction or Consolidation Chemotherapy

Neupogen, Zarxio, Nivestym

Indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia

5 mcg/kg SC/IV qDay initially; may increase by 5 mcg/kg for each chemotherapy cycle according to duration and severity of ANC

Do not administer within the 24-hr period prior to chemotherapy

Bone Marrow Transplantation

Neupogen, Zarxio, Nivestym

Indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg‚ febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT)

Following BMT: 10 mcg/kg/day IV infusion over 4-24 hr (do not exceed 24-hr infusion)

Administer the first dose at least 24 hr after cytotoxic chemotherapy and at least 24 hr after bone marrow infusion

Dose titration

  • During the period of neutrophil recovery‚ titrate the daily dosage against the neutrophil response
  • ANC >1000/mm³ for 3 consecutive days: Reduce dose to 5 mcg/kg/day, THEN
  • If ANC remains >1000/mm³ for 3 more consecutive days: Discontinue filgrastim, THEN
  • If ANC decreases to <1000mm³: Resume at 5 mcg/kg/day
  • Note: If ANC decreases to <1000mm³ at any time during the 5 mcg/kg/day administration, increase dose to 10 mcg/kg/day and then follow above steps

Peripheral Blood Progenitor Cell Collection

Neupogen, Zarxio, Nivestym

Indicated for the mobilization of autologous peripheral blood progenitor cells (PBPCs) into the peripheral blood for collection by leukapheresis

10 mcg/kg/day SC  

Initiate at least 4 days before first leukapheresis; continue until last day of leukapheresis

Optimal duration of administration and leukapheresis schedule have not been established; administration for 6-7 days with leukaphereses on days 5‚ 6‚ and 7 was found to be safe and effective in clinical studies described in prescribing information

Monitor neutrophil counts after 4 days‚ and discontinue if the WBC count rises to >100‚000/mm³

Severe Chronic Neutropenia

Neupogen, Zarxio, Nivestym

Indicated for long-term administration to reduce the incidence and duration of sequelae of neutropenia (eg‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with severe chronic neutropenia (SCN), including congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia

Before initiating therapy in patients with suspected chronic neutropenia, confirm the diagnosis of severe chronic neutropenia SCN by evaluating serial CBC counts with differential and platelet counts‚ and evaluating bone marrow morphology and karyotype; initiating therapy prior to confirmation of a correct diagnosis of SCN may impair diagnostic efforts and may thus impair or delay evaluation and treatment of an underlying condition‚ other than SCN‚ causing the neutropenia

Congenital: Initial 6 mcg/kg SC q12hr  

Idiopathic/cyclic: Initial 5 mcg/kg/day SC

Dosage modifications (SCN)

  • Long-term daily administration is required to maintain clinical benefit
  • Individualize dose based on the clinical course as well as ANC
  • Postmarket analysis showed median daily doses of 6 mcg/kg (congenital neutropenia), 2.1 mcg/kg (cyclic neutropenia), and 1.2 mcg/kg (idiopathic neutropenia)
  • In rare instances, patients with congenital neutropenia have required doses ≥100 mcg/kg/day

Monitoring (SCN)

  • Monitor CBC count (with differential and platelet counts) during the initial 4 weeks and during the 2 weeks following any dosage adjustment
  • Once a patient is clinically stable‚ monitor monthly during the first year of treatment
  • Thereafter, if the patient is clinically stable, less frequent routine monitoring is recommended

Acute Radiation Syndrome

Neupogen

Indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome)

10 mcg/kg SC as a single daily injection for patients exposed to myelosuppressive doses of radiation

Administer as soon as possible after suspected or confirmed exposure to radiation doses >2 Gy

Estimate a patient’s absorbed radiation dose based on information from public health authorities, biodosimetry if available, or clinical findings (eg, time to onset of vomiting, lymphocyte depletion kinetics)

Obtain baseline CBC count and then serial CBC counts ~q3days until the ANC remains >1,000/mm³ for 3 consecutive CBC counts

Do not delay administration if a CBC count is not readily available

Continue administration until the ANC remains >1,000/mm³ for 3 consecutive CBC counts or is >10,000/mm³ after a radiation-induced nadir

Dosing Considerations

Prefilled syringe (Zarxio) with BD UltraSafe Plus 9 Passive Needle Guard may not accurately measure volumes <0.3 mL due to needle spring mechanism design; direct administration of a volume <0.3 mL using prefilled syringe is not recommended due to potential for dosing errors; for direct administration of doses <0.3 mL (180 mcg) use single-dose vial

Monitoring

  • All indications require CBC count and ANC at time of initiating therapy and and throughout treatment
  • Scheduled monitoring and dosage adjustments are specific to the indication
  • Myelosuppressive, induction, or consolidation chemotherapy
    • Obtain a CBC count and platelet count before instituting therapy and monitor twice weekly during therapy
    • A transient increase in neutrophil count is typically seen 1-2 days after initiation; therefore, to ensure a sustained therapeutic response‚ administer daily for up to 2 weeks or until the ANC has reached 10‚000/mm³ following the expected chemotherapy-induced neutrophil nadir
    • Duration of therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen used

Orphan Designations

Ganciclovir-related neutropenia: Treatment of patients with AIDS who, in addition, are afflicted with cytomegalovirus retinitis and are being treated with ganciclovir

Treatment of amyotrophic lateral sclerosis (ALS)

tbo-filgrastim (Granix): Orphan designation for mobilization of peripheral blood progenitor cells (PBPCs) in healthy donors prior to allogeneic PBPC transplantation

Sponsors

  • Amgen, Inc; One Amgen Center Dr; Thousand Oaks, CA 91320-1799
  • Neurovision Pharma GmbH; Emil-Geis Str. 4; Grunwald82031, Germany
  • Sicor Biotech UAB; 5 Moletu pl. 5, Vilnius; Lithuania

Dosage Forms & Strengths

injectable solution, single-dose vials

  • Neupogen, Granix, Nivestym
  • 300mcg/mL
  • 480mcg/1.6mL

injectable solution, prefilled syringe for SC

  • Neupogen, Granix, Nivestym, Zarxio
  • 300mcg/0.5mL
  • 480mcg/0.8mL

Biosimilars to Neupogen

  • Zarxio (filgrastim-sndz)
  • Granix (tbo-filgrastim)
  • Nivestym (filgrastim-aafi)

Autologous Peripheral Blood Progenitor Cell Collection and Therapy

Neupogen, Zarxio, Nivestym

Indicated for mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis

10 mcg/kg/day SC  

Initiate 4 days before leukapheresis; continue until last day of leukapheresis

Patients with Cancer Undergoing Bone Marrow Transplantation

Neupogen, Zarxio, Nivestym

Indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg‚ febrile neutropenia), in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation

10 mcg/kg/day IV infusion

Administer first dose ≥24 hr after cytotoxic chemotherapy and ≥24 hr after bone marrow infusion; monitor CBC and platelet counts frequently

Dosage adjustment

  • When ANC >1000/mm³ for 3 consecutive days: Reduce to 5 mcg/kg/day
  • If ANC remains >1000mm³ for 3 more consecutive days: Discontinue
  • Then, if ANC decreases to <1000/mm³: Resume at 5 mcg/kg/day

Neutropenia

Severe neutropenia caused by myelosuppressive anticancer drugs

  • Neupogen, Zarxio, Nivestym, Granix
  • Indicated to reduce the duration of severe neutropenia in pediatric patients aged ≥1 month with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia
  • Neupogen, Zarxio, Nivestym: 5 mcg/kg/day SC or IV infusion (short 15-30 min or continuous)
  • Granix: 5 mcg/kg/day SC Administer first dose no earlier than 24 hr following myelosuppressive chemotherapy
  • Do not administer within 24 hr prior to chemotherapy
  • Continue daily dose until the expected neutrophil nadir is passed and neutrophil count has recovered to normal range

Severe chronic neutropenia

  • Neupogen, Zarxio, Nivestym
  • Indicated for long-term administration to reduce the incidence and duration of sequelae of neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia
  • Starting doses
    • Congenital neutropenia: 6 mcg/kg/day SC divided BID
    • Idiopathic or cyclic neutropenia: 5 mcg/kg SC qDay
  • Dosage adjustments
    • Chronic daily administration is required to maintain clinical benefit
    • Individualize dose based on clinical course and ANC
    • Congenital neutropenia median daily dose: 6 mcg/kg; in rare instances, required daily dose ≥100 mcg/kg/day
    • Cyclic neutropenia median daily dose: 2.1 mcg/kg
    • Idiopathic neutropenia median daily dose: 1.2 mcg/kg

Dosing Considerations

Prefilled syringe (Zarxio) with BD UltraSafe Plus Passive Needle Guard may not accurately measure volumes <0.3 mL due to needle spring mechanism design; direct administration of a volume <0.3 mL using prefilled syringe is not recommended due to potential for dosing errors; for direct administration of doses <0.3 mL (180 mcg) use single-dose vial

Myelosuppressive chemotherapy

  • Obtain a CBC count and platelet count before instituting therapy and monitor twice weekly during therapy
  • A transient increase in neutrophil count is typically seen 1-2 days after initiation; therefore, to ensure a sustained therapeutic response‚ administer daily for up to 2 weeks or until the ANC has reached 10‚000/mm³ following the expected chemotherapy-induced neutrophil nadir
  • Duration of therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen used
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Adverse Effects

>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

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Warnings

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
  • 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
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Pregnancy & Lactation

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.

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Pharmacology

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

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Administration

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 prefilled syringe with BD UltraSafe Plus Passive Needle Guard; the syringe is 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
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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.