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Pronunciation
(fil GRA stim)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Cancer patients (nonmyeloid malignancies) receiving myelosuppressive chemotherapy to decrease the incidence of infection (febrile neutropenia) in regimens associated with a high incidence of neutropenia with fever
Acute myelogenous leukemia (AML) following induction or consolidation chemotherapy to shorten time to neutrophil recovery and reduce the duration of fever
Cancer patients (nonmyeloid malignancies) receiving bone marrow transplant to shorten the duration of neutropenia and neutropenia-related events (eg, neutropenic fever)
Peripheral stem cell transplantation to mobilize hematopoietic progenitor cells for leukapheresis collection
Severe chronic neutropenia (SCN; chronic administration) to reduce the incidence and duration of neutropenic complications (fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital, cyclic, or idiopathic neutropenia
Use: Unlabeled
Treatment of anemia in myelodysplastic syndrome (in combination with epoetin); mobilization of hematopoietic stem cells (HSC) for collection and subsequent autologous transplantation (in combination with plerixafor) in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM); treatment of neutropenia in HIV-infected patients receiving zidovudine; hepatitis C treatment-associated neutropenia
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal studies have demonstrated adverse effects and fetal loss. Filgrastim has been shown to cross the placenta in humans. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit to mother justifies risk to the fetus. Women who become pregnant during filgrastim treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program (1-800-772-6436).
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to filgrastim, E. coli-derived proteins, or any component of the formulation
Warnings/Precautions
Concerns related to adverse reactions:
• Allergic reactions: Rash, urticaria, facial edema, wheezing, dyspnea, tachycardia, and/or hypotension have occurred with first or subsequent doses. Reactions tended to involve ≥2 body systems and occur more frequently with intravenous administration and generally within 30 minutes of administration. Symptoms recurred in >50% of patients when rechallenged.
• Alveolar hemorrhage: Reports of alveolar hemorrhage, manifested as pulmonary infiltrates and hemoptysis, have occurred in healthy donors undergoing PBPC collection (not FDA approved for use in healthy donors); hemoptysis resolved upon discontinuation.
• Cutaneous vasculitis: Has been reported, generally occurring in SCN patients on long-term therapy; symptoms generally developed with increasing absolute neutrophil count (ANC) and subsided when the ANC decreased; dose reductions may improve symptoms to allow for continued therapy.
• Respiratory distress syndrome: Rare cases of acute respiratory distress syndrome (ARDS) have been reported (possibly due to influx of neutrophils to sites of lung inflammation); withhold or discontinue filgrastim if ARDS occurs; patients must be instructed to report respiratory distress; monitor for fever, infiltrates, or respiratory distress.
• Splenic rupture: Rare cases of splenic rupture have been reported (may be fatal); patients must be instructed to report left upper quadrant pain or shoulder tip pain.
Disease-related concerns:
• Sickle cell disorders: May precipitate severe sickle cell crises, sometimes resulting in fatalities, in patients with sickle cell disorders; carefully evaluate potential risks and benefits.
Concurrent drug therapy issues:
• Cytotoxic chemotherapy: Do not use filgrastim 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.
• Plerixafor: Increases circulating leukocytes when used in conjunction with plerixafor for stem cell mobilization; monitor WBC; use with caution in patients with neutrophil count >50,000/mm3. May also release tumor cells from marrow which could be collected in leukapheresis product; potential effect of tumor cell reinfusion is unknown.
Special populations:
• Myelosuppressive chemotherapy recipients: Safety and efficacy have not been established with patients receiving chemotherapy associated with delayed myelosuppression (eg, nitrosoureas, mitomycin).
• Radiation therapy recipients: Avoid concurrent radiation therapy with filgrastim; safety and efficacy have not been established with patients receiving radiation therapy.
• Severe congenital neutropenia (SCN): Filgrastim use prior to appropriate diagnosis of SCN may impair proper evaluation and treatment for neutropenia not due to SCN. Cytogenetic abnormalities, transformation to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been observed in patients treated with filgrastim for congenital neutropenia; a longer duration of treatment and poorer ANC response appear to increase the risk. Carefully consider the risk of continuing filgrastim in patients who develop abnormal cytogenetics or MDS.
Dosage form specific issues:
• Latex: The packaging of some dosage forms may contain latex.
Other warnings/precautions:
• Tumor growth factor: May potentially act as a growth factor for any tumor type; caution should be exercised when using in any malignancy with myeloid characteristics.
Adverse Reactions
>10%:
Central nervous system: Fever (12%)
Dermatologic: Petechiae (≤17%), rash (≤12%)
Endocrine & metabolic: LDH increased, uric acid increased
Gastrointestinal: Splenomegaly (severe chronic neutropenia: 30%; rare in other patients)
Hepatic: Alkaline phosphatase increased (21%)
Neuromuscular & skeletal: Bone/skeletal pain (22% to 33%; dose related), commonly in the lower back, posterior iliac crest, and sternum
Respiratory: Epistaxis (9% to 15%)
1% to 10%:
Cardiovascular: Hyper-/hypotension (4%), myocardial infarction/arrhythmias (3%)
Central nervous system: Headache (7%)
Gastrointestinal: Nausea (10%), vomiting (7%), peritonitis (≤2%)
Hematologic: Leukocytosis (2%)
Miscellaneous: Transfusion reaction (≤10%)
<1%, postmarketing, and/or case reports: Acute respiratory distress syndrome (ARDS), allergic reactions, alopecia, alveolar hemorrhage, arthralgia, capillary leak syndrome, cerebral hemorrhage, cutaneous vasculitis, dyspnea, edema (facial), erythema nodosum, hematuria, hemoptysis, hepatomegaly, hypersensitivity reaction, injection site reaction, osteoporosis, pericarditis, proteinuria, psoriasis exacerbation, pulmonary infiltrates, renal insufficiency, sickle cell crisis, splenic rupture, Sweet's syndrome (acute febrile dermatosis), tachycardia, thrombocytopenia (in PBPC mobilization), thrombophlebitis, transient supraventricular arrhythmia, urticaria, wheezing
Metabolism/Transport Effects
None known.
Drug Interactions
Bleomycin: Filgrastim may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Risk C: Monitor therapy
Topotecan: Filgrastim may enhance the adverse/toxic effect of Topotecan. Risk D: Consider therapy modification
Storage
Intact vials and prefilled syringes should be stored under refrigeration at 2°C to 8°C (36°F to 46°F) and protected from direct sunlight. Filgrastim should be protected from freezing and temperatures >30°C to avoid aggregation.
Filgrastim vials and prefilled syringes are stable for 24 hours at 9°C to 30°C (47°F to 86°F).
Undiluted filgrastim is stable for 24 hours at 15°C to 30°C (59°F to 86°F) and for up to 14 days at 2°C to 8°C (36°F to 46°F) (data on file, Amgen Medical Information) in BD tuberculin syringes; however, sterility has only been assessed and maintained for up to 7 days when prepared under strict aseptic conditions (Jacobson, 1996; Singh, 1994). The manufacturer recommends using syringes within 24 hours due to the potential for bacterial contamination.
Filgrastim diluted with D5W for I.V. infusion (5-15 mcg/mL) is stable for 7 days at 2°C to 8°C (36°F to 46°F), however, should be used within 24 hours due to the possibility for bacterial contamination.
Reconstitution
Do not dilute with saline at any time; product may precipitate. Filgrastim may be diluted with D5W to a concentration of 5-15 mcg/mL for I.V. infusion administration (minimum concentration: 5 mcg/mL). Concentrations 5-15 mcg/mL require addition of albumin (final albumin concentration of 2 mg/mL) to prevent adsorption to plastics. Dilution to <5 mcg/mL is not recommended. Do not shake.
Compatibility
Stable in D5W; incompatible with NS.
Y-site administration: Compatible: Acyclovir, allopurinol, amikacin, aminophylline, ampicillin, ampicillin/sulbactam, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotetan, ceftazidime, chlorpromazine, cimetidine, cisplatin, cyclophosphamide, cytarabine, dacarbazine, daunorubicin HCl, dexamethasone sodium phosphate, diphenhydramine, doxorubicin HCl, doxycycline, droperidol, enalaprilat, famotidine, floxuridine, fluconazole, fludarabine, gallium nitrate, ganciclovir, granisetron, haloperidol lactate, hydrocortisone sodium succinate, hydromorphone, hydroxyzine, idarubicin, ifosfamide, leucovorin calcium, lorazepam, mechlorethamine, melphalan, meperidine, mesna, methotrexate, metoclopramide, minocycline, mitoxantrone, morphine, nalbuphine, ondansetron, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, sulfamethoxazole/trimethoprim, ticarcillin/clavulanate, tobramycin, vancomycin, vinblastine, vincristine, vinorelbine, zidovudine. Incompatible: Amphotericin B, cefepime, cefotaxime, cefoxitin, ceftriaxone, cefuroxime, clindamycin, etoposide, fluorouracil, furosemide, heparin, mannitol, methylprednisolone sodium succinate, metronidazole, mitomycin, piperacillin, prochlorperazine edisylate, thiotepa. Variable (consult detailed reference): Dactinomycin, gentamicin, imipenem/cilastatin.
Compatibility in syringe: Incompatible: Ceftriaxone.
Mechanism of Action
Stimulates the production, maturation, and activation of neutrophils; filgrastim activates neutrophils to increase both their migration and cytotoxicity.
Pharmacodynamics/Kinetics
Onset of action: ~24 hours; plateaus in 3-5 days
Duration: Neutrophil counts generally return to baseline within 4 days
Absorption: SubQ: 100%
Distribution: Vd: 150 mL/kg; no evidence of drug accumulation over a 11- to 20-day period
Metabolism: Systemically degraded
Half-life elimination: 1.8-3.5 hours
Time to peak, serum: SubQ: 2-8 hours
Dosage
Details concerning dosing in combination regimens and institution protocols should also be consulted. Rounding doses to the nearest vial size may enhance patient convenience and reduce costs without compromising clinical response.
Children: Neutropenia (ANC <500/mm3) due to zidovudine treatment for HIV-infection (unlabeled use): SubQ, I.V.: 5-10 mcg/kg once daily (AIDSinfo guidelines, 2010)
Children and Adults:
Chemotherapy-induced neutropenia: SubQ, I.V.: 5 mcg/kg/day; doses may be increased by 5 mcg/kg (for each chemotherapy cycle) according to the duration and severity of the neutropenia; continue for up to 14 days or until the ANC reaches 10,000/mm3
Bone marrow transplantation (in patients with cancer; to shorten the duration of neutropenia and neutropenia-related events): SubQ, I.V.: 10 mcg/kg/day (administer ≥24 hours after chemotherapy and ≥24 hours after bone marrow infusion); adjust the dose according to the duration and severity of neutropenia; recommended steps based on neutrophil response:
When ANC >1000/mm3 for 3 consecutive days: Reduce filgrastim dose to 5 mcg/kg/day
If ANC remains >1000/mm3 for 3 more consecutive days: Discontinue filgrastim
If ANC decreases to <1000/mm3: Resume at 5 mcg/kg/day
If ANC decreases to <1000/mm3 during the 5 mcg/kg/day dose, increase filgrastim to 10 mcg/kg/day and follow the above steps
Peripheral blood progenitor cell (PBPC) collection: SubQ: 10 mcg/kg daily, usually for 6-7 days. Begin at least 4 days before the first leukapheresis and continue until the last leukapheresis; consider dose adjustment for WBC >100,000/mm3
Severe chronic neutropenia: SubQ:
Congenital: Initial: 6 mcg/kg twice daily; adjust the dose based on ANC and clinical response
Idiopathic/cyclic: Initial: 5 mcg/kg/day; adjust the dose based on ANC and clinical response
Anemia in myelodysplastic syndrome (unlabeled use; in combination with epoetin): SubQ: 30 mcg, 75 mcg, or 150 mcg once daily (Hellstrom-Lindberg, 1998) or 1 mcg/kg once daily (Greenberg, 2009) or 75 mcg, 150 mcg or 300 mcg/dose 3 times/week (Hellstrom-Lindberg, 2003) or 1-2 mcg/kg/dose 1-3 times/week (NCCN MDS guidelines v.2.2011)
Hematopoietic stem cell mobilization in autologous transplantation in patients with non-Hodgkin's lymphoma or multiple myeloma (in combination with plerixafor; unlabeled use): SubQ: 10 mcg/kg once daily; begin 4 days before initiation of plerixafor; continue G-CSF on each day prior to apheresis for up to 8 days (DiPersio, JCO 2009; DiPersio, Blood 2009)
Hepatitis C treatment-associated neutropenia (unlabeled use): SubQ: 150 mcg once weekly to 300 mcg 3 times/week; titrate to maintain ANC between 750-10,000/mm3 (Younossi, 2008)
Dosage: Combination Regimens
Breast cancer: AC/Paclitaxel (Sequential)
Esophageal cancer: Paclitaxel-Cisplatin (Esophageal Cancer)
Leukemia, acute lymphocytic:
Larson Regimen (ALL)
Leukemia, acute myeloid:
CLAG (AML Induction)
CLAG-M (AML Induction)
FLAG (AML Induction)
FLAG-IDA (AML Induction)
MEC-G (AML Induction)
Lymphoma, Hodgkin:
BEACOPP-14 (Hodgkin)
BEACOPP Escalated (Hodgkin)
BEACOPP Escalated Plus Standard (Hodgkin)
DHAP (Hodgkin)
ESHAP (Hodgkin)
ICE (Hodgkin)
IGEV (Hodgkin)
Lymphoma, non-Hodgkin's:
CHOP (NHL)
CODOX-M
CODOX-M/IVAC
EPOCH Dose-Adjusted (AIDS-Related Lymphoma)
EPOCH Dose-Adjusted (NHL)
EPOCH (Dose-Adjusted)-Rituximab (NHL)
ICE (Lymphoma, non-Hodgkin's)
RICE
Rituximab-CHOP (NHL)
Lymphoma, non-Hodgkin's (Burkitt): CODOX-M/IVAC
Sarcoma, soft tissue: AI
Unknown Primary (Adenocarcinoma): Carboplatin-Paclitaxel (Unknown Primary)
Wilms' tumor: Regimen I (Wilms' Tumor)
Administration: I.V.
May be administered I.V. as a short infusion over 15-30 minutes (chemotherapy-induced neutropenia) or by continuous infusion (chemotherapy-induced neutropenia) or as a 4- or 24-hour infusion (bone marrow transplantation). Do not administer earlier than 24 hours after or in the 24 hours prior to cytotoxic chemotherapy.
Administration: Other
May be administered by SubQ injection, either as a bolus injection (chemotherapy-induced neutropenia) or as a continuous infusion (chemotherapy-induced neutropenia, bone marrow transplantation, and peripheral blood progenitor cell collection). Do not administer earlier than 24 hours after or in the 24 hours prior to cytotoxic chemotherapy.
Administration: I.V. Detail
pH: 4
Monitoring Parameters
CBC with differential and platelets prior to treatment and twice weekly during filgrastim treatment for chemotherapy-induced neutropenia (3 times/week following marrow transplantation). For severe chronic neutropenia, monitor CBC with differential and platelets twice weekly during the first month of therapy and for 2 weeks following dose adjustments; once clinically stable, monthly for 1 year and quarterly thereafter; for congenital neutropenia also monitor bone marrow and karyotype prior to treatment; and monitor marrow and cytogenetics annually throughout treatment. Monitor temperature.
Reference Range
No additional clinical benefit seen when filgrastim is used with ANC >10,000/mm3
Test Interactions
May interfere with bone imaging studies; increased hematopoietic activity of the bone marrow may appear as transient positive bone imaging changes
Dietary Considerations
Some products may contain sodium.
Patient Education
If self-administered, follow directions for proper storage and administration of SubQ medication. Never reuse syringes or needles. May cause bone pain, nausea, vomiting, hair loss (reversible), or sore mouth. Report immediately any respiratory difficulty or pain in left shoulder, chest, or back. Report unusual fever or chills; unhealed sores; severe bone pain; pain, redness, or swelling at injection site; unusual swelling of extremities; or chest pain and palpitations.
Geriatric Considerations
Out of 855 participants in randomized, placebo-controlled clinical trials who had received myelosuppressive chemotherapy, a total of 232 subjects were ≥65 years and 22 subjects were ≥75 years. No overall differences in safety or effectiveness were observed between these older and younger subjects; other clinical experience has not identified differences in the responses between elderly and younger patients.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
May be used to treat clozapine-induced agranulocytosis; lithium may potentiate the release of neutrophils; use with caution
Nursing: Physical Assessment/Monitoring
Assess for hypersensitivity to E. coli products prior to beginning therapy. Allergic-type reactions have occurred in patients receiving G-CSF with first or later doses. If self-administered, teach patient proper storage, administration, and syringe/needle disposal. Instruct patient to report upper quadrant pain, shoulder tip pain, or respiratory distress.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]:
Neupogen®: 300 mcg/mL (1 mL, 1.6 mL) [contains polysorbate 80, sodium 0.035 mg/mL, sorbitol; vial]
Neupogen®: 600 mcg/mL (0.5 mL, 0.8 mL) [contains natural rubber/natural latex in packaging, polysorbate 80, sodium 0.035 mg/mL, sorbitol; prefilled syringe]
Pricing: U.S. (www.drugstore.com)
Solution (Neupogen)
300 mcg/0.5 mL (0.5): $298.00
300 mcg/mL (1): $267.99
480 mcg/0.8 mL (0.8): $514.99
References
Calandra G, McCarty J, McGuirk J, et al, “AMD3100 Plus G-CSF Can Successfully Mobilize CD34+ Cells From Non-Hodgkin's Lymphoma, Hodgkin's Disease and Multiple Myeloma Patients Previously Failing Mobilization With Chemotherapy and/or Cytokine Treatment: Compassionate Use Data,” Bone Marrow Transplant, 2008, 41(4):331-8.
DiPersio JF, Micallef I, Stiff PJ, et al, “Phase III Prospective Randomized Double-Blinded Placebo-Controlled Trial of Plerixafor Plus Granulocyte Colony-Stimulating Factor Compared With Placebo Plus Granulocyte Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients With Non-Hodgkin's Lymphoma,” J Clin Oncol, 2009, 27(28):4767-73.
DiPersio JF, Stadtmauer EA, Nadamanee NP, et al, “Plerixafor and G-CSF Versus Placebo and G-CSF to Moboilize Hematopoietic Stem Cells for Autologous Stem Cell Transplantation in Patients With Multiple Myeloma,” Blood, 2009, 113(23):5720-6.
Ghany MG, Strader DB, Thomas DL, et al, “Diagnosis, Management and Treatment of Hepatitis C: An Update,” Hepatology, 2009, 49(4):1335-74.
Greenberg PL, Sun Z, Miller KB, et al, “Treatment of Myelodysplastic Syndrome Patients With Erythropoietin With or Without Granulocyte Colony-Stimulating Factor: Results of a Prospective Randomized Phase 3 Trial by the Eastern Cooperative Oncology Group (E1996),” Blood, 2009, 114(12):2393-400.
“Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, Panel on Clinical Practices for Treatment of HIV Infection,” January 10, 2011. Available at http://www.aidsinfo.nih.gov
“Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children,” August 16, 2010. Available at http://www.aidsinfo.nih.gov
Hellström-Lindberg E, Ahlgren T, Beguin Y, et al, “Treatment of Anemia in Myelodysplastic Syndromes With Granulocyte Colony-Stimulating Factor Plus Erythropoietin: Results from a Randomized Phase II Study and Long-Term Follow-Up of 71 Patients,” Blood, 1998, 92(1):68-75.
Hellström-Lindberg E, Gulbrandsen N, Lindberg G, et al, “A Validated Decision Model for Treating the Anaemia of Myelodysplastic Syndromes With Erythropoietin + Granulocyte Colony-Stimulating Factor: Significant Effects on Quality of Life,” Br J Haematol, 2003, 120(6):1037-46.
Jacobson PA, West NJ, Spadoni V, et al, “Sterility of Filgrastim (G-CSF) in Syringes,” Ann Pharmacother, 1996, 30(11):1238-42.
Jädersten M, Montgomery SM, Dybedal I, et al, “Long-Term Outcome of Treatment of Anemia in MDS with Erythropoietin and G-CSF,” Blood, 2005, 106(3):803-11.
Kuwabara T, Kobayashi S, and Sugiyama Y, “Pharmacokinetics and Pharmacodynamics of a Recombinant Human Granulocyte Colony-Stimulating Factor,” Drug Metab Rev, 1996, 28(4):625-58.
Martin WG, Ristow KM, Habermann TM, et al, “Bleomycin Pulmonary Toxicity has a Negative Impact on the Outcome of Patients With Hodgkin's Lymphoma,” J Clin Oncol, 2005, 23(30):7614-20.
McCullough JM, Sprentall-Nankervis E, Potcova CA, et al, “Recovery and Biological activity of Filgrastim After Injection Through Silicone Rubber Catheters,” Am J Health Syst Pharm, 1995, 52(2):186-8.
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Myelodysplastic Syndromes,” Version 2.2011. Available at http://www.nccn.org/professionals/physician_gls/PDF/mds.pdf
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Myeloid Growth Factors,” Version 1.2011. Available at http://www.nccn.org/professionals/physician_gls/PDF/myeloid_growth.pdf
Nemunaitis J, “A Comparative Review of Colony-Stimulating Factors,” Drugs, 1997, 54(5):709-29.
Rosenberg PS, Alter BP, Bolyard AA, et al, “The Incidence of Leukemia and Mortality From Sepsis in Patients With Severe Congenital Neutropenia Receiving Long-Term G-CSF Therapy,” Blood, 2006, 107(12): 4628-35.
Schaison G, Eden OB, Henze G, et al, “Recommendations on the Use of Colony-Stimulating Factors in Children: Conclusions of a European Panel,” E J Pediatr, 1998, 157(12):955-66.
Singh RF, Corelli RL, and Guglielmo BJ, “Sterility of Unit Dose Syringes of Filgrastim and Sargramostim,” Am J Hosp Pharm, 1994, 51(15):2811-2.
Smith TJ, Khatcheressian J, Lyman GH, et al, “2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline,” J Clin Oncol, 2006, 24(19):3187-205.
Younossi ZM, Nader FH, Bai C, et al, “A Phase II Dose Finding Study of Darbepoetin Alpha and Filgrastim for the Management of Anaemia and Neutropenia in Chronic Hepatitis C Ttreatment,” J Viral Hepat, 2008, 15(5):370-8.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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