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filgrastim [G-CSF] (Neupogen, Lenograstim, Granulokine)

Tradename: Neupogen. Biosimilar filgrastim-sndz (Zarxio) FDA-approved March 2015. Indications: 1) myelosuppression in cancer patients a) adults with AML or myelodysplastic syndrome - no effect on disease-free time - decreased fevers, antibiotics, hospitalization - decreased need for antifungal therapy - risk of febrile neutropenia is > 20% [4] b) pediatric patients with ALL - shorter hospitalizations & fewer infections - no change in 3 year survival 2) myelosuppression in stem cell transplantation or bone marrow transplantation (BMT) 3) HIV therapy-induced myelosuppression when a change in medication regimen is contraindicated 4) absolute neutrophil count < 100/uL expected for > 7 days Contraindications: - risk of febrile neutropenia < 10% [4] - most afebrile patients with neutropenia [3] - routine adjunct to empiric antibiotics presnting with febrile neutropenia [3] - routine adjunct for induction therapy for acute leukemia [3] Pregnancy category C Safety in lactation ? Dosage: 1) round all doses to nearest vial size 2) 5-10 ug/kg/day SC or IV for 14 days or until neutrophil count > 10,000/mm3 (5000/mm3 for HIV) - begin 1 or 2 days after chemotherapy - continue full dose of chemotherapy unless overwise indicated [3] Injectable: 300 ug/mL (1 & 1.6 mL vials), syringe: 2.5-3 mL, needle 25 g, 5/8 inch Pharmacokinetics: 1) rapidly absorbed after SC administration 2) response is noted in 24 hours; plateau in 3-5 days 3) elimination: 1st order, 1/2 life 3-4 hours 4) pegfilgrastim: action for several weeks Adverse effects: 1) common (> 10%) - nausea/vomiting, skeletal pain, alopecia, diarrhea, fever including neutropenic fever, mucositis 2) less common (1-10%) - anorexia, dyspnea, headache, cough, skin rash, chest pain, weakness, sore throat, stomatitis, constipation, pain at injection site, leukocytosis, fluid retention 3) uncommon (< 1%) - transient supraventricular arrhythmia - anaphylactic reaction - pericarditis - thrombophlebitis 4) other - bone pain - hypotension - splenomegaly with long-term use - osteoporosis - neutrophilic dermatosis - pyoderma gangrenosum, Sweet syndrome [3] Mechanism of action: 1) human recombinant G-CSF - O-glycan consisting of gal-galNAc disaccharide which can be modified with up to two sialic acid residues (done in recombinantly expressed G-CSF from CHO cells) 2) stimulates leukopoiesis & enhances the actions of mature neutrophils

Specific

filgrastim-sndz (Zarxio) pegfilgrastim (Neulasta, Fulphila) tbo filgrastim

General

pharmaceutical growth factor granulocyte colony-stimulating factor; colony-stimulating factor 3; G-CSF; pluripoietin (CSF3, C17orf33, GCSF)

References

  1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Medical Knowledge Self Assessment Program (MKSAP) 17, 18, 19 American College of Physicians, Philadelphia 2015, 2018, 2022.
  4. Myeloid Growth Factors National Comprehensive Cancer Network In: Anello J, Feinberg B, Heinegg J et al New Clinical Practice Guidelines, February 2018. Medscape. February 07, 2018 https://reference.medscape.com/viewarticle/892328 - Crawford J, Becker PS, Armitage JO, et al. Myeloid Growth Factors, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017 Dec;15(12):1520-41. PMID: 29223990 http://www.jnccn.org/content/15/12/1520.long
  5. Smith TJ, Bohlke K, Lyman GH et al Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015 Oct 1;33(28):3199-212. Review. PMID: 26169616