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

Introduction

Tradename: Neupogen.

Biosimilar filgrastim-sndz (Zarxio) FDA-approved March 2015.

Indications

• myelosuppression in cancer patients
  • 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%
  • pediatric patients with ALL
    • shorter hospitalizations & fewer infections
    • no change in 3 year survival
• myelosuppression in stem cell transplantation or bone marrow transplantation (BMT)
• HIV therapy-induced myelosuppression when a change in medication regimen is contraindicated
• absolute neutrophil count < 100/uL expected for > 7 days

Contraindications

• risk of febrile neutropenia < 10%
• most afebrile patients with neutropenia
• routine adjunct to empiric antibiotics presnting with febrile neutropenia
• routine adjunct for induction therapy for acute leukemia

Pregnancy category C

Safety in lactation ?

Dosage

• round all doses to nearest vial size
• 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 Injectable: 300 ug/mL (1 & 1.6 mL vials), syringe: 2.5-3 mL, needle 25 g, 5/8 inch

Pharmacokinetics

• rapidly absorbed after SC administration
• response is noted in 24 hours; plateau in 3-5 days
• elimination: 1st order, 1/2 life 3-4 hours
• pegfilgrastim: action for several weeks

Adverse effects

• common (> 10%)
  • nausea/vomiting, skeletal pain, alopecia, diarrhea, fever including neutropenic fever, mucositis
• less common (1-10%)
  • anorexia, dyspnea, headache, cough, skin rash, chest pain, weakness, sore throat, stomatitis, constipation, pain at injection site, leukocytosis, fluid retention
• uncommon (< 1%)
  • transient supraventricular arrhythmia
  • anaphylactic reaction
  • pericarditis
  • thrombophlebitis
• other
  • bone pain
  • hypotension
  • splenomegaly with long-term use
  • osteoporosis
  • neutrophilic dermatosis
    • pyoderma gangrenosum, Sweet syndrome

Mechanism of action

• 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)
• stimulates leukopoiesis & enhances the actions of mature neutrophils

More general terms

• pharmaceutical growth factor
• granulocyte colony-stimulating factor

More specific terms

• filgrastim-sndz (Zarxio)
• pegfilgrastim <G-CSF> (Neulasta, Fulphila)
• tbo filgrastim