sargramostim [GM-CSF] (Leukine, Prokine, Leucomax)

Introduction

Tradenames: Leukine, Prokine. Market withdrawal of liquid formulation Jan 2008

Indications

• neutropenia
  • myeloid reconstitution after autologous bone marrow transplantation or stem-cell transplantation
  • HIV-associated neutropenia
• to accelerate myeloid engraftment following chemotherapy
  • acute myeloid leukemia (AML)
  • accelerate myeloid recovery in patients with non-Hodgkin's lymphoma
  • Hodgkin's lymphoma undergoing autologous stem-cell transplantation
  • acute lymphoblastic leukemia
• myelodysplastic syndrome
• investigational treatment of Alzheimer's disease

Contraindications

Pregnancy category C

Safety in lactation ?

Dosage

• bone marrow transplant:
  • 250 ug/m2/day IV or SC (IV dose over 2 hours)
  • begin 2-4 hours after marrow infusion & not < 24 hours after chemotherapy or < 12 h after radiotherapy
  • therapy should be continued for 30 days or until absolute neutrophil count has reached 1000/mm3
• cancer chemotherapy recovery
  • 3-15 ug/kg/day IV over 2 hours for 14-21 days
• discontinue if neutrophil count > 20,000/mm3 Injectable: 250 & 500 ug powder vials 500 ug/mL liquid preservative-free or multi-dose

Pharmacokinetics

• onset of action: increase in WBC in 7-14 days
• WBC will return to baseline within 1 week of discontinuing drug
• elimination 1/2 life 1 hour

Adverse effects

• common (> 10%)
  • nausea/vomiting, skeletal (bone) pain, alopecia, diarrhea, neutropenic fever, mucositis, thrombocytopenia, tachycardia
• less common (1-10%)
  • anorexia, dyspnea, headache, cough, rash, chest pain, weakness, sore throat, stomatitis, constipation, pain at site of injection, leukocytosis, fluid retention, peripheral edema, capillary leak syndrome
• uncommon (< 1%)
  • transient supraventricular arrhythmia, anaphylactic reaction, pericarditis, thrombophlebitis
• other
  • neutrophilic dermatosis
    • pyoderma gangrenosum, Sweet syndrome
• Market withdrawal of liquid formulation because of an upward trend in spontaneous reports of adverse reactions, including syncope (temporally correlated with change in formulation to include include edetate disodium, EDTA)

More general terms

• pharmaceutical growth factor
• granulocyte-macrophage colony-stimulating factor