Filgrastim
Filgrastim (Neupogen)
Filgrastim
(fill- GRASS-tim)
Pregnancy Category: C Neupogen (Rx)

Classification: Human granulocyte colony-stimulating factor (G-CSF)

Action/Kinetics: Is a human granulocyte colony stimulating factor (G-CSF) produced by recombinant DNA technology by Escherichia coli that has been inserted with the human G-CSF gene. Endogenous G-CSF is a glycoprotein that is produced by monocytes, fibroblasts, and other endothelial cells and that regulates the production of neutrophils in the bone marrow. Has minimal effects, either in vivo or in vitro, on the production of other hematopoietic cell types. Filgrastim has an amino acid sequence that is identical to the natural sequence predicted from human DNA sequence analysis except there is an N-terminal methionine that is required for expression in E. coli. IV infusion of 20 mcg/kg over 24 hr resulted in a mean serum level of 48 ng/mL, whereas SC administration of 11.5 mcg/kg resulted in a maximum serum level of 49 ng/mL within 2-8 hr. t 1/2, elimination: 3.5 hr.

Uses: To decrease the incidence of infection, as manifested by febrile neutropenia, in clients with nonmyeloid malignancies who are receiving myelosuppressive anticancer drugs, which are associated with severe neutropenia with fever. To reduce the duration of neutropenia in clients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation. To reduce infection in severe chronic neutropenia (e.g., congenital, cyclical, or idiopathic neutropenia) after other diseases have been ruled out. For the mobilization of hematopoietic progenitor cells into the peripheral blood for leukapheresis collection. To reduce the time to neutrophil recovery and the duration of fever in clients being treated for acute myelogenous leukemia. Investigational: Use in AIDS, aplastic anemia, hairy cell leukemia, myelodysplasia, drug-induced and congenital agranulocytosis, and alloimmune neonatal neutropenia.

Contraindications: Hypersensitivity to proteins derived from E. coli. The safety and effectiveness of filgrastim given simultaneously with cytotoxic chemotherapy have not been determined; thus, filgrastim should not be given 24 hr before to 24 hr after cytotoxic chemotherapy.

Special Concerns: Use with caution during lactation. Use with caution in any malignancy with myeloid characteristics since the drug may act as a growth factor for any tumor type. Filgrastim does not cause any greater incidence of toxicity in children than in adults. Safety and efficacy have not been determined in neonates and clients with autoimmune neutropenia of infancy. The safety and effectiveness of chronic filgrastim therapy have not been determined. Hypersensitivity reactions usually occur within 30 min after administration and are more frequent in clients receiving the drug IV.

Side Effects: When used for myelosuppressive therapy. Musculoskeletal: Medullary bone pain, skeletal pain. GI: N&V;, diarrhea, anorexia, stomatitis, constipation, peritonitis. Hypersensitivity: Skin rash, facial edema, wheezing, dyspnea, hypotension, tachycardia. Hematologic: Leukocytosis; greater risk of thrombocytopenia and anemia. Respiratory: Dyspnea, cough, chest pain, sore throat. Body as a whole: Alopecia, neutropenic fever, fever, fatigue, headache, skin rash, mucositis, generalized weakness, unspecified pain. CV: Decreased BP (transient), cutaneous vasculitis, hypertension, arrhythmias, MI.
When used for severe chronic neutropenia. Musculoskeletal: Mild to moderate bone pain, abdominal/flank pain, arthralgia, osteoporosis. Hematologic: Thrombocytopenia, epistaxis (associated with thrombocytopenia), anemia, myelodysplasia or myeloid leukemia. Dermatologic: Exacerbation of certain skin conditions (e.g., psoriasis), rash, alopecia. Miscellaneous: Palpable splenomegaly, hepatomegaly, monosomy, reaction at injection site, cutaneous vasculitis, hematuria, proteinuria.
When used for bone marrow transplantation. GI: N&V;, stomatitis, peritonitis. CV: Hypertension, capillary leak syndrome (rare). Miscellaneous: Rash, renal insufficiency, erythema nodosum.
When used for peripheral blood progenitor cell collection. Hematologic: Decreased platelet counts, anemia, increase in neutrophil count, WBC count greater than 100,000/mm ³. Miscellaneous: Mild to moderate musculoskeletal symptoms, medullary bone pain, headache, increases in alkaline phosphatase.

Laboratory Test Alterations: Uric acid, LDH, alkaline phosphatase.

How Supplied: Injection: 300 mcg/mL

Dosage
?SC, IV Myelosuppressive chemotherapy.
Initial: 5 mcg/kg/day as a single injection, either as a SC bolus, by short IV infusion (15-30 min), or by continuous SC or IV infusion (over a 24-hr period). The dose may be increased in increments of 5 mcg/kg for each chemotherapy cycle depending on the duration and severity of the absolute neutrophil count (ANC) nadir. The dose should be given daily for up to 2 weeks, until ANC has reached 10,000/mm ³ following the expected chemotherapy-induced neutrophil nadir.
Severe chronic neutropenia.
5 mcg/kg/day SC for idiopathic and cyclic disease; 6 mcg/kg/day SC for congenital disease.
Bone marrow transplantation.
10 mcg/kg/day given as an IV infusion of 4 or 24 hr or as a continuous 24-hr SC infusion.
NOTE: During the period of neutrophil recovery, the daily dose should be titrated against the neutrophil response as follows:

1. When ANC is greater than 1,000/mm ³ for 3 consecutive days, reduce the dose of filgrastim to 5 mcg/kg/day. If ANC decreases to less than 1,000/mm ³ at any time during the 5-mcg/kg/day dosage, increase filgrastim to 10 mcg/kg/day.

2. If ANC remains greater than 1,000/mm ³ for 3 more consecutive days, discontinue filgrastim.

3. If ANC decreases to less than 1,000/mm ³, resume filgrastim at 5 mcg/kg/day.