Formulation and Stability

G-CSF is supplied as a clear solution of 300 µg/mL in 1 mL or 1.6 mL vials. Vials are preservative-free and intended for single-use. However, the experience at the Hospital for Sick Children and elsewhere suggest that it is safe and more cost-effective to use one vial twice within a 24-hour period. Filgrastim must be stored between 2_C and 8_C. Stability has been demonstrated for at least 24 months when stored under these conditions. Boxes of Filgrastim contain an indicator that turns red when exposed to freezing, after which the drug should not be used. Do not use if the Filgrastim appeared discolored or contain any particulate matter. For intravenous use, dilute in D₅W to concentrations of >15 µg/mL since Filgrastim is incompatible with normal saline. At dilutions of 5-14 µg/mL, add human serum albumin to a final albumin concentration of 2 mg/mL to protect against absorption of G-CSF to glass or plastic container walls. Filgrastim, when diluted as described above, is compatible with a number of plastics commonly used in the manufacture of syringes, intravenous bags, infusion sets and intravenous pump cassettes. These include polyvinyl chloride, polyolefin and polypropylene. Diluted Filgrastim should be stored at 2-8_C and used within 24 hours. Do not shake or freeze.

Guidelines for Subcutaneous Administration

The usual route is to administer once daily by subcutaneous injection without dilution. The suggested starting dose of G-CSF is 5 µg/kg.

Guidelines for Intravenous Administration

Dilute with D₅W to 15 µg/mL or greater if intravenous administration is necessary. Dilutions should be prepared as close to the time of administration as possible (up to 24 hours), since the product is preservative-free. When diluting Filgrastim to 5-14 µg/mL in D₅W, it is necessary at all times to add human serum albumin to reach a final albumin concentration of 2 mg/mL. The suggested starting dose of G-CSF is 5 µg/kg.

Guidelines for Stopping G-CSF

Although not well documented in the literature, most pediatric chemotherapy protocols typically recommend stopping G-CSF when the absolute neutrophil count (ANC = polymorphs + bands + metamyelocytes + myelocytes + promyelocytes) is >5-10 x 10⁹/L after reaching the nadir at 10-14 days after chemotherapy, or ANC is >1.5 x 10⁹/L for 2 consecutive days after reaching the nadir. However, it is adequate for the purpose of this protocol to stop G-CSF when the ANC is >0.5 x 10⁹/L for one day after reaching the nadir. Generally, the ANC decreases by 50% in 24-48 hours after stopping G-CSF. G-CSF should be stopped ~24 hours before restarting chemotherapy.