Filgrastim

Filgrastim is recombinant human granulocyte colony-stimulating factor, given subcutaneously or intravenously to shorten neutropenia after cytotoxic chemotherapy, to mobilise stem cells and to treat severe chronic neutropenia. Biosimilars are widely used; 1 million units equals 10 µg.

Classification. Haematopoietic growth factor; granulocyte colony-stimulating factor.

Mechanism. Binds the granulocyte colony-stimulating factor receptor, stimulating proliferation and differentiation of neutrophil precursors and release of mature neutrophils.

Pharmacokinetics. Subcutaneous bioavailability is about 60%. Half-life is 3 to 4 hours, with clearance by neutrophil receptors and the kidney. Neutrophils rise within 24 hours.

Prevention of febrile neutropenia after chemotherapy.

• Dose: 5 µg/kg subcutaneously once daily, starting at least 24 hours after chemotherapy (and not in the 24 hours before the next cycle).
• Duration: until the neutrophil nadir has passed and the count is back in the normal range, usually up to 14 days.
• Maximum: 10 µg/kg daily for chemotherapy and mobilisation, and 12 µg/kg daily in congenital neutropenia. Loading dose: none. Children: the same dose by weight.

Stem cell mobilisation.

• Filgrastim alone: 10 µg/kg subcutaneously daily for 4 to 7 days before and during apheresis.
• After chemotherapy: 5 µg/kg daily from the day after chemotherapy until neutrophil recovery.

Severe chronic neutropenia.

• Congenital: 12 µg/kg daily, as one or divided doses. Idiopathic or cyclic: 5 µg/kg daily. Adjust to keep neutrophils at 1.5 × 10⁹/L or more.

Neutropenia in advanced HIV infection. 1 µg/kg daily, increasing to 4 µg/kg if needed, to achieve neutrophils of 1 × 10⁹/L or more.

Adjustments. Kidney and liver: no adjustment. Older adults: no adjustment.

Contraindications. Hypersensitivity; severe congenital neutropenia with cytogenetic abnormalities or myelodysplasia.

Warnings. Splenic rupture (left upper quadrant or shoulder tip pain), acute respiratory distress syndrome, capillary leak syndrome, glomerulonephritis, sickle cell crisis in sickle cell disease or trait, leukocytosis above 50 × 10⁹/L, aortitis, and Sweet syndrome. Myelodysplasia and acute myeloid leukaemia occur in severe chronic neutropenia.

Adverse effects. Bone pain (the commonest; treated with paracetamol or a non-steroidal anti-inflammatory drug), injection-site reaction, headache, fever, raised liver enzymes and uric acid.

Interactions. Not given within 24 hours before or after cytotoxic chemotherapy or radiotherapy. Lithium enhances neutrophil release.

Pregnancy and breastfeeding. Limited data; use only if benefit outweighs risk.

Common errors. Starting the same day as chemotherapy; continuing after recovery; using in sickle cell disease without monitoring.

Administration. Subcutaneous injection, or intravenous infusion over 30 minutes in 5% glucose only, never saline. Do not dilute below 2 µg/mL; between 2 and 15 µg/mL add human albumin to 2 mg/mL. Store at 2 to 8°C.

Baseline. Full blood count with differential, spleen examination, creatinine and liver function.

Monitoring. Full blood count twice weekly during mobilisation or the early course; platelets and white cell count during treatment. Stop when neutrophils exceed 10 × 10⁹/L after the nadir, or if white cell count exceeds 50 × 10⁹/L.

Referral and escalation. Left upper quadrant pain needs urgent imaging for splenic rupture. Respiratory distress with infiltrates: stop filgrastim.