No

Colony Stimulating Factor

Patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of neutropenia (FDA-approved indication)

Cancer patients receiving bone marrow transplant (BMT) (FDA-approved indication)

Patients undergoing peripheral blood progenitor cell (PBPC) collection

Patients with severe chronic neutropenia (SCN) (FDA-approved indication)

Chronic administration in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenic; filgrastim should not be started until the diagnosis of SCN is confirmed, as it may interfere with diagnostic efforts

Safety and efficacy of G-CSF given simultaneously with cytotoxic chemotherapy have not been established; concurrent treatment may increase myelosuppression; G-CSF should be avoided in patients receiving concomitant chemotherapy and radiation therapy

C

Patients with known hypersensitivity to E. coli-derived proteins or G-CSF

Complete blood count and platelet count should be obtained prior to chemotherapy. Do not use G-CSF in the period 12-24 hours before to 24 hours after administration of cytotoxic chemotherapy because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy. Precaution should be exercised in the usage of G-CSF in any malignancy with myeloid characteristics. G-CSF can potentially act as a growth factor for any tumor type, particularly myeloid malignancies. Tumors of nonhematopoietic origin may have surface receptors for G-CSF.

Effects are generally mild and dose related

Central nervous system: Neutropenic fever, fever

Dermatologic: Alopecia

Gastrointestinal: Nausea, vomiting, diarrhea, mucositis,

Splenomegaly: This occurs more commonly in patients with cyclic neutropenia/congenital agranulocytosis who received S.C. injections for a prolonged (>14 days) period of time; ~33% of these patients experience subclinical splenomegaly (detected by MRI or CT scan); ~3% of these patients experience clinical splenomegaly

Neuromuscular & skeletal: Medullary bone pain (24% incidence): This occurs most commonly in lower back pain, posterior iliac crest, and sternum and is controlled with non-narcotic analgesics

1% to 10%:

Cardiovascular: Chest pain, fluid retention

Central nervous system: Headache

Dermatologic: Skin rash

Gastrointestinal: Anorexia, stomatitis, constipation

Hematologic: Leukocytosis

Local: Pain at injection site

Neuromuscular & skeletal: Weakness

Respiratory: Dyspnea, cough, sore throat

<1%: Transient supraventricular arrhythmia, pericarditis, thrombophlebitis, anaphylactic reaction

No clinical adverse effects seen with high dose producing ANC >10,000/mm³; leukocytosis which was not associated with any clinical adverse effects

After discontinuing in patients receiving myelosuppressive chemotherapy, there is a 50% decrease in circulating levels of neutrophils within 1-2 days, return to pretreatment levels within 1-7 days

Drugs which may potentiate the release of neutrophils (eg, lithium) should be used with caution

Filgrastim is a clear, colorless solution and should be stored under refrigeration at 2°C to 8°C (36°F to 46°F) and protected from direct sunlight. Filgrastim should be protected from freezing and temperatures >30°C to avoid aggregation. Filgrastim unopened vials are stable at controlled room temperatures (9°C to 30°C/47°F to 86°F) for up to 7 days.

The solution should not be shaken since bubbles and/or foam may form. If foaming occurs, the solution should be left undisturbed for a few minutes until bubbles dissipate.

Filgrastim is stable for 7 days at 9°C to 30°C, however, the manufacturer recommends discarding after 6 hours because of microbiological concerns. The product is packaged as single-use vial without a preservative.

Undiluted filgrastim is stable for 7 days at 15°C to 30°C and 14 days at 2°C to 8°C in tuberculin syringes. However, refrigeration and use within 24 hours are recommended because of concern for bacterial contamination.

Filgrastim may be diluted in dextrose 5% in water to a concentration of greater than or equal to 15 mcg/mL for I.V. infusion administration

Minimum concentration is 15 mcg/mL; concentrations of 5-15 mcg/mL require the addition of albumin (1 mL of 5%) to the bag to prevent absorption to plastics/PVC. Concentrations of <5 mcg/mL should not be used.

This diluted solution is stable for 7 days under refrigeration or at room temperature

Standard diluent: greater than or equal to 375 mcg/25 mL D₅W; filgrastim is incompatible with 0.9% sodium chloride (normal saline)

Stimulates the production, maturation, and activation of neutrophils, G-CSF activates neutrophils to increase both their migration and cytotoxicity

Onset of action: Rapid elevation in neutrophil counts within the first 24 hours, reaching a plateau in 3-5 days

Duration: ANC decreases by 50% within 2 days after discontinuing G-CSF; white counts return to the normal range in 4-7 days

Absorption: S.C.: 100% absorbed; peak plasma levels can be maintained for up to 12 hours

Distribution: V_d: 150 mL/kg; no evidence of drug accumulation over a 11- to 20-day period

Metabolism: Systemically metabolized

Bioavailability: Oral: Not bioavailable

Half-life: 1.8-3.5 hours

Time to peak serum concentration: S.C.: Within 2-6 hours

Children and Adults:

Existing clinical data suggest that starting G-CSF between 24 and 72 hours subsequent to chemotherapy may provide optimal neutrophil recover; continue therapy until the occurrence of an absolute neutrophil count of 10,000 mL after the neutrophil nadir

The available data suggest that rounding the dose to the nearest vial size may enhance patient convenience and reduce costs without clinical detriment

Neonates: 5-10 mcg/kg/day once daily for 3-5 days has been administered to neutropenic neonates with sepsis; there was a rapid and significant increase in peripheral neutrophil counts and the neutrophil storage pool

Children and Adults:

Myelosuppressive chemotherapy S.C. or I.V. infusion: 5 mcg/kg/day

Doses may be increased in increments of 5 mcg/kg for each chemotherapy cycle, according to the duration and severity of the absolute neutrophil count (ANC) nadir

Bone marrow transplant patients: 5-10 mcg/kg/day as an I.V. infusion of 4 or 24 hours or as continuous 24-hour S.C. infusion; administer first dose at least 24 hours after cytotoxic chemotherapy and at least 24 hours after bone marrow infusion; if ANC decreases <1000/mm³ during the 5 mcg/kg/day dose, increase filgrastim to 10 mcg/kg/day and follow the recommended steps based on neutrophil response:

When ANC >1000/mm³ for 3 consecutive days: Reduce Filgrastim dose to 5 mcg/kg/day

If ANC remains >1000/mm³ for 3 more consecutive days: Discontinue filgrastim

If ANC decreases to <1000/mm³ : Resume at 5 mcg/kg/day

If ANC decreases <1000/mm³ during the 5 mcg/kg/day dose, increase filgrastim to 10 mcg/kg/day and follow the above steps

Peripheral blood progenitor cell (PBPC) collection: 10 mcg/kg/day either S.C. or a bolus or continuous I.V. infusion. It is recommended that G-CSF be given for at least 4 days before the first leukapheresis procedure and continued until the last leukapheresis; although the optimal duration of administration and leukapheresis schedule have not been established, administration of G-CSF for 6-7 days with leukaphereses on days 5,6 and 7 was found to be safe and effective; neutrophil counts should be monitored after 4 days of G-CSF, and G-CSF dose-modification should be considered for those patients who develop a white blood cell count >100,000/mm³

Severe chronic neutropenia: S.C.:

Congenital neutropenia: 6 mcg/kg/dose twice daily

Idiopathic/cyclic neutropenia: 5 mcg/kg single dose daily

Chronic daily administration is required to maintain clinical benefit; adjust dose based on the patients' clinical course as well as ANC; in phase III studies, the target ANC was 1500-10,000/mm³. Reduce the dose if the ANC is persistently >10,000/mm³

Premature discontinuation of G-CSF therapy prior to the time of recovery from the expected neutrophil is generally not recommended; a transient increase in neutrophil counts is typically seen 1-2 days after initiation of therapy

Hemodialysis: Supplemental dose is not necessary

Peritoneal dialysis: Supplemental dose is not necessary

Complete blood cell count and platelet count should be obtained twice weekly after chemotherapy or three times weekly after transplant. Leukocytosis (white blood cell counts of greater than or equal to 100,000/mm³) has been observed in ~2% of patients receiving G-CSF at doses above 5 mcg/kg/day. Monitor platelets and hematocrit regularly. Monitor patients with pre-existing cardiac conditions closely as cardiac events (myocardial infarctions, arrhythmias) have been reported in premarketing clinical studies.

No clinical benefit seen with ANC >10,000/mm³

None reported

May be used to treat clozapine-induced agranulocytosis; lithium may potentiate the release of neutrophils; use with caution

No information available to require special precautions

No effects or complications reported

Follow directions for proper storage and administration of S.C. medication. Never reuse syringes or needles. You may experience bone pain (request analgesic); nausea or vomiting (small frequent meals may help); hair loss (reversible); or sore mouth (frequent mouth care with soft toothbrush or cotton swab may help). Report unusual fever or chills; unhealed sores; severe bone pain; pain, redness, or swelling at injection site; unusual swelling of extremities or difficulty breathing; or chest pain and palpitations. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Do not mix with sodium chloride solutions

Injection, preservative free: 300 mcg/mL (1 mL, 1.6 mL)

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