filgrastim

REMS

Prevention of febrile neutropenia and associated infection in patients who have received bone marrow–depressing antineoplastics for the treatment of nonmyeloid malignancies.
Reduction of time for neutrophil recovery and duration of fever in patients undergoing induction and consolidation chemotherapy for acute myelogenous leukemia.
Reduction of time to neutrophil recovery and sequelae of neutropenia in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation.
Mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis.
Management of severe chronic neutropenia.
Survival improvement in patients acutely exposed to myelosuppressive doses of radiation.

Unlabeled Use:

Neutropenia associated with HIV infection.
Neonatal neutropenia.

Action ⬆ ⬇

A glycoprotein, filgrastim binds to and stimulates immature neutrophils to divide and differentiate. Also activates mature neutrophils.

Therapeutic effects:

Decreased incidence of infection in patients who are neutropenic from chemotherapy or other causes.
Improved harvest of progenitor cells for bone marrow transplantation.
Improved survival in patients exposed to myelosuppressive doses of radiation

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed after SUBQ administration.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

Half-Life: Adults: 3.5 hr; Neonates: 4.4 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV, SUBQ	unknown	unknown	4 days‡

‡Return of neutrophil count to baseline.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to filgrastim or
Escherichia coli
-derived proteins.

Use Cautiously in:

Congenital neutropenia (↑ risk of myelodysplastic syndrome or acute myeloid leukemia);
Patients with breast or lung cancer receiving chemotherapy and/or radiotherapy (↑ risk of myelodysplastic syndrome or acute myeloid leukemia);
Patients with sickle cell disease (↑ risk of sickle cell crisis);
Malignancy with myeloid characteristics;
Pre-existing cardiac disease;
OB: Use only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant.

Adv. Reactions/Side Effects ⬆ ⬇

CV: aortitis, vasculitis

EENT: hemoptysis

GI: SPLENIC RUPTURE, splenomegaly

GU: glomerulonephritis

Hemat: ACUTE MYELOID LEUKEMIA, excessive leukocytosis, MYELODYSPLASTIC SYNDROME, sickle cell crises, thrombocytopenia

Local: pain at injection site

MS: medullary bone pain

Resp: ACUTE RESPIRATORY DISTRESS SYNDROME, pulmonary infiltrates

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Simultaneous use with antineoplastics may have adverse effects on rapidly proliferating neutrophils—avoid use for 24 hr before and 24 hr after chemotherapy.
Lithium may potentiate the release of neutrophils; concurrent use should be undertaken cautiously.

Route/Dosage ⬆ ⬇

After Myelosuppressive Chemotherapy

IV SC (Adults and Children ): 5 mcg/kg/day as a single SUBQ injection, by short IV infusion, or via continuous IV infusion for up to 2 wk or until ANC reaches 10,000/mm³. Initiate at least 24 hr after chemotherapy. Dose may be ↑ by 5 mcg/kg during each cycle of chemotherapy, depending on blood counts.

After Bone Marrow Transplantation

IV (Adults ): 10 mcg/kg/day as a continuous IV infusion for up to 24 hr; initiate at least 24 hr after chemotherapy and at least 24 hr after bone marrow transplantation. Subsequent dose is adjusted according to blood counts.

Peripheral Blood Progenitor Cell Collection and Therapy

SC (Adults ): 10 mcg/kg/day for at least 4 days before first leukapheresis and continued until last leukapheresis; Discontinue if WBC >100,000 cells/mm³.

Severe Chronic Neutropenia

SC (Adults ): Congenital neutropenia: 6 mcg/kg twice daily. Idiopathic/cyclical neutropenia: 5 mcg/kg daily (↓ if ANC remains >10,000/mm³).

After Myelosuppressive Radiation

SC (Adults ): 10 mcg/kg once daily; initiate as soon as possible after exposure to radiation doses greater than 2 gray (Gy); continue until ANC remains >1000/mm³ for 3 consecutive blood counts (performed every 3 days) or is >10,000/mm³ after a radiation-induced nadir.

Neonatal Neutropenia

IV SC (Neonates ): 5–10 mcg/kg/day once daily for 3–5 days.

Availability ⬆ ⬇

Solution for injection (prefilled syringes): 300 mcg/0.5 mL; 480 mcg/0.8 mL
Solution for injection (vials): 300 mcg/1 mL; 480 mcg/1.6 mL

Assessment ⬆ ⬇

Monitor heart rate, BP, and respiratory status before and periodically during therapy.
Assess bone pain during therapy. Pain is usually mild to moderate and controllable with nonopioid analgesics, but may require treatment with opioid analgesics, especially in patients receiving high-dose IV therapy. Loratadine 10 mg PO administered before filgrastim dose has been used to prevent bone pain.
Monitor for signs and symptoms of allergic reactions (rash‚ urticaria‚ facial edema, wheezing‚ dyspnea, hypotension‚ tachycardia). Usually occur within 30 min of administration. Treatment includes antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine; may recur with rechallenge.
Assess for signs and symptoms of acute respiratory distress syndrome (fever, lung infiltrates, or respiratory distress). If symptoms occur, withhold filgrastim until symptoms resolve or discontinue.
Monitor for signs and symptoms of splenic enlargement or rupture (left upper abdominal or shoulder pain).
May cause transient positive bone-imaging changes.

Lab Test Considerations:

After chemotherapy, obtain a CBC with differential, including examination for the presence of blast cells, and platelet count before chemotherapy and twice weekly during therapy to avoid leukocytosis. Monitor ANC. A transient rise is seen 1–2 days after initiation of therapy, but therapy should not be discontinued until ANC >10,000/mm³.
- After bone marrow transplant, the daily dose is titrated by the neutrophil response. When the ANC is >1000/mm³ for 3 consecutive days, reduce dose to 5 mcg/kg/day. If the ANC remains >1000/mm³ for 3 or more consecutive days, discontinue filgrastim. If the ANC decreases to <1000/mm³, resume filgrastim at 5 mcg/kg/day.
- For chronic severe neutropenia, monitor CBC with differential and platelet count twice weekly during initial 4 wk of therapy and during 2 wk after any dose adjustment.
- May cause ↓ platelet count and transient ↑ in uric acid, LDH, and alkaline phosphatase concentrations.
- May cause myelodysplastic syndrome and acute myeloid leukemia in patient with severe chronic neutropenia, breast, or lung cancer. Monitor for signs and symptoms (tiredness, fever, easy bruising or bleeding).

Implementation ⬆ ⬇

Administer no earlier than 24 hr after cytotoxic chemotherapy, at least 24 hr after bone marrow infusion, and not during the 24 hr before administration of chemotherapy.
- Refrigerate; do not freeze. Do not shake. Warm to room temperature for at least 30 min and up to 24 hr before injection. Discard if left at room temperature for >24 hr. Vial is for one-time use only.
SC: May be administered in outer area of upper arms, abdomen, thighs, or upper outer areas of buttock. If dose requires >1 mL of solution, may be divided into 2 injection sites.
- Cap of needle contains latex; avoid administration by persons with latex allergy.
- May also be administered as a continuous SUBQ infusion over 24 hr after bone marrow transplantation.

IV Administration:

Diluent: Dilute in D5W; do not dilute with 0.9% NaCl, will precipitate. Refrigerate; do not freeze. Do not shake. May warm to room temperature for up to 4 hr (Releuko) or 24 hr (Neupogen, Zarxio) before injection. Vial is for one-time use only.Concentration: Dilute to a final concentration of at least 15 mcg/mL. If the final concentration is 15 mcg/mL, human albumin in a concentration of 2 mg/mL must be added to D5W before filgrastim to prevent adsorption of the components of the drug delivery system. May be stored at room temperature for up to 4 hr (Releuko) or 24 hr (Neupogen, Zarxio).
Rate: After chemotherapy dose is administered via infusion over 15–60 min.
- After chemotherapy dose may also be administered as a continuous infusion.
- After bone marrow transplant, administer dose as an infusion over 4 or 24 hr.

Patient/Family Teaching ⬆ ⬇

Explain purpose of filgrastim to patient. Instruct patient and caregiver on correct technique for injection, care and disposal of equipment. Advise patient to notify health care professional regarding when to give next dose if a dose is missed. Instruct patient and caregiver to read Instructions for Patients and Caregivers before starting therapy and with each Rx refill in case of changes.
Instruct patient to notify health care professional immediately if signs and symptoms of spleen enlargement or rupture, allergic reaction, ARDS, glomerulonephritis (swelling of face or ankles, dark colored urine or blood in urine, decrease in urine production), MDS, AML, or vasculitis (skin redness, purple spots on skin) occur. Discuss risk of sickle cell crisis with patients with sickle cell disease before administering.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Home Care Issues: Instruct patient on correct technique and proper disposal for home administration. Caution patient not to reuse needle, vial, or syringe. Provide patient with a puncture-proof container for needle and syringe disposal.

Evaluation/Desired Outcomes ⬆ ⬇

Decreased incidence of infection in patients who receive bone marrow–depressing antineoplastics.
Reduction of duration and sequelae of neutropenia after bone marrow transplantation.
Reduction of the incidence and duration of sequelae of neutropenia in patients with severe chronic neutropenia.
Improved harvest of progenitor cells for bone marrow transplantation.
Improved survival in patients exposed to myelosuppressive doses of radiation

US Brand Names ⬆ ⬇

Granix, Neupogen, Nivestym, Releuko, Zarxio

Canadian Brand Names ⬆ ⬇

Code ⬆

NDC Code

55513- Amgen Inc
- 55513-209- NEUPOGEN
  - 55513-209-10- 10 SYRINGE in 1 BOX (55513-209-10) > .8 mL in 1 SYRINGE (55513-209-01)

55513- Amgen Inc
- 55513-209- NEUPOGEN
  - 55513-209-91- .8 mL in 1 SYRINGE (55513-209-91)

55513- Amgen Inc
- 55513-530- NEUPOGEN
  - 55513-530-10- 10 VIAL in 1 PACKAGE (55513-530-10) > 1 mL in 1 VIAL (55513-530-01)

55513- Amgen Inc
- 55513-546- NEUPOGEN
  - 55513-546-10- 10 VIAL in 1 BOX (55513-546-10) > 1.6 mL in 1 VIAL (55513-546-01)

55513- Amgen Inc
- 55513-924- NEUPOGEN
  - 55513-924-10- 10 SYRINGE in 1 BOX (55513-924-10) > .5 mL in 1 SYRINGE (55513-924-01)

55513- Amgen Inc
- 55513-924- NEUPOGEN
  - 55513-924-91- .5 mL in 1 SYRINGE (55513-924-91)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇