filgrastim

REMS

Granix, Neupogen, Nivestym, Nypozi, Releuko, Zarxio

Prevention of febrile neutropenia and associated infection in patients who have received bone marrow–depressing antineoplastics for the treatment of nonmyeloid malignancies.

Neupogen, Nivestym, Nypozi, Releuko, Zarxio

Management of the following:
- 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.
- Severe neutropenia in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia.

Neupogen, Nivestym, Nypozi, Zarxio

Mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis.

Neupogen, Nypozi, Zarxio

Survival improvement in patients acutely exposed to myelosuppressive doses of radiation.

Action ⬆ ⬇

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);
Sickle cell disease (↑ risk of sickle cell crisis);
Malignancy with myeloid characteristics;
Pre-existing cardiac disease;
OB: Use during pregnancy 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 ⬆ ⬇

Receiving Myelosuppressive Chemotherapy

IV SC (Adults and Children ): Granix, Neupogen, Nivestym, Nypozi, Releuko, Zarxio: 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 ≥24 hr after chemotherapy. May ↑ by 5 mcg/kg during each cycle of chemotherapy, depending on blood counts.

Receiving Induction and/or Consolidation Chemotherapy for Acute Myelogenous Leukemia

IV SC (Adults and Children ): Neupogen, Nivestym, Nypozi, Releuko, Zarxio: 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 ≥24 hr after chemotherapy. May ↑ by 5 mcg/kg during each cycle of chemotherapy, depending on blood counts.

After Bone Marrow Transplantation

IV (Adults ): Neupogen, Nivestym, Nypozi, Releuko, Zarxio: 10 mcg/kg/day as a continuous IV infusion for up to 24 hr; initiate ≥24 hr after chemotherapy and ≥24 hr after bone marrow transplantation. Subsequent dose is adjusted according to blood counts.

Peripheral Blood Progenitor Cell Collection and Therapy

SC (Adults ): Neupogen, Nivestym, Nypozi, Zarxio: 10 mcg/kg/day for ≥4 days before first leukapheresis and continued until last leukapheresis. Discontinue if WBC >100,000 cells/mm³.

Severe Neutropenia

SC (Adults ): Neupogen, Nivestym, Nypozi, Releuko, Zarxio: 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 ): Neupogen, Nypozi, Zarxio: 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 three consecutive blood counts (performed every 3 days) or is >10,000/mm³ after a radiation-induced nadir.

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 or opioid analgesics, especially in patients receiving high-dose IV therapy. May pretreat with loratadine 10 mg PO to prevent bone pain.
Monitor for signs and symptoms of severe allergic reactions, including anaphylaxis, especially on initial exposure. If severe allergy occurs, permanently discontinue filgrastim and provide appropriate symptomatic medical treatment. Symptoms may recur days after discontinuation of antiallergy treatment.
Assess for signs and symptoms of acute respiratory distress syndrome (fever, lung infiltrates, respiratory distress). If symptoms occur, hold 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:

Obtain a CBC with differential, including examination for the presence of blast cells, after chemotherapy and before initiating filgrastim and then twice weekly during therapy. Therapy should not be discontinued until ANC >10,000/mm³. For chronic severe neutropenia, monitor CBC with differential twice weekly during initial 4 wk of therapy and for 2 wk after any dose adjustment. For myelosuppressive doses of radiation, obtain baseline CBC, then every third day until ANC >1,000/mm³ for three serial CBCs or ANC >10,000/mm³ after radiation-induced nadir.
- After bone marrow transplant, the daily dose is titrated by the neutrophil response. When the ANC >1000/mm³ for 3 consecutive days, ↓ dose to 5 mcg/kg/day. If the ANC remains >1000/mm³ for ≥3 consecutive days, discontinue filgrastim. If the ANC ↓ to <1000/mm³, resume filgrastim at 5 mcg/kg/day.
- 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, ≥24 hr after bone marrow infusion, and not during the 24 hr before administration of chemotherapy.
SC: May be administered in outer area of upper arm, abdomen, thigh, or upper outer buttock. If dose requires >1 mL of solution, may be divided into two injection sites. Do not use prefilled syringe for dose <0.3 mL.
- Cap of needle contains latex; avoid administration by persons with latex allergy.
- Refrigerate; do not freeze. Do not shake. Warm to room temperature for ≥30 min–24 hr before injection. Solution is clear and colorless to yellowish. Do not administer if discolored or contains particulates. If not used immediately, may be stored at room temperature for ≤8 days. Discard any unused portion.
- May also be administered as a continuous SUBQ infusion over 24 hr after bone marrow transplantation.

IV Administration:

- Refrigerate; do not freeze. Do not shake. Warm to room temperature for ≥30 min–8 days before dilution.
Diluent: Dilute in D5W; do not dilute with 0.9% NaCl; will precipitate. Concentration: >5 mcg/mL. Protect from adsorption to plastics by adding human albumin to final concentration of 2 mg/mL; then filgrastim is compatible with glass, polyvinylchloride, polyolefin, and polypropylene. Diluted solution from prefilled syringe may be stored at room temperature ≤24 hr and vial≤4 hr, including infusion time, or vial may be refrigerated ≤24 hr.
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, acute respiratory distress syndrome, glomerulonephritis (swelling of face or ankles, dark-colored urine or blood in urine, ↓ urine production), myelodysplastic syndrome, acute myeloid leukemia, 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 women 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.

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Pronunciation ⬇

Classifications ⬆ ⬇

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