filgrastim (G-CSF, Neupogen, tbo-filgrastim, Granix, Zarxio, filgrastim-sndz)

Dosing and uses of Neupogen, Granix (filgrastim, tbo-filgrastim, G-CSF)

• Adult
• Pediatric

 

Adult dosage forms and strengths

injectable solution (Neupogen)

• 300mcg/mL
• 480mcg/1.6mL

prefilled syringe for SC injection (Neupogen, tbo-filgrastim [Granix], filgrastim-sndz [Zarxio])

• 300mcg/0.5mL
• 480mcg/0.8mL

Biosimilars to Neupogen

• Zarxio

 

Myelosuppressive Chemotherapy Treatment

Neupogen, Granix, Zarxio

Indicated to decrease infection incidence‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever

5 mcg/kg SC/IV qDay initially, may increase by 5 mcg/kg according to duration and severity of ANC

Do not administer within the 24-hr period prior to chemotherapy

A transient increase in neutrophil count is typically seen 1 to 2 days after initiation; therefore, to ensure a sustained therapeutic response‚ administer daily for up to 2 weeks or until the ANC has reached 10‚000/mm³ following the expected chemotherapy-induced neutrophil nadir

Duration of therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen employed

 

Induction or Consolidation Chemotherapy

Neupogen, Zarxio

Indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia

5 mcg/kg SC/IV qDay intially, may increase by 5 mcg/kg for each chemotherapy cycle according to duration and severity of ANC

Do not administer within the 24-hr period prior to chemotherapy

A transient increase in neutrophil count is typically seen 1 to 2 days after initiation; therefore, to ensure a sustained therapeutic response‚ administer daily for up to 2 weeks or until the ANC has reached 10‚000/mm³ following the expected chemotherapy-induced neutrophil nadir

Duration of therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen employed

 

Bone Marrow Transplantation

Neupogen, Zarxio

Indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg‚ febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation

Following bone marrow transplantation (BMT): 10 mcg/kg/day IV infusion over 4-24 hr (do not exceed 24 hr infusion)

Administer the first dose at least 24 hr after cytotoxic chemotherapy and at least 24 hr after bone marrow infusion

Monitor CBCs and platelet counts frequently following marrow transplantation

Dose titration

• During the period of neutrophil recovery‚ titrate the daily dosage against the neutrophil response
• ANC >1000/mm³: Reduce dose to 5 mcg/kg/day, THEN
• If ANC remains >1000/mm³ for 3 more consecutive days: Discontinue filgrastim, THEN
• If ANC decreases to <1000³: Resume at 5 mcg/kg/day

 

Peripheral Blood Progenitor Cell Collection

Neupogen, Zarxio

Indicated for the mobilization of autologous peripheral blood progenitor cells (PBPC) into the peripheral blood for collection by leukapheresis

10 mcg/kg/day SC

Initiate at least 4 days before first leukapheresis; continue until last day of leukapheresis

Optimal duration of administration and leukapheresis schedule have not been established‚ administration for 6 to 7 days with leukaphereses on days 5‚ 6‚ and 7 was found to be safe and effective in clinical studies described in prescribing information

Monitor neutrophil counts after 4 days‚ and discontinue if the WBC count rises to >100‚000/mm³

 

Severe Chronic Neutropenia

Neupogen, Zarxio

Indicated for chronic administration to reduce the incidence and duration of sequelae of neutropenia (eg‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with severe chronic neutropenia (SCN) including congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia

Congenital: Initial 6 mcg/kg SC q12hr

Idiopathic/cyclic: Initial 5 mcg/kg/day SC

Dosage modifications (SCN)

• Chronic daily administration is required to maintain clinical benefit
• Individualize dose based on the clinical course as well as ANC
• Postmarket analysis showed median daily doses of 6 mcg/kg (congenital neutropenia), 2.1 mcg/kg (cyclic neutropenia), and 1.2 mcg/kg (idiopathic neutropenia)
• In rare instances, patients with congenital neutropenia have required doses ≥100 mcg/kg/day

Monitoring (SCN)

• Monitor CBC count (with differential and platelet counts) during the initial 4 weeks and during the 2 weeks following any dosage adjustment
• Once a patient is clinically stable‚ monitor monthly during the first year of treatment
• Thereafter, if the patient is clinically stable, less frequent routine monitoring is recommended

 

Acute Exposure to Myelosuppressive Radiation Doses

Neupogen

Indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome)

10 mcg/kg SC as a single daily injection for patients exposed to myelosuppressive doses of radiation

Administer as soon as possible after suspected or confirmed exposure to radiation doses >2 gray (Gy)

Estimate a patient’s absorbed radiation dose based on information from public health authorities, biodosimetry if available, or clinical findings (eg, time to onset of vomiting, lymphocyte depletion kinetics)

Obtain baseline CBC and then serial CBCs ~q3days until the ANC remains >1,000/mm³ for 3 consecutive CBCs

Do not delay administration if a CBC is not readily available

Continue administration until the ANC remains >1,000/mm³ for 3 consecutive CBCs or is >10,000/mm³ after a radiation-induced nadir

 

Orphan Designations

Ganciclovir-related neutropenia: Treatment of patients with AIDS who, in addition, are afflicted with cytomegalovirus retinitis and are being treated with ganciclovir

Treatment of amyotropic lateral sclerosis (ALS)

Sponsors

• Amgen, Inc; One Amgen Center Dr; Thousand Oaks, CA 91320-1799
• Neurovision Pharma GmbH; Emil-Geis Str. 4; Grunwald82031, Germany

 

Administration

SC bolus injection

• SC injection may be administered by healthcare professional, caregiver, or patient
• Sites for SC injections include the abdomen (except for the 2-inch area around the navel), the front of the middle thighs, the upper outer areas of the buttocks, or the upper back portion of the upper arms
• Rotate injection site daily
• Do not inject into an area that is tender, red, bruised or hard, or that has scars or stretch marks

 

Pediatric dosage forms and strengths

injectable solution (Neupogen)

• 300mcg/mL
• 480mcg/1.6mL

prefilled syringe for SC injection (Neupogen, tbo-filgrastim [Granix])

• 300mcg/0.5mL
• 480mcg/0.8mL

 

Peripheral Blood Progenitor Cell Collection

As adults; 10 mcg/kg/day SC

Initiate 4 days before leukapheresis; continue until last day of leukapheresis

 

Myelosuppressive Chemotherapy Treatment (Off-label)

5-10 mcg/kg qDay IV/SC for14 days

Give daily until ANC >10,000/mm³

 

Congenital Neutropenia or Agranulocytosis (Off-label)

As adults; Initial 6 mcg/kg SC q12hr

Dosage range: 3-15 mcg/kg/day SC qDay or divided q12hr

 

Administration

SC bolus injection

• SC injection may be administered by healthcare professional, caregiver, or patient
• Sites for SC injections include the abdomen (except for the 2-inch area around the navel), the front of the middle thighs, the upper outer areas of the buttocks, or the upper back portion of the upper arms
• Rotate injection site daily
• Do not inject into an area that is tender, red, bruised or hard, or that has scars or stretch marks

 

Neupogen, Granix (filgrastim, tbo-filgrastim, G-CSF) adverse (side) effects

>10%

Nausea (57%)

Vomiting (57%)

Bone pain (22%-33%)

Alopecia (18%)

Diarrhea (14%)

Fever (12%)

Fatigue (11%)

 

1-10%

Headache

Anorexia

Chest pain

Cough

Dyspnea

Constipation

Stomatitis

Sore throat

Rash

 

Frequency not defined

Elevated uric acid

Elevated lactate dehydrogenase

Elevated alkaline phosphatase

 

Postmarketing Reports

Splenic rupture

ARDs

Glomerulonephritis

Alveolar hemorrhage and hemoptysis

Sickle cell crisis

Cutaneous vasculitis

Sweet’s syndrome (acute febrile neutrophilic dermatosis)

Decreased bone density and osteoporosis in children with severe chronic neutropenia receiving chronic treatment

 

Warnings

Contraindications

Hypersensitivity to E. coli derived proteins

 

Cautions

Allergic reactions reported (angioneurotic edema, dermatitis allergic, hypersensitivity, rash, pruritic rash and urticaria)

Associated with rare cases of potentially fatal splenic rupture; evaluate if patient experiences left upper abdominal and/or shoulder tip pain

Rare cases of acute respiratory distress syndrome reported

Monitor for thrombocytopenia

Sickle cell crisis: Severe and sometimes fatal crisis can occur; discontinue drug if suspected

Glomerulonephritis reported; if suspected, evaluate for cause; if causality likely, consider dose-reduction or interruption

Off-label use for PBPC mobilization has resulted in alveolar hemorrhage, resulting in pulmonary infiltrates and hemoptysis

 

Pregnancy and lactation

Pregnancy category: C

Women who become pregnant during treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program; call 1-800-77-AMGEN (1-800-772-6436) to enrolL

Lactation: excretion in milk unknown; use with caution

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Neupogen, Granix (filgrastim, tbo-filgrastim, G-CSF)

Mechanism of action

Recombinant human G-CSF, acts on hematopoietic cells to stimulate production, maturation and activation of neutrophils; increases migration and cytotoxicity of neutrophils.

 

Absorption

100% (SC)

Peak Plasma Time: 2-8 hr

 

Distribution

Vd: 0.15 L/kg

 

Metabolism

Degraded systemically

 

Elimination

Duration: Neutrophil counts decrease to baseline in approximately 4 days

Half-life elimination: 1.8-3.5 hr

Clearance: 0.5-0.7 mL/min/kg

 

Administration

IV Incompatibilities

Y-site: amphotericin B, cefepime, cefoperazone, cefotaxime, cefoxitin, ceftizoxime, ceftriaxone, cefuroxime, clindamycin, dactinomycin, etoposide, fluorouracil, furosemide, heparin, mannitol, methylprednisolone sodium succinate, metronidazole, mitomycin, piperacillin, prochlorperazine, thiotepa

 

IV Compatibilities

Y-site (partial list): acyclovir, ampicillin, bleomycin, carboplatin, carmustine, cyclophosphamide, diphenhydramine, daunorubicin,. doxorubicin, fluconazole, metoclopramide, morphine SO4, KCl, Na-bicarB

 

IV Preparation

Vials may be diluted in D5W to >15 mcg/mL for infusion

5-15 mcg/mL dilution: Protect from adsorption to plastic materials by the addition of human albumin to a final concentration of 2 mg/mL

Do not dilute with saline at any time, because the product may precipitate

 

IV Administration

Short IV infusion over 15-30 min, Or

Continuous IV infusion

 

SC Administration

Administer undiluted by SC in the outer area of upper arms, abdomen, thighs, or upper outer areas of the buttock

 

Storage

Clear, colorless solution

Store refrigerated and protect from light

Diluted solution: Can be stored at room temperature for up to 24 hr (includes infusion time)

Do not shake