Filgrastim (Neupogen) and biosimilars of Filgrastim is a recombinant non-pegylated granulocyte colony-stimulating factor used in patients with neutropenia.

Filgrastim and Biosimilar Uses:

• Chemotherapy-induced myelosuppression in non-myeloid malignancies:

  • Neupogen and filgrastim biosimilars:
    • the incidence of infection (neutropenic fever) can be minimized in patients with nonmyeloid malignancies and receiving myelosuppressive chemotherapy associated with a considerable incidence of severe neutropenic fever
  • Tbo-filgrastim:
    • The duration of severe neutropenia can be reduced in adult and pediatric patients of age ≥1 month with nonmyeloid malignancies and are receiving myelosuppressive chemotherapy associated with a significant incidence of neutropenic fever

• Acute myeloid leukemia (AML) following induction or consolidation chemotherapy (Neupogen and filgrastim biosimilars):

  • To minimize the neutrophil recovery time and the duration of fever following induction or consolidation chemotherapy in AML

• Bone marrow transplantation (Neupogen and filgrastim biosimilars):

  • To minimize the duration of low ANC and neutropenia-related events (eg, neutropenic fever) in nonmyeloid malignancies and patients receiving myeloablative chemotherapy followed by bone marrow transplantation

• Hematopoietic radiation injury syndrome, acute (Neupogen only):

  • To increase patients survival recently exposed to myelosuppressive doses of radiation

• Peripheral blood progenitor cell collection and therapy (Neupogen and filgrastim biosimilars):

  • To Mobilize autologous hematopoietic progenitor cells into the peripheral blood for apheresis collection

• Severe chronic neutropenia (Neupogen and filgrastim biosimilars):

  • To minimize the incidence and duration of neutropenia complications(e.g, fever, infections, oropharyngeal ulcers) in patients who are symptomatic with congenital, cyclic, or idiopathic neutropenia, Long term Administration is done.
• Note:
  • Nivestym (filgrastim-aafi) and Zarxio (filgrastim-sndz) are labeled as biosimilars to Neupogen (filgrastim).
  • In Canada, Grastofil is approved as a biosimilar to Neupogen (filgrastim).

• Off Label Use of Filgrastim in Adults:

  • Severe Alcoholic hepatitis
  • Anemia in myelodysplastic syndrome
  • Hematopoietic stem cell mobilization for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma or multiple myeloma
  • Neutropenia in advanced HIV infection
  • hepatitis C treatment-associated neutropenia

Neupogen and filgrastim biosimilars dose in Adults

Note:

• Do not administer in the period 24 hours prior to and 24 hours later than cytotoxic chemotherapy.
• The dose may be rounded to the nearest vial size for convenience and cost minimization. Nivestym (filgrastim-aafi) and Zarxio (filgrastim-sndz) are declared as biosimilars to Neupogen (filgrastim).
• In Canada, Grastofil is approved as a biosimilar to Neupogen (filgrastim).
• International considerations:
  • Dosages below are mentioned as micrograms; 1 mcg = 100,000 units.

Neupogen and filgrastim biosimilars dose in Acute myeloid leukemia (AML) following induction or consolidation chemotherapy:

• SubQ, IV: 5 mcg/kg per day; doses may be increased by 5 mcg/kg (for each chemotherapy cycle) based upon the duration and severity of the neutropenia;
• continue for up to 2 weeks until the ANC reaches 10,000/mm³.
• Discontinue if the ANC surpasses 10,000/mm after the expected chemotherapy-induced neutrophil nadir.

Filgrastim Dose in the treatment of Severe Alcoholic hepatitis (off-label):

• SubQ: 5 mcg/kg twice a day for 5 consecutive days in combination with standard medical therapy (pentoxifylline and nutritional therapy) and supportive care.

Filgrastim Dose in the treatment of Anemia in myelodysplastic syndrome (off-label use in combination with epoetin):

• SubQ: 300 mcg every week in 2 to 3 divided doses or 1 mcg/kg once a day or 75 mcg, 150 mcg, or 300 mcg per dose 3 times weekly

Neupogen and filgrastim biosimilars Dose in the Bone marrow transplantation:

• IV infusion: 10 mcg/kg per day (administer ≥24 hours after chemotherapy and ≥24 hours after bone marrow transplant);
• dose adjustment should be done according to the duration and severity of neutropenia; recommended steps based on neutrophil response:
  • When ANC >1,000/mm³ for 3 consecutive days:
    • Reduce dose to 5 mcg/kg/day.
  • If ANC remains >1,000/mm³ for 3 more consecutive days:
    • Discontinue.
  • If ANC decreases to <1,000/mm³:
    • Resume at 5 mcg/kg/day.
  • If ANC decreases to <1,000/mm³ during the 5 mcg/kg/day dose:
    • Increase the dose to 10 mcg/kg/day and follow the above steps.

Neupogen and filgrastim biosimilars Dose in the treatment of Chemotherapy-induced myelosuppression in nonmyeloid malignancies:

• SubQ, IV: 5 mcg/kg/day;
• doses may be increased by 5 mcg/kg (for each chemotherapy cycle) according to the duration and severity of the neutropenia; continue for up to 14 days until the absolute neutrophil count (ANC) reaches 10,000/mm³.
• Discontinue if the ANC surpasses 10,000/mm³ after the expected chemotherapy-induced neutrophil nadir.

Tbo-filgrastimDose in the treatment of Chemotherapy-induced myelosuppression in non-myeloid malignancies:

• SubQ: 5 mcg/kg/day;
• continue until anticipated nadir has passed and the neutrophil count has recovered to normal range.

Neupogen Dose in the treatment of acute Hematopoietic radiation injury syndrome:

• SubQ: 10 mcg/kg once daily;
• begin as soon as possible after suspected or confirmed radiation doses >2 gray (Gy) and continue filgrastim until ANC remains >1,000/mm³ for 3 consecutive CBCs or ANC exceeds 10,000/mm³ after the radiation-induced nadir.
• ASCO guidelines suggest administration within 24 hours of exposure to ≥2 Gy dose and/or a significant decrease in absolute lymphocyte count, or for anticipated neutropenia <500/mm³ for ≥7 days.

Filgrastim dose in the treatment of hematopoietic stem cell mobilization in autologous transplantation in patients with non-Hodgkin lymphoma or multiple myeloma (in combination with plerixafor; off-label combination):

• SubQ: 10 mcg/kg once daily;
• begin 4 days before initiation of plerixafor;
• continue G-CSF on each day prior to apheresis for up to 8 days.

Filgrastim Dose in the Hepatitis C treatment-associated neutropenia (off-label):

• SubQ: 150 mcg once weekly to 300 mcg 3 times weekly;
• titrate to maintain ANC between 750 and 10,000/mm³

Filgrastim Dose in the treatment of Neutropenia in advanced HIV infection (off-label):

• SubQ: Initial: 1 mcg/kg once daily or 300 mcg one to three times per week;
• titrate to maintain ANC 2,000 to 10,000/mm³;
• doses up to 10 mcg/kg/day or 600 mcg daily were studied.

Neupogen and filgrastim biosimilars Dose in the treatment of Peripheral blood progenitor (PBPC) cell collection and therapy:

• SubQ: 10 mcg/kg daily, usually for 6 to 7 days (with apheresis occurring on days 5, 6, and 7).
• Begin at least 4 days before the first apheresis and continue until the last apheresis; discontinue for WBC >100,000/mm³

Neupogen and filgrastim biosimilars dose in the treatment of Severe chronic neutropenia: SubQ:

• Congenital:

  • Initial: 6 mcg/kg per day in 2 divided doses;
  • adjust the dose based on ANC and clinical response;
  • mean dose: 6 mcg/kg/day.

• Idiopathic:

  • Initial: 5 mcg/kg once a day;
  • adjust the dose based on ANC and clinical response;
  • the total daily dose may be administered in 1 or 2 divided doses;
  • mean dose: 1.2 mcg/kg per day

• Cyclic:

  • Initial: 5 mcg/kg once a day;
  • adjust the dose based on ANC and clinical response;
  • the total daily dose may be administered in 1 or 2 divided doses;
  • mean dose: 2.1 mcg/kg per day

Neupogen and filgrastim biosimilars dose in Childrens

Note:

• International considerations:
  • Dosages below are mentioned as micrograms; 1 mcg = 100,000 units.
  • Dosing may differ by the protocol;
  • refer to the specific treatment protocols.
  • For higher doses (eg, adolescents), rounding doses to the nearest vial size may increase patient convenience and minimize costs without compromising clinical response.

Filgrastim and filgrastim biosimilars Dose in the Bone marrow transplantation:

• Children and Adolescents:

  • IV infusion: 10 mcg/kg per day (administer ≥24 hours following chemotherapy and ≥24 hours after bone marrow transplant);
  • dose adjustment should be done according to the duration and severity of neutropenia;
  • dosage adjustment recommended based on neutrophil response:
    • When ANC >1,000/mm for 3 consecutive days:
      • Reduce dose to 5 mcg/kg/day
    • If ANC remains >1,000/mm³ for 3 more consecutive days:
      • Discontinue
    • If ANC decreases to <1,000/mm³:
      • Resume at 5 mcg/kg/day
    • If ANC decreases to <1,000/mm³ during the 5 mcg/kg/day dose, increase the dose to 10 mcg/kg/day and follow the above steps

Filgrastim Dose in the Bone marrow transplantation, slow engraftment:

• IV, SubQ: 5 mcg/kg/day administered ≥24 hours after cytotoxic chemotherapy and ≥24 hours after bone marrow infusion.

Filgrastim and Biosimilar Dose in the treatment of Chemotherapy-induced neutropenia (myelosuppressive chemotherapy recipients with non-myeloid malignancies):

• Infants, Children, and Adolescents:

  • IV, SubQ:
    • 5 mcg/kg/day once daily beginning ≥24 hours after chemotherapy; recommendations for duration of therapy vary:
    • Manufacturer labeling is for up to 14 days or until ANC reaches 10,000/mm³
    • others have suggested a lower target ANC of 5,000/mm³
    • review treatment-specific protocol for guidance.
    • For subsequent chemotherapy cycles, the dose may be increased by 5 mcg/kg based upon the patient's previous response to therapy along with the duration and severity of neutropenia.

Tbo-Filgrastim (Granix):

• Infants, Children, and Adolescents:

  • SubQ: 5 mcg/kg/day once daily; begin ≥24 hours after chemotherapy and continue until anticipated nadir has passed and the neutrophil count has recovered to normal range.

Filgrastim Dose in the treatment of acute Hematopoietic syndrome of acute radiation syndrome: 

• Infants, Children, and Adolescents:

  • SubQ: 10 mcg/kg/day once daily; begin as soon as possible after suspected or confirmed radiation doses >2 gray (Gy) and continue filgrastim until ANC remains >1,000/mm³ for 3 consecutive CBCs or ANC exceeds 10,000/mm³ after the radiation-induced nadir.
  • ASCO guidelines recommend initiating within 24 hours of exposure of a dose ≥2 Gy and/or a significant decrease in absolute lymphocyte count or for anticipated neutropenia <500/mm for ≥7 days.

Filgrastim and filgrastim biosimilars Dose in the treatment of severe chronic Neutropenia:

• Infants, Children, and Adolescents: SubQ:

  • Congenital:

    • Initial: 6 mcg/kg per day in twice a day dose;
    • adjust the dose based on ANC and clinical response;
    • median dose: 6 mcg/kg/day

  • Idiopathic:

    • Initial: 5 mcg/kg per day in 1 or 2 divided doses;
    • dose adjustment based on ANC and clinical response; median dose: 1.2 mcg/kg/day

  • Cyclic:

    • Initial: 5 mcg/kg per day in 1 or 2 divided doses; dose adjustment is based on ANC and clinical response; median dose: 2.1 mcg/kg/day

Filgrastim Dose in the treatment of Neutropenia in HIV infection (eg, drug-induced):

Note: Trials performed with Neupogen product

• Infants and Children:

  • SubQ: Initial: 1 mcg/kg per day, adjust every 3 days to maintain the desired ANC.
  • Doses as high as 20 mcg/kg per day have been suggested.

• Adolescents:

  • Weight-based dosing:

    • SubQ: Initial: 1 mcg/kg per day, adjust every 3 days to maintain the desired ANC.
    • Doses as high as 20 mcg/kg per day have been described.

  • Fixed dosing:

    • SubQ: Initial: 300 mcg 1 to 3 times every week, adjust to desired ANC.
    • Maximum daily dose: 600 mcg/day.

Filgrastim and filgrastim biosimilars Dose in the treatment of Peripheral blood progenitor cell collection and therapy:

• SubQ, IV:
  • 10 mcg/kg/day; begin at least 4 days prior to the first apheresis and continue until apheresis;
  • discontinue if WBC >100,000/mm³.

Filgrastim Pregnancy Risk Category: B3/ C

• Filgrastim crosses over the placenta.
• The evidence to date does not support a link between filgrastim use in pregnancy and high risks of miscarriage, labor, or adverse fetal outcomes such as birth weight or infection after maternal treatment for severe chronic neutropenia.
• Limited information is available on the use of granulocyte-coloy-stimulating factors (G-CSF), in pregnant patients with congenital, cycle, or idiopathic neuopenia, and G-CSF-induced peripheral blood stem cell donation.
• Data from the Severe chronic Neutropenia International Registry, (SCNIR), indicate that dosages for chronic conditions might need to be adjusted in pregnant.
• It is best to keep the absolute neutrophil count at the lowest effective dose.
• A consensus panel of experts has established guidelines for hematologic malignancies in pregnancy.
• These guidelines suggest that, despite the lack of data, administrations of granulocyte growth factor during pregnancy might be acceptable.
• One review suggested that when using for hematopoietic cell mobilization (in healthy donor; not a labeled purpose), it should be stopped during the first three months to ensure additional outcome information.

Filgrastim use during breastfeeding:

• Breast milk can contain endogenous G-CSF. These concentrations increase for at least three days after maternal filgrastim administration.
• Infants were not able to absorb Recombinant G–CSF when it was administered orally.
• Breastfeeding infants were not exposed to adverse events after maternal use of filgrastim (limited evidence).
• According to the manufacturers the decision to breastfeed while on therapy should be based on the risks to infants, the benefits to mothers and the benefits to the mother as well as the mother’s underlying condition.

Filgrastim Dose in Kidney Disease:

• Renal impairment at treatment initiation:

  • Neupogen and filgrastim-biosimilars:
    • No dosage adjustment is necessary.

  • Tbo-filgrastim:

    • Mild impairment:
      • No dosage adjustment is necessary.
    • Moderate to severe impairment:
      • There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

• Renal toxicity during treatment:

  • Glomerulonephritis due to filgrastim:
    • Consider dose reduction or treatment interruption.

Filgrastim Dose in Liver disease:

• Neupogen and filgrastim biosimilars:
  • No dosage adjustment is necessary.
• Tbo-filgrastim:
  • There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Common Side Effects of Filgrastim (Neupogen):

• Cardiovascular:

  • Chest Pain

• Central Nervous System:

  • Fatigue
  • Dizziness
  • Pain

• Dermatologic:

  • Skin Rash

• Gastrointestinal:

  • Nausea

• Hematologic & Oncologic:

  • Thrombocytopenia
  • Splenomegaly

• Hepatic:

  • Increased Serum Alkaline Phosphatase

• Neuromuscular & Skeletal:

  • Ostealgia
  • Back Pain

• Respiratory:

  • Epistaxis
  • Cough
  • Dyspnea

• Miscellaneous:

  • Fever

Less Common Side Effects Of Filgrastim (Neupogen):

• Cardiovascular:

  • Peripheral Edema
  • Hypertension

• Central Nervous System:

  • Headache
  • Hypoesthesia
  • Insomnia
  • Malaise
  • Mouth Pain

• Dermatologic:

  • Alopecia
  • Erythema
  • Maculopapular Rash

• Endocrine & Metabolic:

  • Increased Lactate Dehydrogenase

• Gastrointestinal:

  • Vomiting
  • Decreased Appetite
  • Constipation
  • Diarrhea

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Anemia
  • Decreased Hemoglobin
  • Leukocytosis

• Hypersensitivity:

  • Transfusion Reaction
  • Hypersensitivity Reaction

• Immunologic:

  • Antibody Development

• Infection:

  • Sepsis

• Neuromuscular & Skeletal:

  • Arthralgia
  • Limb Pain
  • Muscle Spasm
  • Musculoskeletal Pain Asthenia

• Respiratory:

  • Bronchitis
  • Oropharyngeal Pain
  • Upper Respiratory Tract Infection

Contraindications to Filgrastim (Neupogen):

• Hypersensitivity or history of severe allergic reactions to human colony-stimulating factor, such as filgrastim and pegfilgrastim, in addition to any component of this formulation

• Canadian labeling: Additional contraindications not in the US labeling

  • Known hypersensitivity to E. coli-derived product

Warnings and precautions

• Allergy reactions:

  • Serious allergic reactions (including anaphylaxis) have been observed, usually with the initial exposure; symptomatic management is done with the administration of antihistamines, steroids, bronchodilators, and/or epinephrine.
  • After initial allergy management is stopped, allergic reactions can recur in a matter of days.
  • Do not give filgrastim products to patients who have developed a serious allergic reaction to filgrastim or pegfilgrastim.
  • Patients with severe allergic reactions should be advised to discontinue use of filgrastim products.

• Alveolar hemorhage

  • In healthy donors, alveolar hemorhage was reported. This is off-label for healthy donors.
  • It was presented as pulmonary hemoptysis and pulmonary infiltrates (requires hospitalization).
  • Although hemoptysis can be resolved by discontinuing medication, it is still a common symptom.

• Aortitis

  • Patients who received filgrastim have reported aortitis. This can occur as soon as the first week following treatment.
  • Aortitis can present as generalized fever, pain, abdomen, malaise or backache. It may also include increased inflammatory markers such as c-reactive proteins, WBC count, and generalized fever.
  • Patients who develop aortitis from other causes may have similar symptoms.
  • If you suspect that you have aortitis, discontinue filgrastim.

• Capillary leak syndrome

  • Patients who take human granulocyte-stimulating factors (G–CSF) may experience capillary leak syndrome (CLS).
  • This is characterized by low blood pressure, low hemoconcentration and low albumin.
  • The frequency and severity of CLS episodes can vary.
  • CLS should be closely monitored and managed symptomatically (may need intensive care).
  • If treatment is not received promptly, CLS can be fatal.

• Cutaneous vasculitis:

  • Patients with severe chronic neutropenia and chronic therapy have been known to experience moderate or severe cutaneous vasculitis.
  • If cutaneous vasculitis is present, discontinue treatment. Once symptoms have resolved and the ANC has dropped, you can restart treatment with a dose reduction.

• Hematologic effects

  • Filgrastim dosages greater than 5 mcg/kg/day have been shown to increase white blood cell counts by >=100,000.
  • To avoid excessive leukocytosis, filgrastim products should be stopped if the ANC is greater than 10,000/mm3 following an adjunctive myelosuppressive treatment.
  • Increases in the ANC above 10,000/mm might not have clinical benefits.
  • During therapy, monitor complete blood cells (CBC) at least twice per week
  • In general, filgrastim discontinuation resulted in a decrease in circulating neutrophils of half, i.e. 50%, in myelosuppressive chemotherapy patients, in 1 to 2 days and then back to pretreatment levels in 1 to 7 days.
  • Stop using filgrastim products if peripheral blood progenitor cells are being collected.
  • Filgrastim products have also been linked to thrombocytopenia; monitor platelet counts.

• Nephrotoxicity:

  • Patients who received filgrastim have been found to have glomerulonephritis based on their findings of azotemia (micro-and macroscopic), hematuria (micro and macro-) and renal biopsy.
  • Glomerulonephritis is usually treated with a reduction in or complete discontinuation of filgrastim.
  • Gglomerulonephritis should be suspected. If filgrastim is likely, consider dose reduction or interruption.

• Syndrome of respiratory distress

  • Reports of acute respiratory distress syndrome (ARDS), have been made
  • For ARDS, examine patients with fever and lung infiltrates.

• Splenic rupture

  • Rare cases of splenic rupturing have been reported (possibly fatal); patients complaining of upper abdominal pain, LUQ or shoulder pain should not be treated. Instead, they should seek evaluation for an enlarged or ruptured spleen.
  • Stop splenic rupture suspected or confirmed.

• Severe chronic neutropenia:

  • Before initiating treatment, confirm the diagnosis of severe chronic neutropenia (SCN).
  • Use of SCN before a proper diagnosis may delay or impair treatment for neutropenia caused by other conditions.
  • In the natural history congenital neutropenia, myelodysplastic syndrome and acute myeloidleukemia (MDS), it has been reported that these conditions can occur without cytokine therapy.
  • Filgrastim has been used to treat SCN and there have been reports of cytogenetic abnormalities and transformations to MDS or AML. However, patients with congenital neutropenia seem to be at higher risk for MDS/AML.
  • AML is often caused by abnormal cytogenetics or MDS.
  • It is not yet known what the results of filgrastim product continuance in patients with abnormal cytogenetics, or MDS are.
  • Consider the risks and benefits of continuing treatment.

• Sickle cell disorders:

  • Patients with sickle cells disorders may experience severe and sometimes fatal sickle-cell crises if they are taking filgrastim products.
  • If sickle cell crises occur, discontinue treatment.

Filgrastim (including biosimilars of filgrastim): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
Bleomycin	Filgrastim may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased.
Cyclophosphamide	Filgrastim may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, the risk of pulmonary toxicity may be enhanced.
Risk Factor D (Consider therapy modification)
Belotecan	Granulocyte Colony-Stimulating Factors may enhance the neutropenic effect of Belotecan.
Topotecan	Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Topotecan. Specifically, the risk for the development of interstitial lung disease may be increased. Granulocyte Colony-Stimulating Factors may enhance the myelosuppressive effect of Topotecan. Management: Avoid use of granulocyte colony-stimulating factors (G-CSFs) until at least 24 hours after the last dose of topotecan. Additionally, monitor patients closely for the development of interstitial lung disease with this combination.
Risk Factor X (Avoid combination)
Tisagenlecleucel	Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Tisagenlecleucel.

Monitoring parameters:

• Chemotherapy-induced neutropenia:
  • Complete blood cell count (CBC) with differential and platelets prior to chemotherapy and twice weekly during growth factor treatment.
• Bone marrow transplantation:
  • CBC with differential and platelets frequently.
• Hematopoietic radiation injury syndrome (acute):
  • CBC at baseline (do not delay filgrastim for baseline CBC) and approximately every 3 days until ANC remains >1,000/mm³ for 3 consecutive CBCs.
  • Radiation exposure i.e Dose of absorbed radiation can be estimated based on information from public health authorities, biodosimetry (if available), or clinical features (such as the onset of vomiting or lymphocyte depletion kinetics).
• Peripheral progenitor cell collection:
  • check Neutrophil counts 4 days after filgrastim treatment.
• Severe chronic neutropenia:
  • CBC with differential and platelets twice a week during the first month of therapy and for 2 weeks after dose adjustments;
  • once clinically stable, monthly for 1 year and quarterly thereafter.
  • Monitor bone marrow and karyotype before treatment, and check marrow and cytogenetics every year throughout treatment.
• Neutropenia in advanced HIV infection (off-label use):
  • ANC 3 times a week for 1st week then once weekly thereafter.
• All patients:
  • Look for signs/symptoms of allergic reactions, aortitis, capillary leak syndrome, cutaneous vasculitis, respiratory distress syndrome, and rupture of the spleen.

How to administer Filgrastim (Neupogen)?

• Do not administer earlier than 24 hours after or in the 24 hours prior to cytotoxic chemotherapy.

• IV (Neupogen and filgrastim biosimilars):

  • It can be administered intravenously as a short infusion over 15 to 30 minutes time (chemotherapy-induced neutropenia) or by continuous infusion (chemotherapy-induced neutropenia) or as an infusion of no longer than 24 hours duration (bone marrow transplantation).

• SubQ:

  • SubQ administration can be done (chemotherapy-induced neutropenia, peripheral blood progenitor cell collection, severe chronic neutropenia, hematopoietic radiation injury syndrome).
  • Administration can be done into the outer upper arm, abdomen (except within 2 inches of the navel), front middle thigh, or the upper outer buttocks area.
  • Change injection site; do not inject into tender, red, bruised, hardened, scaly, or scarred areas, or sites with stretch marks.
  • Some patients (or caregivers) may be suitable candidates for subQ self-administration with proper training;
  • patients/caregivers should follow the drug manufacturer instructions for preparation and administration.
  • Don't skip doses, change schedule, or discontinue without consultation with health care providers.
  • Granix is available as prefilled syringes with and without a needle guard;
  • the prefilled syringe without a safety needle guard is made for patient/caregiver self-administration.
  • Nivestym is available in a prefilled syringe with a safety needle guard and is not made to allow for direct doses administration <0.3 mL (180 mcg);
  • use single-dose vials for doses <0.3 mL (180 mcg).
  • Zarxio is only available in a prefilled syringe with a safety needle guard and is not designed to allow for direct administration of doses <0.3 mL (180 mcg).
  • If filgrastim comes in contact with the skin, wash the area thoroughly with soap and water; if eye contact occurs, flush exposed eye(s) with water.

Mechanism of action of Filgrastim (Neupogen):

• Filgrastim, a granulocyte-coloy-stimulating factors (G-CSF), is produced using recombinant DNA technology. 
• G-CSFs stimulate the maturation, production, and activation neutrophils in order to increase their migration and cytotoxicity.

The onset of action:

• Filgrastim: 1 to 2 days
• Tbo-filgrastim: Time to maximum ANC: 3 to 5 days

Duration of action:

• Filgrastim: Neutrophil counts generally return to baseline within 4 days
• Tbo-filgrastim: ANC returned to baseline by 21 days after completion of chemotherapy

Metabolism:

• Systemically degraded

Bioavailability:

• Filgrastim: SubQ: 60% to 70%; Tbo-filgrastim: SubQ: 33%

Half-life elimination:

• Neonates: 4.4 ± 0.4 hours
• Adults: Filgrastim: ~3.5 hours;
• Tbo-filgrastim: 3 to 3.5 hours

Time to peak serum concentration:

• SubQ: Filgrastim: 2 to 8 hours;
• Tbo-filgrastim: 4 to 6 hours

International Brands of Filgrastim:

• Granix
• Neupogen
• Nivestym
• Zarxio
• Grastofil
• Accofil
• Accufil
• Ambigrast
• Biocilin
• Biofigran
• Biofilgran
• Endufil
• Filatil
• Filgen
• Filgrast
• Grafcel
• Gran
• Granulokine
• Grasin
• Grastim
• Grastofil
• Grimatin
• Inmunef
• Jiexin
• Leuco-Plus
• Leucogen
• Leucostim
• Leukokine
• Macroleuco
• Neograstim
• Neufil
• Neukine
• Neulastim
• Neupogen
• Neutromax
• Nivestim
• Ratiograstim
• Recombicyte
• Religrast
• SciLocyte
• Teva Grastim
• Tevagastrim
• Tevagrastim
• White-C
• Zarzio

Filgrastim Brand Names in Pakistan:

Filgrastim Injection 6 mcg
Neulastim	Roche Pakistan Ltd.

 

Filgrastim Injection 75 mcg
Rh-Gcsf	S. Ejazuddin & Company

 

Filgrastim Injection 150 mcg
Rh-Gcsf	S. Ejazuddin & Company

 

Filgrastim Injection 300 mcg
Grastin	Consolidated Chemical Laboratories (Pvt) Ltd.
Jilfen	A. J. Mirza Pharma (Pvt) Ltd
Rh-Gcsf	S. Ejazuddin & Company

 

Filgrastim Injection 450 mcg
Jilfen	A. J. Mirza Pharma (Pvt) Ltd

 

Filgrastim Injection 75 mcg/ml
Sun-Gran	S. Ejazuddin & Company

 

Filgrastim Injection 150 mcg/ml
Geneleukim	Hoffman Health Pakistan Ltd.
Geneleukim	Hoffman Health Pakistan Ltd.
Topneuter	Biotechna (Pvt) Ltd

 

Filgrastim Injection 300 mcg/ml
Auspogen	Global Pharmaceuticals
Filatil	Medinet Pharmaceuticals
Filgen	Ferozsons Laboratoies Ltd.
Filgras	Pharmedic (Pvt) Ltd.
Geneleukim	Hoffman Health Pakistan Ltd.
Leucostim	Century Pharmaceuticals (Pvt) Ltd.
Neupogen	Roche Pakistan Ltd.
Neutrofil	Atco Laboratories Limited
Neutromax	Seignior Pharma
Pdgrastim	Nextar Pharma (Pvt) Ltd.
Sun-Gran	S. Ejazuddin & Company
Topneuter	Biotechna (Pvt) Ltd

 

Filgrastim Injection 480 mcg/ml
Neutromax	Seignior Pharma

 

Filgrastim Injection 300 mcg/0.5ml
Geneleukim	Hoffman Health Pakistan Ltd.