Filgrastim


Generic Medicine Info
Indications and Dosage
Parenteral
Neutropenia following bone marrow transplantation
Adult: Reduction in duration of neutropenia in myeloablative therapy followed by bone marrow transplantation: Initially, 10 mcg/kg daily given via IV infusion over 30 minutes or 24 hours, or via continuous SC infusion over 24 hours. Must be diluted in 20 mL 5% glucose solution. Dose to be started at least 24 hours following cytotoxic chemotherapy and at least 24 hours after bone marrow infusion; then adjust dose according to neutrophil response. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Parenteral
Chemotherapy-induced neutropenia
Adult: Reduction in duration of neutropenia and incidence of febrile neutropenia in established cytotoxic chemotherapy for malignancy (except chronic myeloid leukaemia and myelodysplastic syndromes): 5 mcg/kg daily given via daily SC inj (preferred), or daily IV infusion over 30 minutes diluted in 5% glucose solution. Dose to be started at least 24 hours after cytotoxic chemotherapy. Continue treatment until the neutrophil count has stabilised within the normal range (may take up to 14 days or more). Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Subcutaneous
Cyclic neutropenia, Idiopathic neutropenia
Adult: In patients with severe cases and a history of severe or recurrent infections; long-term administration to increase neutrophil counts and decrease the incidence and duration of infection-related events: Initially, 5 mcg/kg daily via SC inj in single or divided doses. Adjust dose according to clinical response. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Subcutaneous
Mobilisation of peripheral blood progenitor cells
Adult: In patients undergoing myeloablative or myelosuppressive therapy followed by autologous peripheral blood progenitor cell (PBPC) transplantation: If used alone: 10 mcg/kg daily for 5-7 days, given via SC inj or continuous SC infusion over 24 hours. Maintain dosing until the last leucapheresis. Infusion must be diluted in 20 mL 5% glucose solution. If used following myelosuppressive chemotherapy: 5 mcg/kg daily via SC inj; given from the 1st day after completing chemotherapy until the neutrophil count has stabilised within the normal range, to be able to perform leucapheresis. In normal donors prior to allogeneic PBPC transplantation: 10 mcg/kg daily via SC inj for 4-5 consecutive days until leucapheresis (usually started on day 5). Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Subcutaneous
Congenital neutropenia
Adult: In patients with severe cases and a history of severe or recurrent infections; long-term administration to increase neutrophil counts and decrease the incidence and duration of infection-related events: Initially, 12 mcg/kg daily via SC inj in single or divided doses. Adjust dose according to clinical response. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Subcutaneous
Persistent neutropenia in advanced HIV infection
Adult: To decrease the risk of bacterial infections when other therapeutic options are not appropriate: Reversal of neutropenia: Initially, 1 mcg/kg daily, may be titrated up to Max of 4 mcg/kg daily until a normal neutrophil count is achieved and can be maintained. Maintenance of normal neutrophil count: Initial dose adjustment to alternate day dosing with 300 mcg daily is recommended. Further dose adjustment may be required according to clinical response. Doses to be given via SC inj. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).
Reconstitution
SC/IV infusion: If dilution is needed, may use 5% glucose solution. Do not dilute to a final concentration of <2 mcg/mL. To protect filgrastim diluted to concentrations <15 mcg/mL from adsorption, human serum albumin must be added to make a final concentration of 2,000 mcg/mL. Do not shake. Refer to local detailed product guideline for further dilution instructions.
Incompatibility
May cause precipitation when diluted with NaCl solutions. Diluted solutions may be adsorbed onto glass or plastic materials (unless diluted in 5% glucose solution).
Contraindications
History of serious allergic reactions to human granulocyte colony-stimulating factors (G-CSF) such as filgrastim or pegfilgrastim. Patient with severe congenital neutropenia who develop leukaemia or evidence of leukaemic evolution.
Special Precautions
Patient with pre-malignant or malignant myeloid condition, acute myeloid leukaemia; sickle-cell trait or disease, recent history of pneumonia or lung infiltrates, osteoporotic bone disease. Not indicated for use in chronic myeloid leukaemia or myelodysplastic syndrome. Safety and efficacy have not been established in radiation therapy recipients; avoid concomitant use. Not to be used in the period from 24 hours before to 24 hours after cytotoxic chemotherapy administration. Some available brands (e.g. filgrastim-sndz [Zarxio®], filgrastim-aafi [Nivestym®]) are approved by US FDA as biosimilars to the reference biological, filgrastim (Neupogen®). Biosimilar agents are not interchangeable with filgrastim; instead, they are considered therapeutic alternatives (refer to local product-specific recommendations). Pregnancy and lactation.
Adverse Reactions
Significant: Serious allergic reactions, including anaphylaxis; interstitial lung disease, alveolar haemorrhage (e.g. pulmonary infiltrates, haemoptysis), aortitis, moderate or severe cutaneous vasculitis, haematological effects (e.g. thrombocytopenia, leucocytosis, anaemia), myelodysplastic syndrome, acute myeloid leukaemia, splenomegaly, nephrotoxicity (e.g. haematuria, proteinuria, glomerulonephritis).
Cardiac disorders: Chest pain.
Gastrointestinal disorders: Diarrhoea, nausea, vomiting, constipation, oral pain.
General disorders and administration site conditions: Fatigue, mucosal inflammation, pyrexia, asthenia, malaise, peripheral oedema.
Hepatobiliary disorders: Hepatomegaly.
Infections and infestations: Sepsis.
Injury, poisoning and procedural complications: Transfusion reaction.
Investigations: Increased blood alkaline phosphatase and blood lactate dehydrogenase, decreased Hb.
Metabolism and nutrition disorders: Decreased appetite.
Musculoskeletal and connective tissue disorders: Musculoskeletal pain, muscle spasms, ostealgia, back pain, osteoporosis.
Nervous system disorders: Headache, dizziness, hypoaesthesia, paraesthesia.
Psychiatric disorders: Insomnia.
Renal and urinary disorders: Dysuria, UTI.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, cough, oropharyngeal pain, epistaxis, bronchitis, upper respiratory tract infection.
Skin and subcutaneous tissue disorders: Alopecia, rash, erythema.
Vascular disorders: Hypertension, hypotension.
Potentially Fatal: Severe sickle cell crisis, capillary leak syndrome, respiratory failure or acute respiratory distress syndrome (ARDS). Rarely, splenic rupture.
IM/Parenteral/SC: C
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery. Do not switch between different brands unless advised by your doctor.
Monitoring Parameters
Obtain CBC with differential and platelet count prior to and regularly during therapy. Additionally for severe chronic neutropenias (congenital, cyclic, idiopathic): Perform bone marrow morphology and karyotype before treatment; morphologic and cytogenic bone marrow exam annually. Monitor absolute neutrophil count (ANC) 3 times weekly for the 1st week then weekly thereafter (for neutropenia in advanced HIV infection); urinalysis; spleen size (e.g. ultrasound, clinical exam); bone density (in patients with osteoporosis undergoing >6 months continuous treatment). Assess for signs and symptoms of allergic reactions, capillary leak syndrome, aortitis, cutaneous vasculitis, myelodysplastic syndrome, acute myeloid leukaemia, ARDS, and splenic rupture.
Drug Interactions
Due to the potential sensitivity of rapidly dividing myeloid cells to myelosuppressive cytotoxic chemotherapy, filgrastim use is not recommended in the period 24 hours before to 24 hours after cytotoxic chemotherapy administration. Concurrent use with 5-fluorouracil may exacerbate the severity of neutropenia. Lithium may potentiate the myeloproliferative effects (e.g. promote neutrophil release) of filgrastim. May enhance the adverse effects of bleomycin, cyclophosphamide, and topotecan.
Lab Interference
May interfere with bone imaging studies leading to transient positive bone imaging changes.
Action
Description: Filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF), mainly affects the proliferation and differentiation of neutrophils within the bone marrow. G-CSF is a haematopoietic growth factor that stimulates the production, maturation, and functional activation of neutrophils to increase both their migration and cytotoxicity.
Onset: 1-2 days.
Duration: Return of neutrophil counts to baseline: Within 4 days.
Pharmacokinetics:
Absorption: Bioavailability: 60-70% (SC). Time to peak plasma concentration: 2-8 hours (SC).
Distribution: Crosses the placenta. Volume of distribution: 150 mL/kg (IV).
Metabolism: Systematically degraded.
Excretion: Mainly by neutrophil-mediated clearance. Elimination half-life: Approx 3.5 hours (IV).
Storage
Store between 2-8°C. Protect from light or direct sunlight. Do not freeze.
ATC Classification
L03AA02 - filgrastim ; Belongs to the class of colony stimulating factors. Used as immunostimulants.
References
Anon. Filgrastim. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/01/2021.

Anon. Filgrastim. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/01/2021.

Buckingham R (ed). Filgrastim. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/01/2021.

Joint Formulary Committee. Filgrastim. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/01/2021.

Neupogen 30 MU (0.3 mg/ml) Solution for Injection (Amgen Europe B.V.). MHRA. https://products.mhra.gov.uk. Accessed 06/01/2021.

Neupogen Singleject 30 MU (0.6 mg/mL) Solution for Injection in a Pre-filled Syringe (Amgen Europe B.V.). MHRA. https://products.mhra.gov.uk. Accessed 06/01/2021.

Neupogen Vial 30 MU/mL and Pre-filled Syringe 30 MU/0.5 mL (Amgen Biopharmaceuticals Malaysia Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 15/04/2021.

Nivestim 12 MU/0.2 mL Solution for Injection/Infusion; 30 MU/0.5 mL Solution for Injection/Infusion; 48 MU/0.5 mL Solution for Injection/Infusion (Hospira Malaysia Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 15/04/2021.

Nivestym Injection, Solution (Pfizer Laboratories Div Pfizer Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/01/2021.

Zarxio Injection, Solution (Sandoz Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/01/2021.

Zarzio 30 MU/0.5 mL and 48 MU/0.5 mL Solution for Injection or Infusion in Pre-filled Syringe (Novartis Corporation [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 15/04/2021.

Disclaimer: This information is independently developed by MIMS based on Filgrastim from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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