Schedule H

Subcutaneous, Intravenous infusion

• Injection: 300 mcg/0.5 mL pre-filled syringe

• Injection: 480 mcg/0.8 mL pre-filled syringe

• Injection: 300 mcg/mL vial

• Injection: 480 mcg/1.6 mL vial

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

▶ 1. Chemotherapy-Induced Neutropenia (CIN) — Prophylaxis and Treatment

Parameter Recommendation

Starting dose 5 mcg/kg/day subcutaneously or IV infusion

Titration May increase to 10 mcg/kg/day if inadequate response

Usual maintenance dose 5 mcg/kg/day

Maximum dose 10 mcg/kg/day

Key Clinical Notes:

• Initiate ≥24 hours after completion of cytotoxic chemotherapy

• Do not administer within 24 hours before chemotherapy

• Continue until ANC recovers to normal range (typically ≥2.0 × 10⁹/L post-nadir)

• Duration usually 7–14 days depending on chemotherapy regimen and nadir depth

• Round dose to nearest vial/syringe size to avoid wastage

▶ 2. Neutropenia Following Bone Marrow Transplantation

Parameter Recommendation

Starting dose 10 mcg/kg/day as continuous 24-hour IV infusion

Titration Adjust based on ANC response

Usual maintenance dose 10 mcg/kg/day

Maximum dose 10 mcg/kg/day

Key Clinical Notes:

• Initiate ≥24 hours after bone marrow infusion

• Continue until ANC >1.0 × 10⁹/L for 3 consecutive days

• May switch to subcutaneous administration once clinically stable

▶ 3. Severe Chronic Neutropenia (SCN) — Congenital, Cyclic, or Idiopathic

Parameter Recommendation

Starting dose Congenital: 12 mcg/kg/day SC in 1–2 divided doses; Idiopathic/Cyclic: 5 mcg/kg/day SC

Titration Adjust by 1–2 mcg/kg/day every 1–2 weeks based on ANC (target ANC 1.5–10 × 10⁹/L)

Usual maintenance dose 1–10 mcg/kg/day (highly variable)

Maximum dose 24 mcg/kg/day (congenital); 10 mcg/kg/day (cyclic/idiopathic)

Key Clinical Notes:

• Long-term therapy required; lifelong in congenital neutropenia

• Monitor for splenomegaly with prolonged use

• Regular bone marrow examination recommended to assess for myelodysplasia/AML risk

• Dose requirements may be higher in congenital forms

▶ 4. Peripheral Blood Progenitor Cell (PBPC) Mobilisation

For Autologous Collection (Monotherapy):

Parameter Recommendation

Starting dose 10 mcg/kg/day subcutaneously

Titration Not applicable

Usual maintenance dose 10 mcg/kg/day

Maximum dose 10 mcg/kg/day

Key Clinical Notes:

• Administer for 4–5 consecutive days

• Leukapheresis typically on days 5, 6 (and day 7 if needed)

• Optimal collection when CD34+ cell count ≥20 cells/µL in peripheral blood

Following Myelosuppressive Chemotherapy (for mobilisation):

Parameter Recommendation

Starting dose 5 mcg/kg/day subcutaneously

Titration Not applicable

Usual maintenance dose 5 mcg/kg/day

Maximum dose 5 mcg/kg/day

Key Clinical Notes:

• Begin when WBC nadir expected or when WBC begins to rise post-chemotherapy

• Continue until last leukapheresis completed

• Monitor CD34+ cell counts to optimise collection timing

For Healthy Allogeneic Donors:

Parameter Recommendation

Starting dose 10 mcg/kg/day subcutaneously

Titration Not applicable

Usual maintenance dose 10 mcg/kg/day

Maximum dose 10 mcg/kg/day

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

▶ 1. Chemotherapy-Induced Neutropenia

Parameter Recommendation

Starting dose 5 mcg/kg/day subcutaneously or IV

Titration May increase to 10 mcg/kg/day if inadequate response

Usual maintenance dose 5 mcg/kg/day

Maximum dose 10 mcg/kg/day

Key Clinical Notes:

• Initiate ≥24 hours after completion of chemotherapy

• Continue until ANC >1.5 × 10⁹/L post-nadir

• Same weight-based dosing as adults

▶ 2. Severe Chronic Neutropenia (Congenital, Cyclic, Idiopathic)

Parameter Recommendation

Starting dose Congenital: 6–12 mcg/kg/day SC in 1–2 divided doses; Cyclic/Idiopathic: 5 mcg/kg/day SC

Titration Adjust by 1–2 mcg/kg/day every 1–2 weeks to achieve target ANC

Usual maintenance dose 1–10 mcg/kg/day

Maximum dose 24 mcg/kg/day (congenital neutropenia may require higher doses)

Key Clinical Notes:

• Long-term/lifelong therapy in congenital forms

• Monitor spleen size clinically and by ultrasound every 6–12 months

• Annual bone marrow evaluation to monitor for myelodysplasia/leukaemic transformation

▶ 3. PBPC Mobilisation (Autologous)

Parameter Recommendation

Starting dose 10 mcg/kg/day subcutaneously

Titration Not applicable

Usual maintenance dose 10 mcg/kg/day

Maximum dose 10 mcg/kg/day

Key Clinical Notes:

• Administer for 4–5 days prior to leukapheresis

• Paediatric haematology/oncology supervision mandatory

Safety Monitoring (All Paediatric Indications):

• CBC with differential: daily during active therapy; weekly during chronic use

• Platelet count monitoring (risk of thrombocytopenia)

• Spleen size assessment (clinical examination; ultrasound if prolonged use)

• Bone pain assessment — analgesics as required

• Bone marrow examination annually in SCN patients

⚠️ Not recommended in infants <1 year for non-SCN indications except under specialist haematologist supervision

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Duration Notes

HIV-associated Neutropenia — OFF-LABEL >1 year 1–5 mcg/kg/day SC As needed Specialist only; Evidence: Limited paediatric data; Indian tertiary centre experience

Neonatal Sepsis with Neutropenia — OFF-LABEL Neonates 5–10 mcg/kg/day SC or IV 3–5 days Specialist only (neonatologist); Evidence: Meta-analyses show variable benefit

Kostmann Syndrome — OFF-LABEL (as specific entity) Any age 6–12 mcg/kg/day SC, titrated to response Lifelong Specialist only; Evidence: International registries; tertiary centre protocols

Mild to severe impairment Standard dosing

Haemodialysis Standard dosing; monitor ANC closely; no supplemental dose required post-dialysis

Peritoneal dialysis Standard dosing; limited data

• Known hypersensitivity to filgrastim, pegfilgrastim, or any excipient

• Hypersensitivity to E. coli-derived proteins (filgrastim is recombinant product from E. coli)

• Patients with myeloid malignancy not in remission (may stimulate leukaemic blast proliferation)

• Myeloid malignancies (AML, CML, MDS) — use only in remission phase under close specialist supervision

• Sickle cell disease or sickle cell trait — risk of severe sickle cell crisis; use only if absolutely essential with close monitoring

• Splenomegaly — risk of splenic rupture; monitor spleen size with prolonged use

• Pre-existing pulmonary disease — risk of acute respiratory distress syndrome (ARDS)

• Pre-existing cardiac disease — fluid retention may exacerbate heart failure

• Osteoporosis — long-term use may affect bone density

• History of allergic reactions to G-CSF products

• Concurrent myelosuppressive chemotherapy or radiotherapy — ensure adequate timing separation (≥24 hours)

Aspect Details

Risk category Limited human data; animal studies show embryo/fetal toxicity at very high doses

Safety statement Use only if benefit clearly outweighs potential risk to fetus

Preferred alternatives None — filgrastim is the standard G-CSF when indicated in pregnancy

When to use Severe chemotherapy-induced neutropenia with high infection risk; haematology/oncology input essential

Monitoring Maternal ANC, platelet count; fetal growth surveillance

Aspect Details

Compatibility Likely compatible with breastfeeding

Drug levels in milk Expected to be very low (large molecular weight protein; poor oral bioavailability)

Preferred alternatives None — filgrastim acceptable during lactation if indicated

Infant monitoring Routine monitoring only; no specific adverse effects expected

Aspect Recommendation

Starting dose Same as younger adults (5 mcg/kg/day for CIN)

Titration Consider slower titration; monitor tolerance

Extra risks Increased bone pain; higher risk of splenic complications; reduced marrow reserve may affect response; monitor for pulmonary toxicity

Monitoring More frequent CBC; assess for fluid retention in those with cardiac disease

Interacting Drug Mechanism / Effect Management

Cytotoxic chemotherapy Concurrent use may damage rapidly dividing myeloid progenitors stimulated by G-CSF; reduced filgrastim efficacy; increased toxicity Administer filgrastim ≥24 hours after chemotherapy completion; do not give within 24 hours before next chemotherapy cycle

Radiotherapy Similar mechanism — damage to stimulated progenitor cells Separate administration by ≥24 hours

Bleomycin Possible increased pulmonary toxicity when used with G-CSF Use with caution; monitor for respiratory symptoms

Interacting Drug Mechanism / Effect Management

Lithium May enhance neutrophil release; additive leucocytosis Monitor WBC closely; may potentiate filgrastim effect

Topoisomerase II inhibitors (etoposide, doxorubicin) Theoretical concern of myeloid clonal expansion with prolonged concurrent use Use with standard oncology protocols; monitor for myelodysplastic changes

NSAIDs May mask bone pain induced by filgrastim Use for symptom relief; does not affect efficacy

Corticosteroids May affect neutrophil distribution (demargination) ANC interpretation may be affected; no dose adjustment required

• Bone pain (20–30%) — most common; usually mild to moderate

• Headache

• Fatigue / malaise

• Nausea

• Injection site reactions (erythema, pain, induration)

• Transient leucocytosis

• Arthralgia / myalgia

• Elevated lactate dehydrogenase (LDH)

• Elevated alkaline phosphatase

• Elevated uric acid

Adverse Effect Clinical Action

Splenic rupture Life-threatening; presents as left upper quadrant or shoulder tip pain; discontinue immediately; surgical evaluation

Acute respiratory distress syndrome (ARDS) Discontinue; supportive care; ICU admission may be required

Capillary leak syndrome Discontinue; supportive management with IV fluids and vasopressors

Severe allergic reactions (anaphylaxis, angioedema) Discontinue immediately; standard anaphylaxis management; do not rechallenge

Sickle cell crisis In patients with sickle cell disease; discontinue; supportive care; may be fatal

Severe thrombocytopenia Monitor platelets; may require dose reduction or discontinuation

Glomerulonephritis Rare; monitor renal function; discontinue if confirmed

Aortitis Rare; presents with fever and abdominal/back pain; discontinue; anti-inflammatory treatment

Sweet syndrome (acute febrile neutrophilic dermatosis) Dermatology referral; may require discontinuation

During active treatment (CIN, BMT) ANC: daily or every other day until recovery; platelet count: every 2–3 days; assess bone pain severity

PBPC mobilisation CD34+ cell count in peripheral blood to optimise leukapheresis timing (target ≥20 cells/µL); platelet count

Long-term use (SCN) CBC weekly initially, then monthly once stable; spleen size (clinical ± ultrasound) every 6 months; annual bone marrow examination (cytogenetics, morphology) to detect myelodysplasia/AML

Grafeel Dr. Reddy's Biosimilar

Neukine Intas Biosimilar

Emgrast Emcure Biosimilar

Nufil Biocon Biosimilar

Zarzio Sandoz/Novartis Biosimilar

Neupogen Amgen (limited availability) Reference product

Filgrastim (various) Cipla, Hetero, Glenmark, others Multiple biosimilars available

Note: Multiple biosimilars approved in India with established bioequivalence; verify specific brand quality and regulatory approval status.

NLEM Status Not included in NLEM 2022 Not price-controlled

• Timing with chemotherapy is critical: Always administer ≥24 hours after chemotherapy completion; never give within 24 hours before next chemotherapy cycle — concurrent use reduces efficacy and increases toxicity

• Bone pain management: Most common adverse effect; usually responds to paracetamol or NSAIDs; severe pain may require opioid analgesia; typically resolves 2–3 days after stopping filgrastim

• Do not stop for leucocytosis alone: Transient leucocytosis is expected and not harmful; continue until adequate ANC recovery; base decisions on clinical context

• Pre-filled syringe handling: Allow refrigerated syringes to reach room temperature (15–30 minutes) before injection to reduce pain; do not shake; do not freeze

• Splenic rupture awareness: Rare but potentially fatal; educate patients about left upper quadrant or shoulder pain; requires immediate evaluation

• Biosimilars are cost-effective: Multiple high-quality biosimilars available in India at significantly lower cost; no clinically meaningful difference from reference filgrastim

Filgrastim; G-CSF; neutropenia; chemotherapy-induced neutropenia; PBPC mobilisation; bone marrow transplant; severe chronic neutropenia; oncology supportive care; biosimilar; haematology; renal-safe; Schedule H

RxIndia v1.0 — 02 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia / NFI

• API Textbook of Medicine, 11th Edition

• AIIMS Oncology Supportive Care Protocols

• ICMR Guidelines for Cancer Supportive Care

• National Cancer Grid India — Supportive Care Guidelines

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• International RCTs and meta-analyses (for off-label indications: HIV-associated neutropenia, neonatal sepsis)