Granocyte

Approved Indications:

• Chemotherapy-Induced Neutropenia:
  For reducing the duration of neutropenia and the incidence of febrile neutropenia in patients receiving myelosuppressive chemotherapy for malignancies (excluding chronic myeloid leukemia and myelodysplastic syndromes).
• Bone Marrow Transplantation:
  To shorten the duration of neutropenia and reduce the risk of infection in patients undergoing myeloablative therapy followed by bone marrow transplantation.
• Peripheral Blood Progenitor Cell (PBPC) Mobilization:
  For mobilization of hematopoietic progenitor cells into peripheral blood for collection and subsequent autologous transplantation.

Important Off-Label (Clinically Accepted) Uses:

• Severe Chronic Neutropenia (SCN):
  Includes congenital, cyclic, and idiopathic neutropenia to reduce the frequency and duration of infections.
• HIV-Associated Neutropenia:
  Management of neutropenia associated with antiretroviral therapy or opportunistic infections in HIV-infected individuals.

Route of Administration:
Subcutaneous (SC) or intravenous (IV) injection.

Adults:

• Chemotherapy-Induced Neutropenia:
  150 µg/m²/day SC or IV once daily.
  Start 24 hours after completion of chemotherapy.
  Continue until ANC (absolute neutrophil count) stabilizes within normal range (typically 7–10 days).
• Bone Marrow Transplantation:
  150 µg/m²/day IV over 30 minutes to 1 hour.
  Start at least 24 hours after transplantation.
  Continue until neutrophil recovery.
• PBPC Mobilization:
  10 µg/kg/day SC for 5–7 consecutive days.
  Begin leukapheresis on Day 4 or 5 and continue until target CD34+ cell count is achieved.

Pediatric Patients:
150 µg/m²/day SC or IV. Adjust based on body surface area and clinical response. Safety is established in children.

Elderly:
No dose adjustment is required. Monitor tolerability and hematologic response.

Renal or Hepatic Impairment:
No dose adjustment necessary. Pharmacokinetics are not significantly affected by renal or hepatic dysfunction.

Lenograstim is a recombinant human granulocyte colony-stimulating factor (rhG-CSF) produced in Chinese hamster ovary (CHO) cells. It binds to G-CSF receptors on hematopoietic progenitor cells in the bone marrow, stimulating the proliferation, differentiation, and activation of neutrophil precursors. This leads to an accelerated production and release of mature, functional neutrophils into the bloodstream. Lenograstim also enhances the phagocytic and bactericidal activity of neutrophils, thereby reducing the duration and severity of neutropenia-related infections.

• Absorption (SC): Rapid absorption; peak plasma concentration is reached within 2–8 hours.
• Distribution: Volume of distribution is limited; primarily remains in extracellular fluid.
• Metabolism: Metabolized by neutrophils and kidneys.
• Elimination: Clearance increases with rising neutrophil levels due to receptor-mediated endocytosis.
• Half-Life:
• IV: ~3–4 hours
• SC: ~4–5 hours
• Bioavailability: High after SC administration.
• Onset of Action: Increase in neutrophil count usually observed within 1–2 days of starting therapy.

• Pregnancy:
  There is insufficient data in human pregnancy. Animal studies have not shown teratogenic effects. Use only if clearly needed and when potential benefits outweigh risks.
• Lactation:
  It is not known whether lenograstim is excreted in human breast milk. Breastfeeding is not recommended during treatment due to the potential for adverse effects in the infant.

• Primary Class: Hematopoietic Growth Factor
• Subclass: Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF)

• Known hypersensitivity to lenograstim or any component of the formulation
• Hypersensitivity to proteins derived from Chinese hamster ovary (CHO) cells
• Patients with myeloid malignancies such as chronic myeloid leukemia or myelodysplastic syndromes

• Leukocytosis:
  Excessive WBC elevation may occur. Monitor CBCs regularly to avoid complications.
• Splenic Enlargement and Rupture:
  Rare but serious. Monitor for left upper abdominal pain or shoulder tip pain.
• Acute Respiratory Distress Syndrome (ARDS):
  Discontinue immediately if pulmonary infiltrates and respiratory symptoms develop.
• Hypersensitivity Reactions:
  May include rash, urticaria, angioedema, and anaphylaxis. Discontinue if severe.
• Bone Pain:
  Common and dose-dependent. Manage with analgesics if needed.
• Capillary Leak Syndrome:
  Rare, potentially life-threatening condition characterized by hypotension, hypoalbuminemia, and edema.
• Myelodysplastic Syndrome or Acute Myeloid Leukemia:
  Rare in long-term use, particularly in SCN patients. Monitor periodically.

Common Side Effects:

• Hematologic: Leukocytosis
• Musculoskeletal: Bone pain, myalgia
• General: Fever, fatigue, headache
• Gastrointestinal: Nausea, vomiting
• Local: Injection site redness, swelling, or pain

Serious/Rare Side Effects:

• Splenic rupture
• ARDS
• Capillary leak syndrome
• Hypersensitivity reactions including anaphylaxis
• Vasculitis
• Secondary malignancies (e.g., MDS or AML in long-term use)

• Cytotoxic Chemotherapy:
  Do not administer 24 hours before or after cytotoxic chemotherapy due to potential additive myelosuppression.
• Lithium:
  May potentiate neutrophil production. Monitor WBC closely when used concurrently.
• Corticosteroids:
  May reduce the response to G-CSF; monitor clinical response.
• Food/Alcohol Interactions:
  No significant interactions reported.
• CYP450 Enzyme System:
  Lenograstim does not interact with the CYP450 system and is not subject to hepatic metabolism.

• ASCO/ESMO Guidelines:
  Lenograstim is endorsed as a suitable G-CSF option for primary and secondary prophylaxis of chemotherapy-induced neutropenia.
• EMA Position:
  Biosimilar versions must demonstrate comparability in efficacy and safety; lenograstim is a reference product in some European countries.
• Stem Cell Mobilization Protocols:
  Updated regimens recommend G-CSF alone or in combination with chemotherapy to improve peripheral blood progenitor cell yield.

• Temperature: Store at 2°C to 8°C (36°F to 46°F). Keep refrigerated.
• Do Not Freeze: Freezing may degrade protein activity.
• Light Protection: Store in the original carton to protect from light.
• Handling: Allow to reach room temperature before injection. Do not shake vigorously.
• Reconstitution (if applicable): Use immediately after reconstitution. Discard any unused portion.
• Disposal: Dispose of unused or expired product in accordance with local regulations for biologics or hazardous waste.