Introduction
Granocyte SC Injection 34 MIU/vial is a recombinant granulocyte colony-stimulating factor used as an immunostimulating agent.
Uses
Granocyte SC Injection 34 MIU/vial is a granulocyte colony-stimulating factor indicated in the reduction of duration of neutropenia in bone marrow transplant and cytotoxic chemotherapy, as well as mobilizing hematopoietic stem cells in healthy donors.
The drug is used to reduce the risk of life-threatening infection in patients with neutropenia, particularly after cytotoxic chemotherapy. Granocyte SC Injection 34 MIU/vial is indicated as a treatment to reduce the duration of neutropenia and the severity of infections in patients with non-myeloid malignancy who have undergone autologous or allogeneic bone marrow transplantation, or treatment with established cytotoxic chemotherapy and in addition to reduce the incidence of infection associated with established cytotoxic chemotherapy. Granocyte SC Injection 34 MIU/vial is also indicated to mobilise peripheral blood progenitor cells (PBPCs) with Granocyte SC Injection 34 MIU/vial alone, or after myelosuppressive chemotherapy, in order to accelerate haematopoietic recovery by infusion of such cells, after myelosuppressive or myeloablative therapy. Granocyte SC Injection 34 MIU/vial is also indicated to accelerate the engraftment of these cells after their reinfusion.
GRANOCYTE is also indicated for the treatment of severe chronic neutropenia including congenital agranulocytosis (Kostmann's syndrome).
Associated Conditions
Pharmacodynamics
Granocyte SC Injection 34 MIU/vial has been confirmed as a valuable adjunct to minimise the haematological toxicity of myelosuppressive chemotherapy in patients with malignant disease. The drug also enhances neutrophil recovery in patients undergoing stem cell rescue, and assists peripheral blood progenitor cells mobilisation.
Mechanism of Action
Granocyte SC Injection 34 MIU/vial is the glycosylated recombinant form of human granulocyte colony stimulating factor. Granocyte SC Injection 34 MIU/vial accelerates neutrophil recovery significantly after chemotherapy, with beneficial effects on clinical end-points such as incidence of laboratory-confirmed infection and length of hospital stay. Chemotherapy dose intensity has also been increased in patients receiving lenograstim, notably those with breast or small cell lung cancer, although improvements in tumour response and survival have not been demonstrated. Granocyte SC Injection 34 MIU/vial also assists neutrophil recovery in patients undergoing bone marrow transplantation, and stimulates the production of peripheral blood stem cells (PBSCs) for autologous transfusion after aggressive chemotherapy.
Absorption
During repeated dosing (iv and sc routes), peak serum concentrations (at the end of iv infusion or after sc injection) are proportional to the injected dose. Repeated dosing with lenograstim by the two injection routes results in no evidence of drug accumulation.
Volume of Distribution
Apparent distribution volume (Vd area) is approximately 52 ± 5 mL/kg body weight.
Route of Elimination
Granocyte SC Injection 34 MIU/vial is poorly excreted in urine as intact compound (less than 1% of the dose).
Half Life
The pharmacokinetic profile of lenograstim is similar in healthy volunteers and cancer patients with elimination half-life (t½β) values of 2.3 - 3.3 hrs (volunteers); 2.8-7.5 hrs (cancer patients) following sc administration, and 0.8 - 2.1 hrs (volunteers); 1.1 - 4.0 hrs (cancer patients) following iv administration.
Clearance
Plasma clearance of lenograstim increased 3-fold (from 50 up to 150 mL/min) during repeated sc dosing.
Toxicity
Species observed : Human (Man) Test type: TDLo ( Lowest Published Toxic Dose) Route of exposure: Subcutaneous Dose/Duration: 21428mg/kg/15 Toxic Effect: Skin and appendages: Dermatitis, allergic ( after systemic exposure )
Species observed : Rodent - Rat Test type: LD50 Route of exposure: Oral Dose/Duration: >5mg/kg Toxic Effect: Details of toxic effects not reported other than lethal dose value
Species observed : Rodent - Rat Test type: LD50 Route of exposure: Subcutaneous Dose/Duration: >5mg/kg Toxic Effect: Details of toxic effects not reported other than lethal dose value
Species observed : Rodent - Rat Test type: LD50 Route of exposure: Intravenous Dose/Duration: >5mg/kg Toxic Effect: Details of toxic effects not reported other than lethal dose value
Species observed : Mammal - Dog Test type: LD50 Route of exposure: Intravenous Dose/Duration: >5mg/kg Toxic Effect: Details of toxic effects not reported other than lethal dose value
Species observed : Mammal - Dog Test type: LD50 Route of exposure: Subcutaneous Dose/Duration: >5mg/kg Toxic Effect: Details of toxic effects not reported other than lethal dose value
Dosage
The recommended dose of Granocyte SC Injection 34 MIU/vial is 19.2 MIU (150 µg) per m2 per day, therapeutically equivalent to 0.64 MIU (5 µg) per kg per day for:
- Peripheral Stem Cells or bone marrow transplantation,
- Established cytotoxic chemotherapy
- PBPC mobilisation after chemotherapy.
Granocyte SC Injection 34 MIU/vial 34 million IU/mL can be used in patients with body surface area up to 1.8 m2.
For PBPC mobilisation with Granocyte SC Injection 34 MIU/vial alone, the recommended dose is 1.28 MIU (10 µg) per kg per day.
Elderly: Clinical trials with Granocyte SC Injection 34 MIU/vial have included a small number of patients up to the age of 70 years but special studies have not been performed in the elderly and therefore specific dosage recommendations cannot be made.
Paediatric Population: The dose in children older than 2 years and adolescent is the same as in adults when used to reduce the duration of neutropenia after myeloablative therapy followed by BMT or after cytotoxic chemotherapy.
