Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Chugai Pharma UK Ltd, Mulliner House, Flanders Road, Turnham Green, London W4 1NN
GRANOCYTE is indicated in adults, adolescents and children aged older than 2 years for:
GRANOCYTE can be administered by sub-cutaneous injection or by intravenous infusion. Particular handling of the product or instructions for preparation are given in sections 6.6.
Therapy should only be given in collaboration with an experienced oncology and/or haematology centre.
The recommended dose of GRANOCYTE is 19.2 MIU (150 µg) per m² per day, therapeutically equivalent to 0.64 MIU (5 µg) per kg per day for:
GRANOCYTE 13 million IU/mL can be used in patients with body surface area up to 0.7 m².
GRANOCYTE 34 million IU/mL can be used in patients with body surface area up to 1.8 m².
For PBPC mobilisation with GRANOCYTE alone, the recommended dose is 1.28 MIU (10 µg) per kg per day.
GRANOCYTE should be administered daily at the recommended dose of 19.2 MIU (150 µg) per m² per day as a 30-minute intravenous infusion diluted in isotonic saline solution or as a subcutaneous injection. The first dose should not be administered within 24 hours of the bone marrow infusion. Dosing should continue until the expected nadir has passed and the neutrophil count returns to a stable level compatible with treatment discontinuation, with, if necessary, a maximum of 28 consecutive days of treatment.
It is anticipated that by day 14 following bone marrow transplantation, 50% of patients will achieve neutrophil recovery.
GRANOCYTE should be administered daily at the recommended dose of 19.2 MIU (150 µg) () per m² per day as a subcutaneous injection. The first dose should not be administered less than 24 hours following cytotoxic chemotherapy (see 4.4 and 4.5). Daily administration of GRANOCYTE should continue until the expected nadir has passed and the neutrophil count returns to a stable level compatible with treatment discontinuation, with, if necessary, a maximum of 28 consecutive days of treatment.
A transient increase in neutrophil count may occur within the first 2 days of treatment, however GRANOCYTE treatment should not be stopped, since the subsequent nadir usually occurs earlier and recovers more quickly if treatment continues.
After chemotherapy, GRANOCYTE should be administered daily, at the recommended dose of 19.2 MIU (150 µg) per m² per day as a subcutaneous injection starting within 1 to 5 days after completion of chemotherapy, according to the chemotherapy regimen administered for mobilisation.
GRANOCYTE should be maintained until the last leukapheresis.
Leukapheresis should be performed when the post nadir leukocyte count is rising or after assessment of CD34+ cells in blood with a validated method. For patients who have not had extensive chemotherapy, one leukapheresis is often sufficient to obtain the acceptable minimum yield (≥2.0 × 106 CD34+ cells per kg).
In PBPC mobilisation with GRANOCYTE alone, GRANOCYTE should be administered daily at the recommended dose of 1.28 MIU (10 µg) per kg per day as a subcutaneous injection for 4 to 6 days. Leukapheresis should be performed between day 5 and 7.
In patients who have not had extensive chemotherapy one leukapheresis is often sufficient to obtain the acceptable minimum yield (≥2.0 × 106 CD34+ cells per kg).
In healthy donors, a 10µg/kg daily dose administered subcutaneously for 5-6 days allows a CD34+ cells collection ≥3 × 106/kg body weight with a single leukapheresis in 83% of subjects and with 2 leukapheresis in 97%.
Clinical trials with GRANOCYTE 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.
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.
Very limited data are available for mobilisation of peripheral blood progenitor cells at the adult dose.
The safety and efficacy of GRANOCYTE in children aged less than 2 years have not been established.
GRANOCYTE 13 million IU/mL may be the more appropriate dosage for administration in children with body surface area up to 0.7 m².
GRANOCYTE 34 million IU/mL can be used in patients with body surface area up to 1.8 m².
The effects of GRANOCYTE overdose have not been established (see section 5.3). Discontinuation of GRANOCYTE therapy usually results in a 50% decrease in circulating, neutrophils within 1 to 2 days, with a return to normal levels in 1 to 7 days. A white blood cell count of approximately 50 × 109/L was observed in one patient out of three receiving the highest GRANOCYTE dose of 40 µg/kg/day (5.12 MIU/kg/day) on the 5th day of treatment. In humans, doses up to 40 µg/kg/day were not associated with toxic side effects except musculoskeletal pain.
30 months.
After reconstitution or dilution, an immediate use is recommended. However, in-use stability of the reconstituted/diluted medicinal product has been demonstrated for 24 hours at 2°C-8°C (in a refrigerator).
Do not store above + 30°C.
Do not freeze.
For storage conditions after reconstitution/dilution of the medicinal product, see section 6.3.
105 micrograms of powder in vial (type I glass) with a rubber stopper (type I butyl rubber) + 1 mL of solvent in pre-filled syringe (type I glass) with a tip cap + 2 needles (19G and 26G); pack size of 1 or 5.
263 micrograms of powder in vial (type I glass) with a rubber stopper (type I butyl rubber) + 1 mL of solvent in pre-filled syringe (type I glass) with a tip cap + 2 needles (19G and 26G); pack size of 1 or 5.
or
105 micrograms of powder in vial (type I glass) with a rubber stopper (type I butyl rubber) + 1 mL of solvent in ampoule (type I glass); pack size of 1 or 5.
263 micrograms of powder in vial (type I glass) with a rubber stopper (type I butyl rubber) + 1 mL of solvent in ampoule (type I glass); pack size of 1 or 5.
Not all pack sizes may be marketed.
Any unused product/solution or waste material should be disposed of in accordance with local requirements.
In view of the possible risk of microbial contamination, pre-filled syringe with solvent is for single use only.
Instructions for preparation
GRANOCYTE vials are for single-dose use only.
GRANOCYTE must be reconstituted before sub-cutaneous or intravenous administration.
Preparation of the reconstituted GRANOCYTE solution
Using a graduated syringe fitted with a needle, aseptically withdraw the entire extractable contents of one ampoule of solvent for GRANOCYTE. Inject the entire contents of the syringe into the corresponding GRANOCYTE vial.
Using the 19G needle provided in the pack, and the pre-filled disposable syringe with the solvent for GRANOCYTE ready for immediate use aseptically add the extractable contents of one pre-filled syringe of solvent for GRANOCYTE to the GRANOCYTE vial.
Agitate gently until completely dissolved. Do not shake vigorously.
The reconstituted parenteral solution appears transparent and free of particles.
The reconstituted solution should preferably be used immediately after preparation. For storage conditions of the reconstituted/diluted medicinal product, see section 6.3.
Preparation for the subcutaneous administration
Prepare a reconstituted GRANOCYTE solution as described above.
Keeping the needle and the syringe attached to the vial, withdraw the required volume of reconstituted solution from the vial. Replace the needle used for reconstitution and fit the syringe with an appropriate needle for subcutaneous injection.
Keeping the needle 19G and the syringe attached to the vial , withdraw the required volume of reconstituted solution from the vial. Replace the needle used for reconstitution and fit the syringe with the 26G needle provided for subcutaneous injection.
Administer immediately by sub-cutaneous injection (refer to section 4.2 for administration requirements).
Preparation of the infusion solution for the intravenous administration:
When intravenous use GRANOCYTE has to be diluted after reconstitution.
Prepare a reconstituted GRANOCYTE solution as described above.
Keeping the needle and the syringe attached to the vial, withdraw the required volume of reconstituted solution from the vial.
Dilute the reconstituted GRANOCYTE solution to the required concentration by injecting the required volume into either 0.9% sodium chloride or 5% dextrose solution.
Administer by IV route (refer to section 4.2 for administration requirements)
GRANOCYTE is compatible with the commonly used administration sets for injection when diluted either in a 0.9% saline solution (polyvinyl chloride bags and glass bottles) or in a 5% dextrose solution (glass bottles)
Dilution of GRANOCYTE 13 million IU/mL to a final concentration of less than 0.26 million IU/mL (2 µg/mL) is not recommended. 1 vial of reconstituted GRANOCYTE 13 million IU/mL should not be diluted in more than 50 mL.
Dilution of GRANOCYTE 34 million IU/mL to a final concentration of less than 0.32 million IU/mL (2.5 µg/mL) is not recommended. 1 vial of reconstituted GRANOCYTE 34 million IU/mL should not be diluted in more than 100 mL.
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