Granogen (Solution) Instructions for Use

ATC Code

L03AA02 (Filgrastim)

Active Substance

Filgrastim (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Leukopoiesis stimulant

Pharmacotherapeutic Group

Immunostimulants; colony-stimulating factors

Pharmacological Action

G-CSF. Immunomodulator. It is a highly purified non-glycosylated protein. It regulates the production of functional neutrophils and their release into the blood from the bone marrow.

It causes a noticeable increase in neutrophils within 24 hours and a slight increase in monocytes.

Pharmacokinetics

V_d is about 150 ml/kg. Does not accumulate.

T_1/2 is about 3.5 hours, clearance is about 0.6 ml/min/kg.

Indications

To reduce the duration of neutropenia and the frequency of febrile neutropenia in patients receiving cytotoxic chemotherapy for malignant diseases (except for chronic myeloid leukemia and myelodysplastic syndrome), as well as to reduce the duration of neutropenia and its clinical consequences in patients receiving myeloablative therapy followed by bone marrow transplantation.

For the mobilization of autologous hematopoietic progenitor cells in the peripheral blood (including after myelosuppressive therapy), to accelerate the recovery of hematopoiesis by administering these cells after myelosuppression or myeloablation.

Long-term therapy to increase the number of neutrophils and reduce the frequency and duration of infectious complications in children and adults with severe congenital, cyclic, or idiopathic neutropenia (absolute neutrophil count <500/µl) and a history of severe or recurrent infections.

ICD codes

Dosage Regimen

Administer subcutaneously or intravenously; dosage is individualized based on indication, treatment regimen, and hematological monitoring.

For chemotherapy-induced neutropenia, initiate a single daily dose of 5 mcg/kg no less than 24 hours after cytotoxic chemotherapy completion; continue daily administration until the expected neutrophil nadir has passed and the neutrophil count has recovered to the normal range.

Discontinue therapy if the absolute neutrophil count exceeds 10,000/mm³ after the expected chemotherapy-induced nadir.

For peripheral blood progenitor cell (PBPC) mobilization, administer 10 mcg/kg/day subcutaneously; begin at least 4 days before the first leukapheresis and continue until the last leukapheresis.

For bone marrow transplantation, administer 10 mcg/kg/day as a 4-hour or 24-hour intravenous infusion, or as a 24-hour subcutaneous infusion; initiate at least 24 hours after bone marrow infusion.

For severe chronic neutropenia, the recommended starting dose is 5 mcg/kg subcutaneously once daily; adjust the dose based on the patient’s clinical course and absolute neutrophil count response.

In all cases, monitor complete blood counts, including differential leukocyte and platelet counts, regularly; immediately discontinue if the leukocyte count rises above 50,000/µl during neutropenia therapy or 100,000/µl during PBPC mobilization.

Adverse Reactions

Musculoskeletal system: muscle or bone pain may occur.

Urinary system: dysuria may occur.

Cardiovascular system: transient arterial hypotension may occur.

Laboratory parameters: reversible increase in levels of LDH, ALP and GGT, uric acid in blood plasma.

Other: rarely, predominantly after IV administration – symptoms indicating allergic-type reactions (about half of them were associated with the first dose administration).

Contraindications

Severe congenital neutropenia (Kostmann syndrome) with cytogenetic abnormalities, hypersensitivity to filgrastim.

Use in Pregnancy and Lactation

The safety of use during pregnancy has not been established, so the expected benefit of therapy for the mother and the potential risk to the fetus should be assessed.

If it is necessary to use during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Not recommended for use in patients with severe hepatic impairment, as the efficacy and safety of filgrastim in this category of patients have not been studied.

Use in Renal Impairment

Not recommended for use in patients with severe renal impairment, as the efficacy and safety of filgrastim in this category of patients have not been studied.

Pediatric Use

The safety and efficacy of use in newborns have not been established.

Geriatric Use

No specific studies on the efficacy and safety of filgrastim use in elderly patients have been conducted.

Special Precautions

Not recommended for use in patients with severe renal or hepatic impairment, as the efficacy and safety of filgrastim in this category of patients have not been studied.

Patients with concomitant bone pathology and osteoporosis receiving Filgrastim continuously for more than 6 months are recommended to monitor bone density.

Human G-CSF can cause the growth of myeloid cells in vitro. Similar effects may be observed in vivo and for some non-myeloid cells. The safety and efficacy of filgrastim use in patients with myelodysplastic syndrome and chronic myeloid leukemia have not been established, therefore it is not indicated for these diseases. A particularly thorough differential diagnosis between blast transformation of chronic myeloid leukemia and acute myeloid leukemia should be performed.

During treatment, it is necessary to regularly determine the leukocyte count. If after passing the expected minimum it exceeds 50,000/µl, Filgrastim should be immediately discontinued. If Filgrastim is used for the mobilization of peripheral blood hematopoietic progenitor cells, it is discontinued if the leukocyte count exceeds 100,000/µl.

Use with particular caution in patients receiving high-dose cytotoxic chemotherapy.

Monotherapy with filgrastim does not prevent thrombocytopenia and anemia caused by myelosuppressive chemotherapy. It is recommended to regularly determine the platelet count and hematocrit. Particular caution should be exercised when using single-component or combined chemotherapy regimens known for their ability to cause severe thrombocytopenia.

Before using filgrastim for severe chronic neutropenia, a particularly thorough differential diagnosis with other hematological diseases, such as aplastic anemia, myelodysplasia, and myeloleukemia, should be performed. Before starting treatment, a complete blood count with differential leukocyte count and platelet count should be performed, and the morphological picture of the bone marrow and karyotype should be examined.

The blood picture, including the platelet count, should be carefully monitored, especially during the first few weeks of treatment with filgrastim. In case of thrombocytopenia (platelet count consistently below 100,000/µl), the issue of temporary discontinuation of filgrastim or dose reduction should be considered. Other changes in the blood count requiring its careful monitoring are also observed, including anemia and a transient increase in the number of myeloid progenitor cells.

During treatment, the size of the spleen should be regularly monitored, and urinalysis should be performed.

When assessing the number of progenitor cells mobilized in patients with filgrastim, special attention should be paid to the method of quantitative determination. The results of flow cytometric analysis of CD34⁺ cell counts vary depending on the specific methodology, and caution should be exercised regarding recommendations on their number based on studies conducted in other laboratories.

No specific studies on the efficacy and safety of filgrastim use in elderly patients have been conducted.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.