Zarzio^® (Solution) Instructions for Use

Marketing Authorization Holder

Sandoz, d.d. (Slovenia)

Manufactured By

IDT Biologika, GmbH (Germany)

Packaging and Quality Control Release

IDT Biologika, GmbH (Germany)

Or

SANDOZ, GmbH (Austria)

ATC Code

L03AA02 (Filgrastim)

Active Substance

Filgrastim (Rec.INN registered by WHO)

Dosage Forms

	Zarzio®	Solution for intravenous and subcutaneous administration 30 million IU/0.5 ml: syringes 1 or 5 pcs.
		Solution for intravenous and subcutaneous administration 48 million IU/0.5 ml: syringes 1 or 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and subcutaneous administration clear, colorless or yellowish in color.

Excipients: glutamic acid – 0.736 mg, sorbitol – 25 mg, polysorbate 80 – 0.02 mg, sodium hydroxide – q.s. to pH, water for injections – up to 0.5 ml.

0.5 ml – single-use syringes made of colorless glass with a capacity of 1 ml (1) – blisters (1) – cardboard packs.
0.5 ml – single-use syringes made of colorless glass with a capacity of 1 ml (1) – blisters (5) – cardboard packs.
0.5 ml – single-use syringes made of colorless glass with a capacity of 1 ml (1) with a special needle protection device – blisters (1) – cardboard packs.
0.5 ml – single-use syringes made of colorless glass with a capacity of 1 ml (1) with a special needle protection device – blisters (5) – cardboard packs.

Solution for intravenous and subcutaneous administration clear, colorless or yellowish in color.

Excipients: glutamic acid – 0.736 mg, sorbitol – 25 mg, polysorbate 80 – 0.02 mg, sodium hydroxide – q.s. to pH, water for injections – up to 0.5 ml.

0.5 ml – single-use syringes made of colorless glass with a capacity of 1 ml (1) – blisters (1) – cardboard packs.
0.5 ml – single-use syringes made of colorless glass with a capacity of 1 ml (1) – blisters (5) – cardboard packs.
0.5 ml – single-use syringes made of colorless glass with a capacity of 1 ml (1) with a special needle protection device – blisters (1) – cardboard packs.
0.5 ml – single-use syringes made of colorless glass with a capacity of 1 ml (1) with a special needle protection device – blisters (5) – cardboard packs.

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/mcL) and a history of severe or recurrent infections.

ICD codes

Dosage Regimen

Determine the dosage individually based on indication, treatment regimen, and patient response.

Administer Zarzio^® by subcutaneous injection or intravenous infusion.

For chemotherapy-induced neutropenia, administer a single daily dose of 5 mcg/kg. Initiate administration at least 24 hours after the last cytotoxic chemotherapy cycle. Continue daily dosing 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 neutrophil nadir.

For bone marrow transplantation, administer a single daily dose of 10 mcg/kg. Initiate intravenous infusion at least 24 hours after bone marrow infusion and within 24 hours after the last dose of cytotoxic chemotherapy. Adjust the dose based on the neutrophil count; reduce by 5 mcg/kg if the neutrophil count exceeds 1,000/mm³ for 3 consecutive days, and discontinue if the count surpasses 10,000/mm³.

For peripheral blood progenitor cell (PBPC) mobilization, administer a single daily dose of 10 mcg/kg subcutaneously for 4 to 5 days before the first leukapheresis. Continue daily dosing until the last leukapheresis procedure. Monitor the white blood cell count; discontinue filgrastim if the count exceeds 100,000/mm³.

For severe chronic neutropenia (SCN), the recommended initial dose is 5 mcg/kg subcutaneously, administered once daily. For congenital neutropenia, the typical dose is 12 mcg/kg daily. For idiopathic or cyclic neutropenia, the typical dose is 5 mcg/kg daily. Adjust the dose based on the patient’s clinical course and absolute neutrophil count; titrate to the lowest effective dose.

Do not shake the solution. Inspect visually for particulate matter and discoloration before administration. Discard the syringe after a single use.

Monitor the complete blood count, including platelet count and differential, regularly during therapy. Monitor spleen size periodically in patients with SCN.

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 intravenous 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, because the efficacy and safety of filgrastim in this category of patients has not been studied.

Use in Renal Impairment

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

Patients with concomitant bone pathology and osteoporosis receiving Filgrastim continuously for more than 6 months are recommended to monitor bone mineral 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, so it is not indicated for these diseases. A differential diagnosis between blast transformation of chronic myeloid leukemia and acute myeloid leukemia should be performed with particular care.

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

It should be used 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-agent or combination chemotherapy regimens known for their ability to cause severe thrombocytopenia.

Before using filgrastim for severe chronic neutropenia, a differential diagnosis with other hematological diseases, such as aplastic anemia, myelodysplasia, and myeloid leukemia, should be performed with particular care. Before starting treatment, a complete blood count with differential white blood cell count and platelet count should be performed, and the morphological picture of the bone marrow and karyotype should be examined.

The blood picture, including 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/mcL), 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 evaluating 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.