Religrast

Religrast

filgrastim

Manufacturer:

Reliance

Distributor:

Ambica

Marketer:

Ambica
Full Prescribing Info
Contents
Filgrastim.
Description
Filgrastim (ReliGrast) is a sterile, clear, colorless, preservative-free liquid containing Filgrastim for parenteral administration. It is available as single use Pre-Filled Syringe (PFS) of 0.5 mL containing 300 mcg of Filgrastim concentrated solution Ph.Eur. in a sodium acetate aqueous buffer containing sorbitol and polysorbate 80.
Filgrastim (human granulocyte colony-stimulating factor, G-CSF) is a 175 amino acid protein manufactured by recombinant DNA technology by inserting human gene coding for G-CSF into Escherichia coli (E. Coli). The amino acid sequence in Filgrastim is identical to human G-CSF except for the addition of an N-terminal methionine necessary for expression in E. Coli and is not glycosylated.
Action
Pharmacology: Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors. Endogenous G-CSF is a lineage specific colony-stimulating factor which is produced by monocytes, fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation, differentiation, and selected end-cell functional activation (including enhanced phagocytic ability, priming of the cellular metabolism associated with respiratory burst, antibody dependent killing, and the increased expression of some functions associated with cell surface antigens). G-CSF is not species specific and has been shown to have minimal direct in vivo or in vitro effects on the production of hematopoietic cell types other than the neutrophil lineage.
Pharmacokinetics: There is a positive linear correlation between the dose and the serum concentration of Filgrastim, whether administered intravenously or subcutaneously. Peak serum concentrations following subcutaneous injection are generally attained within 4-5 hours. The volume of distribution averaged 150 mL/kg. Clearance of Filgrastim has been shown to follow first-order pharmacokinetics after both subcutaneous and intravenous administration. The mean serum elimination half-life of Filgrastim is approximately 3.5 hours, with a clearance rate of approximately 0.6 mL/min/kg.
Toxicology: As with other therapeutic proteins, Filgrastim also has a potential for immunogenicity. However the incidence and effect of this has not been adequately determined. The carcinogenic and mutagenic potential of Filgrastim has not been studied. Single dose acute and chronic toxicity studies were conducted for Filgrastim (ReliGrast) with intramuscular and subcutaneous dosing in Swiss Albino mice (1000 mcg/kg body weight) and Sprague Dawley rats (500 mcg/kg body weight). The studies revealed no apparent toxicity in the test animals. Filgrastim (ReliGrast) did not cause any skin sensitization in test animals. It did not induce mutations in the mutagenicity model of Salmonella typhimurium.
Indications/Uses
Filgrastim (ReliGrast) is a granulocyte colony-stimulating factor (G-CSF), a haematopoietic growth factor that stimulates the development of granulocytes. It is used to treat or prevent neutropenia in patients receiving myelosuppressive cancer chemotherapy and to reduce the period of neutropenia in patients undergoing bone marrow transplantation. It is also used to mobilise peripheral blood progenitor cells for use as an alternative to bone marrow transplantation, in the management of chronic neutropenia (congenital, cyclic, or idiopathic), and for persistent neutropenia in patients with advanced HIV infection.
Dosage/Direction for Use
As an adjunct to antineoplastic therapy: Filgrastim is given in a dose of 5 micrograms/kg daily starting not less than 24 hours after the last dose of antineoplastic. It can be given as single daily subcutaneous injection, as a continuous intravenous or subcutaneous infusion, or as a daily intravenous infusion over 15 to 30 minutes. Treatment is continued until the neutrophil count has stabilised within the normal range which may take up to 14 days or more. A formulation of filgrastim conjugated with monomethoxy polyethylene glycol (pegfilgrastim) may also be used to reduce the incidence of neutropenia associated with antineoplastic therapy; it is given subcutaneous injection in a single dose of 6 mg, given not less than 24 hours after the last dose of antineoplastic.
Bone marrow transplantation: The initial dose of Filgrastim following bone marrow transplantation is 10 micrograms/kg daily, adjusted according to response. This may be given intravenous infusion over 30 minutes or 4 hours, or by continuous intravenous or subcutaneous infusion over 24 hours.
For mobilisation of peripheral blood progenitor cells: A dose of 10 micrograms/kg daily of Filgrastim may be given subcutaneously as a single daily injection or by continuous infusion for 4 to 7 days until leucapheresis; if given after myelosuppressive chemotherapy this dose is halved to 5 micrograms/kg daily by subcutaneous injection.
Patients with congenital neutropenia: The initial dose is 12 micrograms/kg daily and in patients with idiopathic or cyclic neutropenia the initial dose is 5 micrograms/kg daily. In these forms of neutropenia the dose is given subcutaneously in single or divided doses and should be adjusted according to response.
Patients with HIV Infection and persistent neutropenia: The initial dose is 1 microgram/kg daily by subcutaneous injection. The dose may be titrated up to a maximum of 4 micrograms/kg daily until a normal neutrophil count is achieved and then adjusted for maintenance according to response. Maintenance doses of 300 micrograms daily on 1 to 7 days a week have been used.
The Filgrastim doses described previously for patients receiving antineoplastic therapy and for chronic neutropenias may also be given to Children. Pegfilgrastim should not be used in children or adolescents weighing less than 4 kg.
Dilution: Filgrastim (ReliGrast) should not be diluted with saline solution for IV administration as the product will precipitate.
Overdosage
Filgrastim therapy should be discontinued if the ANC surpasses 10,000/mm3 after the chemotherapy induced ANC nadir has occurred. Doses of Filgrastim that increase the ANC beyond 10,000/mm3 may not result in any additional clinical benefit and should be avoided. The maximum tolerated dose of Filgrastim (ReliGrast) has not been determined.
Contraindications
Filgrastim (ReliGrast) should not be administered to patients with known hypersensitivity to Filgrastim or to any of the excipients in the preparation.
Special Precautions
Simultaneous use with Chemotherapy and Radiation Therapy: Since the safety and efficacy of Filgrastim given concomitantly with cytotoxic chemotherapy and radiation therapy has not been established, it is advisable that simultaneous use of Filgrastim with chemotherapy and radiation therapy should be avoided. In patients receiving cytotoxic drugs, for 24 hrs prior to and 24 hrs after chemotherapy, Filgrastim administration should be avoided, since the sensitivity of fast proliferating neutrophils to chemotherapy is not established.
Potential Effect on Malignant Cells: Filgrastim is a growth factor that primarily stimulates neutrophils. However, the possibility that Filgrastim can act as a growth factor for any tumor type cannot be excluded.
Use in Pregnancy: Since there are no adequate and well-controlled studies in pregnant women, the effect, if any, of Filgrastim on the developing fetus or the reproductive capacity of the mother is unknown. Filgrastim should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in Lactation: It is not known whether Filgrastim is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if Filgrastim is administered to a nursing woman.
Use in Children: The safety profile of Filgrastim in pediatric patients appears similar to that reported in adults. The safety and efficacy in neonates and patients with autoimmune neutropenia of infancy have not been established. As rhG-CSF can cause increased uric acid levels, patients who have a history of gout or malignancies that are known to be associated with increased uric acid levels, should be monitored regularly.
Use In Pregnancy & Lactation
Use in Pregnancy: Since there are no adequate and well-controlled studies in pregnant women, the effect, if any, of Filgrastim on the developing fetus or the reproductive capacity of the mother is unknown. Filgrastim should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in Lactation: It is not known whether Filgrastim is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if Filgrastim is administered to a nursing woman.
Adverse Reactions
Filgrastim generally is well tolerated, and very rarely produces adverse effects so severe that discontinuation is required. The adverse effect reported most frequently is mild to moderate (occasionally severe) medullary bone pain. The bone pain appears to be dependent on the dose and/or route of administration (lower incidence with subcutaneous injection, and higher with intravenous). The safety profile reveals Filgrastim (ReliGrast) to be well tolerated with no significant adverse reactions observed. The most common adverse events were pyrexia, vomiting, diarrhea, asthenia, generalized pain, cough, abdominal pain, anemia, pain in extremity, nausea, anorexia, hypoaesthesia, paraesthesia, mucosal inflammation and dysuria, all of these being chemotherapy emergent and not treatment related. Most adverse events were of mild severity requiring no hospitalization or medication. The incidence of bone pain was also low, with only two patients complaining of severe bone pain.
Drug Interactions
Drug interactions between Filgrastim and other drugs have not been fully evaluated. Drugs which may potentiate the release of neutrophils, such as lithium, should be used with caution.
Storage
Store at temperatures between 2-8°C. Do not freeze. The shelf-life of the single dose pre-filled syringe is two years from the date of manufacturing.
ATC Classification
L03AA02 - filgrastim ; Belongs to the class of colony stimulating factors. Used as immunostimulants.
Presentation/Packing
Soln for inj (pre-filled syringe) 300 mcg/0.5 mL (sterile, clear, colorless, preservative-free liquid) x 1's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in