Lipegfilgrastim
Lipegfilgrastim Uses, Dosage, Side Effects, Food Interaction and all others data.
Lipegfilgrastim, previously known as XM22, is a pegylated, recombinant granulocyte colony-stimulating factor (G-CSF) that was synthetized using a highly site-specific glycoPEGylation technology . It is used as an alternate to Pegfilgrastim for prophylactic use in cancer patients receiving chemotherapy and at risk for developing chemotherapy-induced neutropenia. Since July 2013, lipegfilgrastim is marketed by the EMA as Lonquex for subcutaneously injection, where it is administered once following cytotoxic chemotherapy for each chemotherapy cycle in adult patients being treated with cytotoxic chemotherapy for malignancy. It aims to reduce the duration of neutropenia and the incidence of febrile neutropenia.
Neutropenia and febrile neutropenia (FN) are frequent and potentially fatal complications that occur from myelosuppressive anticancer treatments . Severe chemotherapy-induced neutropenia and febrile neutropenia significantly increases the risk for life-threatening infection and sepsis. Granulocyte colony-stimulating factors (G-CSFs) were introduced in the 1980's to the clinical setting to stimulate neutrophil proliferation and differentiation, thereby reducing the duration and severity of chemotherapy-induced neutropenia . Lipegfilgrastim is a covalent conjugate of Filgrastim with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine . The average molecular mass of lipegfilgrastim comprises 18,798 Da for Filgrastim, 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG . PEG moiety protects the active molecule from enzyme degradation, which allows longer half-life of drug and less frequent dosing-schedule in addition to acceptable safety and efficacy profile .
Mimicking endogenous granulocyte colony-stimulating factors, lipegfilgrastim enhances the number and function of circulating neutrophils by binding to endogenous G-CSF receptors. A small increase in monocyte and/or lymphocyte counts may also be observed . Following a single subcutaneous dose administration of 100 μg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts . G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis . Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules . However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim .
| Trade Name | Lipegfilgrastim |
| Generic | Lipegfilgrastim |
| Lipegfilgrastim Other Names | Lipegfilgrastim |
| Type | |
| Formula | C866H1372N226O258S9*(C2H4O)n |
| Weight | 39000.0 Da (glycoPEGylated, approximate) |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Lipegfilgrastim is a medication used to reduce the duration of chemotherapy-induced neutropenia and incidence of febrile neutropenia in cytotoxic chemotherapy.
Indicated for the reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes) .
Lipegfilgrastim is also used to associated treatment for these conditions: Febrile Neutropenia, Neutropenia
How Lipegfilgrastim works
Endogenous granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates neutrophil progenitors. It is produced mainly by monocytes, fibroblasts and endothelial cells to promote the development of neutrophils and increase their proliferation and maturation . Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function . Via binding to to the human G-CSF receptors, lipegfilgrastim activates the receptor signalling pathway as a growth factor to stimulate proliferation of haematopoietic progenitor cells and their differentiation into mature cells, and promote subsequent release into the peripheral blood . This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells . The presence of the PEG moiety in lipegfilgrastim decreases the plasma clearance and extends the drug's terminal elimination half-life, allowing for less frequent dosing .
Toxicity
In safety pharmacological studies in rats and dogs, lipegfilgrastim was well tolerated at a single subcutaneous dose of 10 mg/kg. In the renal excretion study in rats, an intravenous dose of 250 μg/kg was well tolerated . While mutagenicity and genotoxicity studies have not been conducted with lipegfilgrastim, G-CSF has been reported to stimulate tumour growth and intratumoural vessel density in animal tumour models .
Food Interaction
No interactions found.Volume of Distribution
Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system .
Elimination Route
In studies of healthy volunteers receiving a single subcutaneous injection of 6 mg of lipegfilgrastim, the peak plasma concentration of lipegfilgrastim was reached after a median of 30 to 36 hours . Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system . Peak concentration and area under the curve, indicating full bioavailability, was lower in injection site of the thigh compared to subcutaneous injection in the abdomen and in the upper arm, with differences among the injection sites being the greatest in males compared to female subjects .
Half Life
The average terminal half-life ranged from approximately 32 to 62 hours after a single subcutaneous injection of 6 mg lipegfilgrastim in healthy individuals .
Clearance
In a phase 1, multinational, open-label, single-arm study of paediatric patients with Ewing family of tumors or rhabdomyosarcoma treated with myelosuppressive chemotherapy, the mean apparent clearance (CL/F) was approximately 71 mL/h, 120 mL/h, and 116 mL/h for age groups of 2-6 years, 6-12 years, and 12-18 years, respectively .
Elimination Route
Lipegfilgrastim undergoes two distinct clearance pathways: linear pathway composed of degradation by proteolytic enzymes and non-linear pathway involving neutrophil-mediated clearance . The elimination pathway by neutrophil-mediated clearance is saturated at higher doses . Lipegfilgrastim and its degraded fragments may undergo renal clearance .
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