Product Information
Registration Status: ActiveLONQUEX SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE 6MG/0.6ML is approved to be sold in Singapore with effective from 2020-09-25. It is marketed by DRUG HOUSES OF AUSTRALIA PTE LTD, with the registration number of SIN16019P.
This product contains Lipegfilgrastim 6mg/0.6ml in the form of INJECTION, SOLUTION. It is approved for SUBCUTANEOUS use.
This product is manufactured by TEVA PHARMACEUTICAL INDUSTRIES LTD. in ISRAEL.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}Description
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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication
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) [L2441].
Mechanism of Action
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Pharmacokinetics
- Absorption
- 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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
- Distribution
- Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
- Metabolism
- Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. Following binding to the G-CSF receptors, it is proposed to be internalized by neutrophils via a non-linear process, and then undergoes degradation within the cell by endogenous proteolytic enzymes. Alternatively, the linear pathway is likely due to extracellular protein degradation by neutrophil elastase and other plasma proteases [L2441].
- Elimination
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 [A32674].
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 [L2449]. 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 [L2449].
Active Ingredient/Synonyms
Lipegfilgrastim | Lipegfilgrastim |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.