me at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
In clinical trials doses of up to 4 mg in monthly intervals have been used and isolated cases of overdoses with 8 mg occurred.
Overdosing with increased injection volume may increase intraocular pressure. Therefore, in case of overdose intraocular pressure should be monitored and if deemed necessary by the treating physician, adequate treatment should be initiated.
Go to top of the page5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmaotherapeutic group: Ophthalmologicals / Antineovascularisation agents
ATC code: S01LA05
Aflibercept is a recombinant fusion protein consisting of portions of human VEGF receptor 1 and 2 extracellular domains fused to the Fc portion of human IgG1.
Aflibercept is produced in Chinese hamster ovary (CHO) K1 cells by recombinant DNA technology.
Aflibercept acts as a soluble decoy receptor that binds VEGF-A and PlGF with higher affinity than their natural receptors, and thereby can inhibit the binding and activation of these cognate VEGF receptors.
Mechanism of action
Vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF) are members of the VEGF family of angiogenic factors that can act as potent mitogenic, chemotactic, and vascular permeability factors for endothelial cells. VEGF acts via two receptor tyrosine kinases; VEGFR-1 and VEGFR-2, present on the surface of endothelial cells. PlGF binds only to VEGFR-1, which is also present on the surface of leucocytes. Excessive activation of these receptors by VEGF-A can result in pathological neovascularisation and excessive vascular permeability. PlGF can synergize with VEGF-A in these processes, and is also known to promote leucocyte infiltration and vascular inflammation.
Pharmacodynamic effects
wet AMD
Wet AMD is characterised by pathological choroidal neovascularisation (CNV). Leakage of blood and fluid from CNV may cause retinal thickening or oedema and/or sub-/intra-retinal haemorrhage, resulting in loss of visual acuity.
In patients treated with Eylea (one injection per month for three consecutive months, followed by one injection every 2 months), retinal thickness decreased soon after treatment initiation, and the mean CNV lesion size was reduced, consistent with the results seen with ranibizumab 0.5 mg every month.
In the VIEW1 study there were mean decreases in retinal thickness on optical coherence tomography (OCT) (-130 and -129 microns at week 52 for the Eylea 2 mg every two months and ranibizumab 0.5 mg every month study groups, respectively). Also at the 52 week time point, in the VIEW2 study there were mean decreases in retinal thickness on OCT (-149 and -139 microns for the Eylea 2 mg every two months and ranibizumab 0.5 mg every month study groups, respectively).
The reduction of CNV size and reduction in retinal thickness were generally maintained in the second year of the studies.
Macular Oedema secondary to CRVO
In CRVO retinal ischaemia occurs and signals the release of VEGF which in turn destabilises the tight junctions and promotes endothelial cell proliferation. Up-regulation of VEGF is associated with the breakdown of the blood retina barrier and this increased vascular permeability results in retinal oedema, stimulation of endothelial cell growth and neovascularisation.
In patients treated with Eylea (one injection every month for six months) there was consistent, rapid and robust response in morpholo |
