EYLEA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EYLEA (EYLEA).
Aflibercept is a recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF-A and VEGF-B) and placental growth factor (PlGF), thereby inhibiting angiogenesis and vascular permeability.
| Metabolism | Aflibercept is a protein; metabolism is expected to be via proteolytic degradation into small peptides and amino acids. |
| Excretion | Primarily eliminated via the reticuloendothelial system; no renal or biliary excretion as intact aflibercept. Systemic clearance involves proteolytic catabolism. |
| Half-life | Intravitreal half-life: approximately 4.8 days in aqueous humor; systemic half-life: approximately 5–6 days after IVT injection due to slow absorption. |
| Protein binding | Free aflibercept in the vitreous and systemic circulation is not extensively protein-bound; the VEGF-binding portion (VEGFR1/2 domains) is fully active. |
| Volume of Distribution | Systemic Vd is approximately 0.1 L/kg, indicating limited distribution primarily within the vascular compartment. |
| Bioavailability | Intravitreal injection: 100% bioavailability (direct administration into vitreous humor); systemic absorption is negligible (<10%) after intravitreal dosing. |
| Onset of Action | Intravitreal: improvement in visual acuity and reduction in central retinal thickness observed as early as 1 week after first injection, with maximal effect by 4 weeks. |
| Duration of Action | Intravitreal: therapeutic effect lasts approximately 4–8 weeks; dosing interval is typically 4–8 weeks for neovascular AMD and 4 weeks for diabetic macular edema. |
Intravitreal injection of 2 mg (0.05 mL) administered monthly (approximately every 4 weeks) for the first 3 months, followed by 2 mg every 8 weeks for neovascular age-related macular degeneration (nAMD). For diabetic macular edema (DME) and macular edema secondary to retinal vein occlusion (RVO), 2 mg monthly for 5 months, then 2 mg every 8 weeks. For diabetic retinopathy (DR) without DME, 2 mg every 8 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required in renal impairment; however, monitor for potential systemic effects as elimination is via proteolysis. |
| Liver impairment | No specific dosing guidelines for hepatic impairment; use with caution as no studies have been conducted. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; no recommended dosing. |
| Geriatric use | No specific dose adjustment is needed for elderly patients; dosing follows adult guidelines as clinical studies included similar numbers of patients aged ≥65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EYLEA (EYLEA).
| Breastfeeding | No data on aflibercept in human milk. Systemic absorption is negligible after intravitreal injection, and the M/P ratio is unknown. Based on the low bioavailability and the large molecular weight (115 kDa), transfer into breast milk is unlikely to be clinically significant. Caution is advised; consider discontinuing breastfeeding or the drug based on importance to mother. |
| Teratogenic Risk | Aflibercept is an anti-VEGF agent. Systemic exposure is minimal after intravitreal injection; however, based on its mechanism of action and animal studies showing reproductive toxicity (embryofetal lethality, skeletal abnormalities) at high systemic doses, it is classified as pregnancy category C. In the first trimester, there is a theoretical risk of teratogenicity if systemic levels are sufficient to inhibit VEGF, which is critical for embryonic vascular development. In the second and third trimesters, risks include potential fetal vascular disruption and oligohydramnios if systemic absorption occurs. Use only if potential benefit justifies risk. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Ocular or periocular infections","Active intraocular inflammation"]
| Precautions | ["Intravitreal injections are associated with endophthalmitis, intraocular inflammation, increased intraocular pressure, and retinal detachment.","Arterial thromboembolic events (ATEs) including stroke and myocardial infarction have been reported, although the risk is low.","Use with caution in patients with active ocular or periocular infections.","Not recommended for use in pregnant women unless the potential benefit outweighs the risk."] |
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| Fetal Monitoring | Monitor intraocular pressure post-injection. No routine fetal monitoring is required due to minimal systemic exposure; however, if used in pregnancy, consider serial prenatal ultrasounds to assess fetal growth and amniotic fluid volume due to theoretical anti-VEGF effects. |
| Fertility Effects | No human studies on fertility. In animal studies, high systemic doses resulted in impaired fertility and increased pre- and post-implantation losses. At intravitreal doses, systemic exposure is low, making significant fertility effects unlikely. Advise patients of unknown risk. |