EYLEA HD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EYLEA HD (EYLEA HD).
EYLEA HD (aflibercept) is a recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF). It binds to VEGF-A and PlGF with high affinity, preventing their interaction with endothelial cell surface receptors VEGFR-1 and VEGFR-2, thereby inhibiting angiogenesis and vascular permeability.
| Metabolism | Aflibercept is expected to be metabolized via proteolysis into small peptides and amino acids. No specific metabolic enzymes are involved. |
| Excretion | Primarily metabolized via catabolic pathways; negligible renal elimination (<1% unchanged in urine). Biliary/fecal excretion of metabolites is minimal; systemic clearance is predominantly through proteolysis. |
| Half-life | Approximately 11-13 days (range 7-19 days) in vitreous humor following intravitreal injection; terminal half-life in plasma is about 11-15 days. This supports monthly or bimonthly dosing intervals. |
| Protein binding | Approximately 90% bound to plasma proteins, mainly albumin and immunoglobulins (Fab fragment binding). |
| Volume of Distribution | Vd is approximately 0.04 L/kg (central compartment) reflecting limited distribution primarily in plasma and vitreous; small volume due to high molecular weight (115 kDa). |
| Bioavailability | Intravitreal injection: 100% bioavailability in vitreous humor. Not administered systemically; oral or intravenous bioavailability not applicable. |
| Onset of Action | Intravitreal: Clinical improvement in visual acuity may be observed as early as 1 week after first injection; maximal effect typically seen after 4-8 weeks. |
| Duration of Action | Intravitreal: Duration of effect on retinal fluid and vision lasts approximately 8-12 weeks; neovascular regression persists for up to 12 weeks, supporting dosing every 8-12 weeks. |
Intravitreal injection: 2 mg (0.04 mL of 50 mg/mL solution) every 4 weeks (monthly) for 3 initial doses, then 2 mg every 8 weeks (2 months) for neovascular (wet) age-related macular degeneration; 2 mg every 4 weeks for diabetic macular edema or macular edema secondary to retinal vein occlusion.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required based on renal function; safety and efficacy not established in patients with severe renal impairment (eGFR <15 mL/min/1.73 m² or on dialysis). |
| Liver impairment | No dose adjustment required based on hepatic function; safety and efficacy not studied in patients with hepatic impairment. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; no recommended dosing available. |
| Geriatric use | No specific dose adjustment required; clinical studies included a majority of patients aged ≥65 years with no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EYLEA HD (EYLEA HD).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Systemic exposure after intravitreal injection is minimal, so transfer into breast milk is likely negligible. M/P ratio is not known. Caution is advised; consider developmental and health benefits of breastfeeding along with mother's clinical need for EYLEA HD and potential adverse effects on breastfed infant. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal reproduction studies, intravitreal administration of aflibercept (the active moiety) did not cause fetal harm at clinically relevant exposures. However, systemic exposure is low after intravitreal injection, and the risk of teratogenicity is considered minimal. However, due to anti-VEGF mechanism, theoretical risk of fetal toxicity exists; use only if potential benefit justifies potential risk to fetus. First trimester: unknown risk; second and third trimesters: low systemic exposure suggests minimal risk. |
■ FDA Black Box Warning
Endophthalmitis and retinal detachments have been reported following intravitreal injections. Proper aseptic injection technique must be used.
| Serious Effects |
["Ocular or periocular infections","Active intraocular inflammation","Known hypersensitivity to aflibercept or any excipients in the formulation"]
| Precautions | ["Increased intraocular pressure (IOP) has been seen within 60 minutes of injection; monitor IOP and manage appropriately.","Arterial thromboembolic events (ATEs), including nonfatal stroke and myocardial infarction, may occur with VEGF inhibitors.","Use with caution in patients with active ocular or periocular infections.","Not recommended for use during pregnancy unless potential benefit justifies risk to fetus."] |
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| Fetal Monitoring | Monitor for intraocular inflammation, elevated intraocular pressure, and thromboembolic events. During pregnancy, assess fetal growth and amniotic fluid volume via ultrasound if systemic exposure is a concern. No specific fetal monitoring indicated for maternal intravitreal injection. |
| Fertility Effects | In animal studies, no effects on fertility were observed with intravitreal administration at clinically relevant exposures. Systemic exposure is low, so effects on human fertility are unlikely. |