Included as part of the PRECAUTIONS section.

Endophthalmitis and Retinal Detachments

Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments [see ADVERSE REACTIONS]. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately [see DOSAGE AND ADMINISTRATION and PATIENT INFORMATION].

Increase in Intraocular Pressure

Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA [see ADVERSE REACTIONS]. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately [see DOSAGE AND ADMINISTRATION].

Thromboembolic Events

There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence in the VIEW1 and VIEW2 wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with EYLEA [see Clinical Studies]. The incidence in the COPERNICUS and GALILEO CRVO studies during the first 6 months was 0% (0/218) in patients treated with EYLEA 2 mg every 4 weeks compared with 1.4% (2/142) in patients receiving sham treatment [see Clinical Studies].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No studies have been conducted on the mutagenic or carcinogenic potential of aflibercept. Effects on male and female fertility were assessed as part of a 6-month study in monkeys with intravenous administration of aflibercept at doses ranging from 3 to 30 mg/kg. Absent or irregular menses associated with alterations in female reproductive hormone levels and changes in sperm morphology and motility were observed at all dose levels. In addition, females showed decreased ovarian and uterine weight accompanied by compromised luteal development and reduction of maturing follicles. These changes correlated with uterine and vaginal atrophy. A No Observed Adverse Effect Level (NOAEL) was not identified. Based on Cmax and AUC for free aflibercept observed at the lowest dose used of 3 mg/kg, the systemic exposures were approximately 4900 times and 1500 times higher, respectively, than the exposure observed in humans after an intravitreal dose of 2 mg. All changes were reversible.

Use In Specific Populations

Pregnancy

Pregnancy Category C

Aflibercept produced embryo-fetal toxicity when administered during organogenesis in pregnant rabbits at intravenous doses of 3 to 60 mg/kg. A series of external, visceral, and skeletal malformations were observed in the fetuses. The maternal No Observed Adverse Effect Level (NOAEL) was 3 mg/kg, whereas the fetal NOAEL was below 3 mg/kg. At this dose, the systemic exposures based on Cmax and AUC for free aflibercept were approximately 2900 times and 600 times higher, respectively, when compared to corresponding values observed in humans after an intravitreal dose of 2 mg.

There are no adequate and well-controlled studies in pregnant women. EYLEA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is unknown whether aflibercept is excreted in human milk. Because many drugs are excreted in human milk, a risk to the breastfed child cannot be excluded. EYLEA is not recommended during breastfeeding. A decision must be made whether to discontinue nursing or to discontinue treatment with EYLEA, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of EYLEA in pediatric patients have not been established.

Geriatric Use

In the clinical studies, approximately 85% (1728/2034) of patients randomized to treatment with EYLEA were ≥ 65 years of age and approximately 58% (1177/2034) were ≥ 75 years of age. No significant differences in efficacy or safety were seen with increasing age in these studies.

Last reviewed on RxList: 10/10/2012
This monograph has been modified to include the generic and brand name in many instances.