EYLEA 114.3 mg/ml Solution for injection Ref.[110823] Active ingredients: Aflibercept

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Intravitreal injection-related reactions

Intravitreal injections, including those with Eylea, have been associated with endophthalmitis, intraocular inflammation, retinal detachment, retinal tear and traumatic cataract (see section 4.8). Proper aseptic injection techniques must always be used when administering Eylea. Patients should be instructed to report any symptoms suggestive of endophthalmitis or any of the above mentioned events without delay and should be managed appropriately.

Intraocular pressure increased

Transient increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection, including those with Eylea (see section 4.8). Both the intraocular pressure and perfusion of the optic nerve head must therefore be monitored and managed appropriately. Special precaution is needed in patients with poorly controlled glaucoma (do not inject Eylea while the intraocular pressure is ≥30 mmHg).

Immunogenicity

As this is a therapeutic protein, there is a potential for immunogenicity with aflibercept (see section 5.1). Patients should be instructed to report any signs or symptoms of intraocular inflammation, e.g. pain, photophobia, or redness, which may be a clinical sign attributable to hypersensitivity.

Systemic effects

Systemic adverse events including non-ocular haemorrhages and arterial thromboembolic events have been reported following intravitreal injection of VEGF inhibitors and there is a theoretical risk that these may relate to VEGF inhibition (see section 4.8).

There are limited data on safety in the treatment of patients with nAMD and DME with a history of stroke, transient ischaemic attacks or myocardial infarction within the last 6 months. Caution should be exercised when treating such patients.

Bilateral treatment

The safety and efficacy of bilateral treatment with Eylea 114.3 mg/ml per eye have not been studied (see section 5.1). If bilateral treatment is performed at the same time this could lead to an increased systemic exposure, which could increase the risk of systemic adverse events.

Concomitant use of other anti-VEGF

There are limited data available on the concomitant use of Eylea with other anti-VEGF medicinal products (systemic or ocular).

Withholding treatment

Treatment should be withheld in the event of:

• a decrease in best corrected visual acuity (BCVA) of ≥30 letters compared with the last assessment of visual acuity
• a rhegmatogenous retinal detachment or stage 3 or 4 macular holes
• a retinal break
• a subretinal haemorrhage involving the centre of the fovea, or, if the size of the haemorrhage is ≥50% of the total lesion area
• performed or planned intraocular surgery within the previous or next 28 days.

Retinal pigment epithelial tear

Risk factors associated with the development of a retinal pigment epithelial tear after anti-VEGF therapy for nAMD include a large and/or high pigment epithelial retinal detachment. When initiating aflibercept therapy, caution should be used in patients with these risk factors for retinal pigment epithelial tears.

Women of childbearing potential

Women of childbearing potential have to use effective contraception during treatment and for at least 4 months after the last intravitreal injection with Eylea 114.3 mg/ml (see section 4.6).

Populations with limited data

There is only limited experience with Eylea treatment in diabetic patients with an HbA1c over 12% or with proliferative diabetic retinopathy.

Eylea has not been studied in patients with active systemic infections or in patients with concurrent eye conditions such as retinal detachment or macular hole. There is also no experience of treatment with Eylea in diabetic patients with uncontrolled hypertension. This lack of information should be considered by the physician when treating such patients.

No interaction studies have been performed.

Women of childbearing potential

Women of childbearing potential have to use effective contraception during treatment and for at least 4 months after the last intravitreal injection with Eylea 114.3 mg/ml.

Pregnancy

There are limited data on the use of aflibercept in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Eylea 114.3 mg/ml should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus.

Breast-feeding

Based on very limited human data, aflibercept may be excreted in human milk at low levels. Aflibercept is a large protein molecule and the amount of medication absorbed by the infant is expected to be minimal. The effect of aflibercept on a breast-fed newborn/infant is unknown. As a precautionary measure breast-feeding is not recommended during the use of Eylea 114.3 mg/ml.

Fertility

There are no fertility data in humans. Results from animal studies with high systemic exposure indicate that aflibercept can impair male and female fertility (see section 5.3).

Injection with Eylea has minor influence on the ability to drive and use machines due to possible temporary visual disturbance associated either with the injection or eye examination. Patients should not drive or use machines until their visual function has recovered sufficiently.

Summary of the safety profile

Serious adverse reactions were cataract (8.2%), retinal haemorrhage (3.6%), intraocular pressure increased (2.8%), vitreous haemorrhage (1.2%), cataract subcapsular (0.9%), cataract nuclear (0.6%), retinal detachment (0.6%), and retinal tear (0.5%).

The most frequently observed adverse reactions in patients treated with Eylea 114.3 mg/ml were cataract (8.2%), visual acuity reduced (4.4%), vitreous floaters (4.0%), conjunctival haemorrhage (3.8%), vitreous detachment (3.7%), retinal haemorrhage (3.6%), intraocular pressure increased (2.8%), and eye pain (2.0%).

The safety profile observed in the 3 clinical studies was similar in patients treated with Eylea 114.3 mg/ml (N=1 217) and Eylea 40 mg/ml (N=556), and in patients with nAMD and DME.

Tabulated list of adverse reactions

A total of 1 217 patients treated with Eylea 114.3 mg/ml constituted the safety population in 3 clinical phase II/III studies (CANDELA, PULSAR, PHOTON). The safety data described below include all adverse reactions with a reasonable possibility of causality to the injection procedure or medicinal product reported.

The adverse reactions are listed by system organ class and frequency using the following convention: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. All treatment-emergent adverse reactions reported in patients with nAMD or DME treated with Eylea 114.3 mg/ml in phase II/III studies:

^* Reports of hypersensitivity included rash, pruritus, urticaria.

The following adverse reactions of Eylea 40 mg/ml are also considered expected with Eylea 114.3 mg/ml but have not been reported in the clinical studies with Eylea 114.3 mg/ml: abnormal sensation in eye, corneal epithelium defect, anterior chamber flare, endophthalmitis, blindness, traumatic cataract, hypopyon, severe anaphylactic/anaphylactoid reactions.

Description of selected adverse reactions

Product-class-related adverse reactions

Arterial thromboembolic events (ATEs) are adverse reactions potentially related to systemic VEGF inhibition. There is a theoretical risk of ATEs, including stroke and myocardial infarction, following intravitreal use of VEGF inhibitors. A low incidence rate of ATEs was observed in the aflibercept clinical studies in patients with nAMD and DME. Across indications, no notable difference between the groups treated with Eylea 114.3 mg/ml and the comparator groups treated with Eylea 40 mg/ml were observed.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.