Aflibercept

Name: Aflibercept

Side effects

The following potentially serious adverse reactions are described elsewhere in the labeling:

  • Hypersensitivity [see CONTRAINDICATIONS]
  • Endophthalmitis and retinal detachments [see WARNINGS AND PRECAUTIONS]
  • Increase in intraocular pressure [see WARNINGS AND PRECAUTIONS]
  • Thromboembolic events [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials of the same or another drug and may not reflect the rates observed in practice.

A total of 2711 patients treated with EYLEA constituted the safety population in seven phase 3 studies. Among those, 2110 patients were treated with the recommended dose of 2 mg. Serious adverse reactions related to the injection procedure have occurred in < 0.1% of intravitreal injections with EYLEA including endophthalmitis and retinal detachment. The most common adverse reactions ( ≥ 5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous floaters, intraocular pressure increased, and vitreous detachment.

Neovascular (Wet) Age-Related Macular Degeneration (AMD)

The data described below reflect exposure to EYLEA in 1824 patients with wet AMD, including 1223 patients treated with the 2-mg dose, in 2 double-masked, active-controlled clinical studies (VIEW1 and VIEW2) for 12 months [see Clinical Studies].

Table 1: Most Common Adverse Reactions ( ≥ 1%) in Wet AMD Studies

Adverse Reactions EYLEA
(N=1824)
Active Control (ranibizumab)
(N=595)
Conjunctival hemorrhage 25% 28%
Eye pain 9% 9%
Cataract 7% 7%
Vitreous detachment 6% 6%
Vitreous floaters 6% 7%
Intraocular pressure increased 5% 7%
Ocular hyperemia 4% 8%
Corneal epithelium defect 4% 5%
Detachment of the retinal pigment epithelium 3% 3%
Injection site pain 3% 3%
Foreign body sensation in eyes 3% 4%
Lacrimation increased 3% 1%
Vision blurred 2% 2%
Intraocular inflammation 2% 3%
Retinal pigment epithelium tear 2% 1%
Injection site hemorrhage 1% 2%
Eyelid edema 1% 2%
Corneal edema 1% 1%

Less common serious adverse reactions reported in < 1% of the patients treated with EYLEA were hypersensitivity, retinal detachment, retinal tear, and endophthalmitis.

Macular Edema Following Retinal Vein Occlusion (RVO)

The data described below reflect 6 months exposure to EYLEA with a monthly 2 mg dose in 218 patients following CRVO in 2 clinical studies (COPERNICUS and GALILEO) and 91 patients following BRVO in one clinical study (VIBRANT) [see Clinical Studies].

Table 2: Most Common Adverse Reactions ( ≥ 1%) in RVO Studies

Adverse Reactions CRVO BRVO
EYLEA
(N=218)
Control
(N=142)
EYLEA
(N=91)
Control
(N=92)
Eye pain 13% 5% 4% 5%
Conjunctival hemorrhage 12% 11% 20% 4%
Intraocular pressure increased 8% 6% 2% 0%
Corneal epithelium defect 5% 4% 2% 0%
Vitreous floaters 5% 1% 1% 0%
Ocular hyperemia 5% 3% 2% 2%
Foreign body sensation in eyes 3% 5% 3% 0%
Vitreous detachment 3% 4% 2% 0%
Lacrimation increased 3% 4% 3% 0%
Injection site pain 3% 1% 1% 0%
Vision blurred 1% < 1% 1% 1%
Intraocular inflammation 1% 1% 0% 0%
Cataract < 1% 1% 5% 0%
Eyelid edema < 1% 1% 1% 0%

Less common adverse reactions reported in < 1% of the patients treated with EYLEA in the CRVO studies were corneal edema, retinal tear, hypersensitivity, and endophthalmitis.

Diabetic Macular Edema (DME)

The data described below reflect exposure to EYLEA in 578 patients with DME treated with the 2-mg dose in 2 double-masked, controlled clinical studies (VIVID and VISTA) from baseline to week 52 and from baseline to week 100 [see Clinical Studies].

Table 3: Most Common Adverse Reactions ( ≥ 1%) in DME Studies

Adverse Reactions Baseline to Week 52 Baseline to Week 100
EYLEA
(N=578)
Control
(N=287)
EYLEA
(N=578)
Control
(N=287)
Conjunctival hemorrhage 28% 17% 31% 21%
Eye pain 9% 6% 11% 9%
Cataract 8% 9% 19% 17%
Vitreous floaters 6% 3% 8% 6%
Corneal epithelium defect 5% 3% 7% 5%
Intraocular pressure increased 5% 3% 9% 5%
Ocular hyperemia 5% 6% 5% 6%
Vitreous detachment 3% 3% 8% 6%
Foreign body sensation in eyes 3% 3% 3% 3%
Lacrimation increased 3% 2% 4% 2%
Vision blurred 2% 2% 3% 4%
Intraocular inflammation 2% < 1% 3% 1%
Injection site pain 2% < 1% 2% < 1%
Eyelid edema < 1% 1% 2% 1%

Less common adverse reactions reported in < 1% of the patients treated with EYLEA were hypersensitivity, retinal detachment, retinal tear, corneal edema, and injection site hemorrhage.

Immunogenicity

As with all therapeutic proteins, there is a potential for an immune response in patients treated with EYLEA. The immunogenicity of EYLEA was evaluated in serum samples. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to EYLEA in immunoassays. The detection of an immune response is highly dependent on the sensitivity and specificity of the assays used, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to EYLEA with the incidence of antibodies to other products may be misleading.

In the wet AMD, RVO, and DME studies, the pre-treatment incidence of immunoreactivity to EYLEA was approximately 1% to 3% across treatment groups. After dosing with EYLEA for 24-100 weeks, antibodies to EYLEA were detected in a similar percentage range of patients. There were no differences in efficacy or safety between patients with or without immunoreactivity.

Warnings

Included as part of the PRECAUTIONS section.

Patient information

In the days following EYLEA administration, patients are at risk of developing endophthalmitis or retinal detachment. If the eye becomes red, sensitive to light, painful, or develops a change in vision, advise patients to seek immediate care from an ophthalmologist [see WARNINGS AND PRECAUTIONS].

Patients may experience temporary visual disturbances after an intravitreal injection with EYLEA and the associated eye examinations [see ADVERSE REACTIONS]. Advise patients not to drive or use machinery until visual function has recovered sufficiently.

Side Effects of Aflibercept

The most common aflibercept side effects include:

  • conjunctival hemorrhage (bleeding in the eye)
  • eye pain
  • cataract
  • vitreous detachment
  • vitreous floaters
  • increased pressure in the eye

This is not a complete list of aflibercept side effects. Ask your doctor or pharmacist for more information.

Serious side effects have occurred with aflibercept injections. See "Drug Precautions" section.

Aflibercept Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. The dose your doctor recommends may be based on the following:

  • the condition being treated
  • other medical conditions you have
  • other medications you are taking
  • how you respond to this medication
  • your weight
  • your height
  • your age
  • your gender

Wet Age-related Macular Degeneration (AMD): The recommended dose for aflibercept is 2 mg administered by injection in the eye every 2 months (8 weeks) following 3 initial monthly (4 weeks) injections. Aflibercept may be dosed once per month, but additional benefit was not seen with this dosing plan.

Macular Edema following Retinal Vein Occlusion (RVO): The recommended dose for aflibercept is 2 mg administered by injection in the eye monthly (every 4 weeks).

Diabetic Macular Edema (DME):  The recommended dose for aflibercept is 2 mg administered by injection in the eye every 2 months (8 weeks) following 5 initial monthly (4 weeks) injections. Aflibercept may be dosed once per month, but additional benefit was not seen with this dosing plan.

Diabetic retinopathy in patients with diabetic macular edema:  The recommended dose for aflibercept is 2 mg administered by injection in the eye every 4 weeks (monthly) for the first 5 injections then followed by 2 mg once every 8 weeks (2 months).

Introduction

Recombinant humanized fusion protein; a vascular endothelial growth factor A (VEGF-A) and placental growth factor (PlGF) antagonist.1 2 3

Stability

Storage

Ophthalmic

2–8°C.1 Do not freeze; protect from light.1 Store in original carton until use.1

Where can i get more information?

Your pharmacist can provide more information about aflibercept ophthalmic.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Usual Adult Dose for Macular Degeneration

Neovascular (Wet) Age Related Macular Degeneration (AMD):
2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).

Comments: Additional efficacy was not demonstrated when dosed every 4 weeks compared to every 8 weeks.

Liver Dose Adjustments

No adjustment recommended.

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