Aflibercept

Class: EENT Drugs, Miscellaneous
Chemical Name: Vascular endothelial growth factor receptor type VEGFR1 (synthetic human immunoglobulin domain 2 fragment) fusion protein with vascular endothelial growth factor receptor type VEGFR2 (synthetic human immunoglobulin domain 3 fragment) fusion protein with immunoglobulin G1 (synthetic Fc fragment), dimer
Molecular Formula: C₄₃₁₈H₆₇₈₈N₁₁₆₄O₁₃₀₄S₃₂
CAS Number: 862111-32-8
Brands: Eylea

Medically reviewed by Drugs.com. Last updated on Apr 1, 2019.

• Overview
• Side Effects
• Dosage
• Professional
• Pregnancy
• Reviews
• More

Introduction

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

Uses for Aflibercept

Neovascular Age-related Macular Degeneration

Treatment of neovascular (wet) age-related macular degeneration.^{1 5 7 9 22}

Clinically equivalent to ranibizumab.¹ May provide some advantages (e.g., decreased treatment burden) over other agents (e.g., bevacizumab†, ranibizumab) because of less frequent administration.^{5 6 7 8} (See Dosage under Dosage and Administration.)

Macular Edema Following Retinal Vein Occlusion

Treatment of macular edema following retinal vein occlusion.^{1 11 12 13 15 16 17 18 19 26}

Diabetic Macular Edema

Treatment of diabetic macular edema.^{1 14 20}

Diabetic Retinopathy in Patients with Diabetic Macular Edema

Treatment of diabetic retinopathy in patients with diabetic macular edema.^{1 14 20}

Aflibercept Dosage and Administration

Administration

Ophthalmic

Administer by intravitreal injection only into the affected eye(s); must be administered only by a qualified physician.¹

Prior to intravitreal administration, withdraw entire contents of aflibercept vial through a sterile 5-µm, 19-gauge filter needle (provided by manufacturer) into a 1-mL syringe (provided by manufacturer) using aseptic technique.¹ Prior to intravitreal injection, replace filter needle with a sterile 30-gauge, ½-inch needle (provided by manufacturer).¹ To obtain appropriate dose (2 mg), expel contents in syringe until plunger tip is aligned with the line that marks 0.05 mL on the syringe.¹

Inject under controlled aseptic conditions (including surgical hand disinfection and use of sterile gloves, sterile drape, and sterile eyelid speculum [or equivalent]) following adequate anesthesia and administration of a topical broad-spectrum anti-infective agent.¹

Monitor patients for elevation of IOP immediately following intravitreal injection;¹ monitoring may include evaluation of optic nerve head perfusion or tonometry.¹ A sterile paracentesis needle should be available, if required.¹

Use each vial only for treatment of a single eye; discard any unused portion.¹ If contralateral eye requires treatment, use a new vial; change sterile field, syringe, gloves, drape, eyelid speculum, and filter and injection needles before administering to the other eye.¹

Dosage

Adults

Neovascular Age-related Macular Degeneration

Ophthalmic

Intravitreal injection: 2 mg into the affected eye(s) once every 4 weeks for 12 weeks, then 2 mg once every 8 weeks.¹

Additional efficacy not demonstrated following administration every 4 weeks compared with every 8 weeks.¹

Macular Edema Following Retinal Vein Occlusion

Ophthalmic

Intravitreal injection: 2 mg into the affected eye(s) once every 4 weeks.¹

Diabetic Macular Edema

Ophthalmic

Intravitreal injection: 2 mg into the affected eye(s) once every 4 weeks for the first 5 injections, followed by 2 mg once every 8 weeks.¹

Additional efficacy not demonstrated following administration every 4 weeks compared with every 8 weeks.¹

Diabetic Retinopathy in Patients with Diabetic Macular Edema

Ophthalmic

Intravitreal injection: 2 mg into the affected eye(s) once every 4 weeks for the first 5 injections, followed by 2 mg once every 8 weeks.¹

Additional efficacy not demonstrated following administration every 4 weeks compared with every 8 weeks.¹

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹

Renal Impairment

No dosage adjustment required.¹

Geriatric Patients

No dosage adjustment required.¹

Cautions for Aflibercept

Contraindications

• Ocular or periocular infections.¹

• Active intraocular inflammation.¹

• Known hypersensitivity (e.g., severe intraocular inflammation) to aflibercept or any ingredient in the formulation.¹

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions reported.¹ (See Contraindications under Cautions.)

Endophthalmitis and Retinal Detachment

Intravitreal injections, including with aflibercept, associated with endophthalmitis and retinal detachment.¹ Always use proper aseptic injection technique.¹

If signs or symptoms of endophthalmitis or retinal detachment (e.g., redness, sensitivity to light, pain, changes in vision [including blurred vision]) occur, manage appropriately.¹

Increased IOP

Acute increases in IOP observed within 60 minutes of intravitreal injection.¹ Sustained increases in IOP also observed following repeated intravitreal injections of VEGF antagonists.¹ Monitor IOP and perfusion of optic nerve head and manage appropriately.¹

Thromboembolic Events

Potential risk of arterial thromboembolic events following intravitreal injection of VEGF antagonists, including aflibercept.¹

Immunogenicity

Incidence of immunoreactivity to aflibercept was similar before and after 24–100 weeks of therapy.¹ No differences in efficacy or safety between patients with or without immunoreactivity.¹

Specific Populations

Pregnancy

Category C.¹

No adequate and well-controlled studies in pregnant women.¹ Animal studies suggest a possibility of adverse embryofetal effects.¹

Use only if potential benefits justify potential risk to fetus.¹ Women of childbearing potential should use effective contraception prior to initiating therapy, during treatment, and for ≥3 months after last intravitreal injection is administered.¹

Lactation

Not known whether aflibercept is distributed into milk.¹ Use not recommended in nursing women.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults.¹

Renal Impairment

No differences in plasma concentrations observed with various degrees of renal impairment.¹ (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Conjunctival hemorrhage,^{1 2 3} eye pain,^{1 2 3} cataract,¹ vitreous detachment,^{1 2 3} vitreous floaters,^{1 2} increased IOP.^{1 2 3}

Interactions for Aflibercept

No formal drug interaction studies to date.¹

Aflibercept Pharmacokinetics

Absorption

Bioavailability

Following intravitreal injection, mean peak plasma concentration attained in 1–3 days; peak plasma concentration estimated to be >100-fold lower than concentration required to half-maximally bind systemic VEGF.¹

Free aflibercept undetectable in plasma 2 weeks after intravitreal injection.¹

No accumulation observed following repeated intravitreal injections (i.e., once every 4 weeks).¹

Special Populations

Following intravitreal injection every 4 or 8 weeks, no differences in free plasma aflibercept concentrations observed between patients with mild, moderate, or severe renal impairment.¹

Distribution

Extent

Not known whether aflibercept is distributed into milk.¹

Elimination

Metabolism

Expected to undergo elimination through both target-mediated disposition via binding to free endogenous VEGF and via proteolysis.¹

Half-life

Approximately 5–6 days following IV administration of doses of 2–4 mg/kg.¹

Stability

Storage

Ophthalmic

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

Actions

• Acts as a soluble decoy receptor that binds to VEGF-A and PlGF and inhibits their biologic activity.^{1 2 7}

• VEGF-A induces neovascularization (angiogenesis) and increases vascular permeability,¹ which appear to play a role in the pathogenesis and progression of neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy.^{2 3 4 5 7 8 25 27 28 29}

• Binding to VEGF-A and PlGF prevents these factors from binding to endogenous VEGF receptors (i.e., VEGFR-1, VEGFR-2), reducing endothelial cell proliferation, angiogenesis, and vascular permeability.

• Binding affinity of aflibercept for VEGF-A isoforms is higher than that of endogenous receptors; aflibercept blocks VEGF binding and activation of VEGFR-1 and VEGFR-2 even at low concentrations.^{2 3 4}

Advice to Patients

• Possible temporary visual disturbances after intravitreal injection and associated eye examinations; importance of avoiding driving a vehicle or operating machinery until visual function has recovered sufficiently.¹

• Risk of endophthalmitis or retinal detachment; importance of immediately seeking care from an ophthalmologist if change in vision occurs or if the treated eye becomes red, sensitive to light, or painful.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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