aflibercept

General

Pronunciation:
a-fli-ber-sept


Trade Name(s)

  • Ahzantive
  • Eylea
  • Eylea HD
  • Opuviz
  • Yesafili

Ther. Class.

ocular agents

Pharm. Class.

vascular endothelial growth factor antagonists

Indications

  • Ahzantive, Eyelea, Eyelea HD, Opuviz, and Yesafili:

    Treatment of the following conditions:

    • Neovascular (wet) age-related macular degeneration (AMD),
    • Diabetic macular edema,
    • Diabetic retinopathy.
  • Ahzantive, Eyelea, Opuviz, and Yesafili: Macular edema following central retinal vein occlusion.
  • Eyelea: Retinopathy of prematurity.

Action

Binds to and inactivates vascular endothelial growth factor (VEGF) receptors, which normally promote neovascularization and vascular permeability.

Therapeutic Effect(s):

  • Slowed progression of AMD.
  • Decreased macular edema following central retinal vein occlusion.
  • Improved visual acuity in diabetic macular edema
  • Decreased severity of diabetic retinopathy
  • Absence of both active retinopathy of prematurity and unfavorable structural outcomes.

Pharmacokinetics

Absorption: Action is local following intravitreal injection; minimal systemic absorption occurs.

Distribution: Distribution occurs mainly in the vitreal space.

Metabolism and Excretion: Used up in the binding process and degraded by proteolytic enzymes.

Half-life: 5–6 days (plasma).

TIME/ACTION PROFILE (improved visual acuity)

ROUTEONSETPEAKDURATION
intravitrealrapid (within 4 wk)8–12 wkmaintained throughout treatment

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;

  • Ocular/periocular infection;

    Active intraocular inflammation;
  • Lactation: Lactation.

Use Cautiously in:

  • Rep:  Women of reproductive potential;
  • OB:  Use during pregnancy only if potential maternal benefit justifies fetal risk;
  • Pedi:   Safety and effectiveness only established in preterm infants with retinopathy of prematurity. Safety and effectiveness not established in children <18 yr for all other indications.

Adverse Reactions/Side Effects

CV: MI

EENT: conjunctival hemorrhage, eye pain, blurred vision, cataract, corneal edema, corneal erosion, conjunctival hyperemia, detachment of retinal pigment epithelium, endophthalmitis (from procedure), eyelid edema, foreign body sensation, injection site hemorrhage/pain, intraocular inflammation, ↑ intraocular pressure, ↑ lacrimation, retinal detachment (from procedure), retinal vasculitis (with or without occlusion), vitreous detachment, vitreous floaters

Neuro: STROKE

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

Neovascular (Wet) AMD

Intravitreal (Adults): Ahzantive, Eyelea, Opuviz, and Yesafili: 2 mg every 4 wk for first 3 doses; then 2 mg every 8 wk (some patients may continue to require every 4 wk dosing). After one yr of therapy, may consider dosing every 12 wk.  Eyelea HD: 8 mg every 4 wk for first 3 doses; then 8 mg every 8–16 wk.

Macular Edema Following Central Retinal Vein Occlusion

Intravitreal (Adults): Ahzantive, Eyelea, Opuviz, and Yesafili: 2 mg every 4 wk.

Diabetic Macular Edema

Intravitreal (Adults): Ahzantive, Eyelea, Opuviz, and Yesafili: 2 mg every 4 wk for first 5 injections; then 2 mg every 8 wk (some patients may continue to require every 4 wk dosing).  Eyelea HD: 8 mg every 4 wk for first 3 doses; then 8 mg every 8–16 wk.

Diabetic Retinopathy

Intravitreal (Adults): Ahzantive, Eyelea, Opuviz, and Yesafili: 2 mg every 4 wk for first 5 injections; then 2 mg every 8 wk (some patients may continue to require every 4 wk dosing).  Eyelea HD: 8 mg every 4 wk for first 3 doses; then 8 mg every 8–12 wk.

Retinopathy of Prematurity

Intravitreal (Children [Preterm Infants]): Eyelea: 0.4 mg in affected eye(s). Dose may be repeated after 10 days, if needed.

Availability

Solution for injection (vials and prefilled syringes) (Eyelea): 2 mg/0.05 mL

Solution for injection (vials) (Ahzantive, Opuviz and Yesafili): 2 mg/0.05 mL

Solution for injection (vials) (Eyelea HD): 8 mg/0.07 mL

Assessment

  • Monitor for elevation in intraocular pressure immediately following injection; may occur within 60 min. Check for perfusion of optic nerve head or tonometry.
  • Monitor infants closely after injection until retinal vascularization has completed or until examiner is assured that reactivation of retinopathy of prematurity will not occur. In infants with retinopathy of prematurity, treatment will necessitate extended periods of monitoring, and additional aflibercept injections and/or laser treatments may be necessary.

Implementation

  • Prior to intravitreal injection under controlled aseptic conditions, administer adequate anesthesia and a broad-spectrum topical antimicrobial.
  • Intravitreal 

    Use a 5-micron sterile filter needle (18-gauge × 1½-inch) to withdraw solution from vial; do not use filter needle for injection. Each vial is for single eye use only; discard after using. Use a 1-mL sterile Luer lock syringe with marking to measure 0.05 mL for adults or 0.01 mL for preterm infants with retinopathy of prematurity.

    • Also available in a prefilled syringe. Solution is clear, colorless to pale yellow; do not use solutions that are cloudy, discolored, or contain particulate matter. Do not use if any part of the prefilled syringe is damaged or if syringe cap is detached from Luer lock. Do not use prefilled syringe for retinopathy of prematurity. Use a sterile injection needle (30-gauge × ½-inch) for injection.

Patient/Family Teaching

  • Explain purpose of aflibercept to patient.
  • Advise patient to notify health care professional immediately if signs and symptoms of endophthalmitis or retinal detachment (eye pain, redness of eye, photophobia, blurring of vision) or hypersensitivity reactions (anaphylaxis, rash, pruritus, urticaria, or severe intraocular inflammation) occur.
  • May cause visual disturbances. Caution patient not to drive until visual function has sufficiently recovered.
  • Rep:  Advise females of reproductive potential to use effective contraceptives prior to the initial dose, during treatment, and for at least 3 mo (Eylea) or 4 mo (Eylea HD) following completion of therapy and to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Slowed progression of AMD.
  • Decreased macular edema following central retinal vein occlusion.
  • Improved visual acuity in diabetic macular edema.
  • Decreased severity of diabetic retinopathy.
  • Absence of both active retinopathy of prematurity and unfavorable structural outcomes.