Aflibercept

• Approved Indications:
• Neovascular (wet) age-related macular degeneration (AMD).
• Macular edema following central retinal vein occlusion (CRVO).
• Diabetic macular edema (DME).
• Diabetic retinopathy in patients with DME.
• Macular edema following branch retinal vein occlusion (BRVO).
• Myopic choroidal neovascularization (off-label in some regions).
• Off-label/Clinically Accepted Uses:
• Other retinal vascular diseases associated with neovascularization and macular edema as determined by clinical practice.

• Adults:
• Administered via intravitreal injection directly into the vitreous humor of the eye.
• Typical initial dose: 2 mg (0.05 mL) injected every 4 weeks for the first 3 months.
• Maintenance dosing: every 8 weeks thereafter, based on clinical response.
• For DME and diabetic retinopathy, dosing intervals may vary depending on disease severity and response.
• Pediatrics:
• Safety and efficacy not established.
• Elderly:
• No specific dose adjustment required.
• Renal/Hepatic Impairment:
• No dose adjustment necessary as systemic exposure is minimal.
• Route:
• Intravitreal injection by a trained ophthalmologist under sterile conditions.

Aflibercept is a recombinant fusion protein acting as a soluble decoy receptor that binds to vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PlGF). By sequestering these ligands, aflibercept prevents their interaction with endogenous VEGF receptors on endothelial cells, thereby inhibiting pathological angiogenesis and vascular permeability. This blockade reduces abnormal blood vessel growth and leakage in the retina, improving vision and preventing further damage.

• Absorption: Administered intravitreally; systemic absorption is low but measurable.
• Distribution: Localized primarily within the vitreous cavity; systemic circulation exposure is minimal.
• Metabolism: Catabolized by proteolytic enzymes to small peptides and amino acids.
• Elimination: Clearance from systemic circulation primarily by proteolysis.
• Half-life: Vitreal half-life approximately 5-6 days; systemic half-life approximately 5-6 days.

• Pregnancy: No adequate and well-controlled studies in pregnant women. Animal studies do not indicate direct fetal harm but caution is advised. Use only if potential benefit justifies the risk.
• Lactation: Unknown if excreted in human milk. Use with caution during breastfeeding.

• Anti-vascular endothelial growth factor (anti-VEGF) agent
• VEGF receptor fusion protein

• Known hypersensitivity to aflibercept or any excipients.
• Ocular or periocular infections.
• Active intraocular inflammation.
• Presence of vitreous hemorrhage or media opacity precluding safe injection.

• Risk of endophthalmitis, increased intraocular pressure, retinal detachment, and intraocular inflammation.
• Careful monitoring for signs of infection or inflammation post-injection is essential.
• Use caution in patients with recent thromboembolic events.
• Not recommended for use in patients with severe uncontrolled hypertension.
• Immediate attention required if patient experiences sudden vision loss, eye pain, or redness.

• Common:
• Conjunctival hemorrhage
• Eye pain or discomfort
• Vitreous floaters
• Increased intraocular pressure
• Blurred vision
• Serious/Rare:
• Endophthalmitis (ocular infection)
• Retinal detachment
• Intraocular inflammation
• Thromboembolic events (systemic) in rare cases

• No significant systemic drug interactions reported due to localized administration.
• Concomitant use with other intravitreal drugs requires clinical judgment and monitoring.

• Updated ophthalmology guidelines recommend aflibercept as a first-line agent for wet AMD and DME.
• New dosing regimens allow for extended intervals between injections based on individual response, improving patient compliance.
• No recent changes in FDA labeling; ongoing studies assess expanded indications.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Protect from light; keep in original packaging until use.
• Do not freeze.
• Use immediately upon opening; discard any unused portion.