Introduction
Yesafili (aflibercept) is a recombinant fusion protein specifically designed as a vascular endothelial growth factor (VEGF) inhibitor. It is a biosimilar to Eylea® (aflibercept) and is approved for the treatment of various retinal conditions characterized by abnormal angiogenesis. As an anti-VEGF therapy, Yesafili represents an important therapeutic option in ophthalmology, particularly for managing sight-threatening conditions.
Mechanism of Action
Yesafili functions as a soluble decoy receptor that binds to VEGF-A, VEGF-B, and placental growth factor (PlGF). By binding these ligands with high affinity, Yesafili prevents their interaction with native VEGF receptors (VEGFR-1 and VEGFR-2) on endothelial cells. This inhibition blocks VEGF-mediated angiogenesis and vascular permeability, thereby reducing pathologic blood vessel growth and edema in retinal diseases. The drug's mechanism specifically targets the underlying pathologic processes in neovascular age-related macular degeneration, diabetic macular edema, and other retinal vascular disorders.
Indications
Yesafili is approved for:
- Neovascular (wet) age-related macular degeneration (AMD)
- Macular edema following retinal vein occlusion (branch RVO or central RVO)
- Diabetic macular edema (DME)
- Diabetic retinopathy in patients with DME
Dosage and Administration
Standard dosing: 2 mg (0.05 mL) by intravitreal injection Administration schedule:- Initial phase: Monthly injections for 3 months
- Maintenance: Every 2 months thereafter
- Some patients may require monthly dosing if needed
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Elderly: No dosage adjustment required
- Must be administered by qualified healthcare professionals
- Proper aseptic technique is mandatory
- Preoperative antiseptic preparation required
- Intraocular pressure monitoring pre- and post-injection
Pharmacokinetics
Absorption: Administered directly into vitreous humor; systemic absorption is minimal Distribution: Primarily confined to the vitreous humor and retina; minimal systemic distribution Metabolism: Expected to undergo proteolytic degradation similar to endogenous proteins Elimination: Systemic elimination half-life is approximately 5-6 days when administered intravitreally Vitreous half-life: Approximately 7 daysContraindications
- Ocular or periocular infections
- Active intraocular inflammation
- Hypersensitivity to aflibercept or any component of the formulation
- Patients with known hypersensitivity to Chinese Hamster Ovary (CHO) cell products
Warnings and Precautions
Endophthalmitis and retinal detachment: Intravitreal injections may cause endophthalmitis, retinal detachment, and intraocular inflammation Intraocular pressure increase: Transient increases in intraocular pressure may occur within 60 minutes of injection Thromboembolic events: Potential risk of arterial thromboembolic events Bilateral treatment: Caution advised when treating both eyes simultaneously Pregnancy: Category C - Use only if potential benefit justifies potential risk to fetus Lactation: Exercise caution when administering to nursing womenDrug Interactions
Formal interaction studies have not been conducted, but potential interactions include:
- Other VEGF inhibitors (increased risk of systemic VEGF suppression)
- Anticoagulants or antiplatelet agents (may increase risk of bleeding complications)
- Other intraocular medications (safety of concomitant administration not established)
Adverse Effects
Most common ocular adverse reactions (≥5%):- Conjunctival hemorrhage (25-77%)
- Eye pain (5-28%)
- Cataract (5-15%)
- Vitreous detachment (5-15%)
- Vitreous floaters (5-15%)
- Intraocular pressure increased (5-15%)
- Endophthalmitis (<1%)
- Retinal detachment (<1%)
- Traumatic cataract (<1%)
- Arterial thromboembolic events (1-2%)
- Hypertension (2-4%)
Monitoring Parameters
Ophthalmic monitoring:- Visual acuity assessment at each visit
- Intraocular pressure monitoring pre- and post-injection
- Fundoscopic examination for retinal changes
- Assessment for signs of ocular infection or inflammation
- Blood pressure monitoring
- Neurological assessment for thromboembolic events
- Monitoring for systemic hypersensitivity reactions
- Optical coherence tomography (OCT) for retinal thickness
- Fluorescein angiography for disease activity
- Visual field testing when indicated
Patient Education
- Report any eye pain, redness, sensitivity to light, or vision changes immediately
- Understand that multiple injections are typically required
- Be aware of potential temporary visual disturbances after injection
- Inform all healthcare providers about Yesafili treatment
- Keep all scheduled follow-up appointments
- Report any systemic symptoms such as headache, weakness, or chest pain
- Understand that driving may be impaired temporarily after the procedure
- Recognize signs of eye infection (increasing redness, pain, or discharge)
References
1. European Medicines Agency. Yesafili product information. 2023 2. Heier JS, et al. Ophthalmology. 2012;119(12):2537-2548 3. Schmidt-Erfurth U, et al. Ophthalmology. 2014;121(1):193-201 4. Korobelnik JF, et al. Br J Ophthalmol. 2017;101(11):1563-1572 5. ClinicalTrials.gov: Biosimilar studies for aflibercept 6. American Academy of Ophthalmology Retina/Vitreous Preferred Practice Patterns. 2022
Note: This monograph is based on current available evidence and may be updated as new clinical data emerges. Always consult current prescribing information and clinical guidelines before making treatment decisions.