Usage
- Aflibercept is prescribed for the treatment of neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy (DR), and retinopathy of prematurity (ROP).
- Pharmacological Classification: Vascular endothelial growth factor (VEGF) inhibitor; anti-angiogenic agent.
- Mechanism of Action: Aflibercept binds to and inhibits the activity of vascular endothelial growth factors (VEGF-A and VEGF-B, as well as placental growth factor, PlGF), thereby reducing neovascularization and vascular permeability in the retina.
Alternate Names
- International Nonproprietary Name (INN): Aflibercept
- Brand names: Eylea, Eylea HD, Ziv-aflibercept, Opuviz, Yesafili, Pavblu, Ahzantive, Enzeevu.
How It Works
- Pharmacodynamics: Aflibercept binds with greater affinity to VEGF than naturally occurring VEGF receptors, effectively neutralizing VEGF activity and suppressing neovascularization and vascular leakage in retinal diseases.
- Pharmacokinetics: Aflibercept is administered via intravitreal injection. Systemic absorption is minimal. The vitreous humor acts as the primary compartment for distribution, metabolism, and elimination of the drug. Elimination occurs by proteolytic degradation. The half-life in the vitreous humor is approximately 2 weeks.
- Mode of Action: Aflibercept is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 fused to the Fc portion of human IgG1. It acts as a decoy receptor, binding to VEGF-A, VEGF-B, and PlGF with high affinity, preventing their interaction with endogenous receptors and thus inhibiting angiogenesis.
- Receptor Binding: Aflibercept binds to VEGF-A, VEGF-B, and PlGF, acting as a soluble decoy receptor.
- Elimination Pathways: Primarily eliminated by proteolytic degradation within the vitreous humor, with minimal systemic involvement.
Dosage
Standard Dosage
Adults:
- Wet AMD, DME, DR: 2 mg (0.05 mL of 40 mg/mL solution) intravitreally every 4 weeks for the initial 3 months (AMD) or 5 months (DME/DR), followed by 2 mg every 8 weeks.
- Macular edema following RVO: 2 mg (0.05 mL of 40 mg/mL solution) intravitreally every 4 weeks.
- ROP: In preterm infants weighing less than 1250 g or less than or equal to 30 weeks gestational age with ROP in Zone I, stage 1+, stage 2+, or stage 3+, and ROP in Zone II, stage 3+, the recommended dose is 0.4 mg in 0.01 mL.
Children:
- ROP: See above
- Other indications: The safety and efficacy of aflibercept have not been established in other pediatric populations.
Special Cases:
- Elderly Patients: No dosage adjustment is generally required.
- Patients with Renal Impairment: No dosage adjustment is generally required.
- Patients with Hepatic Dysfunction: No dosage adjustment is generally required.
- Patients with Comorbid Conditions: Dosage adjustments are not typically needed, but caution is advised in patients with active systemic infections, uncontrolled high blood pressure, and other concurrent eye conditions.
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: Aflibercept is not indicated for use in these situations.
Dosage Adjustments:
- No specific dosage adjustments are routinely needed for renal/hepatic impairment, metabolic disorders, or genetic polymorphisms.
Side Effects
Common Side Effects:
- Conjunctival hemorrhage
- Eye pain
- Reduced visual acuity
- Increased intraocular pressure
- Vitreous floaters
- Blurred vision
Rare but Serious Side Effects:
- Endophthalmitis
- Retinal detachment
- Retinal tear
- Retinal pigment epithelial tear
- Severe allergic reactions (including rash, itching, hives, difficulty breathing or swallowing).
- Increased risk of arterial thromboembolic events such as stroke or myocardial infarction has been reported with systemic anti-VEGF agents and is theoretically possible with intravitreal aflibercept.
Long-Term Effects:
- The long-term safety profile of aflibercept is still under investigation, but cataract formation is a potential concern.
Adverse Drug Reactions (ADR):
- Endophthalmitis, retinal detachment, and severe allergic reactions require immediate intervention.
Contraindications:
- Ocular or periocular infections.
- Active intraocular inflammation.
- Known hypersensitivity to aflibercept or any of its excipients.
Drug Interactions:
- No clinically significant drug interactions have been identified.
Pregnancy and Breastfeeding:
- Pregnancy Safety Category: C (FDA classification) or D (Australian TGA classification)
- Fetal Risks: Aflibercept can cause fetal harm. Animal studies have shown embryo-fetal toxicity, including malformations. Use during pregnancy only if the potential benefit outweighs the risk. Women of childbearing potential should use effective contraception during treatment and for at least 3 months after the last injection.
- Breastfeeding: It is unknown if aflibercept is excreted in human milk. Due to the potential for serious adverse reactions in the breastfed infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: VEGF inhibitor, suppressing angiogenesis and vascular permeability.
- Side Effects: Common: Conjunctival hemorrhage, eye pain, decreased visual acuity. Serious: Endophthalmitis, retinal detachment.
- Contraindications: Ocular/periocular infections, active intraocular inflammation, hypersensitivity.
- Drug Interactions: None known.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: 2 mg intravitreally; initial dosing varies by condition.
- Monitoring Parameters: Visual acuity, intraocular pressure, signs of infection or inflammation.
Popular Combinations
- Aflibercept is typically used as monotherapy. There are currently no established combination therapies involving intravitreal aflibercept for the approved indications.
Precautions
- General Precautions: Ensure aseptic technique during administration. Monitor for signs of endophthalmitis and retinal detachment. Evaluate for risk factors for retinal pigment epithelial tears.
- Specific Populations:
- Pregnant Women: Avoid use unless potential benefit outweighs risk. Effective contraception is essential.
- Breastfeeding Mothers: Not recommended.
- Children & Elderly: No specific dosage adjustments. Monitor closely for adverse effects.
- Lifestyle Considerations: Transient visual disturbances may occur after injection; patients should avoid driving or operating machinery until vision clears.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aflibercept?
A: The standard dosage is 2 mg (0.05 mL) administered via intravitreal injection. The initial dosing frequency varies depending on the specific condition being treated (every 4 weeks initially for wet AMD, DME, and DR; every 4 weeks for macular edema following RVO). After the initial phase, injections are typically given every 8 weeks.
Q2: What are the most common side effects of Aflibercept?
A: The most common side effects include conjunctival hemorrhage, eye pain, decreased visual acuity, increased intraocular pressure, and vitreous floaters.
Q3: What are the serious side effects of Aflibercept?
A: Rare but serious side effects include endophthalmitis, retinal detachment, retinal tear, and severe allergic reactions.
Q4: Is Aflibercept safe to use during pregnancy?
A: Aflibercept is not recommended during pregnancy. It is Pregnancy Safety Category C (US FDA) or D (Australian TGA). There is a risk of fetal harm.
Q5: Can Aflibercept be used during breastfeeding?
A: Aflibercept is not recommended during breastfeeding. It is unknown if it is excreted in human milk.
Q6: Are there any drug interactions with Aflibercept?
A: No clinically significant drug interactions have been reported.
Q7: How is Aflibercept administered?
A: Aflibercept is administered as an intravitreal injection by a qualified ophthalmologist.
Q8: How long does Aflibercept last in the eye?
A: The half-life of aflibercept in the vitreous humor is approximately 2 weeks. However, the therapeutic effect can last longer, which is why injections are typically given every 8 weeks after the initial treatment phase.
Q9: What should patients be instructed to do after receiving an Aflibercept injection?
A: Patients should be monitored for elevation in intraocular pressure immediately after the injection. They should also be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment, such as eye pain, redness, photophobia, or blurred vision, without delay.
Q10: What are the contraindications to Aflibercept?
A: Aflibercept is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or any of its excipients.
