Brolucizumab

• Neovascular (Wet) Age-Related Macular Degeneration (AMD):
• Approved for the treatment of patients with neovascular (wet) AMD to inhibit abnormal blood vessel growth and leakage under the retina.
• Diabetic Macular Edema (DME):
• Approved for adults with DME to reduce retinal swelling and improve vision.
• Off-label Uses:
• Use in other retinal vascular diseases (e.g., retinal vein occlusion) is not widely established and remains investigational.

• Route: Intravitreal injection into the vitreous humor of the eye.
• Neovascular AMD:
• Initial dosing: 6 mg intravitreal injection every 4 weeks for the first 3 doses.
• Maintenance: Every 8 to 12 weeks thereafter, individualized based on disease activity.
• Diabetic Macular Edema:
• Initial dosing: 6 mg intravitreal injection every 4 weeks for the first 5 doses.
• Maintenance: Every 8 to 12 weeks thereafter, depending on patient response.
• Special Populations:
• No established dose adjustments for elderly or renal/hepatic impairment due to local ocular administration.
• Administration Precautions:
• Must be administered by a qualified ophthalmologist under aseptic conditions.
• Monitor for intraocular inflammation and infection post-injection.

Brolucizumab is a humanized single-chain antibody fragment that binds with high affinity and specificity to all isoforms of vascular endothelial growth factor A (VEGF-A). By inhibiting VEGF-A, it suppresses abnormal blood vessel proliferation and vascular permeability in the retina, reducing edema and preventing vision loss in neovascular AMD and DME. Its small molecular size enables enhanced tissue penetration and prolonged ocular duration of action.

• Absorption: Administered intravitreally; systemic absorption is minimal and transient.
• Distribution: Primarily confined to ocular tissues; low systemic exposure.
• Metabolism: Metabolized via proteolytic enzymes to small peptides and amino acids.
• Elimination: Cleared through ocular clearance pathways; systemic clearance is rapid due to proteolysis.
• Half-life: Intravitreal half-life is approximately 4.4 to 5.1 days.
• Systemic Exposure: Systemic levels are low and typically undetectable beyond 7 days post-injection.

• Pregnancy:
• No formal FDA pregnancy category assigned.
• Animal studies show no direct teratogenic effects, but systemic safety in pregnancy is unknown. Use only if benefits outweigh risks.
• Lactation:
• It is unknown whether brolucizumab is excreted in human milk.
• Caution is advised when administering to breastfeeding women.

• Primary Class: Ophthalmic Anti-VEGF Agent
• Subclass: Humanized Single-Chain Antibody Fragment (Anti-VEGF-A therapy)

• Known hypersensitivity to brolucizumab or any excipients.
• Active ocular or periocular infections.
• Intraocular inflammation at the time of injection.

• Intraocular Inflammation (IOI): Risk of uveitis, iritis, and retinal vasculitis including occlusive vasculitis; may lead to vision loss.
• Endophthalmitis: Potential for severe eye infection; strict aseptic technique required.
• Increased Intraocular Pressure (IOP): Monitor post-injection.
• Hypersensitivity Reactions: Monitor for systemic allergic reactions.
• Patient Monitoring: Careful post-injection monitoring recommended to detect early signs of inflammation or vision changes.
• Avoid Bilateral Same-Day Injections: Due to increased risk of inflammation.

Common:

• Conjunctival hemorrhage
• Eye pain
• Increased intraocular pressure
• Vitreous floaters
• Blurred vision

Serious (Rare):

• Intraocular inflammation (uveitis, iritis)
• Retinal vasculitis, including occlusive retinal vasculitis
• Endophthalmitis
• Retinal artery occlusion
• Hypersensitivity reactions

Onset:

• Most serious ocular events occur within the first few weeks post-injection.

• No known systemic drug-drug interactions due to local administration and minimal systemic absorption.
• Concomitant ocular medications should be used with caution.
• Avoid concurrent intraocular injections of other anti-VEGF agents on the same day.

• Post-marketing safety reports have identified increased cases of retinal vasculitis and retinal vascular occlusion; labeling updated to include boxed warnings and monitoring guidelines.
• FDA and EMA recommend caution and enhanced patient monitoring for signs of IOI.
• Recommended dosing intervals have been individualized based on ongoing clinical assessments per latest ophthalmology guidelines.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Protect from light.
• Do not freeze.
• Maintain sterile conditions until administration.
• Discard any unused portion after opening.