Introduction

Recombinant humanized monoclonal single-chain antibody fragment; a vascular endothelial growth factor A (VEGF-A) antagonist.

Uses for Brolucizumab

Neovascular Age-related Macular Degeneration

Treatment of neovascular (wet) age-related macular degeneration (AMD). When administered every 8 or 12 weeks (depending on clinician assessment of disease activity), brolucizumab-dbll was noninferior to aflibercept administered every 8 weeks in improving visual acuity and preventing further vision loss.

Brolucizumab Dosage and Administration

Administration

Ophthalmic Administration

Administer by intravitreal injection into the affected eye(s). Only qualified clinicians should administer the drug.

Because of the risk of infection and endophthalmitis, always use proper aseptic technique when preparing and administering the drug. (See Endophthalmitis and Other Serious Ocular Effects under Cautions.)

Commercially available in single-use vials containing 6 mg of the drug for intravitreal injection. Prior to administration, allow the vial to come to room temperature. Solution should appear clear to slightly opalescent and colorless to slightly brownish-yellow; do not use if it contains particles or appears cloudy or discolored.

Withdraw entire vial contents through a sterile 5-µm, 18-gauge filter needle (provided by manufacturer) into a 1-mL syringe. Next, replace filter needle with a sterile 30-gauge, ½-inch needle for intravitreal injection. Expel air from the syringe and align plunger tip to the 0.05-mL mark on the syringe. Administer immediately following preparation.

Inject under aseptic conditions (including use of surgical hand disinfection, sterile gloves, sterile drape, sterile eyelid speculum [or equivalent], and availability of sterile paracentesis equipment [if required]) following adequate anesthesia and administration of a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid, and ocular surface.

Each vial is intended for treatment of a single eye only. If the contralateral eye requires treatment, use a new vial; change the sterile field, syringe, gloves, drape, eyelid speculum, and filter and injection needles before administering brolucizumab in the other eye.

Immediately following intravitreal injection, monitor for elevation in IOP via tonometry or by checking for perfusion of the optic nerve head. (See Increased Intraocular Pressure under Cautions.)

Dosage

Adults

Neovascular Age-related Macular Degeneration

Ophthalmic

6 mg (0.05 mL of a solution containing 120 mg/mL) by intravitreal injection into the affected eye(s) once every month (approximately every 25–31 days) for the first 3 doses, followed by 6 mg once every 8–12 weeks.

In pivotal clinical trials, 51–56% of patients received brolucizumab-dbll 6 mg every 12 weeks from the beginning of maintenance treatment through week 48, while 39–45% of patients received this dosing schedule through week 96. Selection of dosing interval (8 or 12 weeks) in these studies was based on clinician assessment of disease activity.

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with hepatic impairment.

Renal Impairment

No dosage adjustment required in patients with renal impairment.

Geriatric Patients

No dosage adjustment required in patients ≥65 years of age.

Contraindications

• Ocular or periocular infection.

• Active intraocular inflammation.

• Known hypersensitivity (e.g., rash, pruritus, urticaria, erythema, severe intraocular inflammation) to brolucizumab or any ingredient in the formulation.

Warnings/Precautions

Endophthalmitis and Other Serious Ocular Effects

Intravitreal injections, including those of brolucizumab, associated with endophthalmitis and retinal detachment. Always use proper aseptic injection technique when administering the drug. (See Ophthalmic Administration under Dosage and Administration.)

Appropriately manage any symptoms suggestive of endophthalmitis or retinal detachment (e.g., eye pain, ocular redness, photophobia, blurred vision). (See Advice to Patients.)

Increased Intraocular Pressure

Acute increases in IOP observed within 30 minutes following intravitreal injections, including those of brolucizumab. Sustained increases in IOP also reported. Monitor IOP and perfusion of optic nerve head and manage appropriately. (See Ophthalmic Administration under Dosage and Administration.)

Arterial Thromboembolic Events

Potential risk of arterial thromboembolic events (e.g., nonfatal stroke, nonfatal MI, vascular death [including deaths from unknown causes]) in patients receiving intravitreal VEGF antagonists. In pivotal phase 3 studies, arterial thromboembolic events reported during 96 weeks of treatment in 4.5 or 4.7% of patients receiving brolucizumab-dbll or aflibercept, respectively.

Immunogenicity

Anti-brolucizumab antibodies detected in pretreatment serum samples in 36–52% of treatment-naive patients; after initiation of brolucizumab-dbll therapy, anti-brolucizumab antibodies detected in ≥1 serum sample in 53–67% of patients. Intraocular inflammation observed in 6% of patients with anti-brolucizumab antibodies detected during therapy. Potential for anti-brolucizumab antibodies to affect efficacy or safety of the drug is unknown.

Specific Populations

Pregnancy

No adequate and well-controlled studies in pregnant women.

Based on mechanism of action, may adversely affect embryofetal development or reproductive capacity. In animal studies, VEGF inhibition caused malformations, embryofetal resorption, and decreased fetal weight and also affected follicular development, corpus luteum function, and fertility.

Use during pregnancy only if potential benefits justify potential risk to fetus. Women of reproductive potential should use highly effective methods of contraception during therapy and for ≥1 month after last dose.

Lactation

Not known whether brolucizumab distributes into human milk, affects the breast-fed infant, or affects milk production.

Breast-feeding is not recommended during brolucizumab therapy and for ≥1 month after last dose.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Approximately 90% of brolucizumab-dbll-treated patients in clinical trials were ≥65 years of age and 60% were ≥75 years of age; no substantial differences in efficacy or safety observed with increasing age.

No dosage adjustment required in patients ≥65 years of age.

Hepatic Impairment

Effect of hepatic impairment on brolucizumab pharmacokinetics is unknown.

No dosage adjustment required in patients with hepatic impairment since intravitreal injection of brolucizumab is not expected to result in clinically important systemic exposure.

Renal Impairment

Mild to moderate renal impairment (GFR 30–70 mL/minute) does not alter systemic pharmacokinetics of brolucizumab-dbll. Effect of severe renal impairment on the drug's pharmacokinetics is unknown.

No dosage adjustment required in patients with renal impairment since intravitreal injection of brolucizumab is not expected to result in clinically important systemic exposure.

Common Adverse Effects

Blurred vision, cataract, conjunctival hemorrhage, eye pain, vitreous floaters.

Administration

Ophthalmic Administration

Administer by intravitreal injection into the affected eye(s). Only qualified clinicians should administer the drug.

Because of the risk of infection and endophthalmitis, always use proper aseptic technique when preparing and administering the drug. (See Endophthalmitis and Other Serious Ocular Effects under Cautions.)

Commercially available in single-use vials containing 6 mg of the drug for intravitreal injection. Prior to administration, allow the vial to come to room temperature. Solution should appear clear to slightly opalescent and colorless to slightly brownish-yellow; do not use if it contains particles or appears cloudy or discolored.

Withdraw entire vial contents through a sterile 5-µm, 18-gauge filter needle (provided by manufacturer) into a 1-mL syringe. Next, replace filter needle with a sterile 30-gauge, ½-inch needle for intravitreal injection. Expel air from the syringe and align plunger tip to the 0.05-mL mark on the syringe. Administer immediately following preparation.

Inject under aseptic conditions (including use of surgical hand disinfection, sterile gloves, sterile drape, sterile eyelid speculum [or equivalent], and availability of sterile paracentesis equipment [if required]) following adequate anesthesia and administration of a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid, and ocular surface.

Each vial is intended for treatment of a single eye only. If the contralateral eye requires treatment, use a new vial; change the sterile field, syringe, gloves, drape, eyelid speculum, and filter and injection needles before administering brolucizumab in the other eye.

Immediately following intravitreal injection, monitor for elevation in IOP via tonometry or by checking for perfusion of the optic nerve head. (See Increased Intraocular Pressure under Cautions.)

Dosage

Adults

Neovascular Age-related Macular Degeneration

Ophthalmic

6 mg (0.05 mL of a solution containing 120 mg/mL) by intravitreal injection into the affected eye(s) once every month (approximately every 25–31 days) for the first 3 doses, followed by 6 mg once every 8–12 weeks.

In pivotal clinical trials, 51–56% of patients received brolucizumab-dbll 6 mg every 12 weeks from the beginning of maintenance treatment through week 48, while 39–45% of patients received this dosing schedule through week 96. Selection of dosing interval (8 or 12 weeks) in these studies was based on clinician assessment of disease activity.

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with hepatic impairment.

Renal Impairment

No dosage adjustment required in patients with renal impairment.

Geriatric Patients

No dosage adjustment required in patients ≥65 years of age.