brolucizumab intravitreal (Rx)

1-10%

Blurred vision (10%)

Cataract (7%)

Conjunctival hemorrhage (6%)

Vitreous floaters (5%)

Eye pain (5%)

Intraocular inflammation (4%)

Intraocular pressure increased (4%)

Retinal hemorrhage (4%)

Vitreous detachment (4%)

Conjunctivitis (3%)

Retinal pigment epithelial tear (3%)

Corneal abrasion (2%)

Hypersensitivity (2%)

Punctate keratitis (1%)

Retinal tear (1%)

Endophthalmitis (1%)

Blindness (1%)

Retinal artery occlusion (1%)

Retinal detachment (1%)

Conjunctival hyperemia (1%)

Lacrimation increased (1%)

Abnormal sensation in eye (1%)

Detachment of retinal pigment epithelium (1%)

Postmarketing Reports

Endophthalmitis and retinal detachment

Retinal vasculitis and/or retinal vascular occlusion

Vitreous hemorrhage

Contraindications

Ocular or periocular infections

Active intraocular inflammation

Hypersensitivity

Cautions

Hypersensitivity reactions may manifest as rash, pruritus, urticaria, erythema, or severe intraocular inflammation

Intravitreal injections are associated with endophthalmitis and retinal detachments; instruct patients to immediately report any symptoms suggestive of endophthalmitis or retinal detachment

Acute increases in intraocular pressure (IOP) have been seen within 30 minutes of intravitreal injection; sustained IOP increases have also been reported; both IOP and perfusion of the optic nerve head must be monitored and managed appropriately

A low rate of arterial thromboembolic events observed during clinical trials following intravitreal use of vascular endothelial growth factor (VEGF) inhibitors

Retinal vasculitis

• Retinal vasculitis and/or retinal vascular occlusion, typically in presence of intraocular inflammation, reported with therapy
• Retinal vasculitis and/or retinal vascular occlusion, typically in presence of intraocular inflammation, are immune-mediated adverse events related to exposure to the drug; this treatment-emergent antibody response may develop following the first intravitreal injection
• The immune-mediated adverse events may occur following first intravitreal injection; discontinue treatment in patients who develop these events
• Patients who experience intraocular inflammation following treatment may be at risk of developing retinal vasculitis and/or retinal vascular occlusion and should be closely monitored; patients should be instructed to report any change in vision without delay

Pregnancy

There are no adequate and well-controlled studies in pregnant women

Based on anti-VEGF mechanism of action, treatment may pose risk to human embryofetal development

Use during pregnancy only if the potential benefit outweighs the potential fetal risk

Animal data

• Intravitreal administration to pregnant monkeys once every 4 weeks in one eye from organogenesis to birth caused fetal loss and a structural abnormality (bilateral absent metatarsal) in offspring at 10-fold the maximum recommended human dose (MRHD) on mg/kg basis
• VEGF inhibition has also been shown to affect follicular development, corpus luteum function, and fertility

Contraception

• Females of reproductive potential should use highly effective contraception (methods that result in <1% pregnancy rates) during treatment and for at least 1 month after the last dose following brolucizumab discontinuation

Infertility

• No studies have been conducted and it is not known whether brolucizumab can affect reproductive capacity
• Based on its anti-VEGF mechanism of action, treatment may pose a risk to reproductive capacity

Lactation

No data are available regarding the presence of brolucizumab in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production/excretion

Because many drugs are transferred in human milk and because of the potential for absorption and adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for at least 1 month after the last dose following discontinuation

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Human VEGF inhibitor; binds to the 3 major VEGF-A isoforms (eg, VEGF110, VEGF121, VEGF165), thereby preventing interaction with receptors VEGFR-1 and VEGFR-2

By inhibiting VEGF-A, brolucizumab suppresses endothelial cell proliferation, neovascularization, and vascular permeability

Absorption

Peak plasma time: 24 hr

Peak plasma level: 49 ng/mL

Metabolism

Not fully characterized; however, free brolucizumab is expected to undergo metabolism via proteolysis

Elimination

Half-life: 4.4 days

Excretion: Not fully characterized; however, free brolucizumab is expected to undergo target-mediated disposition and/or passive renal excretion

Intravitreal Preparation

Before use, unopened glass vial or prefilled syringe may be kept at room temperature (20-25ºC [68-77ºF]) for up to 24 hr

See prescribing information with diagrams for precise steps to aseptically prepare dose

Vial

• After vial is opened, proceed under aseptic conditions
• Inspect visually before administration; discard if particulates, cloudiness, or discoloration are visible
• Kit includes sterile glass vial and filter needle which are for single use only
• Do not use if packaging, vial and/or filter needle are damaged or expired

Prefilled syringe

• Inspect visually before administration; discard if packaging, or prefilled syringe are opened, damaged or expired
• Snap off syringe cap and discard it; do not turn or twist syringe cap
• Aseptically and firmly assemble a 30-gauge x 0.5-inch sterile injection needle (not included) onto syringe
• If there are any air bubbles, gently tap syringe with finger until bubbles rise to the top; carefully remove needle cap by pulling it straight off

Intravitreal Administration

Administer immediately after dose preparation

Intravitreal injection procedure must be carried out under aseptic conditions, which includes surgical hand disinfection, sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent), and availability of sterile paracentesis equipment (if required)

Administer adequate anesthesia and a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid, and ocular surface beforehand

Inject slowly until rubber stopper reaches the end of the syringe to deliver the volume of 0.05 mL; confirm delivery of the full dose by checking that the rubber stopper has reached the end of the syringe barrel

Immediately following the intravitreal injection, monitor for elevated IOP; check for perfusion of the optic nerve head or tonometry; if required, a sterile paracentesis needle should be available

Following injection, instruct patient to report any symptoms suggestive of endophthalmitis or retinal detachment (eg, eye pain, redness of the eye, photophobia, blurring of vision) without delay

Vial is for treatment of a single eye; if contralateral eye requires treatment, a new vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles should be changed before brolucizumab is administered to the other eye

Dispose of unused medicinal product or waste material according to local regulations

Storage

Vial and prefilled syringe

• Refrigerate at 2-8ºC (36-46ºF)
• Unopened glass vial or prefilled syringe may be kept at room temperature (20-25ºC [68-77ºF]) for up to 24 hr
• Do not freeze
• Protect from light