Class: EENT Drugs, Miscellaneous
Chemical Name: Anti-(human vascular endothelial growth factor A) (human-Oryctolagus cuniculus monoclonal ESBA1008 scFv fragment) immunoglobulin
Molecular Formula: C1164H1768N310O372S8
CAS Number: 1531589-13-5
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
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.)
Neovascular Age-related Macular Degeneration
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.
No dosage adjustment required in patients with hepatic impairment.
No dosage adjustment required in patients with renal impairment.
No dosage adjustment required in patients ≥65 years of age.
Cautions for Brolucizumab
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.
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.
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.
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.
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.
Safety and efficacy not established in pediatric patients.
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.
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.
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.
Interactions for Brolucizumab
No formal drug interaction studies to date.
Mean peak serum concentrations of free (unbound to VEGF-A) brolucizumab attained 24 hours following a single 6-mg intravitreal dose.
Following repeated intravitreal doses, serum concentrations were near or below lower limit of assay quantitation at approximately 4 weeks postdose, with no accumulation observed in most patients.
Metabolic pathways not fully characterized; free brolucizumab is expected to undergo metabolism via proteolysis.
Elimination pathways not fully characterized; free brolucizumab is expected to undergo elimination via target-mediated disposition and/or passive renal excretion.
Estimated mean systemic half-life following single intravitreal dose: 4.4 days.
Age (≥50 years) and sex do not alter systemic pharmacokinetics.
Injection, for intravitreal use
2–8°C in the original carton; do not freeze; protect from light. May store unopened vial at 20–25°C for up to 24 hours prior to use.
Binds to the 3 major isoforms of VEGF-A (i.e., VEGF110, VEGF121, VEGF165) and inhibits their biologic activity.
VEGF-A induces neovascularization (angiogenesis) and increases vascular permeability, which appear to play a role in the pathogenesis and progression of neovascular (wet) age-related macular degeneration.
Binding to VEGF-A prevents VEGF-A from binding to VEGF receptors (i.e., VEGFR-1, VEGFR-2), reducing endothelial cell proliferation, neovascularization, and vascular permeability.
Reduces central retinal subfield thickness associated with age-related macular degeneration.
As the smallest functional antibody unit, single-chain antibody fragments (e.g., brolucizumab) offer the potential for delivering a larger molar dose compared with larger molecules and achieving greater ocular tissue penetration, which may provide a longer duration of effect and reduced systemic exposure.
Advice to Patients
Necessity of advising patients about the risk of developing endophthalmitis. Importance of patients informing their ophthalmologist immediately if a change in vision occurs or if the treated eye becomes red, sensitive to light, or painful.
Importance of informing patients that they may experience temporary visual disturbances after an intravitreal injection of brolucizumab and the associated eye examination. Advise patients not to drive or use machinery until visual function has recovered sufficiently.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise women of reproductive potential that they should use a highly effective method of contraception during brolucizumab therapy and for ≥1 month after the last dose. Advise women that breast-feeding is not recommended during brolucizumab therapy and for ≥1 month after the last dose.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Injection, for intravitreal use only
6 mg/0.05 mL
Beovu (available as single-dose vial with filter needle)
AHFS DI Essentials™. © Copyright 2022, Selected Revisions July 20, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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