.png?width=200&height=94&name=PDR_stacked_purple%20(002).png)
BEOVU
Classes
Wet AMD Treatment Agents
Administration
Must be administered by a qualified physician.
Adequate anesthesia and broad-spectrum topical microbicides to disinfect the periocular skin, eyelid, and ocular surface should be administered prior to the intravitreal injection.
Visually inspect parenteral products for particulate matter and discoloration prior to administration. The solution is clear to slightly opalescent and colorless to slightly brownish-yellow. Do not administer solution if particulates, cloudiness, or discoloration are visible. Do not use if the packaging, pre-filled syringe, vial, or filter needle are opened, damaged, or expired.
Product Preparation
The product is available as a pre-filled syringe and a vial kit (i.e., single-use glass vial and filter needle).
Before use, allow the unopened glass vial or sealed blister pack to come to room temperature. The unopened product may be kept at room temperature, between 20 and 25 degrees C (68 to 77 degrees F), for up to 24 hours.
After opening, the dose must be prepared under aseptic conditions.
Preparation of the pre-filled syringe:
Peel the lid off the blister package and, using aseptic technique, remove the sterile syringe.
Snap off the syringe cap and dispose of it. DO NOT turn or twist the syringe cap.
Aseptically and firmly assemble a 30-gauge x 0.5 inch sterile injection needle (not included) onto the Luer lock syringe.
Hold the syringe with the needle pointing up to check for air bubbles. If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top.
Carefully remove the needle cap by pulling it straight off.
Hold the syringe at eye level and carefully push the plunger until the edge below the dome of the rubber stopper is aligned with the 0.05 mL dose mark. This will expel the air and excess liquid.
Preparation of the vial kit:
Gather the needle supplies: one brolucizumab vial (included), one sterile 5-micron blunt filter needle (included), one sterile 30-gauge x 0.5 inch injection needle (not included), one sterile 1 mL syringe with a 0.05 mL dose mark (not included), alcohol swab (not included).
Remove the vial cap and clean the vial septum with an alcohol swab.
Attach the 5-micron filter needle (18-gauge by 1.5 inches) onto a 1-mL syringe using aseptic technique.
Push the filter needle into the center of the vial septum until the needle touches the bottom of the vial.
To withdraw the liquid, hold the vial slightly inclined and slowly withdraw all the liquid from the vial and filter needle. Ensure that the plunger rod is drawn sufficiently back when emptying the vial in order to completely empty the filter needle.
Disconnect the filter needle from the syringe and dispose of it. The filter needle MUST NOT be used for the intravitreal injection.
Aseptically and firmly attach a 30-gauge by 0.5 inch injection needle onto the syringe.
Check for air bubbles by holding the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top.
Carefully expel the air from the syringe and adjust the dose to the 0.05 mL mark.
Intravitreal Administration
Ensure the injection is administered immediately after preparation of the dose.
The intravitreal injection procedure must be carried out under aseptic conditions, which includes use of surgical hand disinfection, sterile gloves, a sterile drape, and sterile eyelid speculum (or equivalent). Also, ensure the availability of sterile paracentesis equipment (if required).
Adequate anesthesia and a broad-spectrum, topical microbicide to disinfect the periocular skin, eyelid, and ocular surface should be administered prior to the injection.
Slowly inject the dose until the rubber stopper reaches the end of the syringe to deliver the 0.05 mL volume. 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 elevation of intraocular pressure. Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry.
Instruct patients to urgently report any symptoms suggestive of endophthalmitis or retinal detachment (e.g., ocular pain, redness of the eye, photophobia, blurred vision).
Each vial or pre-filled syringe should only be used for treatment of a single eye. If the contralateral eye requires treatment, a new vial or pre-filled syringe should be used, and the sterile field, gloves, drapes, eyelid speculum, syringe, and filter and injection needles should be changed.
Adverse Reactions
visual impairment / Early / 1.0-10.0
ocular hemorrhage / Delayed / 6.0-6.0
thromboembolism / Delayed / 0-4.5
retinal hemorrhage / Delayed / 4.0-4.0
ocular hypertension / Delayed / 2.0-4.0
corneal erosion / Delayed / 1.0-2.0
keratitis / Delayed / 1.0-1.0
retinal detachment / Delayed / 1.0-1.0
endophthalmitis / Delayed / 0-1.0
stroke / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
uveitis / Delayed / Incidence not known
blurred vision / Early / 2.0-10.0
cataracts / Delayed / 4.0-7.0
ocular inflammation / Early / 3.0-4.0
conjunctivitis / Delayed / 2.0-3.0
conjunctival hyperemia / Early / 0-1.0
ocular infection / Delayed / Incidence not known
iritis / Delayed / Incidence not known
erythema / Early / Incidence not known
antibody formation / Delayed / Incidence not known
ocular pain / Early / 3.0-5.0
foreign body sensation / Rapid / 0-1.0
lacrimation / Early / 0-1.0
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
Common Brand Names
BEOVU
Dea Class
Rx
Description
Vascular endothelial growth factor (VEGF) inhibitor
Approved for the treatment of neovascular (wet) age-related macular degeneration and diabetic macular edema (DME)
Contraindicated for use in patients with ocular or periocular infections and in patients with active intraocular inflammation
Dosage And Indications
6 mg (0.05 mL) via intravitreal injection into the affected eye(s) once monthly (approximately every 25 to 31 days) for the first 3 doses. Then give 6 mg (0.05 mL) intravitreally every 8 to 12 weeks.
6 mg (0.05 mL) via intravitreal injection into the affected eye(s) once every 6 weeks (approximately every 39 to 45 days) for the first 5 doses. Then give 6 mg (0.05 mL) intravitreally every 8 to 12 weeks.
Dosing Considerations
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
There are no drug interactions associated with Brolucizumab products.
How Supplied
BEOVU Intravitreal Inj Sol: 0.05mL, 6mg
Maximum Dosage
6 mg per eye intravitreally.
6 mg per eye intravitreally.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Mechanism Of Action
Brolucizumab is a recombinant humanized monoclonal single-chain Fv (scFv) antibody fragment. The drug binds to and blocks the 3 major isoforms of vascular endothelial growth factor-A (e.g., VEGF110, VEGF121, and VEGF165). VEGF-A is a member of the VEGF family of angiogenic factors that act as mitogenic, chemotactic, and vascular permeability factors for endothelial cells. VEGF-A interacts with 2 receptors, VEGFR-1 and VEGFR-2, on the surface of endothelial cells. Activation of VEGFR-1 and VEGFR-2 can result in neovascularization and vascular permeability. By blocking VEGF-A, brolucizumab suppresses endothelial cell proliferation, neovascularization, and vascular permeability.
Pharmacokinetics
Brolucizumab is administered via intravitreal injection.
The pharmacokinetics of brolucizumab have not been fully characterized; however, systemically circulating drug is expected to undergo metabolism via proteolysis. Excretion is thought to occur by target-mediated disposition and passive renal excretion. The estimated mean systemic half-life of a single intravitreal dose is 4.4 days (+/- 2 days).
Affected cytochrome P450 isoenzymes and transporters: none
Intravitreal Route
Administration of a single 6 mg intravitreal dose to 25 patients resulted in a mean maximum plasma concentration (Cmax) of free brolucizumab that was 49 ng/mL (range: 9 to 548 ng/mL); the time to reach peak concentration (i.e., Tmax) was 24 hours post-dose. Brolucizumab systemic concentrations were near or less than 0.5 ng/mL (lower limit of assay quantitation) at approximately 4 weeks after repeated dose administration. Drug accumulation was not observed in most patients.
Pregnancy And Lactation
There are no adequate and well-controlled studies regarding the use of brolucizumab during human pregnancy. In an animal reproduction study, intravitreal administration of brolucizumab 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 a mg/kg basis. Brolucizumab is a vascular endothelial growth factor (VEGF) inhibitor. In animal studies, VEGF inhibition has been shown to cause malformations, embryo-fetal resorption, and decreased fetal weight. Based on the anti-VEGF mechanism of action, treatment with brolucizumab may pose a risk to human embryo-fetal development. The drug should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.
The manufacturer recommends against breast-feeding during brolucizumab treatment and for at least 1 month after the last dose. It is unknown whether brolucizumab is excreted in human milk, affects milk production, or has an adverse effect on the breastfed infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.