Health Canada has issued new safety information concerning Novartis Pharmaceuticals Canada’s Beovu (brolucizumab) and an increased incidence of intraocular inflammation, including retinal vasculitis and retinal vascular occlusion, which was observed in patients receiving Beovu 6 mg every 4 weeks beyond the first 3 doses. These events were seen in patients who developed anti-brolucizumab antibodies during treatment. Health care providers are advised of the following:
Treatment with Beovu is contraindicated in patients with active intraocular inflammation.
Patients should not be treated with Beovu 6 mg at intervals less than 8 weeks beyond the first 3 doses.
Treatment with Beovu should be discontinued in patients who develop retinal vasculitis and/or retinal vascular occlusion.
Intraocular inflammation–related adverse events were reported more frequently in female patients.
Patients with a history of intraocular inflammation and/or retinal vascular occlusion in the year prior to treatment with Beovu are at increased risk and should be closely monitored.
Health Canada is working with Novartis Pharmaceuticals Canada to update the Beovu prescribing information to reflect the most recent evidence and the new recommendations.
Further information may be found at https://recalls-rappels.canada.ca/en/alert-recall/beovu-brolucizumab-risk-intraocular-inflammation-retinal-vasculitis-andor-retinal.
Age-related macular degeneration, wet (neovascular): Intravitreal: 6 mg once per month (approximately every 25 to 31 days) for 3 months, followed by 6 mg once every 8 to 12 weeks.
Diabetic macular edema: Intravitreal: 6 mg every 6 weeks (approximately every 39 to 45 days) for 5 doses, followed by 6 mg once every 8 to 12 weeks.
No dosage adjustment necessary.
No dosage adjustment necessary.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravitreal [preservative free]:
Beovu: Brolucizumab-dbll 6 mg/0.05 mL (0.05 mL) [contains polysorbate 80]
Solution Prefilled Syringe, Intravitreal:
Beovu: Brolucizumab-dbll 6 mg/0.05 mL (0.05 mL) [contains polysorbate 80]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Prefilled Syringe, Intravitreal:
Beovu: 6 mg/0.05 mL (0.05 mL) [contains polysorbate 80]
Intravitreal: For ophthalmic intravitreal injection only. Each prefilled syringe or vial should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new prefilled syringe or 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. Adequate anesthesia and a topical broad-spectrum antimicrobial agent should be administered prior to the procedure. Refer to manufacturer's labeling for additional detailed information.
Age-related macular degeneration, wet (neovascular): Treatment of neovascular (wet) age-related macular degeneration.
Diabetic macular edema: Treatment of diabetic macular edema.
Brolucizumab may be confused with bevacizumab
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Immunologic: Antibody development (53% to 67%)
1% to 10%:
Cardiovascular: Arterial thromboembolism (5%)
Hypersensitivity: Hypersensitivity reaction (2%)
Ophthalmic: Abnormal sensation in eyes (1%), blindness (1%), blurred vision (10%), cataract (7%), conjunctival hemorrhage (6%), conjunctival hyperemia (1%), conjunctivitis (3%), corneal abrasion (2%), endophthalmitis (1%), eye pain (5%), increased intraocular pressure (4%), increased lacrimation (1%), intraocular inflammation (4% to 6%, including retinal vasculitis), punctate keratitis (1%), retinal artery occlusion (1%), retinal detachment (1%), retinal hemorrhage (4%), retinal hole without detachment (1%), retinal pigment epithelium detachment (1%), retinal pigment epithelium tear (3%), vitreous detachment (4%), vitreous opacity (5%)
Postmarketing: Ophthalmic: Retinal vein occlusion
Hypersensitivity (eg, rash, pruritus, urticaria, erythema, severe intraocular inflammation) to brolucizumab or any component of the formulation; ocular or periocular infections; active intraocular inflammation.
Concerns related to adverse effects:
• Endophthalmitis and retinal detachment: Intravitreal injections may be associated with endophthalmitis and retinal detachment. Use proper aseptic injection technique. Monitor for and report symptoms (eg, eye pain, redness of the eye, photophobia, blurred vision) immediately.
• Increased intraocular pressure: Acute (within 30 minutes) and sustained increases in increased intraocular pressure (IOP) have occurred. Monitor IOP (via tonometry) and optic nerve head perfusion immediately following administration and manage appropriately.
• Retinal vasculitis/retinal vascular occlusion: Cases of retinal vasculitis and/or retinal vascular occlusion have been reported, usually associated with intraocular inflammation, and are attributed to an immune-mediated adverse event; may occur with the first intravitreal injection. Discontinue therapy if signs and symptoms occur.
• Thromboembolic events: Risk of arterial thromboembolic events (eg, nonfatal stroke, nonfatal myocardial infarction, vascular death) may be increased with intravitreal use of vascular endothelial growth factor inhibitors.
None known.
There are no known significant interactions.
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use highly effective contraception (methods with pregnancy rates <1%) during therapy and for ≥1 month following the last brolucizumab dose.
Brolucizumab is a vascular endothelial growth factor (VEGF) inhibitor; VEGF is required to achieve and maintain normal pregnancies (Peracha 2016). Based on findings in animal reproduction studies and on the mechanism of action, brolucizumab may cause fetal harm if administered to a pregnant female.
It is not known if brolucizumab is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for ≥1 month following the last brolucizumab dose.
Intraocular pressure (via tonometry) and optic nerve head perfusion immediately following administration; symptoms of endophthalmitis and retinal detachment; symptoms of retinal vasculitis and retinal vascular occlusion (especially in patients with intraocular inflammation), vision changes.
Brolucizumab is a recombinant humanized monoclonal antibody vascular endothelial growth factor (VEGF) inhibitor that binds to the 3 major isoforms of VEGF-A, thereby suppressing endothelial cell proliferation, neovascularization, and vascular permeability to slow vision loss.
Metabolism: Not fully characterized; free brolucizumab is expected to undergo proteolysis.
Half-life elimination: 4.4 ± 2 days.
Time to peak: Serum: 24 hours (free brolucizumab).
Solution (Beovu Intravitreal)
6 mg/0.05 mL (per 0.05 mL): $2,220.00
Solution Prefilled Syringe (Beovu Intravitreal)
6 mg/0.05 mL (per 0.05 mL): $2,220.00
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