Brolucizumab

Registered South African indications:

• Neovascular (wet) age-related macular degeneration (AMD)

Contraindications
South African manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Active or suspected ocular or periocular infections
• Active intraocular inflammation
• Pregnancy
• Breastfeeding

International manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Active or suspected ocular or periocular infections
• Active intraocular inflammation

Cautions
South African manufacturer recommendations

• Women of childbearing potential and for at least one month after last dose of brolucizumab (if not on effective contraception)
• Diabetes mellitus
• Fructose intolerance
• Sucrase-isomaltase insufficiency
• Glucose-galactose malabsorption
• Interval between two brolucizumab doses during maintenance treatment <8 weeks
• May impair ability to drive and operate machinery

International manufacturer recommendations

• Pregnancy
• Breastfeeding
• Women of childbearing potential and for at least one month after last dose of brolucizumab (if not on effective contraception)
• Hepatic impairment
• Female patients
• Japanese ethnicity
• History of intraocular inflammation and/or retinal vascular occlusion (within 12 months prior to the first brolucizumab injection)
• Interval between two brolucizumab doses during maintenance treatment <8 weeks
• Poorly controlled glaucoma
  - Intraocular pressure ≥30mmHg
• Concurrent administration of brolucizumab in both eyes
• Decrease in best-corrected visual acuity (BCVA) of ≥30 letters compared with the last assessment of visual acuity
• Retinal break
• Subretinal haemorrhage involving the centre of the fovea, or, if the size of the haemorrhage is ≥50% of the total lesion area
• Performed or planned intraocular surgery within the previous or next 28 days
• Risk factors associated with the development of a retinal pigment epithelial tear after anti-VEGF therapy for wet AMD
  - Large and/or high pigment epithelial retinal detachment
• Rhegmatogenous retinal detachment or stage 3 or 4 macular holes
• History of stroke, transient ischaemic attacks or myocardial infarction within the last 3 months
• Diabetics with HbA1c >10% or with proliferative diabetic retinopathy
• Diabetics with uncontrolled hypertension
• Coadministration with other vascular endothelial growth factor (VEGF) inhibitors (systemic or ocular)
• May impair ability to drive or operate machinery

Forms avail. in SA and covered in this monograph: inj
Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Neovascular (wet) age-related macular degeneration (AMD) 

• Intravitreal (inj): Initial: 6mg, monthly (every 4 weeks) for 3 consecutive doses; Then: every 12 weeks (3 months)

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Brolucizumab must be administered by a qualified medical practitioner

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Medical practitioner may individualise treatment intervals based on disease activity as assessed by visual acuity and/or anatomical parameters. The treatment interval could be as frequent as every 8 weeks (2 months). The interval between two doses should not be less than every 8 weeks (2 months)

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International manufacturer recommendations

Neovascular (wet) age-related macular degeneration (AMD)

• Intravitreal (inj): Initial: 6mg, monthly (every 4 weeks) for 3 consecutive doses; Then: Individualise treatment intervals based on disease activity as assessed by visual acuity and/or anatomical parameters

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  A disease activity assessment is suggested 16 weeks (4 months) after treatment start

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Without disease activity: Treatment every 12 weeks (3 months) should be considered

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With disease activity: Treatment every 8 weeks (2 months) should be considered

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If visual and anatomical outcomes indicate that there is no benefit from continued treatment, brolucizumab should be discontinued

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Visual impairment due to diabetic macular oedema (DME)

• Intravitreal (inj): Initial: 6mg, every 6 weeks for 5 consecutive doses; Then: Individualise treatment intervals based on disease activity as assessed by visual acuity and/or anatomical parameters

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Without disease activity: Treatment every 12 weeks (3 months) should be considered

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With disease activity: Treatment every 8 weeks (2 months) should be considered

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If visual and anatomical outcomes indicate that there is no benefit from continued treatment, brolucizumab should be discontinued

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Brolucizumab must be administered by a qualified ophthalmologist experienced in intravitreal injections

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See additional prescribing points 

Not established for use in children below 18 years

Pregnancy
South African manufacturer recommendations

• Contraindicated
• Based on the anti-VEGF mechanism of action, brolucizumab must be regarded as potentially teratogenic and embryo/foetotoxic. Therefore, brolucizumab should not be used during pregnancy
• Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) during treatment with brolucizumab and for at least one month after the last dose when stopping treatment with brolucizumab

International manufacturer recommendations

• Caution; positive evidence of risk in animal studies 
• There are no or limited amount of data from the use of brolucizumab in pregnant women. A study in pregnant cynomolgus monkeys did not indicate any harmful effects with respect to reproductive toxicity. Animal studies are insufficient with respect to reproductive toxicity. Although the systemic exposure after ocular administration is very low due to its mechanism of action, there is a potential risk to embryofoetal development. Therefore, brolucizumab should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus
• Women of childbearing potential should use effective contraception during treatment with brolucizumab and for at least one month after the last dose when stopping treatment with brolucizumab

Breastfeeding
South African manufacturer recommendations

• Contraindicated 
• Because of the potential for adverse drug reactions in the breastfed newborn/infant, breastfeeding is not recommended during treatment and for at least one month after the last dose when stopping treatment with brolucizumab

International manufacturer recommendations

• Caution; not recommended
• It is unknown whether brolucizumab is excreted in human milk
• In a reproductive toxicity study, brolucizumab was not detected in the maternal milk or infant serum of cynomolgus monkeys
• A risk to the breastfed newborn/infant cannot be excluded. Brolucizumab is not recommended during breastfeeding and breastfeeding should not be started for at least one month after the last dose when stopping treatment with brolucizumab
• A decision must be made whether to discontinue breastfeeding or to abstain from brolucizumab therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility

South African manufacturer recommendations

• Caution
• Vascular endothelial growth factor (VEGF) inhibition has been shown to affect follicular development, corpus luteum function and fertility. Based on the mechanism of action of brolucizumab, there is a potential risk for female reproduction, and to embryofoetal development

International manufacturer recommendations

• Caution
• No reproductive or fertility studies have been conducted. VEGF inhibition has been shown to affect follicular development, corpus luteum function and fertility. Based on the mechanism of action of VEGF inhibitors, there is a potential risk for female reproduction

Renal Impairment

• No dose adjustment recommended 

Hepatic Impairment
South African manufacturer recommendations

• No dose adjustment recommended 

International manufacturer recommendations

• Caution; no dose adjustment recommended 
• Brolucizumab has not been studied in patients with hepatic impairment

Elderly

• No dose adjustment recommended 

Drugs in Sport

• Permitted - No warnings

Cardiovascular Disorders

• Arterial thromboembolic events
  - Stroke
  - Myocardial infarction

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
  - Urticaria
  - Rash
  - Pruritus
  - Erythema
• Immunogenicity
  - Eye pain
  - Increased discomfort
  - Worsening of eye redness
  - Blurred or decreased vision
  - Increased number of small particles in vision
  - Increased sensitivity to light

Sensory Disorders

• Reduced visual acuity
• Retinal haemorrhage
• Uveitis
• Iritis
• Vitreous detachment
• Retinal tear
• Cataract
  - Traumatic cataract
• Conjunctival haemorrhage
• Vitreous floaters
• Eye pain
• Increased intraocular pressure
• Conjunctivitis
• Retinal pigment epithelial tear
• Blurred vision
• Corneal abrasion
• Punctate keratitis
• Blindness
• Endophthalmitis
• Retinal artery occlusion
• Retinal detachment
• Conjunctival hyperaemia
• Increased lacrimation
• Abnormal sensation in eye
• Detachment of retinal pigment epithelium
• Vitritis
• Anterior chamber inflammation
• Iridocyclitis
• Anterior chamber flare
• Corneal oedema
• Vitreous haemorrhage
• Retinal vascular occlusion
• Retinal vasculitis
• Intraocular inflammation

Others

• Non-ocular haemorrhages

No information available

• Intraocular pressure
  - Tonometry
• Perfusion of the optic nerve head

Additional observations

• Symptoms of endophthalmitis and retinal detachment

Traceability

• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Method of administration

• Brolucizumab is for intravitreal use only
• The solution for injection should be inspected visually prior to administration
• The intravitreal injection procedure should be carried out under aseptic conditions, which includes the use of surgical hand disinfection, sterile gloves, a sterile drape and a sterile eyelid speculum (or equivalent)
• Sterile paracentesis equipment should be available as a precautionary measure
• The patient's medical history for hypersensitivity reactions should be carefully evaluated prior to performing the intravitreal procedure
• Adequate anaesthesia and a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid and ocular surface should be administered prior to the injection
• The injection needle should be inserted 3.5-4.0mm posterior to the limbus into the vitreous cavity, avoiding the horizontal meridian and aiming towards the centre of the globe
• The injection volume of 0.05ml is then delivered slowly. A different scleral site should be used for subsequent injections
• Immediately following the intravitreal injection, patients should be monitored for elevation in intraocular pressure
• Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry. If required, sterile equipment for paracentesis should be available
• Following intravitreal injection patients should be instructed to report any symptoms suggestive of endophthalmitis (e.g. eye pain, redness of the eye, photophobia, blurring of vision) without delay

Vial

• The vial is for single use only. Each vial should only be used for the treatment of a single eye

Brolucizumab is a humanised monoclonal single-chain Fv (scFv) antibody fragment with a molecular weight of ~26 kDa. Increased levels of signalling through the vascular endothelial growth factor A (VEGF-A) pathway are associated with pathological ocular angiogenesis and retinal oedema. Brolucizumab binds with high affinity to VEGF-A isoforms (e.g. VEGF110, VEGF121, and VEGF165), thereby preventing binding of VEGF-A to its receptors VEGFR-1 and VEGFR-2. By inhibiting VEGF-A binding, brolucizumab suppresses endothelial cell proliferation, thereby reducing pathological neovascularization and decreasing vascular permeability.

Injection (per ml) 120mg

• Vsiqq (Novartis) originator