Aflibercept

Registered South African indications:

• Neovascular (wet) age-related macular degeneration
• Macular oedema following central retinal vein occlusion

Contraindications

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

Cautions

• Pregnancy
• Breastfeeding
• Women of childbearing potential
• Renal impairment
• Hepatic impairment
• Elderly >75 years
• Poorly controlled glaucoma
• History of stroke or transient ischaemic attacks or myocardial infarction within the last 6 months
• Concurrent bilateral treatment
• Risk factors for retinal pigment epithelial tears
• Large and/or high pigment epithelial retinal detachment
• Ischaemic central retinal vein occlusion and branch retinal vein occlusion
• Active systemic infections
• Patients with concurrent eye conditions
• Macular hole
• Type 1 diabetes
• Diabetic patients with HbA1c >12%
• Proliferative diabetic retinopathy
• Uncontrolled hypertension
• Non-Asian patients with myopic choroidal neovascularisation
• History of treatment for myopic choroidal neovascularisation
• Extrafoveal lesions
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Neovascular (wet) age-related macular degeneration

• Intravitreal (inj): Initial: 2mg, monthly for 3 consecutive doses; Maintenance: 2mg, every 2 months

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Based on visual and/or anatomic outcomes, treatment interval may be maintained at 2 months or further extended by 2-or 4-weekly increments. If visual and/or anatomic outcomes deteriorate, treatment interval should be shortened to a minimum of 2 months during the first 12 months of treatment  

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Visual impairment due to macular oedema secondary to retinal vein occlusion (branch retinal vein occlusion or central retinal vein occlusion)

• Intravitreal (inj): Initial: 2mg; Maintenance: 2mg, monthly until maximum visual acuity achieved and/or no signs of disease activity

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Dosing interval should not be shorter than 1 month

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Monitoring and treatment schedule should be determined by the treating physician based on the individual patient's response

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Discontinue if visual and anatomic outcomes indicate patient is not benefiting from continued treatment

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Visual impairment due to diabetic macular oedema 

• Intravitreal (inj): Initial: 2mg, monthly for 5 consecutive doses; Maintenance: 2mg, every 2 months

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Monitoring and treatment schedule should be determined by the treating physician based on the individual patient's response

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Discontinue if visual and anatomic outcomes indicate patient is not benefiting from continued treatment

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Visual impairment due to myopic choroidal neovascularisation

• Intravitreal (inj): 2mg

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Additional doses may be administered if visual and/or anatomic outcomes indicated persistent disease. Recurrences should be treated as a new manifestation of the disease

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Schedule for monitoring should be determined by the treating physician

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Dosing interval should not be shorter than 1 month

Not established for use in children

Pregnancy

• Caution
• There is no data on the use of aflibercept in pregnant women. Studies in animals have shown embryo-foetal toxicity
• Women of childbearing potential have to use effective contraception during treatment and for at least 3 months after the last intravitreal injection of aflibercept
• Although systemic exposure after ocular administration is very low, aflibercept should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus

Breastfeeding

• Caution; not recommended
• It is unknown whether aflibercept is excreted in human milk. A risk to the breastfed child cannot be excluded
• Aflibercept is not recommended during breastfeeding. A decision must be made whether to discontinue breastfeeding or to abstain from aflibercept therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility

• Results from animal studies with high systemic exposure indicate that aflibercept can impair male and female fertility. Such effects are not expected after ocular administration with very low systemic exposure

Renal Impairment

• Caution; no information available
  No specific studies in patients with renal impairment have been conducted with aflibercept. Available data do not suggest a need for dose adjustment in these patients

Hepatic Impairment

• Caution; no information available
  No specific studies in patients with hepatic impairment have been conducted with aflibercept. Available data do not suggest a need for dose adjustment in these patients

Elderly

• Caution; no dose adjustment recommended
  There is limited experience with patients >75 years

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Cardiovascular Disorders

• Arterial thromboembolic events
• Stroke
• Myocardial infarction
• Haemorrhage

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
  - Rash
  - Pruritis
  - Urticaria
  - Severe anaphylactic/anaphylactoid reactions

Sensory Disorders

• Reduced visual acuity
• Conjunctival haemorrhage
• Eye pain
• Retinal pigment epithelial tear (wet age-related macular degeneration)
• Detachment of the retinal pigment epithelium
• Retinal degeneration
• Vitreous haemorrhage
• Cataract
• Cortical cataract
• Nuclear cataract
• Subcapsular cataract
• Corneal erosion
• Corneal abrasion
• Increased intraocular pressure  
• Blurred vision
• Vitreous floaters
• Vitreous detachment
• Injection site pain
• Foreign body sensation in eyes
• Increased lacrimation
• Eyelid oedema
• Injection site haemorrhage
• Punctate keratitis
• Conjunctival hyperaemia
• Ocular hyperaemia
• Endophthalmitis (culture positive and culture negative)
• Retinal detachment
• Retinal tear
• Iritis
• Uveitis
• Iridocyclitis
• Lenticular opacities
• Corneal epithelium defect
• Abnormal sensation in eye
• Eyelid irritation
• Anterior chamber flare
• Corneal oedema
• Blindness
• Traumatic cataract
• Vitritis
• Hypopyon

• Other anti-vascular endothelial growth factors (systemic or ocular)
  (see addtional prescribing points)

• Intraocular pressure

Specific cases may require

• Optical coherence tomography
• Fluorescein angiography
• Pregnancy test

Immunogenicity

• As this is a therapeutic protein, there is a potential for immunogenicity with aflibercept
• Patients should be instructed to report any signs or symptoms of intraocular inflammation e.g. pain, photophobia, or redness, which may be a clinical sign attributable to hypersensitivity

Withholding treatment

Treatment should be withheld in:

• Patients with rhegmatogenous retinal detachment
• Patients with stage 3 or 4 macular holes
• The dose should be withheld within the previous or next 28 days in the event of performed or planned intraocular surgery
• Intraocular pressure >30mmHg

The dose should be withheld and treatment should not be resumed earlier than the next scheduled treatment in the event of:

• A decrease in best-corrected visual acuity (BCVA) of >30 letters compared with the last assessment of visual acuity;
• A subretinal haemorrhage involving the centre of the fovea, or if the size of the haemorrhage is >50%, of the total lesion area

Interactions

Adjunctive use of verteporfin photodynamic therapy (PDT) and aflibercept has not been studied, therefore, a safety profile is not established

Aflibercept is a recombinant fusion protein consisting of portions of human Vascular Endothelial Growth Factor (VEGF) receptor 1 and 2 extracellular domains fused to the Fc portion of human IgG1. Aflibercept acts as a soluble decoy receptor that binds VEGF-A and PlGF with higher affinity than their natural receptors, and thereby can inhibit the binding and activation of these cognate VEGF receptors. Vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF) are members of the VEGF family of angiogenic factors that can act as potent mitogenic, chemotactic, and vascular permeability factors for endothelial cells. VEGF acts via two receptor tyrosine kinases; VEGFR-1 and VEGFR-2, present on the surface of endothelial cells. PlGF binds only to VEGFR-1, which is also present on the surface of leucocytes. Excessive activation of these receptors by VEGF-A can result in pathological neovascularisation and excessive vascular permeability. PlGF can synergize with VEGF-A in these processes, and is also known to promote leucocyte infiltration and vascular inflammation.

Injection (per ml) 40mg

• Eylea (Bayer)