Afqlir · 4.1 Therapeutic indications · 1

HOS-100616 · has-adverse-reaction-information · PDF-Seite 37

Summary of the safety profile A total of 3 102 patients constituted the safety population in the eight phase III studies. Among those, 2 501 patients were treated with the recommended dose of 2 mg. Serious ocular adverse reactions in the study eye related to the injection procedure have occurred in less than 1 in 1 900 intravitreal injections with aflibercept and included blindness, endophthalmitis, retinal detachment, cataract traumatic, cataract, vitreous haemorrhage, vitreous detachment, and intraocular pressure increased (see section 4.4). The most frequently observed adverse reactions (in at least 5% of patients treated with aflibercept) were conjunctival haemorrhage (25%), retinal haemorrhage (11%), visual acuity reduced (11%), eye pain (10%), cataract (8%), intraocular pressure increased (8%), vitreous detachment (7%), and vitreous floaters (7%). Tabulated list of adverse reactions The safety data described below include all adverse reactions from the eight phase III studies in the indications wet AMD, CRVO, BRVO, DME and myopic CNV with a reasonable possibility of causality to the injection procedure or medicinal product. The adverse reactions are listed by system organ class and frequency using the following convention: 37 Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. Table 1: All treatment-emergent adverse drug reactions reported in patients in phase III studies (pooled data of the phase III studies for the indications wet AMD, CRVO, BRVO, DME and myopic CNV) or during post-marketing surveillance System Organ Class Frequency Adverse reaction Immune system disorders Uncommon Hypersensitivity*** Eye disorders Very common Visual acuity reduced, Retinal haemorrhage, Conjunctival haemorrhage, Eye pain Common Retinal pigment epithelial tear*, Detachment of the retinal pigment epithelium, Retinal degeneration, Vitreous haemorrhage, Cataract, Cataract cortical,

Auszug; vollständigen Abschnitt im Original lesen.

HOS-100610 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile A total of 3 102 patients constituted the safety population in the eight phase III studies. Among those, 2 501 patients were treated with the recommended dose of 2 mg. Serious ocular adverse reactions in the study eye related to the injection procedure have occurred in less than 1 in 1 900 intravitreal injections with aflibercept and included blindness, endophthalmitis, retinal detachment, cataract traumatic, cataract, vitreous haemorrhage, vitreous detachment, and intraocular pressure increased (see section 4.4). The most frequently observed adverse reactions (in at least 5% of patients treated with aflibercept) were conjunctival haemorrhage (25%), retinal haemorrhage (11%), visual acuity reduced (11%), eye pain (10%), cataract (8%), intraocular pressure increased (8%), vitreous detachment (7%), and vitreous floaters (7%). Tabulated list of adverse reactions The safety data described below include all adverse reactions from the eight phase III studies in the indications wet AMD, CRVO, BRVO, DME and myopic CNV with a reasonable possibility of causality to the injection procedure or medicinal product. The adverse reactions are listed by system organ class and frequency using the following convention: 7 Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. Table 1: All treatment-emergent adverse drug reactions reported in patients in phase III studies (pooled data of the phase III studies for the indications wet AMD, CRVO, BRVO, DME and myopic CNV) or during post-marketing surveillance System Organ Class Frequency Adverse reaction Immune system disorders Uncommon Hypersensitivity*** Eye disorders Very common Visual acuity reduced, Retinal haemorrhage, Conjunctival haemorrhage, Eye pain Common Retinal pigment epithelial tear*, Detachment of the retinal pigment epithelium, Retinal degeneration, Vitreous haemorrhage, Cataract, Cataract cortical,

Auszug; vollständigen Abschnitt im Original lesen.

HOS-100612 · has-contraindication-information · PDF-Seite 35

Hypersensitivity to the active substance aflibercept or to any of the excipients listed in section 6.1. Active or suspected ocular or periocular infection. Active severe intraocular inflammation.

HOS-100606 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance aflibercept or to any of the excipients listed in section 6.1. Active or suspected ocular or periocular infection. Active severe intraocular inflammation.

HOS-100605 · has-indication-information · PDF-Seite 2

Afqlir is indicated for adults for the treatment of • neovascular (wet) age-related macular degeneration (AMD) (see section 5.1), • visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO) (see section 5.1), • visual impairment due to diabetic macular oedema (DME) (see section 5.1), • visual impairment due to myopic choroidal neovascularisation (myopic CNV) (see section 5.1).

HOS-100611 · has-indication-information · PDF-Seite 32

Afqlir is indicated for adults for the treatment of • neovascular (wet) age-related macular degeneration (AMD) (see section 5.1), • visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO) (see section 5.1), • visual impairment due to diabetic macular oedema (DME) (see section 5.1), • visual impairment due to myopic choroidal neovascularisation (myopic CNV) (see section 5.1).

HOS-100608 · has-interaction-information · PDF-Seite 6

No interaction studies have been performed. Adjunctive use of verteporfin photodynamic therapy (PDT) and aflibercept has not been studied, therefore, a safety profile is not established. 6

HOS-100614 · has-interaction-information · PDF-Seite 36

No interaction studies have been performed. Adjunctive use of verteporfin photodynamic therapy (PDT) and aflibercept has not been studied, therefore, a safety profile is not established. 36

HOS-100615 · has-pregnancy-information · PDF-Seite 37

Women of childbearing potential Women of childbearing potential have to use effective contraception during treatment and for at least 3 months after the last intravitreal injection of aflibercept (see section 4.4). Pregnancy There are no data on the use of aflibercept in pregnant women. Studies in animals have shown embryo-foetal toxicity (see section 5.3). Although the systemic exposure after ocular administration is very low, Afqlir should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus. Breast-feeding Based on very limited human data, aflibercept may be excreted in human milk at low levels. Aflibercept is a large protein molecule and the amount of medication absorbed by the infant is expected to be minimal. The effects of aflibercept on a breast-fed newborn/infant are unknown. As a precautionary measure, breast-feeding is not recommended during the use of Afqlir. Fertility Results from animal studies with high systemic exposure indicate that aflibercept can impair male and female fertility (see section 5.3). Such effects are not expected after ocular administration with very low systemic exposure.

HOS-100609 · has-pregnancy-information · PDF-Seite 7

Women of childbearing potential Women of childbearing potential have to use effective contraception during treatment and for at least 3 months after the last intravitreal injection of aflibercept (see section 4.4). Pregnancy There are no data on the use of aflibercept in pregnant women. Studies in animals have shown embryo-foetal toxicity (see section 5.3). Although the systemic exposure after ocular administration is very low, Afqlir should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus. Breast-feeding Based on very limited human data, aflibercept may be excreted in human milk at low levels. Aflibercept is a large protein molecule and the amount of medication absorbed by the infant is expected to be minimal. The effects of aflibercept on a breast-fed newborn/infant are unknown. As a precautionary measure, breast-feeding is not recommended during the use of Afqlir. Fertility Results from animal studies with high systemic exposure indicate that aflibercept can impair male and female fertility (see section 5.3). Such effects are not expected after ocular administration with very low systemic exposure.

HOS-100607 · has-warning-information · PDF-Seite 5

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. Intravitreal injection-related reactions Intravitreal injections, including those with aflibercept have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract (see section 4.8). Proper aseptic injection techniques must always be used when administering Afqlir. In addition, patients should be monitored during the week following the injection to permit early treatment if an infection occurs. Patients should be instructed to report any symptoms suggestive of endophthalmitis or any of the above mentioned events without delay. The pre-filled syringe contains more than the recommended dose of 2 mg aflibercept (equivalent to 0.05 ml). The excess volume must be expelled prior to administration (see sections 4.2 and 6.6). Increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including those with aflibercept (see section 4.8). Special precaution is needed in patients with poorly controlled glaucoma (do not inject Afqlir while the intraocular pressure is ≥ 30 mmHg). In all cases, both the intraocular pressure and the perfusion of the optic nerve head must therefore be monitored and managed appropriately. Immunogenicity As this is a therapeutic protein, there is a potential for immunogenicity with Afqlir (see section 4.8). 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. Systemic effects Systemic adverse events including non-ocular haemorrhages and arterial thromboembolic events have been reported following intravitreal injection of VEGF inhibitors and there is a theoretical risk that these may relate to VEGF inhibition. There are limited data on safety in the treatment of patients with CRVO, BRVO, DME or myopic CNV with a history of stroke or transient ischaemic attacks or myocardial infarction within the last 6 months. Caution should be exercised when treating such patients. Other As with other intravitreal anti-VEGF treatments for AMD, CRVO, BRVO, DME and myopic CNV the following also applies: 5 • The safety and efficacy of aflibercept therapy administered to both eyes

Auszug; vollständigen Abschnitt im Original lesen.

HOS-100613 · has-warning-information · PDF-Seite 35

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. Intravitreal injection-related reactions Intravitreal injections, including those with aflibercept, have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract (see section 4.8). Proper aseptic injection techniques must always be used when administering Afqlir. In addition, patients should be monitored during the week following the injection to permit early treatment if an infection occurs. Patients should be instructed to report any symptoms suggestive of endophthalmitis or any of the above mentioned events without delay. The vial contains more than the recommended dose of 2 mg aflibercept (equivalent to 0.05 ml). The excess volume must be discarded prior to administration (see sections 4.2 and 6.6). Increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including those with aflibercept (see section 4.8). Special precaution is needed in patients with poorly controlled glaucoma (do not inject Afqlir while the intraocular pressure is ≥ 30 mmHg). In all cases, both the intraocular pressure and the perfusion of the optic nerve head must therefore be monitored and managed appropriately. Immunogenicity As this is a therapeutic protein, there is a potential for immunogenicity with Afqlir (see section 4.8). 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. Systemic effects Systemic adverse events including non-ocular haemorrhages and arterial thromboembolic events have been reported following intravitreal injection of VEGF inhibitors and there is a theoretical risk that these may relate to VEGF inhibition. There are limited data on safety in the treatment of patients with CRVO, BRVO, DME or myopic CNV with a history of stroke or transient ischaemic attacks or myocardial infarction within the last 6 months. Caution should be exercised when treating such patients. Other As with other intravitreal anti-VEGF treatments for AMD, CRVO, BRVO, DME and myopic CNV the following also applies: 35 • The safety and efficacy of aflibercept therapy administered to both eyes concurrent

Auszug; vollständigen Abschnitt im Original lesen.