Safety Information¹

Cataract formation

In the 3-year DME clinical studies, at baseline, 87% of patients with a phakic study eye treated with OZURDEX® had some degree of lens
opacification/early cataract.

The incidence of all observed cataract types (i.e. cataract cortical, cataract diabetic, cataract nuclear, cataract subcapsular, cataract lenticular, cataract) was 68% in OZURDEX® treated patients with a phakic study eye across the 3-year studies.
59% of patients with a phakic study eye required cataract surgery by the 3-year final visit, with the majority performed in the second and third years.

IOP management

The rise in IOP is normally manageable with IOP lowering medication. Of the patients experiencing an increase of IOP of ≥10 mmHg from baseline, the greatest proportion showed this IOP increase between 45 and 60 days following an injection.

Regular monitoring of IOP, irrespective of baseline IOP, is required and any elevation should be managed appropriately post-injection as needed. Patients of less than 45 years of age with ME following RVO or inflammation of the posterior segment of the eye presenting as non-infectious uveitis are more likely to experience increases in IOP.

Ocular infection

Corticosteroids should be used cautiously in patients with a history of ocular viral (e.g. herpes simplex) infection and not be used in active ocular herpes simplex.

OZURDEX® is contraindicated in patients with active or suspected ocular or periocular infection, including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.

Visual disturbance

If a patient presents with symptoms such as blurred vision or other visual disturbances, consider evaluating for possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Contraindications:

• Hypersensitivity to the active substance or to any of the excipients
• Active or suspected ocular or periocular infection
• Advanced glaucoma which cannot be adequately controlled by medicinal products alone
• Aphakic eyes with ruptured posterior lens capsule
• Eyes with Anterior Chamber Intraocular Lens (ACIOL), iris or transscleral fixated intraocular lens and ruptured posterior lens capsule

Abbreviated safety summary* May 2023

OZURDEX^®- Intravitreal implant in applicator. Contains 700 micrograms of dexamethasone

Indication and usage OZURDEX is indicated for the treatment of adult patients with: • diabetic macular oedema (DME) • macular oedema following either Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO) • inflammation of the posterior segment of the eye presenting as non-infectious uveitis
Posology and method of administration: OZURDEX must be administered by a qualified ophthalmologist experienced in intravitreal injections. Posology The recommended dose is one OZURDEX implant to be administered intra-vitreally to the affected eye. Administration to both eyes concurrently is not recommended (see section 4.4). DME Patients treated with OZURDEX who have experienced an initial response and in the physician’s opinion may benefit from retreatment without being exposed to significant risk should be considered for retreatment. Retreatment may be performed after approximately 6 months if the patient experiences decreased vision and/or an increase in retinal thickness, secondary to recurrent or worsening diabetic macular oedema. There is currently no experience of the efficacy or safety of repeat administrations in DME beyond 7 implants. RVO and uveitis Repeat doses should be considered when a patient experiences a response to treatment followed subsequently by a loss in visual acuity and in the physician’s opinion may benefit from retreatment without being exposed to significant risk. Patients who experience and retain improved vision should not be retreated. Patients who experience deterioration in vision, which is not slowed by OZURDEX, should not be retreated. Patients should be monitored following the injection to permit early treatment if an infection or increased intraocular pressure occurs. Special populations: Elderly (≥65 years old) No dose adjustment is required for elderly patients. Renal impairment OZURDEX has not been studied in patients with renal impairment however no special considerations are needed in this population. Hepatic impairment OZURDEX has not been studied in patients with hepatic impairment; however, no special considerations are needed in this population. The safety and efficacy of OZURDEX in uveitis in the paediatric population have not been established. No data are available

Method of administration: OZURDEX is a single-use intravitreal implant in applicator for intravitreal use only. Each applicator can only be used for the treatment of a single eye. The intravitreal injection procedure should be carried out under controlled aseptic conditions.

The patient should be instructed to self-administer broad spectrum antimicrobial drops daily for 3 days before and after each injection. Before the injection, the periocular skin, eyelid and ocular surface should be disinfected and adequate local anaesthesia should be administered. Immediately after injecting OZURDEX, use indirect ophthalmoscopy in the quadrant of injection to confirm successful implantation. Visualization is possible in the large majority of cases. In cases in which the implant cannot be visualized, take a sterile cotton bud and lightly depress over the injection site to bring the implant into view. Following the intravitreal injection patients should continue to be treated with a broad spectrum antimicrobial.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. • Active or suspected ocular or periocular infection including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases. • Advanced glaucoma which cannot be adequately controlled by medicinal products alone. • Aphakic eyes with ruptured posterior lens capsule. • Eyes with Anterior Chamber Intraocular Lens (ACIOL), iris or transscleral fixated intraocular lens and ruptured posterior lens capsule.

Warnings and precautions: Intravitreous injections, including those with OZURDEX, can be associated with endophthalmitis, intraocular inflammation, increased intraocular pressure and retinal detachment. Proper aseptic injection techniques must always be used. In addition, patients should be monitored following the injection to permit early treatment if an infection or increased intraocular pressure occurs. Monitoring may consist of a check for perfusion of the optic nerve head immediately after the injection, tonometry within 30 minutes following the injection, and biomicroscopy between two and seven days following the injection. Patients must be instructed to report any symptoms suggestive of endophthalmitis or any of the abovementioned events without delay e.g. eye pain, blurred vision etc.

All patients with posterior capsule tear, such as those with a posterior lens (e.g. due to cataract surgery), and/or those who have an iris opening to the vitreous cavity (e.g. due to iridectomy) with or without a history of vitrectomy, are at risk of implant migration into the anterior chamber. Implant migration to the anterior chamber may lead to corneal oedema. Persistent severe corneal oedema could progress to the need for corneal transplantation. Patients should be closely monitored to allow for early diagnosis and management of device migration. Use of

Corticosteroides, may induce cataracts (including posterior subcapsular cataracts), increased IOP, steroid induced glaucoma and may result in secondary ocular infections. The prevalence of conjunctival haemorrhage in patients with non-infectious uveitis of the posterior segment appears to be higher compared with BRVO/CRVO and DME. No treatment is required since spontaneous resolution occurs. As expected with ocular steroid treatment and intravitreal injections, increases in intraocular pressure (IOP) may be seen. The rise in IOP is normally manageable with IOP lowering medication. Of the patients experiencing an increase of IOP of ≥10 mmHg from baseline, the greatest proportion showed this IOP increase between 45 and 60 days following an injection. Therefore, regular monitoring of IOP, irrespective of baseline IOP, is required and any elevation should be managed appropriately post-injection as needed. Corticosteroids should be used cautiously in patients with a history of ocular viral (e.g. herpes simplex) infection and not be used in active ocular herpes simplex. The safety and efficacy of OZURDEX administered to both eyes concurrently have not been studied. Therefore, administration to both eyes concurrently is not recommended. OZURDEX has not been studied in patients with macular oedema secondary to RVO with significant retinal ischemia. Therefore, OZURDEX is not recommended. OZURDEX should be used with caution in patients taking anti-coagulant or anti-platelet medicinal products. Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, consider evaluating for possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids. OZURDEX is not recommended during pregnancy unless the potential benefit justifies the potential risk to the fetus. OZURDEX is not recommended during breast feeding unless clearly necessary. OZURDEX may have a moderate influence on the ability to drive and use machines. Patients may experience temporarily reduced vision after receiving OZURDEX by intravitreal injection (see section 4.8). They should not drive or use machines until this has resolved.

Adverse reactions (AEs): The most commonly-reported adverse events reported following treatment with OZURDEX are those frequently observed with ophthalmic steroid treatment or intravitreal injections (elevated IOP, cataract formation and conjunctival or vitreal haemorrhage respectively). Less frequently reported, but more serious, adverse reactions include endophthalmitis, necrotizing retinitis, retinal detachment and retinal tear. With the exception of headache and migraine, no systemic adverse drug reactions were identified with the use of OZURDEX.

*For full information please see OZURDEX MoH approved Prescribing Information, May 2023

Full prescribing information can be received from Abbvie Biopharmaceuticals Ltd. Israel at 4 Hacharash Street, Hod Hasharon 4524075. Tel: 09-7909600, Fax: 09-7909606