Ozurdex

Patient Information Leaflet

OZURDEX 700 micrograms intravitreal implant in applicator

dexamethasone
Please read all of this leaflet carefully before you use this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If any of the side effects worsens, or if you notice any side effects not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

1. What OZURDEX is and what it is used for
2. What you need to know before using OZURDEX
3. How to use OZURDEX
4. Possible side effects
5. How to store OZURDEX
6. Contents of the pack and other information

1. What OZURDEX is and what it is used for

The active substance of OZURDEX is dexamethasone. Dexamethasone belongs to a group of
medicines called corticosteroids.
OZURDEX is used to treat adult patients with:

• Reduced visual acuity due to diabetic macular edema (DME) in patients who have already undergone cataract surgery, or in patients who are considered to have an inadequate response or are unsuitable for other types of treatment. Diabetic macular edema consists of swelling of the light-sensitive layer at the back of the eye called the macula. DME is a condition affecting some people with diabetes.
• Vision loss in adult patients caused by blockage of the veins inside the eye. This blockage leads to fluid accumulation, resulting in swelling in the area of the retina (the light-sensitive layer at the back of the eye) known as the macula.

Swelling of the macula may cause damage, affecting central vision used for activities such as reading. OZURDEX works by reducing the swelling, thereby helping to reduce or prevent further damage to the macula.

• Inflammation of the back of the eye. This inflammation leads to reduced vision and/or the presence of floaters in the eye (black spots or thin lines that move across the visual field). OZURDEX acts to reduce this inflammation.

2. What you need to know before using OZURDEX

Do not use OZURDEX

• if you are allergic to dexamethasone or to any of the other ingredients of this medicine (listed in section 6);
• if you have any type of infection inside or around the eye (bacterial, viral, or fungal);
• if you have glaucoma or uncontrolled high pressure inside the eye that is not adequately managed with medications already prescribed for these conditions;
• if the eye to be treated is aphakic (lacks a natural lens) and the posterior part of the lens capsule (the "capsular bag") has been ruptured;
• if the eye to be treated has undergone cataract surgery and contains an intraocular lens implanted in the anterior chamber of the eye (an anterior chamber intraocular lens), or fixed to the white part of the eye (sclera) or to the colored part (iris), and the posterior part of the lens capsule (the "capsular bag") has been ruptured.

Warnings and precautions
Before receiving an injection of OZURDEX, tell your doctor if:

• you have had cataract surgery, iris surgery (the colored part of the eye that controls the amount of light entering the eye), or surgery to remove the gel (called vitreous) from inside the eye;
• you are taking blood-thinning medicines;
• you are taking oral or topical ocular steroid or non-steroidal anti-inflammatory drugs;
• you have previously had an eye infection caused by herpes simplex (a long-lasting eye ulcer, or eye injuries).

Sometimes, an injection of OZURDEX may cause an infection inside the eye, eye pain or redness, or retinal detachment or tear. It is important to identify and treat these conditions as early as possible.
Contact your doctor immediately if you experience increased eye pain and/or discomfort, worsening eye redness, flashes of light, a sudden increase in floaters, partial loss of vision, reduced vision, or increased sensitivity to light after the injection.

In some patients, eye pressure may increase, possibly leading to glaucoma. This may not be noticeable to the patient, so your doctor will perform regular monitoring and, if necessary, prescribe treatment to reduce intraocular pressure.

In most patients who have not yet undergone cataract surgery, clouding of the eye's natural lens (cataract) may occur after repeated treatment with OZURDEX. In such cases, vision will decrease and cataract surgery may become necessary. Your doctor will help you decide the best time for surgery, but you should be aware that until surgery is performed, vision may remain poor or may worsen compared to before starting OZURDEX injections.

The implant may move from the back to the front part of the eye in patients with a tear in the posterior capsule and/or in those who have an opening in the iris. This may cause swelling of the transparent layer at the front of the eye (cornea) and lead to blurred vision. If this condition persists and is not treated, a tissue transplant may be required.

Concurrent administration of OZURDEX in both eyes has not been studied and is not recommended. Your doctor must not inject OZURDEX into both eyes at the same time.

Children and adolescents
The use of OZURDEX in children and adolescents has not been studied and is therefore not recommended.

Other medicines and OZURDEX
Tell your doctor if you are taking or have recently taken any other medicines, including those not requiring a prescription.

Pregnancy and breastfeeding
There are no data available on the use of OZURDEX in pregnant or breastfeeding women.
OZURDEX must not be used during pregnancy or breastfeeding unless your clinical condition requires treatment with OZURDEX. If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before starting treatment with OZURDEX. Ask your doctor for advice before taking any medicine.

Driving and using machines
After treatment with OZURDEX, vision may be slightly reduced for short periods. If this occurs, do not drive or operate machinery until your vision has fully returned.

3. How to use OZURDEX

All OZURDEX injections must be administered by a qualified ophthalmologist.
The recommended dose is one implant injected into the eye. If the effect of this injection begins to wear off, a second implant may be injected into the eye, if the doctor considers it necessary.
To prevent possible eye infections, your doctor will prescribe antibiotic eye drops to be used daily for 3 days before and after each injection. Follow these instructions carefully.
On the day of the injection, your doctor may administer antibiotic eye drops to prevent possible infections.
Prior to the injection, your doctor will clean your eye and eyelid. At the time of injection, your doctor will also administer a local anesthetic to reduce or prevent eye pain.
During the OZURDEX injection, you may hear a distinct clicking sound; this is normal.
Detailed instructions for the doctor on how to perform the OZURDEX injection are provided inside the medicine package.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects have been observed with OZURDEX:
Very common (may affect more than 1 in 10 people):

• increased eye pressure
• clouding of the lens (cataract), bleeding on the surface of the eye*

Common (may affect up to 1 in 10 people):

• elevated eye pressure
• clouding of the back of the natural lens
• bleeding inside the eye*
• worsening of vision*
• difficulty seeing clearly
• separation of the gel-like layer inside the eye from the light-sensitive layer at the back of the eye (vitreous detachment)*
• sensation of spots in the visual field (including “floaters”)*
• sensation of looking through a haze or fog*
• eyelid inflammation
• eye pain*
• flashes of light*
• swelling of the layer over the white part of the eye*
• eye redness*
• headache

Uncommon (may affect up to 1 in 100 people):

• severe inflammation in the back of the eye (usually due to viral infection)
• severe infection or inflammation inside the eye*
• glaucoma (an eye condition in which increased intraocular pressure is associated with damage to the optic nerve)
• detachment of the light-sensitive layer from the back of the eye* (retinal detachment)
• tear in the light-sensitive layer at the back of the eye (retinal tear)*
• reduced eye pressure associated with loss of the gel-like substance (vitreous) from inside the eye*
• inflammation in the front of the eye*
• increased proteins and cells in the front of the eye due to inflammation*
• abnormal sensation in the eye*
• eyelid itching
• redness of the white part of the eye*
• migration of the OZURDEX implant from the back to the front part of the eye causing blurred or reduced vision, which may eventually cause swelling of the transparent part of the eye (cornea)*
• inadvertent misplacement of the OZURDEX implant*
• migraine

*These side effects may be caused by the injection procedure and not by the OZURDEX implant itself. The more injections performed, the greater the number of side effects that may occur.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store OZURDEX

Keep this medicine out of the sight and reach of children.
The physician must not use OZURDEX after the expiry date which is stated on the carton and the pouch following "Exp." The expiry date refers to the last day of the month.
This medicine does not require any special storage conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What OZURDEX contains

• The active substance is dexamethasone.
• Each implant contains 700 micrograms of dexamethasone.
• The other components are: 50:50 poly D,L-lactide-co-glycolide terminating in ester and 50:50 poly D,L-lactide-co-glycolide terminating in acid.

Description of the appearance of OZURDEX and contents of the pack
OZURDEX is a cylindrical-shaped implant contained within the needle of an applicator.
The applicator and a desiccant pouch are sealed in a pouch inside a cardboard box. Each box contains one single-use applicator with one implant, which must be discarded immediately after use.

Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
Allergan Pharmaceuticals Ireland
Castlebar Road
Westport
Co. Mayo
Ireland

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: + 370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел:+359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel.: +420 233 098 111 Tel:+36 1 455 8600

Danmark Malta
AbbVie A/S Vivian Corporation Ltd.
Tlf.: +45 72 30 20 28 Tel: +356 27780331

Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel.: 00800 222843 33 (toll-free) Tel: +31 (0)88 322 2843
Tel.: +49 (0) 611 / 1720-0

Eesti Norge
AbbVie OÜ AbbVie AS
Tel. +372 6231011 Tlf: +47 67 81 80 00

Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0

España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 913840910 Tel.: +48 22 372 78 00

France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0) 1 45 60 13 00 Tel.: +351 (0)21 1908400

Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel: + 385 (0)1 5625 501 Tel: +40 21 529 30 35

Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060

Ísland Slovenská republika
Vistor hf. AbbVie s.r.o.
Sími: +354 535 7000 Tel: +421 2 5050 0777

Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200

Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ: +357 22 34 74 40 Tel: +46 (0)8 684 44 600

Latvija United Kingdom (Northern Ireland)
AbbVie SIA AbbVie Deutschland GmbH & Co. KG
Tel: +371 67605000 Tel: +44 (0)1628 561090

More detailed information on this medicinal product is available on the website of the European Medicines Agency at http://www.ema.europa.eu/ .
To listen to or request a copy of this summary of product characteristics in an alternative format, such as large print or audio, please contact the local representative of the Marketing Authorisation Holder.

[To be provided in the package]
The following information is intended exclusively for medical or healthcare personnel and includes numbered sections of the SmPC containing practical information for the use of the medicinal product. For complete product information, please refer to the SmPC.
INFORMATION FOR HEALTHCARE PROFESSIONALS

1. NAME OF THE MEDICINAL PRODUCT

OZURDEX 700 micrograms intravitreal implant in applicator

4. CLINICAL INFORMATION

4.1 Therapeutic Indications
OZURDEX is indicated for the treatment of adult patients with:

• reduced visual acuity due to diabetic macular edema (DME) in pseudophakic patients, or in patients considered to have an inadequate response or who are unsuitable for non-corticosteroid therapy.
• macular edema secondary to Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO) (see section 5.1 of the SmPC).
• inflammation of the posterior segment of the eye caused by non-infectious uveitis.

4.2 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 administered intravitreally into the affected eye.
Simultaneous administration in both eyes is not recommended (see section 4.4 of the SmPC).
After injection, patients must be monitored to allow prompt intervention in case of infection or elevated intraocular pressure (see section 4.4 of the SmPC).

Special Populations
Elderly patients (aged 65 years and older)
No dose adjustment is required in elderly patients.

Method of Administration
OZURDEX is a single-use intravitreal implant in a pre-filled applicator intended solely for intravitreal use.
Each individual applicator is for use in one eye only.
The intravitreal injection procedure must be performed under controlled aseptic conditions, including the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent).
Patients should be instructed to self-administer a broad-spectrum antimicrobial eye drop daily for 3 days before and after each injection. Prior to injection, the ocular, eyelid, and periocular skin surfaces must be disinfected (e.g., using drops of 5% povidone-iodine solution on the conjunctiva, as performed in the clinical trials supporting OZURDEX approval), and adequate local anaesthesia must be administered. Remove the pouch from the box and check for damage (see section 6.6 of the SmPC). Open the pouch in a sterile field and gently place the applicator on a sterile tray. Carefully remove the cap from the applicator. Once the pouch is opened, the applicator must be used immediately.
Hold the applicator in one hand and pull the safety tab. Do not twist or bend the tab. With the bevel of the needle facing upward, insert the needle into the sclera approximately 1 mm and direct it toward the center of the vitreous cavity until the silicone sleeve is in contact with the conjunctiva. Slowly press the activation button until a distinct click is heard. Before removing the applicator from the eye, ensure that the activation button has been fully depressed and locked flush with the surface of the applicator. Remove the needle in the same direction used for insertion.
For instructions on administration of the intravitreal implant, see section 6.6.
Immediately after OZURDEX injection, perform indirect ophthalmoscopy in the injection quadrant to confirm correct implant placement. Visualization is possible in the vast majority of cases. If the implant is not visible, use a sterile cotton-tipped applicator to apply gentle pressure at the injection site to visualize the implant.
After intravitreal injection, patients should continue treatment with a broad-spectrum antimicrobial.

4.3 Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SmPC.
• Active or suspected ocular or periocular infections, including most viral diseases of the cornea and conjunctiva, such as active herpes simplex epithelial keratitis (dendritic keratitis), vaccinia virus infection, varicella, mycobacterial infection, and fungal diseases.
• Advanced glaucoma not adequately controlled with medication alone.
• Aphakic eyes with posterior lens capsule rupture.
• Eyes with anterior chamber intraocular lens (ACIOL), iris-fixated or transscleral-fixated intraocular lens, and posterior lens capsule rupture.

4.4 Special Warnings and Precautions for Use
Intravitreal injections, including those with OZURDEX, may be associated with endophthalmitis, intraocular inflammation, increased intraocular pressure, and retinal detachment. Appropriate aseptic injection techniques must always be used. In addition, patients must be monitored after injection to allow prompt intervention in case of infection or increased intraocular pressure. Monitoring may include assessment of optic nerve head perfusion immediately after injection, tonometry within 30 minutes of injection, and biomicroscopic examination between 2 and 7 days after injection.
Patients must be informed to immediately report any symptoms suggestive of endophthalmitis or other events listed above, such as eye pain or blurred vision (see section 4.8 of the SmPC).
All patients with a ruptured posterior lens capsule, including those with posterior chamber lenses (e.g., following cataract surgery) and/or those with an iris opening into the vitreous cavity (e.g., following iridectomy), with or without a history of vitrectomy, are at risk of implant migration into the anterior chamber. Migration of the implant into the anterior chamber may lead to corneal oedema. Persistent severe corneal oedema may progress to require corneal transplantation. Except for patients with contraindications (see section 4.3), for whom OZURDEX must not be used, OZURDEX should be used with caution and only after careful risk-benefit assessment. These patients must be closely monitored to allow early diagnosis and management of device migration.
The use of corticosteroids, including OZURDEX, may induce cataracts (including posterior subcapsular cataracts), increased intraocular pressure (IOP), steroid-induced glaucoma, and may lead to secondary ocular infections.
In 3-year clinical studies on DME, 59% of phakic study eye patients treated with OZURDEX underwent cataract surgery in the study eye (see section 4.8 of the SmPC).
After the first injection, the incidence of cataract appears higher in patients with non-infectious posterior segment uveitis compared to BRVO/CRVO patients. In BRVO/CRVO clinical studies, cataract cases were reported more frequently in phakic patients receiving a second injection (see section 4.8 of the SmPC). Only one out of 368 patients required cataract surgery during the first treatment, and three out of 302 during the second treatment.
In the non-infectious uveitis study, one out of 62 phakic patients underwent cataract surgery after a single injection.
The prevalence of conjunctival haemorrhage appears higher in patients with non-infectious posterior segment uveitis compared to BRVO/CRVO and DME patients. This may be attributable to the intravitreal injection procedure or concomitant use of topical and/or systemic corticosteroids or non-steroidal anti-inflammatory drugs. No treatment is required as spontaneous resolution occurs.
As expected with ocular steroid administration and intravitreal injections, an increase in intraocular pressure (IOP) may occur. Elevated IOP is usually manageable with IOP-lowering medications (see section 4.8). Among patients reporting IOP increases ≥10 mmHg from baseline, most showed such increases between 45 and 60 days after injection. Therefore, regular monitoring of IOP is required regardless of baseline IOP, and any post-injection increase should be managed appropriately. Patients under 45 years of age with macular edema following retinal vein occlusion or posterior segment inflammation due to non-infectious uveitis are more susceptible to IOP elevation.
In patients with a history of ocular viral infection (e.g., herpes simplex), corticosteroids should be used with caution and must not be used in the presence of active ocular herpes simplex.
The safety and efficacy of OZURDEX administered simultaneously in both eyes have not been evaluated. Therefore, simultaneous administration in both eyes is not recommended.
OZURDEX has not been studied in patients with macular edema secondary to RVO with significant retinal ischaemia. OZURDEX is therefore not recommended for these patients.
A limited number of patients with type 1 diabetes were included in phase 3 studies, and their response to OZURDEX was not significantly different from that of patients with type 2 diabetes.
In RVO, anticoagulant therapy was used in 2% of patients treated with OZURDEX; no haemorrhagic adverse events were reported in these patients. In DME, anticoagulant therapy was used in 8% of patients. Among patients receiving anticoagulant therapy, the frequency of haemorrhagic adverse events was similar in the OZURDEX group compared to the sham treatment group (29% vs. 32%). Among patients not receiving anticoagulant therapy, 27% of those treated with OZURDEX reported haemorrhagic adverse events compared to 20% in the sham treatment group. Vitreous haemorrhage was reported in a higher proportion of OZURDEX-treated patients receiving anticoagulant therapy (11%) compared to those not receiving it (6%).
Antiplatelet agents, such as clopidogrel, were used in up to 56% of patients in some clinical studies. Among patients receiving concomitant antiplatelet therapy, haemorrhagic adverse events were reported in a slightly higher proportion of patients treated with OZURDEX (up to 29%) compared to the sham treatment group (up to 23%), regardless of therapeutic indication or number of treatments. The most commonly reported haemorrhagic adverse event was conjunctival haemorrhage (up to 24%).
OZURDEX should be used with caution in patients taking anticoagulant or antiplatelet medications.

Visual disturbances
Visual disturbances may occur with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, consider evaluating possible causes including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy (CSCR), which have been reported following systemic and topical corticosteroid use.

4.5 Interaction with Other Medicinal Products and Other Forms of Interaction
No interaction studies have been conducted.
Systemic absorption is minimal and interactions are not expected.

4.6 Fertility, Pregnancy and Lactation
Pregnancy
Animal studies have shown teratogenic effects following topical ophthalmic administration (see section 5.3 of the SmPC). Adequate data on the use of intravitreal dexamethasone in pregnant women are not available. Long-term systemic glucocorticosteroid treatment during pregnancy increases the risk of intrauterine growth retardation and neonatal adrenal insufficiency. Therefore, although systemic exposure to dexamethasone following intraocular administration is expected to be very low, OZURDEX is not recommended during pregnancy unless the potential benefit justifies the potential risk to the fetus.

Lactation
Dexamethasone is excreted in breast milk. Due to the route of administration and resulting systemic levels, effects on the infant are not expected. However, OZURDEX is not recommended during breastfeeding unless clearly necessary.

Fertility
No data are available regarding fertility.

4.7 Effects on Ability to Drive and Use Machines
OZURDEX may have a moderate effect on the ability to drive and use machines. After administration of OZURDEX via intravitreal injection, patients may experience temporary visual disturbances (see section 4.8). Therefore, patients should avoid driving or operating machinery until these effects have resolved.

4.8 Undesirable Effects
Summary of the Safety Profile
The most commonly reported adverse events following OZURDEX treatment are those frequently observed with ophthalmic corticosteroid therapy or intravitreal injections (elevated IOP, cataract formation, and conjunctival or vitreous 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 have been identified with OZURDEX use.

Table listing adverse reactions
Adverse reactions considered related to OZURDEX treatment observed in phase III clinical trials (DME, BRVO/CRVO, and uveitis) and spontaneously reported are listed in the table below by MedDRA system organ class, according to the following convention:
Very common (≥ 1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000), very rare (<1/10,000). Within each frequency category, adverse reactions are listed in descending order of severity.

Table 1 Adverse Reactions

* indicates adverse reactions considered related to the intravitreal injection procedure (the frequency of these
adverse reactions is proportional to the number of administered treatments).
** in a 24-month real-world observational study on the treatment of macular edema following RVO and non-infectious posterior segment uveitis, these adverse events were reported more frequently in
patients receiving >2 injections compared to patients receiving ≤2 injections; cataract formation (24.7% vs.
17.7%), cataract progression (32.0% vs. 13.1%), vitreous hemorrhage (6.0% vs. 2.0%), and increased IOP
(24% vs. 16.6%).
Description of selected adverse reactions
Diabetic macular edema
The clinical safety of OZURDEX in patients with diabetic macular edema was evaluated in
two randomized, double-blind, sham-controlled phase III studies. In both studies, a total of 347 patients were randomized to receive OZURDEX, while 350 patients received sham treatment.
The most frequently reported adverse reactions during the entire study period in the study eye of patients treated with OZURDEX were cataract and increased IOP (see below).
In the 3-year DME clinical studies, 87% of phakic patients in the study eye treated with OZURDEX had some degree of lens opacification/early cataract at baseline. The incidence of all types of observed cataracts (i.e., cortical cataract, diabetic cataract, nuclear cataract, subcapsular cataract, lenticular cataract, cataract) in the 3-year studies was 68% in phakic patients treated with OZURDEX in the study eye. 59% of phakic study eye patients required cataract surgery by the final visit of the 3rd year; most procedures were performed in the 2nd and 3rd year.
Mean baseline IOP in the study eye was the same in both treatment groups (15.3 mmHg). The mean increase from baseline IOP did not exceed 3.2 mmHg at any visit in the OZURDEX-treated group, with peak mean IOP occurring at the visit 1.5 months after injection and returning approximately to baseline levels by 6 months after each injection. The frequency and magnitude of IOP increase following OZURDEX treatment did not increase with repeated OZURDEX injections.
28% of patients treated with OZURDEX experienced an IOP increase ≥10 mmHg from baseline at one or more visits during the study. At baseline, 3% of patients required medication(s) for IOP reduction. Overall, 42% of patients required IOP-lowering medication(s) in the study eye at some point during the 3-year studies, with the majority of patients requiring more than one medication. Peak usage (33%) occurred during the first 12 months and remained similar from year to year.
A total of 4 patients (1%) treated with OZURDEX underwent intraocular procedures in the study eye to manage increased IOP. One patient treated with OZURDEX required incisional surgery (trabeculectomy) to manage steroid-induced IOP elevation; one patient underwent trabeculectomy due to fibrin formation in the anterior chamber obstructing aqueous outflow and causing IOP elevation; one patient underwent iridotomy due to angle-closure glaucoma; and one patient underwent iridectomy due to cataract surgery. No patient required implant removal via vitrectomy to control IOP.
BRVO/CRVO
The clinical safety of OZURDEX in patients with macular edema secondary to central or branch retinal vein occlusion was evaluated in two randomized, double-blind, sham-controlled phase III studies. In the two phase III studies, 427 patients were randomized to receive OZURDEX and 426 to receive sham treatment. In total, 401 (94%) patients randomized and treated with OZURDEX completed the initial treatment period (up to day 180).
Overall, 47.3% of patients reported at least one adverse reaction. The most frequently reported adverse reactions in patients treated with OZURDEX were increased intraocular pressure (24.0%) and conjunctival hemorrhage (14.7%).
The adverse reaction profile for patients with BRVO was similar to that observed in patients with CRVO, although the overall incidence of adverse reactions was higher in the CRVO subgroup.
IOP increase with OZURDEX peaked at day 60 and returned to baseline levels by day 180. Elevated IOP either required no treatment or was managed with temporary use of topical therapy for IOP control. During the initial treatment period, 0.7% (3/421) of patients who received OZURDEX required laser or surgical intervention procedures to manage elevated IOP in the study eye, compared to 0.2% (1/423) of patients receiving sham treatment.
The adverse reaction profile in 341 patients evaluated after a second OZURDEX injection was similar to that observed after the first injection. Overall, 54% of patients reported at least one adverse reaction. The incidence of IOP increase (24.9%) was similar to that observed after the first injection and similarly returned to baseline by day 180.
The overall incidence of cataract was higher after one year compared to the first six months.
Uveitis
The clinical safety of OZURDEX in patients with posterior segment inflammation due to non-infectious uveitis was evaluated in a single randomized, multicenter, masked study.
In total, 77 patients were randomized to receive OZURDEX, and 76 received sham treatment. Overall, 73 patients (95%) randomized and treated with OZURDEX completed the 26-week study.
The most frequently reported adverse reactions in the study eye of patients treated with OZURDEX were conjunctival hemorrhage (30.3%), increased intraocular pressure (25.0%), and cataract (11.8%).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after marketing authorization is important, as it allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system detailed in Annex V.
4.9 OVERDOSAGE
In case of overdose, intraocular pressure should be monitored and, if deemed necessary by the physician, treated.
5.3 PRECLINICAL SAFETY DATA
In preclinical studies, effects were observed only at doses considered substantially higher than the maximum dose in humans, indicating low clinical relevance.
For OZURDEX, data on mutagenicity, carcinogenicity, or reproductive and developmental toxicity are not available. Dexamethasone has been shown to be teratogenic in mice and rabbits following topical ophthalmic administration.
In rabbits, dexamethasone exposure was observed in the healthy/untreated eye following contralateral diffusion after implant insertion into the posterior segment of the eye.

6. PHARMACEUTICAL INFORMATION

6.6 Special precautions for disposal and handling
OZURDEX is for single use only.
A single applicator may be used only for the treatment of one eye.
The applicator must not be used if the seal of the pouch containing the applicator is damaged.
Once the pouch has been opened, the applicator must be used immediately.

Administration of OZURDEX

1. Hold the applicator with its long axis parallel to the limbus.

2. Place the applicator needle onto the sclera, holding it at an oblique angle with the bevel facing upward.
   Push the needle tip into the sclera approximately 1 mm, keeping the needle parallel to the limbus.

3. Direct the needle toward the center of the eye into the vitreous cavity.

This procedure will create a scleral tunnel.
Proceed until the needle enters the vitreous chamber.
Do not push the needle further once the silicone sleeve comes into contact with the conjunctiva.
4) Slowly press the activation button until a "click" is heard.

Before removing the applicator from the eye, ensure that the activation button has been fully depressed and locked flush with the surface of the applicator.
5) Remove the applicator in the same direction used for insertion into the eye.

6. Dispose of the applicator safely immediately after use.
   OZURDEX is a single-use applicator only.
   Any unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.