OZURDEX 700 MICROGRAMS Имплант

Содержание инструкции

1. OZURDEX 700 micrograms intravitreal implant in applicator
   1. What is OZURDEX and what is it used for
   2. What you need to know before you use OZURDEX
   3. How to use OZURDEX
   4. Possible side effects
   5. How to store OZURDEX
   6. Package contents and other information
   7. MEDICINE NAME
   8. 2 Dosage and Administration
   9. 3 Contraindications
   10. 4 Special warnings and precautions for use
   11. 5 Interactions with other medicinal products and other forms of interaction
   12. 6 Fertility, pregnancy and lactation
   13. 7 Effects on the ability to drive and operate machinery
   14. 8 Undesirable effects
   15. 9 Overdosage
   16. 3 Preclinical safety data

OZURDEX 700 micrograms intravitreal implant in applicator

desametasone

Read this leaflet carefully before using this medicine as 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 gets worse, or if you notice any side effect

Contents of this leaflet

• 1. What OZURDEX is and what it is used for
• 2. What you need to know before you use 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 is OZURDEX and what is it used for

The active ingredient of OZURDEX is dexamethasone. Dexamethasone belongs to a group of
medicines called corticosteroids.
OZURDEX is used for the treatment of adult patients with:

• Reduction of 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 insufficient response or are not suitable for other types of treatments. Diabetic macular edema consists of swelling of the light-sensitive layer located at the back of the eye called the macula. DME is a condition that affects some individuals with diabetes.
• Loss of vision in adult patients caused by blockage of the veins inside the eye. This blockage leads to an accumulation of fluids which causes swelling in the area of the retina (the light-sensitive layer located in the back of the eye) called the macula.

Swelling of the macula can cause damage, with effects on central vision used for
activities such as reading. OZURDEX works by reducing swelling and thus helping to reduce or
prevent further damage to the macula.

• Inflammation of the back of the eye. This inflammation leads to a reduction in vision and/or the presence of floaters in the eye (black dots or thin lines that move in the field of vision). The action of OZURDEX reduces this inflammation.

2. What you need to know before you use OZURDEX

Do not use OZURDEX

• if you are allergic to dexamethasone or any of the other ingredients of this medicine (listed in section 6);
• if you have any type of infection inside or around your eyes (bacterial, viral or fungal);
• if you have glaucoma or uncontrolled high pressure inside your eye with medicines already prescribed for these conditions.
• if the eye to be treated does not have a lens and the back part of the lens capsule (the “capsular bag”) has been broken.
• if the eye to be treated has had cataract surgery and contains an artificial lens in the front compartment of the eye (an anterior chamber intraocular lens) or is attached to the white part of the eye (sclera) or the coloured part (iris) and the back part of the lens capsule (the “capsular bag”) has been broken.

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

• you have had cataract surgery, iris (the coloured part of your eye that controls the amount of light entering your eye) surgery or surgery to remove the gel (called vitreous) from inside your eye;
• you are taking medicines to thin your blood;
• you are taking steroid medicines or non-steroidal anti-inflammatory drugs by mouth or as eye drops;
• you have previously had an eye infection with herpes simplex(a long-lasting eye ulcer, or sores on your eyes).

Sometimes the injection of OZURDEX can cause infection inside the eye, pain or
eye redness or detachment or tear of the retina. It is important to identify and treat
these conditions as soon as possible.
Tell your doctor immediately if you experience increased eye pain and/or discomfort,
worsening eye redness, flashes and a sudden increase in floaters, partially blocked vision, decreased vision or increased sensitivity to light after
the injection.
In some patients, the pressure in your eye may increase, potentially leading to glaucoma. This is an
event that may not be noticed by the patient, so your doctor will monitor you regularly and, if
necessary, prescribe treatment to reduce eye pressure.
In the majority of patients who have not yet had cataract surgery, clouding of the eye’s natural lens (cataract) may occur after repeated treatment with
OZURDEX. In this case, your vision will be reduced and you will likely need cataract surgery. Your doctor will help you decide the best time to have this surgery, but it is
important to know that until the surgery your vision may remain as poor as it was before you started receiving OZURDEX injections, or may even be
worse.
The implant may move from the back to the front of the eye in patients with
a tear in the back of the eye capsule and/or those with an opening
in the iris. This can cause swelling of the clear layer at the front of the eye and
cause blurred vision. If this condition persists and is not treated, a tissue transplant may be
necessary.
Simultaneous injection of OZURDEX into both eyes has not been studied and is not recommended. Your
doctor should 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 available without a prescription.

Pregnancy and breastfeeding
There are no data on the use of OZURDEX in pregnant women or during breastfeeding.
OZURDEX should not be used during pregnancy or breastfeeding unless the
woman’s clinical condition requires treatment with OZURDEX. If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding, ask
your doctor for advice before starting treatment with OZURDEX. Ask your doctor for advice before
using any medicine.

Driving and using machines
After treatment with OZURDEX, a slight decrease in vision may occur for short periods. If this
happens, do not drive or use machines until your vision has fully recovered.

3. How to use OZURDEX

All OZURDEX injections must be administered by an ophthalmologist appropriately
qualified.
The recommended dose is one implant via injection into the eye. If the effect of this injection
tends to diminish, a second implant can be injected into the eye, if the doctor deems it
necessary.
In order to prevent any eye infections, your doctor will prescribe the use of antibiotic eye drops
every day for 3 days before and after each injection. Follow these instructions carefully.
On the day of the injection, the doctor may apply antibiotic eye drops to prevent possible infections.
Before the injection, the doctor will clean the eye and eyelid. On the occasion
of the injection, the doctor will also administer a local anesthetic to reduce or prevent pain
to the eye. During the OZURDEX injection, you may hear a clicking sound; this is normal.

Detailed instructions for the doctor on how to perform the OZURDEX injection are provided
inside the package leaflet.
If you have any doubts about the use of this medicine, ask 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):

• high eye pressure
• clouding of the back of the natural lens
• bleeding inside the eye*
• worsening of vision*
• difficulty seeing clearly
• detachment of the gel-like substance inside the eye from the light-sensitive layer at the back of the eye (vitreous detachment)*
• seeing spots in your field of vision (including “floaters”)*
• feeling like you are looking through haze or mist*
• inflammation of the eyelids
• eye pain*
• flashes of light*
• swelling of the layer above the white of the eye*
• redness of the eye*
• headache

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

• severe inflammation at the back of the eye (usually due to viral infection)
• infection or severe inflammation inside the eye*
• glaucoma (an eye condition in which increased pressure inside the eye is associated with damage to the optic nerve)
• detachment of the light-sensitive layer at the back of the eye* (retinal detachment)
• tearing of the light-sensitive layer at the back of the eye (retinal tear)*
• decrease in eye pressure associated with loss of the gel-like substance (vitreous) from inside the eye*
• inflammation at the front of the eye*
• increase in proteins and cells in the front of the eye due to inflammation*
• abnormal sensation in the eye*
• itchy eyelids
• redness of the white of the eye*
• migration of the OZURDEX implant from the back to the front of the eye causing blurred or reduced vision and which may eventually cause swelling of the clear front part of the eye (cornea)*
• inadvertent incorrect positioning 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 you have, the more effects you may experience.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through 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 sight and reach of children.
The doctor must not use OZURDEX after the expiry date stated on the box and on the sachet
after 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 ingredient 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 package contents
OZURDEX is a cylindrical implant contained within the needle of an applicator.
The applicator and a desiccant pouch are sealed in a closed pouch inside a
cardboard box. Each box contains one applicator with an implant for single use and
immediate disposal 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 on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
AbbVie SA
Tél/Tel: +32 10 477811

Lietuva
AbbVie UAB
Tel: + 370 5 205 3023

България
АбВи ЕООД
Тел:+359 2 90 30 430

Luxembourg/Luxemburg
AbbVie SA
Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika
AbbVie s.r.o.
Tel.: +420 233 098 111

Magyarország
AbbVie Kft.
Tel:+36 1 455 8600

Danmark
AbbVie A/S
Tlf.: +45 72 30 20 28

Malta
Vivian Corporation Ltd.
Tel: +356 27780331

Deutschland
AbbVie Deutschland GmbH & Co. KG
Tel.: 00800 222843 33 (gebührenfrei)
Tel.: +49 (0) 611 / 1720-0

Nederland
AbbVie B.V.
Tel: +31 (0)88 322 2843

Eesti
AbbVie OÜ
Tel. +372 6231011

Norge
AbbVie AS
Tlf: +47 67 81 80 00

Ελλάδα
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε.
Τηλ: +30 214 4165 555

Österreich
AbbVie GmbH
Tel: +43 1 20589-0

España
AbbVie Spain, S.L.U.
Tel: +34 913840910

Polska
AbbVie Sp. z o.o.
Tel.: +48 22 372 78 00

France
AbbVie
Tél: +33 (0) 1 45 60 13 00

Portugal
AbbVie, Lda.
Tel.: +351 (0)21 1908400

Hrvatska
AbbVie d.o.o.
Tel: + 385 (0)1 5625 501

România
AbbVie S.R.L.
Tel: +40 21 529 30 35

Ireland
AbbVie Limited
Tel: +353 (0)1 4287900

Slovenija
AbbVie Biofarmacevtska družba d.o.o.
Tel: +386 (1)32 08 060

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
AbbVie s.r.o.
Tel: +421 2 5050 0777

Italia
AbbVie S.r.l.
Tel: +39 06 928921

Suomi/Finland
AbbVie Oy
Puh/Tel: +358 (0)10 2411 200

Κύπρος
Lifepharma (Z.A.M.) Ltd
Τηλ: +357 22 34 74 40

Sverige
AbbVie AB
Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

United Kingdom (Northern Ireland)
AbbVie Deutschland GmbH & Co. KG
Tel: +44 (0)1628 561090
More detailed information on this medicinal product is available on the European Medicines Agency website at http://www.ema.europa.eu/ .
enlarged> or
authorisation holder.
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[To be included in the package]
The following information is intended exclusively for medical or healthcare professionals and includes
the numbered paragraphs of the SmPC that contain practical information for the use of the medicinal product. For
complete product information, please refer to the SmPC.

INFORMATION FOR HEALTHCARE PROFESSIONALS

1. MEDICINE NAME

OZURDEX 700 micrograms intravitreal implant in applicator

4. CLINICAL INFORMATION

4.1 Therapeutic indications

OZURDEX is indicated for the treatment of adult patients with:

• reduction of visual acuity due to diabetic macular edema (DME) in pseudophakic patients, or in patients who are considered to have an insufficient response or are not suitable 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 that is caused by non-infectious uveitis

4.2 Dosage and Administration

OZURDEX must be administered by a qualified ophthalmologist experienced in intravitreal injections.
Dosage
The recommended dose is one OZURDEX implant administered intravitreally into the affected eye.
Simultaneous administration into both eyes is not recommended (see section 4.4 of the SmPC).
Patients must be monitored after the injection, in order to be able to intervene quickly in case of
infection or increased intraocular pressure (see section 4.4 of the SmPC).

Special populations

Elderly patients (aged 65 years and over)
No dose adjustment is necessary in elderly patients.
Method of administration
OZURDEX is a single-use intravitreal implant in an applicator for intravitreal use only.
Each individual applicator can only be used for the treatment of a single eye.
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 every
day for 3 days before and after each injection. Before the injection, the
ocular, eyelid and periocular skin surface must be disinfected (using, for example, 5% povidone-iodine solution on the conjunctiva as performed in clinical trials for
the approval of OZURDEX) and adequate local anesthesia performed. Remove the pouch from the
box and check for damage (see section 6.6 of the SmPC). Then 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 bevelled end of the needle facing upwards, insert the needle into the sclera for approximately 1 mm and direct it
towards the centre of the eye into the vitreous chamber until the silicone sleeve comes into contact with the
conjunctiva. Slowly press the activation button until a clear click is heard. Before
removing the applicator from the eye, ensure that the activation button has been fully pressed,
locking at the level of the applicator surface. Remove the needle in the same direction as it was inserted
into the eye.
For instructions on administering the intravitreal implant, see section 6.6
Immediately after the injection of OZURDEX, perform indirect ophthalmoscopy in the injection quadrant to verify that the implant insertion procedure has been performed correctly.
Visualization is possible in the vast majority of cases. If the implant is not visible,
use a sterile cotton swab to apply gentle pressure at the injection site
in order to be able to see the implant.
After the intravitreal injection, patients must 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 pathologies of the cornea and conjunctiva, including current cases of herpes simplex epithelial keratitis (dendritic keratitis), vaccinia virus infection, varicella, mycobacterial infection and fungal pathologies.
• Advanced glaucoma not adequately controlled with medicinal use alone.
• Aphakic eyes with rupture of the posterior capsule of the crystalline lens.
• Eyes with an anterior chamber intraocular lens ( Anterior Chamber Intraocular Lens, ACIOL), iris-fixated or transscleral ocular lens and rupture of the posterior capsule of the crystalline lens.

4.4 Special warnings and precautions for use

Intravitreal injections, including those of 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 the injection,
in order to be able to intervene quickly in case of infection or increased intraocular pressure. Monitoring
may require a check of the optic nerve head perfusion immediately after the injection, tonometry within
30 minutes of the injection and a biomicroscopic examination from two to seven days after the injection.
Patients should be instructed to immediately report any symptoms indicating the presence of
endophthalmitis or any of the above-mentioned events, such as eye pain, blurred vision, etc. (see section
4.8 of the SmPC).
All patients with a posterior lens capsule that presents with laceration, such as those with a posterior
chamber lens (e.g. due to cataract surgery) and/or those who have an iris opening into 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. Migration of the implant into the anterior chamber can cause corneal edema. Severe
persistent corneal edema may progress to require corneal transplantation. Except for patients who
present with contraindications (see section 4.3), for whom OZURDEX should not be used, OZURDEX
should be used with caution and only after a careful risk-benefit assessment. These patients must be
carefully monitored to allow for early diagnosis and management of device migration.
The use of corticosteroids, including OZURDEX, may induce cataracts (including posterior subcapsular
cataracts), increased IOP, steroid-induced glaucoma and may cause secondary ocular infections.
In clinical studies on DME lasting 3 years, 59% of patients with a phakic eye in the study 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 to be higher in patients with non-infectious
posterior segment uveitis compared to BRVO/CRVO patients. In clinical studies on BRVO/CRVO, cases
of cataract 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
patients out of 302 during the second treatment.
In the non-infectious uveitis study, 1 out of 62 phakic patients underwent cataract surgery after a single
injection.
The prevalence of conjunctival hemorrhage in patients with non-infectious posterior segment uveitis
appears to be higher compared to BRVO/CRVO and DME. This may be attributable to the intravitreal
injection procedure or the concomitant use of corticosteroids or topical and/or systemic non-steroidal
anti-inflammatory drugs. No treatment is required as it resolves spontaneously.
As expected with the administration of ocular steroids and intravitreal injections, an increase in
intraocular pressure (IOP) may occur. The increase in IOP is usually manageable with the use of drugs
that reduce IOP (see section 4.8). Among patients who reported cases of IOP increase greater than or
equal to 10 mmHg compared to baseline, most of these showed such an increase between 45 and 60
days after the injection. Therefore, regular IOP monitoring is necessary, regardless of baseline IOP, and
any increase after the injection should be managed appropriately. Patients under the age of 45 with
macular edema following retinal vein occlusion or inflammation of the posterior segment of the eye caused
by non-infectious uveitis are more likely to experience an increase in IOP.
In patients with a history of ocular viral infection (e.g. herpes simplex), corticosteroids should be used
with caution and should not be used in the presence of active ocular herpes simplex.
The safety and efficacy of OZURDEX administered simultaneously in both eyes have not yet been
evaluated. For this reason, simultaneous administration in both eyes is not recommended.
OZURDEX has not been studied in patients with macular edema secondary to RVO with significant
retinal ischemia. OZURDEX is therefore not recommended for these patients.
A limited number of subjects with type 1 diabetes have been examined in phase 3 studies and the
response to OZURDEX in these subjects was not significantly different from subjects with type 2 diabetes.
In RVO, anticoagulant therapy was used in 2% of patients treated with OZURDEX; in these patients no
cases of adverse events of a hemorrhagic nature were reported. In DME, anticoagulant therapy was used in
8% of patients. Among patients who used anticoagulant therapy, the frequency of hemorrhagic adverse
events was similar in the group treated with OZURDEX compared to the sham treatment group (29% vs.
32%). Among patients who did not use anticoagulant therapy, 27% of patients treated with OZURDEX
reported hemorrhagic adverse events compared to 20% of those in the sham treatment group.
Vitreous hemorrhage was reported in a higher percentage of patients treated with OZURDEX who were
taking anticoagulant therapy (11%) compared to those who did not receive it (6%).
Antiplatelet drugs, such as clopidogrel, were used in some phases of the clinical studies in up to 56% of
patients. For patients who used concomitant antiplatelet drugs, hemorrhagic adverse events were reported
in a slightly higher percentage of patients who were administered OZURDEX (up to 29%) compared to the
sham treatment group (up to 23%), regardless of the therapeutic indication or the number of treatments.
The most common hemorrhagic adverse event reported was conjunctival hemorrhage (up to 24%).
OZURDEX should be used with caution in patients taking anticoagulant or antiplatelet drugs.
Visual disturbances
With the use of systemic and topical corticosteroids, visual disturbances can be reported. If a patient
presents with symptoms such as blurred vision or other visual disturbances, consider evaluating the
possible causes that may include cataract, glaucoma or rare diseases such as central serous
chorioretinopathy (CSCR), which have been reported after the use of systemic and topical corticosteroids.

4.5 Interactions with other medicinal products and other forms of interaction

Interaction studies have not been performed.
Systemic absorption is minimal and interactions are not expected.

4.6 Fertility, pregnancy and lactation

Pregnancy
Studies performed on animals have shown teratogenic effects following topical
ophthalmic administration (see section 5.3 of the SmPC). Adequate data regarding the use of
desamethasone administered to pregnant women via intravitreal route are not available. Long-term systemic
treatment with glucocorticosteroids during pregnancy increases the risk of intrauterine growth retardation and
adrenal insufficiency in the newborn. Therefore, although systemic exposure to desamethasone expected
following local intraocular treatment is very low, OZURDEX is not recommended during
pregnancy, unless the potential benefit justifies the potential risk to the fetus.
Lactation
Desamethasone is excreted in breast milk. Following this route of administration, and the
consequent systemic levels, no effects on the infant are expected. However, OZURDEX is not
recommended during lactation, unless it is expressly necessary.
Fertility
No data are available in relation to fertility.

4.7 Effects on the ability to drive and operate machinery

OZURDEX may moderately impair the ability to drive and use machinery. Following the
administration of OZURDEX via intravitreal injection, patients may experience a
temporary reduction in vision (see section 4.8). They should therefore avoid driving or
operating machinery until these effects have subsided.

4.8 Undesirable effects

Summary of the safety profile
The most commonly reported adverse events following treatment with OZURDEX are those
frequently observed with ophthalmic steroid therapy or intravitreal injections
(respectively, increased IOP, cataract formation and conjunctival or vitreous haemorrhage).
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 drug-related adverse reactions have been identified with the use of OZURDEX.
Table listing adverse reactions
Adverse reactions considered to be related to treatment with OZURDEX observed in phase III clinical trials (DME, BRVO/CRVO and uveitis) and reported spontaneously are listed in the
table below according to the MedDRA system organ and class classification, based on 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 class, adverse reactions
are presented 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 treatments administered).
** in an observational real worldstudy of 24 months on the treatment of macular oedema after RVO and non-infectious posterior segment uveitis
these adverse events were reported more frequently in patients undergoing >2 injections compared to patients undergoing ≤2 injections; cataract formation (24.7% vs.
17.7%), cataract progression (32.0% vs. 13.1%), vitreous haemorrhage (6.0% vs. 2.0%) and increased IOP
(24% vs. 16.6%).
Description of selected adverse reactions

Diabetic macular oedema
The clinical safety of OZURDEX in patients with diabetic macular oedema was evaluated in
two randomised, double-blind, sham-controlled phase III studies. A total of 347 patients were randomised to receive
OZURDEX, while 350 patients received sham treatment in both studies.
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 DME clinical studies over 3 years, 87% of patients with a phakic eye in the study
treated with OZURDEX had some degree of crystalline lens opacification/early cataract at baseline. The incidence of all types of cataract observed (i.e. cortical cataract, diabetic cataract,
nuclear cataract, subcapsular cataract, lenticular cataract, cataract) in the 3-year studies was
68% in patients treated with OZURDEX with a phakic eye in the study. 59% of patients with
a phakic study eye required cataract surgery by the final visit of year 3; most performed in year 2 and 3.
The 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 all visits in the OZURDEX-treated group, with peak mean IOP at the visit performed after 1.5 months from the injection,
with a return to approximately baseline levels within 6 months after each injection. The
percentage and magnitude of IOP increase following treatment with OZURDEX did not
increase with repeated OZURDEX injection.
28% of patients treated with OZURDEX experienced an IOP increase ≥10 mmHg compared to
baseline at one or more visits during the study. At baseline, 3% of patients required IOP-lowering medication(s). Overall, 42% of patients required IOP-lowering medications at some point in the study eye at some point during the 3-year studies, with the
majority of patients requiring more than one medication. Peak use (33%)
occurred during the first 12 months and remained similar year-on-year.
A total of 4 patients, 1%, treated with OZURDEX underwent eye procedures
in the study eye for the treatment of increased IOP. One patient treated with OZURDEX required
incisional surgery (trabeculectomy) to manage steroid-induced IOP elevation,
1 patient underwent trabeculectomy due to fibrin formation in the anterior chamber blocking aqueous outflow resulting in increased IOP, 1 patient underwent iridotomy due to angle-closure glaucoma and 1 patient underwent
iridectomy due to cataract surgery. For no patient was removal of the implant necessary via vitrectomy in order to control IOP.

BRVO/CRVO
The clinical safety of OZURDEX in patients with macular oedema secondary to central or branch retinal vein occlusion has been evaluated in two phase III randomised, double-blind,
sham-controlled studies. In the two phase III studies 427 patients were
randomised to receive OZURDEX and 426 to receive sham treatment. In total, 401
(94%) patients randomised and treated with OZURDEX completed the initial treatment period (up to day 180).
In total, 47.3% of patients reported at least one adverse reaction. The most
frequently reported adverse reactions in patients who had been treated with OZURDEX were
increased intraocular pressure (24.0%) and conjunctival haemorrhage (14.7%).
The profile of adverse reactions for patients with BRVO cases was similar to that observed
for patients with CRVO, although the overall incidence of adverse reactions was higher for the subgroup of patients with CRVO.
The increase in intraocular pressure (IOP) with OZURDEX peaks at day
60, then returns to baseline levels by day 180. The IOP elevation required no treatment or was managed with temporary use of topical therapy to control IOP. During the
initial treatment period, 0.7% (3/421) of patients who received OZURDEX
required laser or surgical procedures to manage elevated IOP in the study eye,
compared to 0.2% (1/423) of patients receiving sham treatment.
The profile of adverse reactions in 341 patients analysed after a second OZURDEX injection
was similar to that observed with the first injection. In total, 54% of patients reported
at least one adverse reaction. The incidence of IOP increase (24.9%) was similar to that
recorded 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 of the eye
caused by non-infectious uveitis was evaluated in a single randomised, multicentre, blinded study.
In total, 77 patients were randomised to receive OZURDEX, and 76 to receive a sham
treatment. In total, 73 patients (95%) randomised and treated with OZURDEX completed
the 26-week study.
The most frequently reported adverse reactions in the study eye of patients who had
been treated with OZURDEX were conjunctival haemorrhage (30.3%), increased
intraocular pressure (25.0%) and cataract (11.8%).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions that occur after authorisation of the medicinal
product is important, as it allows continuous monitoring of the benefit/risk balance of the
medicinal product. Healthcare professionals are requested to report any suspected adverse reactions through the
national reporting system listed in Appendix V.

4.9 Overdosage

In case of overdosage, intraocular pressure must be checked and, if deemed necessary by the
physician, must be treated.

5.3 Preclinical safety data

In preclinical studies, effects were observed only at dosages considered sufficiently
higher than the maximum dose for humans, which indicates poor clinical relevance.
No data are available for OZURDEX regarding mutagenicity, carcinogenicity or reproductive and
developmental toxicity. Dexamethasone has shown to be teratogenic in mice and rabbits after
topical ophthalmic applications.
In rabbits, exposure to dexamethasone was observed following contralateral diffusion
into the healthy/untreated eye after implantation of an implant in the posterior part of the eye.

6. PHARMACEUTICAL INFORMATION

6.6 Special precautions for disposal and handling

OZURDEX is for single use only.
A single applicator can only be used for the treatment of one eye.
The applicator must not be used if the seal of the bag containing the applicator is damaged.
Once the bag is opened, the applicator must be used immediately.

Administration of OZURDEX

• 1) Hold the long axis of the applicator parallel to the limbus.

• 2) Rest the applicator needle on the sclera, holding it at an oblique angle and with the bevel facing upwards. Push the tip of the needle into the sclera for approximately 1 mm, keeping the needle parallel to the limbus.

• 3) Direct the needle towards the centre 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 beyond the point where the silicone sleeve comes into contact with the conjunctiva.

• 4) Slowly press the activation button until you hear a “click”. Before removing the applicator from the eye, make sure that the activation button has been fully pressed, locking at the level of the applicator surface.

• 5) Remove the applicator in the same direction as it was inserted into the eye.

• 6) Dispose of the applicator safely immediately after treatment. OZURDEX is a single-use applicator only.

Unused medicine and waste derived from such medicine must be disposed of in accordance with
current local regulations.