- fluocinolone acetonide
POM: Prescription only medicine
This information is intended for use by health professionals
PosologyThe recommended dose is one ILUVIEN implant in the affected eye. Administration in both eyes concurrently is not recommended (see Section 4.4).Each ILUVIEN implant releases fluocinolone acetonide for up to 36 months. An additional implant may be administered after 12 months if the patient experiences decreased vision or an increase in retinal thickness secondary to recurrent or worsening diabetic macular oedema (see Section 5.1).Retreatments should not be administered unless the potential benefits outweigh the risks.Only patients who have been insufficiently responsive to prior treatment with laser photocoagulation or other available therapies for diabetic macular oedema should be treated with ILUVIEN.
Paediatric populationThere is no relevant use of intravitreally administered fluocinolone acetonide in the paediatric population in diabetic macular oedema (DMO).
Special populationsNo dosage adjustments are necessary in elderly patients, or those with renal or hepatic impairment.
Method of administrationFOR INTRAVITREAL USE ONLY.Treatment with ILUVIEN is for intravitreal use only and should be administered by an ophthalmologist experienced in intravitreal injections. The intravitreal injection procedure should be carried out under controlled aseptic conditions, which include use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anaesthesia and a broad-spectrum microbicide should be given prior to the injection.The injection procedure for ILUVIEN is as follows:1. Preoperative antibiotic drops may be administered at the discretion of the treating ophthalmologist.2. Just prior to injection, administer topical anaesthesia over the injection site (inferotemporal quadrant recommended) as one drop followed by either a cotton-tipped applicator soaked in anaesthetic or as subconjunctival administration of adequate anaesthesia.3. Administer 2-3 drops of adequate topical antiseptic into the lower fornix. The lids may be scrubbed with cotton-tipped applicators soaked with an adequate topical antiseptic. Place a sterile lid speculum. Have the subject look up and apply a cotton-tipped applicator soaked with an adequate antiseptic to the injection site. Allow 30-60 seconds for the topical antiseptic to dry prior to injection of ILUVIEN.4. The exterior of the tray should not be considered sterile. An assistant (non-sterile) should remove the tray from the carton and examine the tray and lid for damage. If damaged, do not use unit.If acceptable, the assistant should peel the lid from the tray without touching the interior surface. 5. Visually check through the viewing window of the preloaded applicator to ensure that there is a drug implant inside. 6. Remove the applicator from the tray with sterile gloved hands touching only the sterile surface and applicator. The protective cap on the needle should not be removed until ILUVIEN is ready to be injected.Prior to injection, the applicator tip must be kept above the horizontal plane to ensure that the implant is properly positioned within the applicator.7. To reduce the amount of air administered with the implant, the administration procedure requires two steps. Before injecting the needle in the eye, push the button down and slide it to the first stop (at the curved black marks alongside the button track). At the first stop, release the button and it will move to the UP position. If the button does not rise to the UP position, do not proceed with this unit.8. Optimal placement of the implant is inferior to the optic disc and posterior to the equator of the eye. Measure 4 millimeters inferotemporal from the limbus with the aid of calipers.9. Carefully remove the protective cap from the needle and inspect the tip to ensure it is not bent. 10. Gently displace the conjunctiva so that after withdrawing the needle, the conjunctival and scleral needle entry sites will not align. Care should be taken to avoid contact between the needle and the lid margin or lashes. Inject the needle in the eye. To release the implant, while the button is in the UP position, advance the button by sliding it forward to the end of the button track and remove the needle. Note: Ensure that the button reaches the end of the track before removing the needle.11. Remove the lid speculum and perform indirect ophthalmoscopy to verify placement of the implant, adequate central retinal artery perfusion and absence of any other complications. Scleral depression may enhance visualisation of the implant. Examination should include a check for perfusion of the optic nerve head immediately after the injection. Immediate IOP measurement may be performed at the discretion of the ophthalmologist.Following the procedure, patients should be monitored for potential complications such as endophthalmitis, increased intraocular pressure, retinal detachments, and vitreous haemorrhages or detachments. Biomicroscopy with tonometry should be performed between two and seven days after the implant injection.Thereafter it is recommended that patients are monitored at least quarterly for potential complications, due to the extended duration of release of fluocinolone acetonide, of approximately 36 months (see Section 4.4).
PregnancyThere are no data from the use of intravitreally administered fluocinolone acetonide in pregnant women. Animal studies are insufficient with respect to the reproductive toxicity of intravitreally administered fluocinolone acetonide (See Section 5.3). Although fluocinolone acetonide is undectable in the systemic circulation after local, intraocular treatment, fluocinolone is nonetheless a potent corticosteroid and even very low levels of systemic exposure may present some risk to the developing foetus. As a precautionary measure it is preferable to avoid the use of ILUVIEN during pregnancy.
Breast-feedingSystemically administered fluocinolone acetonide is excreted in breast milk. Although the systemic exposure of the breast-feeding woman to intravitreally administered fluocinolone acetonide is expected to be very low, a decision must be made whether to discontinue breast-feeding or to abstain from ILUVIEN therapy, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
FertilityThere are no fertility data available. However, effects on either male or female fertility are unlikely since the systemic exposure to fluocinolone acetonide following intravitreal administration is very low.
Summary of the safety profileIntravitreally administered fluocinolone acetonide was evaluated in 768 subjects (375 in the 0.2 µg/day/ILUVIEN group; 393 in the 0.5 µg/day group) with diabetic macular oedema across the FAME clinical trials. The most frequently reported adverse drug reactions included cataract operation, cataract and increased intraocular pressure.In the Phase 3 studies, 38.4% of subjects treated with ILUVIEN required IOP-lowering medication and 4.8% required IOP-lowering surgeries. The use of IOP-lowering medication was similar in subjects who received two or more treatments with ILUVIEN. Two cases of endophthalmitis were reported in subjects treated with ILUVIEN during the Phase 3 studies. This represents an incidence rate of 0.2% (2 cases divided by 1,022 injections).While the majority of subjects in the FAME clinical trials received only one implant (see Section 5.1), the long-term safety implications of retention of the non-bioerodable implant inside the eye are not known. In the FAME clinical trials, 3-year data show that events such as cataract, increased intraocular pressure and floaters occurred only slightly more frequently in subjects receiving 2 or more implants. This is considered a function of the increased exposure to the drug rather than an effect of the implant itself. In non-clinical studies, there were no indications of an increase in safety issues other than lens changes in the rabbit eyes with 2-4 implants over 24 months. The implant is made of polyimide and is essentially similar to an intraocular lens haptic; it is therefore expected to remain inert inside the eye.
Tabulated list of adverse eventsThe following undesirable effects were assessed to be treatment-related and are classified according to the following convention: 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); and very rare (≤ 1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
|Infections and infestations||Uncommon: endophthalmitis|
|Nervous system disorders||Uncommon: headache|
|Eye disorders||Very Common: cataract1, increased intraocular pressure2 Common: glaucoma3, eye pain4, vitreous haemorrhage, conjunctival haemorrhage, blurred vision5, reduced visual acuity, vitreous floaters Uncommon: retinal vascular occlusion6, optic nerve disorder, maculopathy, optic atrophy, conjunctival ulcer, iris neovascularisation, retinal exudates, vitreous degeneration, vitreous detachment, posterior capsule opacification, iris adhesions, ocular hyperaemia, sclera thinning, eye discharge, eye pruritus|
|Injury, poisoning and procedural complications||Uncommon: extrusion of implant, implant in line of sight, procedural complication, procedural pain|
|Surgical and medical procedures||Very Common: cataract operation Common: trabeculectomy, glaucoma surgery, vitrectomy, trabeculoplasty Uncommon: removal of extruded implant from sclera|
|General disorders and administration site conditions||Uncommon: Device dislocation|
Description of selected adverse reactionsThe long-term use of corticosteroids may cause cataracts and increased intraocular pressure. The frequencies stated below reflect the findings in all patients in the FAME studies. The observed frequencies in patients with chronic DMO were not significantly different to those in the overall population. The incidence of cataract in phakic subjects was approximately 82% in ILUVIEN treated subjects and 50% in sham treated subjects in the Phase 3 clinical trials. 80% of phakic subjects treated with ILUVIEN required cataract surgery by Year 3 compared to 27% of the sham treated subjects, with most subjects requiring surgery by 21 months. Posterior subcapsular cataract is the most common type of corticosteroid -related cataract. Surgery for this type of cataract is more difficult and may be associated with greater risk of surgical complications.In the FAME studies subjects with a baseline IOP of > 21 mm Hg were excluded. The incidence of increased intraocular pressure was 37%, and 38% of subjects required IOP-lowering medication, with half of these requiring at least two medications to control the IOP. The use of IOP-lowering medication was similar in subjects who received retreatment with an additional implant during the study. Additionally, 5.6% (21/375) of subjects who received an implant required a surgical or laser procedure to control the IOP (trabeculoplasty 5 (1.3%), trabeculectomy 10 (2.7%), endocycloablation 2 (0.5%), and other surgical procedures 6 (1.6%)). In the subset of subjects with greater than median IOP at baseline (≥15 mmHg), 47% required IOP-lowering medication and the proportion of surgical or laser procedures increased to 7.1%. In this subset, there were 5 (2.2%) subjects treated with trabeculoplasty, 7 (3.1%) with trabeculectomy, 2 (0.9%) with endocycloablation and 4 (1.8%) with other glaucoma surgical procedures.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. 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: Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard
Royal Pavilion, Wellesley Road, Aldershot, Hamsphire, GU11 1PZ
+44 (0) 1252 354 000
0800 019 1253
0800 148 8274