Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Oxurion NV, Gaston Geenslaan 1, B-3001, Leuven, Belgium
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Active or suspected ocular or periocular infections.
JETREA is administered by intravitreal injection only. Intravitreal injections have been associated with intraocular inflammation/infection, intraocular haemorrhage and increased intraocular pressure (IOP). Proper aseptic injection techniques must always be used. Following the intravitreal injection, patients should be monitored for any side effects such as (but not limited to) intraocular inflammation/infection and elevation in IOP. Transient increases in IOP including transient blindness and non-perfusion of the optic nerve have been seen within 60 minutes of injection of JETREA.
Monitoring for increases in IOP may consist of a check for perfusion of the optic nerve head immediately after the injection and tonometry within 30 minutes following the injection. Intraocular inflammation/infection may be assessed using biomicroscopy between 2 and 7 days following the injection. Patients should be instructed to report symptoms suggestive of intraocular inflammation/infection or any other visual or ocular symptoms without delay. If any of the above events occur the patient should be treated according to standard medical practice.
The safety and efficacy of JETREA administered to both eyes concurrently has not been studied. Therefore administration to both eyes concurrently is not recommended.
Repeated administration of JETREA in the same eye has not been adequately studied and is therefore not recommended.
JETREA has not been studied in patients with large diameter macular holes (> 400 microns), high myopia (>8 dioptre spherical correction or axial length > 28 mm), aphakia, history of rhegmatogenous retinal detachment, lens zonule instability, recent ocular surgery or intraocular injection (including laser therapy), proliferative diabetic retinopathy, ischaemic retinopathies, retinal vein occlusions, exudative age-related macular degeneration (AMD) and vitreous haemorrhage. Treatment is not recommended in such patients.
There is limited experience in patients with non-proliferative diabetic retinopathy or history of uveitis (including active severe inflammation) or significant eye trauma. Caution should be exercised when treating such patients.
The potential for lens subluxation or phacodonesis cannot be ruled out. If this event occurs, it should be treated according to standard medical practice. Patients should be monitored appropriately (see section 4.8 and 5.3).
The effect of ocriplasmin (particularly in inducing resolution of vitreomacular adhesion or causing total posterior vitreous detachment [PVD]) is reduced in subjects with an epiretinal membrane (ERM) or a diameter of VMA >1500 microns (see section 5.1).
There is a risk for a significant decrease in visual acuity during the first week after the injection. Patients should be monitored appropriately (see section 4.8).
Ophthalmological examinations may be abnormal following the administration of JETREA. These include optical coherence tomography (OCT), ophthalmoscopy (foveal reflex), colour vision test (Roth 28-hue) and full-field ERG. This should be taken into consideration when using these tests for the diagnosis or monitoring of other conditions (see section 4.8).
No formal interaction studies have been performed.
Ocriplasmin is a proteolytic enzyme with serine protease activity which could be present in the eye for several days after intravitreal injection (see section 5.2). Administration in close temporal association with other medicinal products in the same eye may affect the activity of both medicinal products and is therefore not recommended.
There are no clinical data on concomitant use of ocriplasmin with VEGF-inhibitors (vascular endothelial growth factor) and therefore it is not recommended.
No systemic interactions are anticipated.
There are no data for the use of JETREA in pregnant women. No reproductive toxicology studies have been performed. The systemic exposure of JETREA is expected to be very low after intravitreal injection. JETREA should be used during pregnancy only if the clinical benefit outweighs the potential risks.
It is unknown whether JETREA is excreted in human milk. JETREA should be used during breast-feeding only if the clinical benefit outweighs the potential risks.
There are no data on the effect of JETREA on fertility.
The intravitreal injection of JETREA may have a moderate influence on the ability to drive and use machines due to possible temporary visual disturbances (see section 4.8). In these cases, patients should not drive or use machines until the visual disturbances have resolved.
Over 1400 patients have been treated with the recommended dose of 0.125 mg of JETREA in interventional clinical studies.
All adverse reactions were ocular. In 3 clinical studies with follow-up from 6 months (TG-MV-006 and TG-MV-007) to 24 months (TG-MV-014), the most commonly reported adverse reactions were vitreous floaters, eye pain, photopsia and chromatopsia as well as conjunctival haemorrhage resulting from the injection procedure. Most of the adverse reactions occurred within the first week after the injection. The majority of these reactions were non-serious, mild to moderate in intensity and resolved within 2 to 3 weeks. Information on resolution of specific events such as chromatopsia and ERG changes can be found in the relevant paragraph of the ‘description of selected adverse reactions’ section.
The most clinically relevant adverse reactions included blindness transient, retinal tear, retinal detachment, lens subluxation and macular hole progression.
The following table summarises the adverse reactions reported in the treated eye in clinical studies and/or from post-marketing experience.
Visual symptoms perceived in the contralateral eye or bilaterally have also been reported.
The adverse reactions with a reasonable possibility of causal relationship to the injection procedure or JETREA are listed by MedDRA system organ class and frequency using 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); very rare (<1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Very common: Vitreous floaters, eye pain, conjunctival haemorrhage, chromatopsia*
Common: Visual acuity reduced*, visual impairment1, visual field defect2), vision blurred, retinal haemorrhage, vitreous haemorrhage, macular hole*, macular degeneration, retinal degeneration, macular oedema3, retinal oedema4, retinal pigment epitheliopathy, metamorphopsia, conjunctival oedema, eyelid oedema, vitritis, anterior chamber cell, anterior chamber flare, iritis, photopsia, conjunctival hyperaemia, ocular hyperaemia, vitreous detachment, eye irritation, dry eye, foreign body sensation in eyes, eye pruritus, ocular discomfort, photophobia, lacrimation increased
Uncommon: Blindness transient, lens subluxation*, retinal tear*5), retinal detachment*5, night blindness, pupillary reflex impaired, diplopia, hyphaema, miosis, pupils unequal, corneal abrasion, anterior chamber inflammation, eye inflammation, conjunctival irritation
Very common: Retinogram abnormal*, colour vision test abnormal†
Common: Intraocular pressure increased, macular reflex abnormal, optical coherence tomography (OCT) abnormal*
* see section 'Description of selected adverse reactions'
1 including dim vision
2 including scotoma
3 including cystoid macular oedema
4 including subretinal fluid
5 events occurring pre-vitrectomy
† using the Roth 28-hue colour vision test. See also section 4.4.
In the placebo-controlled pivotal phase III studies (TG-MV-006 and TG-MV-007), 7.7% of JETREA patients and 1.6% of placebo patients had acute ≥2-line (≥10 ETDRS letters) loss in best-corrected visual acuity (BCVA) during the first week after injection with no alternative explanation for the change. The visual acuity decrease had resolved by the end of the studies for the majority of JETREA patients (80.6%) but there were some patients who had not recovered despite vitrectomy. The median time to resolution was 22 days. In study TG-MV-014, 2.8% of JETREA patients and 1.4% of sham patients had acute ≥2-line loss in BCVA during the first week after injection. Out of the 4 JETREA patients with acute visual acuity decrease, 3 recovered following vitrectomy. See section 4.4 for monitoring recommendations.
Colour vision alterations (including yellowish vision and abnormal Roth 28-hue colour vision test) have been reported as a very common adverse reaction in patients injected with JETREA. The majority of events were non-serious, mild and generally resolved spontaneously. The median time to resolution was 3 months.
Electroretinographic (ERG) changes (a- and b-wave amplitude decrease) have been reported as a very common adverse reaction in patients injected with JETREA; in the majority of cases visual impairment and chromatopsia were also reported.
In study TG-MV-014, a sub-set of 40 patients receiving JETREA systematically underwent ERG testing; the ERG changes which had developed in 16 out of 40 patients resolved in the majority of patients (13 out of 16). The median time to resolution was 6 months. ERG changes were not predictive of negative outcomes in terms of visual acuity; visual acuity improved or was maintained in 15 out of 16 patients compared to baseline.
In the placebo-controlled pivotal phase III studies (TG-MV-006 and TG-MV-007), retinal breaks (tears and detachment) were reported in 1.9% of patients injected with JETREA vs. 4.3% injected with placebo. Most of these events occurred during or after vitrectomy in both groups. The incidence of retinal detachment that occurred pre-vitrectomy was 0.4% in the JETREA group and none in the placebo group, while the incidence of retinal tears (without detachment) that occurred pre-vitrectomy was 0.2% in the JETREA group and 0.5% in the placebo group. In study TG-MV-014, retinal tear was reported in 1.4% of patients injected with JETREA and 6.8% of sham recipients; the incidence of retinal detachment was 1.4% in both arms. In the sham group, no events occurred prior to vitrectomy. In the JETREA group, 1 patient (0.7%) developed retinal tear and retinal detachment between Day 0 and Day 7 post-injection.
In the placebo-controlled pivotal phase III studies (TG-MV-006 and TG-MV-007), events of macular hole (including both progression and new onset) were reported for 6.7% of all patients injected with JETREA vs. 9.6% injected with placebo at Month 6. In study TG-MV-014, events of macular hole (including both progression and new onset) were reported in 15.8% JETREA vs. 13.5% sham recipients at Month 24.
Early progression rates of full-thickness macular hole (until Day 7 post-injection) at RPE (retinal pigment epithelium) level were higher in the JETREA treated patients compared to sham or placebo. Progression rates after Month 6, however, were higher in sham or placebo than in those treated with JETREA. Any persistence or progression of macular hole should be treated according to usual practice.
One case of lens subluxation/phacodonesis was reported in clinical studies in adults and appears to have been possibly related to treatment with JETREA. In a paediatric study evaluating JETREA as an adjunct to vitrectomy, one case of subluxation was reported in a premature infant who received a single intravitreal injection of JETREA 0.175 mg. Lens subluxation was observed in 3 animal species at ocriplasmin concentrations above the intended clinical concentration (see section 5.3).
Based on the proteolytic activity of ocriplasmin, preclinical and clinical findings, the potential for lens subluxation or phacodonesis cannot be ruled out. If this event occurs, it should be treated according to standard medical practice.
In study TG-MV-014, incomplete Inner Segment/Outer Segment (IS/OS) band, also referred to as Ellipsoid Zone, in the central area was very common at baseline (65.8% in the JETREA group and 62.2% in the sham group). However, after treatment, a higher proportion of patients in the JETREA group had a change from an intact IS/OS band at baseline to an incomplete IS/OS band in the central area at a later time point compared with the sham group (7.7% and 2.8%, respectively at Day 28). Beyond the central area, abnormal aspects of the IS/OS band attributed to JETREA have been observed in up to 10% of patients.
Ellipsoid Zone disruption within and outside the central area has been reported in non-interventional studies and post-marketing reports. In the majority of cases recovery occurred within 6 months. Subretinal fluid and signs and symptoms of impaired photoreceptor function including decreased visual acuity (in some cases severe) were reported in association with these events.
See section 4.4 for monitoring recommendations. Routine observation is recommended in all above situations.
Reporting 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 listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products, other than sterile, preservative-free, non-buffered diluent sodium chloride 9 mg/mL (0.9%) solution for injection.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
