Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Outlook Therapeutics Limited, 10 Earlsfort Terrace, Dublin 2, D02 T380, Ireland
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Patients with active or suspected ocular or periocular infections.
Active intraocular inflammation.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Intravitreal injections have been associated with endophthalmitis, intraocular inflammation and retinal detachments/tears (see section 4.8). Proper aseptic injection technique should always be used when administering the medicinal product.
Immediately following the intravitreal injection, patients should be monitored for elevation in intraocular pressure. Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry. If required, sterile equipment for paracentesis should be available. In addition, patients should be monitored following the injection to permit early treatment should an infection occur.
Patients should be instructed to report any symptoms, such as eye pain, loss of vision, photophobia, blurred vision, floaters, or redness, suggestive of endophthalmitis or any of the above-mentioned events without delay, to permit prompt and appropriate management.
Increases in intraocular pressure have been noted post-injection (up to 60 minutes) while being treated with vascular endothelial growth factor (VEGF) inhibitors, including bevacizumab gamma (see section 4.8). Both intraocular pressure and the perfusion of the optic nerve head must be monitored prior to and following intravitreal injection with Lytenava and managed appropriately.
Special precaution is needed in patients with poorly controlled glaucoma (do not inject the medicinal product while the intraocular pressure is ≥30 mmHg).
The safety and efficacy of bevacizumab gamma administered in both eyes concurrently have not been studied. If bilateral treatment is performed at the same time, this could lead to an increased potential for adverse events, both ocular and systemic due to increased exposure.
As this is a therapeutic protein, there is a potential for immunogenicity with bevacizumab gamma. Patients should be instructed to inform their physician if they develop symptoms such as eye pain or increased discomfort, worsening eye redness, blurred or decreased vision, an increased number of small particles in their vision, or increased sensitivity to light.
There are no data available on the concomitant use of bevacizumab gamma with other anti-VEGF medicinal products in the same eye. Bevacizumab gamma should not be administered concurrently with other anti-VEGF medicinal products (systemic or ocular).
The dose should be withheld and treatment should not be resumed earlier than the next scheduled treatment in the event of:
Risk factors associated with the development of a retinal pigment epithelial tear after anti-VEGF therapy for nAMD include a large and/or high pigment epithelial retinal detachment. When initiating bevacizumab gamma therapy, caution should be used in patients with these risk factors for retinal pigment epithelial tears.
Treatment should be discontinued in subjects with rhegmatogenous retinal detachment or stage 3 or 4 macular holes.
Non-ocular haemorrhages and arterial thromboembolic events, have been reported following intravitreal injection of VEGF inhibitors, (see section 4.8). There are limited data on safety in the treatment of patients with nAMD with a history of stroke, transient ischaemic attacks or myocardial infarction within the last 3 months. Caution should be exercised when treating such patients.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.
No interaction studies have been performed. Based on the elimination of bevacizumab, no interactions are expected. However, bevacizumab gamma should not be administered concurrently with other systemic or ocular anti-VEGF medicinal products (see section 4.4).
Women of childbearing potential should use effective contraception during treatment with bevacizumab gamma and for at least three months after the last dose when stopping treatment with bevacizumab gamma.
There are no data on the use of bevacizumab gamma in pregnant women. Based on studies in animals with other anti-VEGFs, treatment with bevacizumab gamma may pose a risk to human embryo foetal development. Therefore, bevacizumab gamma should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus.
There are no data available on the presence of bevacizumab gamma in human milk, the effects of bevacizumab gamma on the breast-fed infant or the effects of bevacizumab gamma on milk production/excretion. A risk to the breast-fed newborn/infant cannot be excluded. A decision must be made whether to discontinue breast-feeding or to abstain from Lytenava therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
No reproductive or fertility studies have been conducted with bevacizumab gamma. VEGF inhibition has been shown to affect follicular development, corpus luteum function and fertility (see section 5.3). Ovarian effects can be attributed to a direct result of the local inhibition of VEGF on active angiogenesis, which is profound in the ovary.
Lytenava has a minor influence on the ability to drive and use machines due to possible temporary visual disturbances following the intravitreal injection and the associated eye examination. Patients should not drive or use machines until these temporary visual disturbances subside.
The majority of adverse reactions reported following administration of bevacizumab gamma are related to the intravitreal injection procedure. The most frequently reported adverse reactions were conjunctival haemorrhage (5.0%), vitreous floaters (1.5%), eye pain (1.2%), and intraocular pressure increased (1.2%). Less frequently reported, but more serious adverse reactions were intraocular pressure increases (0.6%), blindness transient (0.3%), endophthalmitis (0.3%), intraocular inflammation (0.3%).
A total of 341 patients from two randomized and one open-label clinical studies were treated with the recommended dose of 1.25 mg. The adverse reactions reported in clinical studies of bevacizumab gamma are listed in Table 1 below.
Adverse reactions are listed according to the MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Frequency categories for each adverse reaction are based on 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), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 1. Frequencies of adverse reactions:
| System organ class | Common | Uncommon |
|---|---|---|
| Infections and infestations | Endophthalmitis | |
| Immune system disorders | Iodine allergy | |
| Eye disorders | Vitreous floaters Eye pain Conjunctival haemorrhage | Retinal pigment epithelial tear, Vitreous haemorrhage, Iritis, Corneal scar, Keratopathy, Punctate keratitis, Blindness transient, Vitreous detachment, Photopsia, Ocular discomfort, Corneal abrasion, Eye irritation, Eye pruritus, Dry eye, Ocular hyperaemia |
| Investigations | Intraocular pressure increased |
Product-class-related adverse reactions There is a theoretical risk of arterial thromboembolic events, including stroke and myocardial infarction, following intravitreal use of VEGF inhibitors. A low incidence rate of arterial thromboembolic events was observed in the bevacizumab gamma clinical studies in patients with nAMD (see section 4.4).
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.
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