Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Endophthalmitis, intraocular inflammation, traumatic cataract, retinal detachment, retinal tear, retinal vasculitis, and/or retinal vascular occlusion

Intravitreal injections, including those with Beovu, have been associated with endophthalmitis, intraocular inflammation, traumatic cataract, retinal detachment and retinal tear (see section 4.8).
Proper aseptic injection techniques must always be used when administering Beovu.

Patients should be instructed to report any symptoms suggestive of the above-mentioned events without delay.

Intraocular inflammation, including retinal vasculitis and/or retinal vascular occlusion 
Intraocular inflammation, including retinal vasculitis and/or retinal vascular occlusion, has been reported with the use of Beovu (see sections 4.3 and 4.8). A higher number of intraocular inflammation events were observed among patients with treatment-emergent antibodies. After 
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investigation, retinal vasculitis and/or retinal vascular occlusion were found to be immune-mediated events. Intraocular inflammation, including retinal vasculitis and/or retinal vascular occlusion, may occur following the first intravitreal injection and at any time of treatment. These events were observed more frequently at the beginning of the treatment.

Based on clinical studies these events were more frequent in female patients treated with Beovu than male patients (e.g., 5.3% females vs. 3.2% males in HAWK and HARRIER) and in Japanese patients.

In patients developing these events, treatment with Beovu should be discontinued and the events should be promptly managed. Patients treated with Beovu with a medical history of intraocular inflammation and/or retinal vascular occlusion (within 12 months prior to the first brolucizumab injection) should be closely monitored, since they are at increased risk of developing retinal vasculitis and/or retinal vascular occlusion.
The interval between two Beovu doses during maintenance treatment should not be less than 8 weeks considering that a higher incidence of intraocular inflammation (including retinal vasculitis) and retinal vascular occlusion was reported in patients with nAMD who received Beovu every 4 week maintenance dosing in a clinical study compared to patients who received Beovu every 8 or 12 week maintenance dosing in the pivotal Phase III clinical studies.

Intraocular pressure increases

Transient increases in intraocular pressure have been seen within 30 minutes of intravitreal injection with vascular endothelial growth factor (VEGF) inhibitors, including brolucizumab (see section 4.8).
Special precaution is needed in patients with poorly controlled glaucoma (do not inject Beovu while the intraocular pressure is ≥30 mmHg). Both intraocular pressure and perfusion of the optic nerve head must be monitored and managed appropriately.

Bilateral treatment

The safety and efficacy of brolucizumab administered in both eyes concurrently have not been studied.
Immunogenicity

As this is a therapeutic protein, there is a potential for immunogenicity with brolucizumab (see section 4.8). 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 (see section 4.8).

Concomitant use of other anti-VEGF

There are no data available on the concomitant use of Beovu with other anti-VEGF medicinal products in the same eye. Brolucizumab should not be administered concurrently with other anti-VEGF medicinal products (systemic or ocular) (see section 4.5).

Withholding treatment

In intravitreal anti-VEGF treatments, the dose should be withheld and treatment should not be resumed earlier than the next scheduled treatment in the event of:
•      a decrease in best-corrected visual acuity (BCVA) of ≥30 letters compared with the last assessment of visual acuity;
•      a retinal break;
•      a subretinal haemorrhage involving the centre of the fovea, or, if the size of the haemorrhage is ≥50% of the total lesion area;
•      performed or planned intraocular surgery within the previous or next 28 days.



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Retinal pigment epithelial tear

Risk factors associated with the development of a retinal pigment epithelial tear after anti-VEGF therapy for wet AMD include a large and/or high pigment epithelial retinal detachment. When initiating brolucizumab therapy, caution should be used in patients with these risk factors for retinal pigment epithelial tears.

Rhegmatogenous retinal detachment or macular holes

Treatment should be discontinued in subjects with rhegmatogenous retinal detachment or stage 3 or 4 macular holes.

Systemic effects following intravitreal use

Systemic adverse events, including non-ocular haemorrhages and arterial thromboembolic events, have been reported following intravitreal injection of VEGF inhibitors and there is a theoretical risk that these may relate to VEGF inhibition. There are limited data on safety in the treatment of patients with AMD with a history of stroke, transient ischaemic attacks or myocardial infarction within the last 3 months. Caution should be exercised when treating such patients.

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free”.

Polysorbate 80 content

This medicinal product contains 0.01 mg polysorbate 80 per dose (0.05 ml). Polysorbates may cause allergic reactions. Patients need to be instructed to tell their doctor if they have any known allergies.

Effects on Driving

4.7    Effects on ability to drive and use machines

Beovu 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 visual function has recovered sufficiently.