Ranivisio

/ Dexcel

Ranibizumab must be administered by a qualified ophthalmologist experienced in intravitreal injections.
Adults
The recommended dose for ranibizumab in adults is 0.5 mg given as a single intravitreal injection. This corresponds to an injection volume of 0.05 ml. The interval between two doses injected into the same eye should be at least four weeks.
Treatment in adults is initiated with one injection per month until maximum visual acuity is achieved and/or there are no signs of disease activity. i.e. no change in visual acuity and in other signs and symptoms of the disease under continued treatment. In patients with wet AMD, DME, PDR and RVO, initially, three or more consecutive, monthly injections may be needed.
Thereafter, monitoring and treatment intervals should be determined by the physician and should be based on disease activity, as assessed by visual acuity and/or anatomical parameters. If, in the physician’s opinion, visual and anatomic parameters indicate that the patient is not benefiting from continued treatment, ranibizumab should be discontinued.
Monitoring for disease activity may include clinical examination, functional testing or imaging techniques (e.g. optical coherence tomography or fluorescein angiography).
If patients are being treated according to a treat-and-extend regimen, once maximum visual acuity is achieved and/or there are no signs of disease activity, the treatment intervals can be extended stepwise until signs of disease activity or visual impairment recur. The treatment interval should be extended by two weeks at a time for wet AMD and may be extended by up to one month at a time for DME. For PDR and RVO, treatment intervals may also be gradually extended, however there are insufficient data to conclude on the length of these intervals. If disease activity recurs, the treatment interval should be shortened accordingly.
The treatment of visual impairment due to CNV should be determined individually per patient based on disease activity.
Ranibizumab and laser photocoagulation in DME and in macular oedema secondary to BRVO- There is some experience of ranibizumab administered concomitantly with laser photocoagulation. When given on the same day, ranibizumab should be administered at least 30 minutes after laser photocoagulation

Treatment of patients with neovascular (wet) age-related macular degeneration (AMD).
Treatment of adult patients with visual impairment due to diabetic macular oedema (DME).
Treatment of visual impairment due to macular oedema secondary to retinal vein occlusion (RVO).
Treatment of visual impairment due to choroidal neovascularization (CNV).
Treatment of proliferative diabetic retinopathy (PDR).

* Hypersensitivity to the active substance or to any of the excipients.
* Patients with active or suspected ocular or periocular infections.
* Patients with active severe intraocular inflammation.

Intravitreal injection-related reactions: Intravitreous injections, including those with ranibizumab, have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract. Proper aseptic injection techniques must always be used when administering ranibizumab. In addition, patients should be monitored during the week following the injection to permit early treatment if an infection occurs. Patients should be instructed to report any symptoms suggestive of endophthalmitis or any of the above mentioned events without delay.
Intraocular pressure increases: In adults transient increases in intraocular pressure (IOP) have been seen within 60 minutes of injection of ranibizumab. Sustained IOP increases have also been identified. Both intraocular pressure and the perfusion of the optic nerve head must be monitored and managed appropriately. Patients should be informed of the symptoms of these potential adverse reactions and instructed to inform their physician if they develop signs 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.
Bilateral treatment: Limited data on bilateral use of ranibizumab (including same-day administration) do not suggest an increased risk of systemic adverse events compared with unilateral treatment.
Immunogenicity: There is a potential for immunogenicity with ranibizumab. Since there is a potential for an increased systemic exposure in subjects with DME, an increased risk for developing hypersensitivity in this patient population cannot be excluded. Patients should also be instructed to report if an intraocular inflammation increases in severity, which may be a clinical sign attributable to intraocular antibody formation.
Concomitant use of other anti-VEGF (vascular endothelial growth factor):
Ranibizumab should not be administered concurrently with other anti-VEGF medicinal products (systemic or ocular).
Withholding ranibizumab in adults:
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;
* An intraocular pressure of ≥30 mmHg;
* 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.
Retinal pigment epithelial tear
Risk factors associated with the development of a retinal pigment epithelial tear after anti-VEGF therapy for wet AMD and potentially also other forms of CNV, include a large and/or high pigment epithelial retinal detachment. When initiating ranibizumab therapy, caution should be used in patients with these risk factors for retinal pigment epithelial tears.
Rhegmatogenous retinal detachment or macular holes in adults
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.
There are limited data on safety in the treatment of DME, macular oedema due to RVO and CNV secondary to PM patients with prior history of stroke or transient ischaemic attacks. Caution should be exercised when treating such patients
See prescribing information for full details.

The majority of adverse reactions reported following administration of ranibizumab are related to the intravitreal injection procedure.
The most frequently reported ocular adverse reactions following injection of ranibizumab are: eye pain, ocular hyperaemia, increased intraocular pressure, vitritis, vitreous detachment, retinal haemorrhage, visual disturbance, vitreous floaters, conjunctival haemorrhage, eye irritation, foreign body sensation in eyes, increased lacrimation, blepharitis, dry eye and eye pruritus.
The most frequently reported non-ocular adverse reactions are headache, nasopharyngitis and arthralgia.
See prescribing information for full details.

No formal interaction studies have been performed.
In clinical studies for the treatment of visual impairment due to DME, the outcome with regard to visual acuity or central retinal subfield thickness (CSFT) in patients treated with ranibizumab was not affected by concomitant treatment with thiazolidinediones.

Pregnancy: For ranibizumab no clinical data on exposed pregnancies are available. The systemic exposure to ranibizumab is low after ocular administration, but due to its mechanism of action, ranibizumab must be regarded as potentially teratogenic and embryo-/foetotoxic. Therefore, ranibizumab should not be used during pregnancy unless the expected benefit outweighs the potential risk to the foetus. For women who wish to become pregnant and have been treated with ranibizumab, it is recommended to wait at least 3 months after the last dose of ranibizumab before conceiving a child.
Lactation: Based on very limited data, ranibizumab may be excreted in human milk at low levels. The effect of ranibizumab on a breast-fed newborn/infant is unknown. As a precautionary measure, breast-feeding is not recommended during the use of ranibizumab.

Cases of accidental overdose have been reported from the clinical studies in wet AMD and post- marketing data. Adverse reactions associated with these reported cases were intraocular pressure increased, transient blindness, reduced visual acuity, corneal oedema, corneal pain, and eye pain. If an overdose occurs, consider monitoring and treating intraocular pressure.