Posology : מינונים

4.2   Posology and method of administration

Treatment should be initiated and administered by a retinal surgeon experienced in performing macular surgery.

Posology

Patients will receive a single dose of 1.5 × 1011 vector genomes voretigene neparvovec in each eye.
Each dose will be delivered into the subretinal space in a total volume of 0.3 mL. The individual administration procedure to each eye is performed on separate days within a close interval, but no fewer than 6 days apart.

Immunomodulatory regimen
Prior to initiation of the immunomodulatory regimen and prior to administration of voretigene neparvovec, the patient must be checked for symptoms of active infectious disease of any nature, and in case of such infection the start of treatment must be postponed until after the patient has recovered.

Starting 3 days prior to the administration of voretigene neparvovec to the first eye, it is recommended that an immunomodulatory regimen is initiated following the schedule below (Table 1). Initiation of the immunomodulatory regimen for the second eye should follow the same schedule and supersede completion of the immunomodulatory regimen of the first eye.

Table 1     Pre- and post-operative immunomodulatory regimen for each eye 
Prednisone (or equivalent)
3 days prior to Luxturna
Pre-operative                                                       1 mg/kg/day administration
(maximum of 40 mg/day)
4 days                            Prednisone (or equivalent)
(including the day of             1 mg/kg/day administration)                   (maximum of 40 mg/day)
Prednisone (or equivalent)
Post-operative                    Followed by 5 days                0.5 mg/kg/day (maximum of 20 mg/day)
Prednisone (or equivalent)
Followed by 5 days of one dose
0.5 mg/kg every other day every other day
(maximum of 20 mg/day)

Special populations
Elderly
The safet a d effi a of oretige e epar o e i patie ts            years old have not been established. Data are limited. However, no adjustment in dose is necessary for elderly patients.

Hepatic and renal impairment
The safety and efficacy of voretigene neparvovec have not been established in patients with hepatic or renal impairment. No dose adjustment is required in these patients (see section 5.2).

Paediatric population
The safety and efficacy of voretigene neparvovec in children aged up to 4 years have not been established. Data are limited. No adjustment in dose is necessary for paediatric patients.
LUX API DEC23 V5                                                          Based on EU SmPC JUL23 Method of administration

Subretinal use.

Luxturna is a sterile concentrate solution for subretinal injection that requires thawing and dilution prior to administration (see section 6.6).

This medicinal product must not be administered by intravitreal injection.

Luxturna is a single-use vial for a single administration in one eye only. The product is administered as a subretinal injection after vitrectomy in each eye. It should not be administered in the immediate vicinity of the fovea to maintain foveal integrity (see section 4.4).

The administration of voretigene neparvovec should be carried out in the surgical suite under controlled aseptic conditions. Adequate anaesthesia should be given to the patient prior to the procedure. The pupil of the eye to be injected must be dilated and a broad-spectrum microbicide should be topically administered prior to the surgery according to standard medical practice.

For instructions for preparation, accidental exposure to and disposal of Luxturna, see section 6.6.

Administration
Follow the steps below to administer voretigene neparvovec to patients:
•     Diluted Luxturna should be inspected visually prior to administration. If particulates, cloudiness, or discoloration are visible, the medicinal product must not be used.
•     Connect the syringe containing the diluted product to the extension tube and subretinal injection cannula. The product is slowly injected through the extension tube and subretinal injection cannula to eliminate any air bubbles in the system.
•     The volume of product available for injection is confirmed in the syringe, by aligning the plunger tip with the line that marks 0.3 mL.
•     After vitrectomy is completed, Luxturna is administered by subretinal injection using a subretinal injection cannula introduced via pars plana (Figure 1A).
•     Under direct visualisation, the tip of the subretinal injection cannula is placed in contact with the retinal surface. The recommended site of injection should be located along the superior vascular arcade, at least 2 mm distal to the centre of the fovea (Figure 1B). A small amount of the product is slowly injected until an initial subretinal bleb is observed, and then the remaining volume is slowly injected until the total 0.3 mL is delivered.



LUX API DEC23 V5                                                             Based on EU SmPC JUL23 Figure 1A    Subretinal injection cannula introduced via pars plana



Figure 1B     Tip of the subretinal injection cannula placed within the recommended site of injection (surgeon’s view)



•     At the completion of the injection, the subretinal injection cannula is removed from the eye.
•     After injection, any unused product must be discarded. The back-up syringe may not be retained.
•     Fluid-air exchange is performed, carefully avoiding fluid drainage near the retinotomy created for the subretinal injection.
•     Supine head positioning is initiated immediately in the post-operative period and upon discharge should be maintained by the patient for 24 hours.