WARNING: ENDOPHTHALMITIS
The SUSVIMO implant has been associated with an up to 3-fold higher rate of endophthalmitis than monthly intravitreal injections of ranibizumab. Many of these events were associated with conjunctival retractions or erosions. Appropriate conjunctiva management and early detection with surgical repair of conjunctival retractions or erosions may reduce the risk of endophthalmitis.
Contraindications
SUSVIMO is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or hypersensitivity to ranibizumab products or any of the excipients in SUSVIMO.
Warnings and Precautions
The SUSVIMO implant and/or implant-related procedures have been associated with endophthalmitis, rhegmatogenous retinal detachment, implant dislocation, septum dislodgement, vitreous hemorrhage, conjunctival erosion, conjunctival retraction, and conjunctival blebs. Patients should be instructed to report any signs or symptoms that could be associated with these events without delay. In some cases, these events can present asymptomatically. The implant and the tissue overlying the implant flange should be monitored routinely following the implant insertion and refill-exchange procedures to permit early medical or surgical intervention as necessary. Special precautions need to be taken when handling SUSVIMO components.
Endophthalmitis
In the active comparator period of controlled clinical trials in AMD, the ranibizumab implant has been associated with a 3-fold higher rate of endophthalmitis than monthly intravitreal injections of ranibizumab (1.7% in the SUSVIMO arm vs 0.5% in the intravitreal arm). When including extension phases of clinical trials, 2.0% (11/555) of patients receiving the ranibizumab implant experienced an episode of endophthalmitis. Reports occurred between Day 5 and Day 853, with a median of Day 173. Many, but not all, of the cases of endophthalmitis reported a preceding or concurrent conjunctival retraction or erosion event.
In the active comparator period of the controlled clinical trial in DME, 0.0% of patients in the SUSVIMO arm compared to 0.3% in the intravitreal arm experienced an episode of endophthalmitis. When including the extension phase of the clinical trial, 0.7% (4/556) of patients receiving the ranibizumab implant experienced an episode of endophthalmitis. Reports occurred between Days 625 and 1016, with a median of 824 Days.
Endophthalmitis should be treated promptly in an effort to reduce the risk of vision loss and maximize recovery. The SUSVIMO dose (refill-exchange) should be delayed until resolution of endophthalmitis. Patients should not have an active or suspected ocular or periocular infection or severe systemic infection at the time of any SUSVIMO implant or refill procedure. Appropriate intraoperative handling followed by secure closure of the conjunctiva and Tenon’s capsule, early detection and surgical repair of conjunctival erosions or retractions and strict/controlled aseptic technique conditions throughout refill-exchange procedures may reduce the risk of endophthalmitis.
Rhegmatogenous Retinal Detachment
Rhegmatogenous retinal detachments have occurred in clinical trials of SUSVIMO and may result in vision loss. Rhegmatogenous retinal detachments should be promptly treated with an intervention (e.g., pneumatic retinopexy, vitrectomy, or laser photocoagulation). SUSVIMO (ranibizumab injection) dose (refill-exchange) should be delayed in the presence of a retinal detachment or retinal break.
Careful evaluation of the retinal periphery is recommended and any suspected areas of abnormal vitreo-retinal adhesion or retinal breaks should be treated before inserting the implant in the eye.
Implant Dislocation
In clinical trials, the device has dislocated/subluxated into the vitreous cavity or has extended outside the vitreous cavity into or beyond the subconjunctival space. Device dislocation requires urgent surgical intervention. Strict adherence to the scleral incision length and appropriate targeting of the pars plana during laser ablation may reduce the risk of implant dislocation.
Septum Dislodgement
In clinical trials, a type of implant damage where the septum has dislodged into the implant body has been reported. Perform a dilated slit lamp exam and/or dilated indirect ophthalmoscopy to inspect the implant in the vitreous cavity through the pupil prior to and after the refill-exchange procedure to identify if septum dislodgement has occurred. Discontinue treatment with SUSVIMO following septum dislodgement and consider implant removal should the benefit of the removal procedure outweigh the risk.
Appropriate handling and insertion of the refill needle into the septum (avoid twisting and/or rotation) is required to minimize the risk of septum dislodgement.
Vitreous Hemorrhage
Vitreous hemorrhages may result in temporary vision loss. Vitrectomy may be needed in the case of a nonclearing vitreous hemorrhage.
In the SUSVIMO arm of clinical trials (including extension phases), vitreous hemorrhages were reported in 5.2% (23/443) of patients with AMD and 10.1% (56/556) of patients with DME.
The majority of these hemorrhages occurred within the first postoperative month following surgical implantation, and the majority of vitreous hemorrhages resolved spontaneously. Patients on antithrombotic medication (e.g., oral anticoagulants, aspirin, nonsteroidal anti-inflammatory drugs) may be at increased risk of vitreous hemorrhage. Antithrombotic medications are recommended to be temporarily interrupted prior to the implant insertion procedure. The SUSVIMO dose (refill-exchange) should be delayed in the event of sight-threatening vitreous hemorrhage. The use of pars plana laser ablation and scleral cauterization should be performed to reduce the risk of vitreous hemorrhage.
Conjunctival Erosion or Retraction
A conjunctival erosion is a full-thickness degradation or breakdown of the conjunctiva in the area of the implant flange. A conjunctival retraction is a recession or opening of the limbal and/or radial peritomy. Conjunctival erosions or retractions have been associated with an increased risk of endophthalmitis, especially if the implant becomes exposed. Surgical intervention (e.g., conjunctival/Tenon’s capsule repair) is recommended in cases of conjunctival erosion or retraction with or without exposure of the implant flange.
In the SUSVIMO arm of clinical trials (including extension phases), conjunctival erosion in the study eye was reported in 3.6% (16/443) of patients with AMD and 2.2% (12/556) of patients with DME. The incidence of reported conjunctival retraction in the study eye was 1.6% (7/443) in the AMD trial and 1.3% (7/556) in the DME trial.
Appropriate intraoperative handling of the conjunctiva and Tenon’s capsule to preserve tissue integrity and secure closure of peritomy while ensuring placement of sutures away from implant edge may reduce the risk of conjunctival erosion or retraction. The implant and the tissue overlying the implant flange should be monitored routinely following the implant insertion.
Conjunctival Bleb
A conjunctival bleb is an encapsulated elevation of the conjunctiva above the implant flange, which may be secondary to subconjunctival thickening or fluid. Conjunctival blebs may require surgical management to avoid further complications, especially if the implant septum is no longer identifiable due to the conjunctival bleb.
In the SUSVIMO arm of clinical trials (including extension phases), conjunctival bleb/conjunctival filtering bleb leak was reported in the study eye of 5.9% (26/443) of patients with AMD and 9.0% (50/556) of patients with DME.
Strict adherence to the scleral incision length, appropriate intraoperative handling of the conjunctiva and Tenon’s capsule to preserve tissue integrity and secure closure of peritomy, and proper seating of the refill needle during refill-exchange procedures may reduce the risk of conjunctival bleb.
Postoperative Decrease in Visual Acuity
Visual acuity was decreased by an average of 4 letters in the first postoperative month and an average of 2 letters in the second postoperative month following initial implantation of SUSVIMO in patients with AMD. Visual acuity was decreased by 7 letters on average in the first postoperative month and 3 letters on average in the second postoperative month following initial implantation of SUSVIMO in patients with DME.
Air Bubbles Causing Improper Filling of the Implant
Minimize air bubbles within the implant reservoir, as they may cause slower drug release. During the initial fill procedure, if an air bubble is present, it must be no larger than ⅓ of the widest diameter of the implant. If excess air is observed after initial fill, do not use the implant. During the refill-exchange procedure, if excess air is present in the syringe and needle, do not use the syringe and needle. If excess air bubbles are observed after the refill-exchange procedure, consider repeating the refill-exchange procedure.
Deflection or Movement of the Implant
Use caution when performing ophthalmic procedures (e.g., B-scan ophthalmic ultrasound, scleral depression, or gonioscopy) that may cause deflection or movement of the implant and subsequent injury.
Adverse Reactions
In clinical trials of SUSVIMO, the most common (≥10%) adverse reactions reported up to Week 40 in patients with AMD were conjunctival hemorrhage (72%), conjunctival hyperemia (26%), iritis (23%), and eye pain (10%). Septum dislodgement was reported in 0.4% of the AMD patient population. In patients with DME, the most common adverse reactions reported up to Week 64 were conjunctival hemorrhage (62%), conjunctival hyperemia (15%), iritis (14%), eye pain (13%), cataract (11%), conjunctival disorder (10%) and vitreous hemorrhage (10%).
Females and Males of Reproductive Potential
Females of reproductive potential should use effective contraception during treatment with SUSVIMO and for at least 12 months after the last dose of SUSVIMO. No studies on the effects of ranibizumab on fertility have been conducted and it is not known whether ranibizumab can affect reproduction capacity. Based on the anti-VEGF mechanism of action for ranibizumab, treatment with SUSVIMO may pose a risk to reproductive capacity.
You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.
Please see additional Important Safety Information in the full SUSVIMO Prescribing Information, including BOXED WARNING.
