Dosing & Uses
Dosage Forms & Strengths
solution, intravitreal (via implant)
- 100mg/mL single-dose glass vial
- Initial kit and refill also contain fill needle (34-gauge needle with a 5-micron integrated filter)
Neovascular (Wet) Age-related Macular Degeneration
Indicated for treatment of neovascular (wet) AMD in patients who have previously responded to ≥2 intravitreal injections of a vascular endothelial growth factor (VEGF) inhibitor medication
2 mg (0.02 mL of 100 mg/mL solution) continuously delivered via ocular implant q24Weeks (~6 months)
Supplemental treatment: 0.5 mg (0.05 mL of 10 mg/mL) ranibizumab intravitreal injection in the affected eye while implant is in place and if clinically necessary
Dosage Modifications
Withhold dose (refill-exchange) for the following:
- Intraocular inflammation ≥1+ cells or flare
- Sight threatening events (eg, rhegmatogenous retinal detachment, vitreous hemorrhage, unexplained vision loss)
- Local infections of either eye
- Infectious endophthalmitis
- Severe systemic infection
- Observed damage to the implant; consider implant removal
Renal impairment
- Systemic clearance of ranibizumab was slightly lower in renally impaired patients, but was not clinically significant
Dosing Considerations
Do not administer ranibizumab intravitreal implant as a bolus intravitreal injection
Do not substitute with other ranibizumab products
Safety and efficacy not established
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (0)
Minor (0)
Adverse Effects
>10%
Conjunctival hemorrhage (72%)
Conjunctival hyperemia (26%)
Iritis (23%)
1-10%
Eye pain (10%)
Vitreous floaters (9%)
Conjunctival bleb/ filtering bleb leak (9%)
Foreign body sensation in eyes (7%)
Headache (7%)
Hypotony of eye (6%)
Vitreous detachment (6%)
Vitreous hemorrhage (5%)
Conjunctival edema (5%)
Corneal disorder (4%)
Corneal abrasion (4%)
Corneal edema (4%)
Warnings
Black Box Warnings
Endophthalmitis
- Implant associated with 3-fold higher rate of endophthalmitis than monthly intravitreal injections
- 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
Ocular or periocular infections
Active intraocular inflammation
Hypersensitivity to ranibizumab or product excipients
Cautions
Rhegmatogenous retinal detachments (eg, pneumatic retinopexy, vitrectomy, or laser photocoagulation) occurred and may result in vision loss; if this occurs, delay refill-exchange if retinal detachment or retinal break is present; carefully evaluate retinal periphery and treat any suspected areas of abnormal vitreoretinal adhesion or retinal breaks before inserting the implant
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
Conjunctival erosions or retractions have been associated with increased risk of endophthalmitis; especially when implant is exposed; perform surgical intervention (eg, conjunctival/Tenon’s capsule repair) is recommended if conjunctival erosion or retraction with or without exposure of the implant flange is present
Conjunctival blebs may require surgical management to avoid further complications, especially if implant septum is no longer identifiable due to the conjunctival bleb
Visual acuity was decreased by 4 letters on average in the first postoperative month and 2 letters on average in the second postoperative month following initial implantation
Use caution when performing ophthalmic procedures (eg, B-scan ophthalmic ultrasound, scleral depression, gonioscopy) that may cause deflection of the implant and subsequent injury
Endophthalmitis
- Risk of endophthalmitis or retinal detachment with intravitreous injections; cases more prevalent in intravitreal implant
- Always use proper aseptic injection technique when administering therapy
- Monitor and treat promptly to reduce the risk of vision loss and maximize recovery
- Patients should not have an active or suspected ocular or periocular infection or severe systemic infection at the time of any implant or refill procedure
- Appropriate intraoperative handling followed by secure closure of the conjunctiva and Tenon’s capsule, and early detection and surgical repair of conjunctival erosions or retractions may reduce the risk of endophthalmitis
Air bubbles in implant reservoir
- Minimize air bubbles within implant reservoir as they may cause slower drug release
- During initial fill procedure, if an air bubble is present, it must be ≤1/3 of the widest diameter of the implant; if excess air is observed after initial fill, do not use the implant
- During 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.
Vitreous hemorrhages
- Vitreous hemorrhages may result in temporary vision loss; vitrectomy may be needed in the case of a non-clearing vitreous hemorrhage
- Patients on antithrombotic medication (eg, oral anticoagulants, aspirin, nonsteroidal anti-inflammatory drugs) may be at increased risk of vitreous hemorrhage; temporarily hold antithrombotic medications before implant insertion
- Delay dose (refill-exchange) in the event of sight-threatening vitreous hemorrhage
- Use of pars plana laser ablation and perform scleral cauterization to reduce the risk of vitreous hemorrhage
Septum dislodgement
- Appropriate handling and insertion of refill needle into septum (avoid twisting and/or rotation) required to minimize risk of septum dislodgement
- Implant damage where the septum has dislodged into implant body reported
- Perform a dilated slit lamp exam and/or dilated indirect ophthalmoscopy to inspect the implant in vitreous cavity through the pupil before and after refill-exchange procedure to identify if septum dislodgement has occurred
- Discontinue treatment following septum dislodgement and consider implant removal should benefit outweigh the risk
Pregnancy & Lactation
Pregnancy
There are no adequate and well-controlled studies of ranibizumab intravitreal implant in pregnant females
Based on mechanism of action, treatment may pose a risk to human embryofetal development
Animal data
- Administration of ranibizumab to pregnant monkeys during organogenesis resulted in a low incidence of skeletal abnormalities at intravitreal doses up to 41 times of the human exposure
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for at least 12 months after the last dose
Infertility
- 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 mechanism of action, treatment may pose a risk to reproductive capacity
Lactation
No data are available on drug presence in human milk, its effects on breastfed infants, or its effects on milk production/excretion
Use drug with caution when administering to nursing females
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Recombinant humanized monoclonal antibody binds and inhibits human vascular endothelial growth factor (VEGF-A)
Binding to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation
Absorption
Peak plasma concentration: 0.48 ng/mL
Peak plasma time: 26 days
No accumulation in serum when administered with refills every 24 weeks
Elimination
Excretion profile for ranibizumab following administration is unknown
Administration
Intravitreal injection preparation
Transfer dose from 100 mg/mL-vial to 1-mL Luer lock syringe by using a 5-micron filter needle (not included in kit) to withdraw all contents of vial; do NOT use initial fill needle for this step
With filter needle attached, hold syringe with needle pointing up
Gently tap syringe with your finger to allow any air bubbles rise to the top
Slowly push plunger rod until air is fully expelled from syringe and needle
Remove and discard filter needle
Attach initial fill needle (34-gauge, with integrated 5-micron filter and blue cap; provided in kit)
Carefully remove cap by pulling straight off; do NOT wipe needle at any time
Gently tap syringe to remove bubbles; expel air and set dose
Use the syringe within 15 minutes of removing all air to avoid drug from drying in the needle and impeding fluid flow
Load syringe into carrier; do not hold or push on the plunger of the syringe while inserting needle into the implant septum
Under the microscope, slowly administer ranibizumab into the ocular implant by slightly tilting the carrier upwards; implant should be filled over ~5 to 10 seconds, to help avoid air entrapment in the implant reservoir
If solution is leaking from implant at a different location (eg, side of the implant), do not use the ocular implant
Inspect ocular implant under the microscope to ensure that implant is completely full of drug solution; ≤30 minutes should pass between initial fill of the implant and insertion into the patient’s eye to ensure that the release control element remains saturated
Remove syringe and guide sleeve from carrier by pulling back on the syringe; dispose used syringe and guide sleeve in accordance with local requirements
Slide insertion tool handle into carrier; do not withdraw handle and implant until eye is ready for insertion
Implant properties
- Implant holds 0.02 mL of drug, and is secured within the sclera, by the extrascleral flange that remains visible through the conjunctiva following insertion
- Implant septum is self-sealing interface through which ranibizumab is administered to fill the implant
Intravitreal Implant Administration
Do not administer ranibizumab as a bolus intravitreal injection; do not substitute ranibizumab intravitreal implant with other ranibizumab products
See complete instructions for implant initial fill and ocular refill-exchange procedure in the prescribing information
Following procedures must be performed under aseptic conditions
- Initial fill and ocular implant insertion and implant removal procedures by a physician experienced in vitreoretinal surgery
- Ocular implant must be surgically implanted in the eye or removed from the eye (if medically necessary) in an operating room
- Refill-exchange procedures by a physician experienced in ophthalmic surgery
Handling
Do not reprocess, resterilize, or reuse
Do not use if sterility has been compromised or contents have been dropped, damaged, or tampered with
Do not use past expiration date printed on label
Do not open sealed tray until time of use
Avoid contact between sharp surgical instruments and implant
Storage
Initial needle kit
- Refrigerate at 2-8ºC (36-46ºF)
- Do not freeze
- Protect from light
- Do NOT shake
- Initial fill needle has been sterilized with electron beam processing
Unused vials
- Refrigerate at 2-8ºC (36-46ºF)
- Do not freeze
- Protect from light
- Do NOT shake
- Before use, may be kept at 9-30ºC (48-86ºF) for up to 24 hr provided it is protected from light
Implant, insertion tool assembly, refill needle, and explant tool
- Store at room temperature 15-25ºC (59-77ºF)
- Implant and insertion tool assembly has been sterilized with ethylene oxide gas
- Refill needle and explant tool have been sterilized with electron beam processing
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