Lucentis

Wet AMD Treatment Agents

 
NOTE: Ranibizumab is available as a solution for intravitreal injection (Lucentis, Byooviz, Cimerli) and as a solution for ocular implantation (Susvimo). These formulations are not interchangable. Do NOT substitute the solution for ocular implantation with the solution for intravitreal injection. Do NOT administer the solution for ocular implantation as a bolus intravitreal injection.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Ranibizumab solution for intravitreal injection should be clear to slightly opalescent and colorless to pale yellow.

Use the solution for intravitreal injection (Lucentis, Byooviz, or Cimerli). Other ranibizumab products, such as Susvimo, MUST NOT be given via bolus intravitreal injection.
 
Intravitreal Product Preparation
Vial (Lucentis, Byooviz, or Cimerli)
Using aseptic technique, withdraw the entire contents of the vial through a sterile 5-micron, 19-gauge by 1.5 inch filter needle attached to a 1 mL tuberculin syringe.
Discard the filter needle and replace with a sterile 30-gauge by 0.5 inch needle for the intravitreal injection.
Hold the syringe with the needle pointing up and gently tap the syringe until any air bubbles rise to the top
Hold the syringe at eye level and carefully push the plunger rod until the plunger tip is aligned with the 0.05 mL dose mark.
 
Prefilled Syringe (Lucentis)
Prefilled syringes are available in 2 dose strengths. Check labels on the carton, syringe tray, and prefilled syringe to make sure you have the correct dose strength.
0.5 mg prefilled syringe (10 mg/mL) with clear finger grip.
0.3 mg prefilled syringe (6 mg/mL) with orange finger grip.
After removing the syringe from the sealed tray, snap off the syringe cap; do not turn or twist the cap.
Attach a 30-gauge by 0.5 inch needle firmly onto the syringe, and remove the needle cap.
Hold the syringe with the needle pointing up and gently tap the syringe until any air bubbles rise to the top.
Hold the syringe at eye level and carefully push the plunger until the edge below the dome of the rubber stopper is aligned with the 0.05 mL dose mark. To prevent air being drawn into the syringe, the plunger rod is not attached to the rubber stopper.
 
Intravitreal Administration
Only for use by ophthalmologists trained in these specialized administration techniques.
The intravitreal injection procedure must be carried out under aseptic conditions, which includes use of surgical hand disinfection, sterile gloves, a sterile drape, and sterile eye speculum (or equivalent).
Adequate anesthesia and broad-spectrum topical microbicides should be given prior to the injection.
Each prefilled syringe or vial should be used for the treatment of a single eye. If the contralateral eye requires treatment, a new prefilled syringe or vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, and needles should be changed before administration to the other eye.
Prior to and 30 minutes following the intravitreal injection, monitor patients for elevation in intraocular pressure, perfusion of the optic nerve head, and for endophthalmitis.
Instruct patients to urgently report any symptoms suggestive of endophthalmitis or retinal detachment (e.g., ocular pain, redness of the eye, photophobia, blurred vision).

Ocular Implantation
Only use the solution for ocular implantation (Susvimo). Other ranibizumab products MUST NOT be used to fill the ocular implant.
Visually inspect for particulate matter and discoloration prior to administration whenever solution and container permit. Ranibizumab solution for ocular implantation should be clear to slightly opalescent and colorless to pale brown. Do NOT use if particulate, cloudiness, or discoloration are visible.
Inspect the packaging for damage and check the expiration date. Do NOT use if sterility has been compromised or the contents have been dropped, damaged, or tampered with.
 
Ocular Implant Initial Fill
The initial fill of the ocular implant must be performed under aseptic conditions by a physician experienced in vitreoretinal surgery.
The implant will be filled with 0.02 mL of solution prior to insertion into the patient's eye.
Gather the following supplies:
Ocular implant with insertion tool assembly (included)
Initial fill needle (34-gauge with integrated 5 micrometer filter) with BLUE cap (included)
Ranibizumab 100 mg/mL vial (included)
Sterile 5-micron filter needle (19-gauge x 1.5 inches) (not included)
Sterile 1 mL Luer lock syringe (not included)
Using the FILTER NEEDLE attached to the Luer lock syringe, aseptically withdraw all the contents of the vial into the syringe.
With the filter needle still attached, hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with a finger until the bubbles rise to the top. Slowly push the plunger rod just until all air is expelled from the syringe and needle. Take care to preserve as much drug as possible. Once the air is expelled, remove and properly discard the filter needle.
Attach the INITIAL FILL NEEDLE to the Luer lock syringe. Do NOT wipe the needle at any time.
With the initial fill needle attached, hold the syringe with the needle pointing. If there are any air bubbles, gently tap the syringe with a finger until the bubbles rise to the top. Slowly push the plunger rod until all air is expelled and a drop of solution is seen at the needle tip. Take care to preserve as much drug as possible.
Inspect the syringe for air bubbles. If air bubbles are present, continue to remove air and reinspect. The syringe must be used within 15 minutes of removing all air in order to avoid the solution from drying in the needle and impeding fluid flow. Do NOT use if the needle is clogged.
Use the following step to load the syringe into the carrier. Do NOT hold or push the plunger rod of the syringe while inserting the needle into the implant septum.
Retrieve the insertion tool carrier with pre-positioned implant from the inner tray.
Align the syringe Luer lock above the Luer lock slot in the carrier to protect the needle from being damaged.
Lower the syringe into the carrier.
Taking care to avoid touching the plunger rod, push the syringe forward until it stops. This will penetrate the implant septum.
Under the microscope, SLOWLY administer the solution into the ocular implant by slightly tilting the carrier upwards. The implant should be filled over approximately 5 to 10 seconds to help avoid air entrapment in the implant reservoir.
NOTE: When filling the implant, solution should only exit the implant from the release control element. If solution is leaking from the implant at a different location (e.g., sides), do NOT use the implant. If solution is leaking from the septum at the needle insertion site, the needle may not be fully penetrating the implant septum. Fully push the syringe forward before continuing to fill the implant.
Continue filling the implant until it is completely full of solution and all air has been expelled as indicated by a dome of drug solution forming at the tip of the implant on the release control element.
Inspect the implant under a microscope to ensure it is completely full of drug solution.
NOTE: Minimize air bubbles within the implant reservoir as they may slow drug release. If a bubble is present, it must be no larger than one-third of the widest diameter of the implant. Do NOT use the implant if excess air is observed.
Insert the implant into the patients eye WITHIN 30 minutes of the initial filling to ensure the release control element remain saturated with ranibizumab solution. If ranibizumab solution dries in the release control element, the drug may not properly release from the implant into the vitreous after insertion.
Remove the syringe and guide sleeve from the carrier by pulling back on the syringe. Properly dispose of the used syringe, needle, and guide sleeve.
Slide the insertion tool handle into the guide channel of the carrier, ensuring that both components are facing upwards. Push the handle forward as far as it will go into the gripper tips. Do NOT withdraw the handle and implant until the eye is ready for insertion.
 
Ocular Implant Insertion
Insertion of the implant must be performed in an operating room under aseptic conditions by a physician experienced in vitreoretinal surgery.
After placing an infusion line in the eye, create at least a 6x6 mm peritomy of the conjunctiva and Tenon's capsule centered around the selected implant location in the supero-temporal quadrant.
Perform careful conjunctival incision, hemostasis of the underlying sclera, and generous undermining of Tenon's capsule.
NOTE: At this point, the implant is filled as described above.
Using an MVR blade, create a full thickness dissection of the sclera 4 mm from the limbus until the pars plana is fully visible, with final target scleral incision length of 3.5 mm.
Using a 532 nm laser endoprobe, apply contiguous, overlapping laser spots starting at 300 mW 1,000 ms along the full length of the exposed pars plana and repeat until complete ablation is achieved.
Pass a 3.2 mm slit knife perpendicularly through the center of the scleral dissection to open the underlying pars plana.
Use the insertion tool to slowly insert the implant into the sclero-pars plana incision perpendicular to the globe, ensuring that the long axis of the implant flange is properly aligned with the sclero-pars plana incision.
Using the closed gripper tips of the insertion tool, seat the implant flush against the sclera.
Clean any residual vitreous around the implant flange using a vitrector.
Suture both Tenon's capsule and conjunctiva, using scleral anchoring at the apex of the peritomy, ensuring complete coverage of the implant flange.
 
Ocular Implant Removal
Removal of the implant must be performed in an operating room under aseptic conditions by a physician experienced in vitreoretinal surgery.
After placing an infusion line in the eye, create at least a 6x6 peritomy of the conjunctiva and Tenon's capsule around the ocular implant flange.
Remove any fibrous capsule or scar tissue that may have formed over the implant flange and septum using scalpel and forceps.
With the explant tool oriented perpendicular to the globe, align the contoured tips with the long axis of the implant flange and grasp underneath the implant flange.
Once the implant is secured in the explant tool, pull the implant from the eye in a perpendicular motion.
Clear any vitreous prolapse present within or around the scleral wound using a vitrector.
Completely close the scleral incision with multiple non-absorbable sutures.
Close the Tenon's capsule and conjunctiva to completely cover the scleral incision.
 
Ocular Implant Refill-Exchange Procedure
Before and after the refill-exchange procedure, perform a dilated slit lamp exam and/or dilated indirect ophthalmoscopy to inspect the implant in the vitreous cavity through the pupil to identify if dislodgement of the implant septum has occurred. If the septum has dislodged, any further refill-exchange procedures SHOULD NOT be performed because normal device functioning cannot be assured. Discontinue treatment following septum dislodgement and consider implant removal should the benefit of the removal procedure outweigh the risk.
The refill-exchange procedure must be performed under aseptic conditions by a physician experienced in ophthalmic surgery; including use of surgical mask, gloves, and a lid speculum. Use aseptic technique when opening packaging and removing the sterile refill needle.
NOTE: The outside of the ranibizumab vial is not sterile.
Gather the following supplies:
Refill needle (34-gauge with integrated 5 micrometer filter) with CLEAR cap (included)
Ranibizumab 100 mg/mL vial (included)
Sterile 5-micron filter needle (19-gauge x 1.5 inches) (not included)
Sterile 1 mL Luer lock syringe (not included)
Additional non-included materials: anesthetic ophthalmic solutions, ophthalmic broad-spectrum microbicide solution, cotton tips and gauze, sterile powder-free gloves, face masks, lid speculum, sterile drape (optional), magnification (e.g., visor or loupes), task lighting, indirect ophthalmoscope and lens.
Patient preparation:
Dilate the pupil of the eye.
Perform slit lamp examination and/or indirect ophthalmoscopy to inspect the implant and its components in the` vitreous cavity through the dilated pupil.
Position the patient on exam chair in the supine position at approximately a 20- to 30-degree angle for optimal visualization of the implant.
Apply a broad-spectrum microbicide to the periocular skin, eyelid, and ocular surface prior to the procedure. Use of a sterile drape is up to physician's discretion.
Perform the procedure under topical anesthesia. If needed, subconjunctival anesthesia may be administered in the nasal quadrant, away from the implant.
Using the FILTER NEEDLE attached to the Luer lock syringe, aseptically withdraw all the solution from the vial into the syringe.
With the filter needle still attached, hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with a finger until the bubbles rise to the top. Slowly push the plunger rod just until all air is expelled from the syringe and needle. Take care to preserve as much drug as possible. Once the air is expelled, remove and properly discard the filter needle.
Attach the REFILL NEEDLE securely to the Luer lock syringe. Do NOT wipe the needle at any time.
With the refill needle attached, hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with a finger until the bubbles rise to the top. Slowly push the plunger rod until all air is expelled from the syringe and the uppermost edge of the black plunger tip is aligned with the 0.1 mL dose mark.
Inspect the syringe and needle hub using magnification to ensure that no air bubbles are present. Air injected into the implant could result in slower drug release. Use the syringe within 15 minutes of removing all air to avoid the solution drying in the needle and impeding fluid flow. Do NOT use the refill needle or syringe if the needle is clogged.
Perform the refill-exchange procedure using magnification.
Place the lid speculum in the eye and stabilize the globe with a cotton-tipped applicator to minimize eye movement.
To optimally expose the implant, stand on the contralateral side of the implanted eye with the patient looking down and toward their nose.
Orient the refill needle perpendicular to the globe.
Insert the needle at the very center of the implant septum and perpendicular to the implant. Do NOT maneuver if there is resistance as it will bend the needle. Do NOT use a bent refill needle; replace if bent or damage is suspected.
Targeting the center of the implant septum, insert the refill needle perpendicularly through the conjunctiva and into the implant septum. If excess resistance occurs, withdraw the needle, reorient, and insert again. Do NOT twist when encountering conjunctiva and Tenon's capsule to gain acces to the septum, as damage to the overlying tissue and septum of the device may result. Continue inserting the needle until the soft stop of the refill needle makes physical contact with the conjunctiva.
To avoid pressure build-up in the implant reservoir, refill the implant SLOWLY, by delivering the entire contents of the syringe into the implant over approximately 5 to 10 seconds. The soft stop of the needle must remain in contact with the conjunctiva throughout the procedure.
As the solution is administered into the implant, existing solution from the implant should immediately begin to fill the refill needle fluid collection chamber. If fluid is not observed in the collection chamber, stop injecting and ensure the refill needle is inserted into the center of the implant septum at a perpendicular angle and the soft stop is in contact with the conjunctiva.
Administer all the syringe contents in order to achieve the target replacement concentration in the implant reservoir.
Withdraw the syringe perpendicular to the globe to avoid damaging the septum. A cotton-tipped applicator may be used to provide counter traction to the conjunctiva during withdrawal.
Properly dispose of the used syringe and refill needle.
Perform dilated indirect ophthalmoscopy (and slit lamp exam as needed) to ensure continued proper position of the implant and its components (e.g., septum) in the vitreous cavity and to examine for complications.

ocular hemorrhage / Delayed / 5.2-74.0
ocular hypertension / Delayed / 7.0-24.0
renal failure (unspecified) / Delayed / 0-7.0
atrial fibrillation / Early / 1.0-5.0
stroke / Early / 0.2-4.8
endophthalmitis / Delayed / 1.7-2.0
retinal detachment / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known

cataracts / Delayed / 2.0-28.0
conjunctival hyperemia / Early / 0-26.0
iritis / Delayed / 23.0-23.0
blurred vision / Early / 5.0-18.0
ocular inflammation / Early / 1.0-18.0
blepharitis / Early / 0-12.0
antibody formation / Delayed / 1.0-12.0
hyperemia / Delayed / 5.0-11.0
anemia / Delayed / 1.0-11.0
constipation / Delayed / 0-8.0
hypercholesterolemia / Delayed / 1.0-7.0
peripheral edema / Delayed / 0-6.0
peripheral neuropathy / Delayed / 0-5.0
corneal edema / Early / 4.0-4.0
impaired wound healing / Delayed / 0-1.0
ocular infection / Delayed / Incidence not known

ocular pain / Early / 10.0-35.0
foreign body sensation / Rapid / 7.0-16.0
pharyngitis / Delayed / 5.0-16.0
ocular irritation / Rapid / 7.0-15.0
lacrimation / Early / 2.0-14.0
ocular pruritus / Rapid / 1.0-12.0
headache / Early / 3.0-12.0
arthralgia / Delayed / 2.0-11.0
nausea / Early / 1.0-10.0
cough / Delayed / 1.0-9.0
sinusitis / Delayed / 3.0-8.0
influenza / Delayed / 3.0-7.0
gastroesophageal reflux / Delayed / 1.0-6.0
injection site reaction / Rapid / 0-5.0

Ranibizumab intravitreal injections and ocular implants are contraindicated for use in patients with an ocular infection or periocular infection. Additionally, the instillation and refill procedures of the ocular implants should be delayed in any patient with a severe systemic infection. Cases of endophthalmitis have been reported with both the intravitreal injections and ocular implants; however, the ocular implants are associated with a 3-fold higher rate of endophthalmitis than the monthly intravitreal injections (1.7% to 2% vs. 0.5%). Many of the endophthalmitis cases reported preceding or concurrent conjunctival retraction or erosion events. The risk of endophthalmitis is increased in the presence of conjunctival retractions or erosions, especially if the implant becomes exposed. The implant and the tissue overlying the implant flange should be monitored routinely. Appropriate intraoperative handling, conjunctiva management, and early detection can preserve the tissue integrity may reduce the risk of endophthalmitis. In cases of conjunctival retraction or erosion with or without exposure of the implant flange, surgical intervention (e.g., conjunctival or Tenon's capsule repair) is recommended. Additionally, a broad-spectrum ocular microbicide should be given prior to the intravitreal injection or implant refill procedure. Use controlled aseptic conditions, which includes the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Patients should be monitored to permit early treatment should an infection occur. Instruct patients to immediately report any signs or symptoms that could be associated with an infection (e.g., pain, redness, sensitive to light, decreased visual acuity).

Byooviz, CIMERLI, Lucentis, Susvimo

Rx

Recombinant humanized monoclonal antibody fragment which binds to all active isoforms of vascular endothelial growth factor (VEGF)
Used intravitreally for neovascular (wet) age-related macular degeneration (AMD), macular edema after retinal vein occlusion, diabetic macular edema (DME), diabetic retinopathy, and myopic choroidal neovascularization (CNV); used as an ocular implant for AMD
Ocular implant has black box warning due to a 3-fold higher rate of endophthalmitis as compared to intravitreal injections

2 mg (0.02 mL of 100 mg/mL solution) continuously delivered via an ocular implant. The implant is refilled every 24 weeks (approximately 6 months). If a planned refill-exchange dose is missed, it should be administered as soon as possible and the subsequent refill-exchange procedures should be performed 24 weeks thereafter. If clinically necessary, supplemental treatment with 0.5 mg (0.05 mL of 10 mg/mL solution) intravitreal ranibizumab injection may be administered in the affected eye while the implant is in place.

0.5 mg by intravitreal injection to affected eye once a month (approximately every 28 days). Although less effective, treatment may be reduced to 3 once monthly doses, followed by less frequent dosing (i.e., an average of 4 to 5 injections over the subsequent 9 months), Visual acuity can be expected to be maintained with the less frequent dosing, whereas monthly dosing would result in a visual acuity gain of 1 to 2 letters. Alternatively, patients may also receive 4 once monthly injections, then 1 injection every 3 months. Compared to continued monthly dosing, extending the dosing interval to every 3 months will lead to an approximate 5 letter (1 line) loss of visual acuity benefit, on average, over the subsequent 9 months. Regularly evaluate patients.

0.3 mg by intravitreal injection in the affected eye(s) once monthly (approximately every 28 days). Guidelines recommend intravitreous anti-vascular endothelial growth factor (anti-VEGF) agents, such as ranibizumab, as first-line therapies for the management of central-involved diabetic macular edema. Anti-VEGF agents may be considered for management of proliferative diabetic retinopathy (PDR), especially if high-risk characteristics are present. Intravitreous anti-VEGF agents can reduce the risk of vision loss in patients with PDR. Ranibizumab efficacy for these conditions has been shown in several studies.

0.5 mg by intravitreal injection to affected eye once a month (approximately every 28 days). In studies, patients received monthly injections for 6 months. Patients who were not treated at month 6 experienced a loss of visual acuity as compared to patients who were treated at month 6.

0.5 mg by intravitreal injection to affected eye once a month (approximately every 28 days) for up to 3 months. Patients may be retreated if needed.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; reduction in ranibizumab clearance is minimal in patients with renal impairment and is considered clinically insignificant. It appears that no dosage adjustments are needed.

There are no drug interactions associated with Ranibizumab products.

Byooviz/CIMERLI/Lucentis/Susvimo Intravitreal Inj Sol: 0.05mL, 0.1mL, 0.3mg, 0.5mg, 10mg

2 mg single ocular implant; 0.5 mg single intravitreal dose monocular. Intravitreal doses up to 2 mg monocular have been clinically evaluated in 6 patients during a dose escalating study; higher doses were well tolerated and biologically active through 20 weeks of treatment.

2 mg single ocular implant; 0.5 mg single intravitreal dose monocular. Intravitreal doses up to 2 mg monocular have been clinically evaluated in 6 patients during a dose escalating study; higher doses were well tolerated and biologically active through 20 weeks of treatment.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Ranibizumab is a recombinant humanized anti-VEGF antibody fragment which binds competitively to the receptor binding sites of active forms of VEGF-A. VEGF-A is a glycoprotein involved in angiogenesis and cell proliferation. Although the pathogenesis of neovascular (wet) age-related macular degeneration (AMD) is not completely defined, VEGF-A is expressed in choroidal neovascular membranes and is thought to contribute to the induction of angiogenesis and microvascular leakage in AMD. The binding of ranibizumab to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells thus reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation. At 48 kilodalton, one third the length of its full length parent molecule bevacizumab, ranibizumab easily penetrates all layers of the retina. Intravitreal injection and ocular implantation delivers the drug to the site of neovascularization, occurring in the retina or within the retina, while minimizing systemic exposure and interference with the normal extraocular roles of VEGF.

Ranibizumab is administered by intravitreal injection and as an ocular implant. The metabolism of ranibizumab has not been studied; however, the drug is a monoclonal antibody fragment and antibodies are cleared predominately by catabolism. The full excretion profile is unknown.
 
Affected cytochrome P450 isoenzymes: none

Intravitreal Route
Intravitreal administration allows ranibizumab to penetrate all layers of the retina while minimizing the amount of drug reaching the systemic circulation. With monthly intravitreal injections, mean maximum serum concentrations (Cmax) were 1.7 ng/mL, which were below the concentration range of ranibizumab (11 to 27 ng/mL) necessary to inhibit the biological activity of vascular endothelial growth factor A (VEGF-A) by 50% as measured in an in vitro cellular proliferation assay. Based on a population pharmacokinetic analysis, maximum serum concentrations are predicted to be reached at approximately 1 day after monthly intravitreal administration of ranibizumab 0.5 mg per eye. Serum ranibizumab concentrations are predicted to be approximately 90,000-fold lower than vitreal concentrations, with a minimum steady state concentration (Cmin) of approximately 0.22 ng/mL with a monthly dosing regimen. Based on the disappearance of ranibizumab from serum, the estimated average vitreous elimination half-life is approximately 9 days. No anti-ranibizumab antibodies are detected in serum after multiple doses.
 
Ocular Implant Route
The ocular implant provides continuous release of ranibizumab into the vitreous; however, the amount of drug released decreases over time as the concentration within the implant decreases with a half-life of approximately 25 weeks. Following implant insertion, the mean Cmax of ranibizumab is 0.48 +/- 0.17 ng/mL and the median time to reach peak serum concentration (Tmax) is 26 day (range: 1 to 89 days). Serum concentrations from the ocular implant (refilled every 24 weeks) are maintained below the Cmax and above the Cmin achieved with monthly intravitreal injections. Additionally, the Cmax of ranibizumab after the initial fill and after refills of the implant reservoir are below the drug concentrations needed to inhibit the biological activity of vascular endothelial growth factor (VEGF) by 50%. Ranibizumab does not accumulate in the serum when administered with refills every 24 weeks.

There are no studies of ranibizumab in pregnant patients. It is unknown whether ranibizumab can cause fetal harm when administered during pregnancy or whether it can affect reproductive capacity. When administered intravenously to pregnant cynomolgus monkeys at doses which resulted in trough exposures equivalent to single eye treatment in humans, no skeletal abnormalities were seen. However, when administered at doses resulting in 13-times the predicted maximum exposure of a single intravitreal eye treatment or 41-times the maximum exposure after treatment with an ocular implant in humans, skeletal abnormalities including incomplete or irregular ossification of bones in the skull, vertebral column, and hind limbs and shortened supernumerary ribs were observed. No effect on weight or structure of the placenta, maternal toxicity, or embryotoxicity was observed.

There are no data available on the presence of ranibizumab in human milk, the effects on a breast-fed infant, or the effects on milk production. Because many drugs are excreted in breast milk and the potential for absorption and harm to infant growth and development exists, use caution when administering ranibizumab to a breast-feeding woman. However, with monthly intravitreal injections, maximum serum concentrations are dose proportional and are predicted to be approximately 90,000-fold lower than vitreal concentrations, which may limit exposure of the infant through breast-feeding. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for ranibizumab and any potential adverse effects on the breast-fed infant from exposure to the drug.