Lucentis
(ranibizumab)Dosage & Administration
For ophthalmic intravitreal injection only
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Lucentis Prescribing Information
LUCENTIS is indicated for the treatment of patients with:
Neovascular (Wet) Age-Related Macular Degeneration (AMD)
Macular Edema Following Retinal Vein Occlusion (RVO)
Diabetic Macular Edema (DME)
Diabetic Retinopathy (DR)
Myopic Choroidal Neovascularization (mCNV)
General Dosing Information
FOR OPHTHALMIC INTRAVITREAL INJECTION.
Neovascular (Wet) Age-Related Macular Degeneration (AMD)
LUCENTIS 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).
Although not as effective, patients may be treated with 3 monthly doses followed by less frequent dosing with regular assessment. In the 9 months after three initial monthly doses, less frequent dosing with 4-5 doses on average is expected to maintain visual acuity while monthly dosing may be expected to result in an additional average 1-2 letter gain. Patients should be assessed regularly [see Clinical Studies (14.1)].
Although not as effective, patients may also be treated with one dose every 3 months after 4 monthly doses. Compared with continued monthly dosing, dosing every 3 months over the next 9 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average. Patients should be assessed regularly [see Clinical Studies (14.1)].
Macular Edema Following Retinal Vein Occlusion (RVO)
LUCENTIS 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).
In Studies RVO-1 and RVO-2, patients received monthly injections of LUCENTIS for 6 months. In spite of being guided by optical coherence tomography and visual acuity re-treatment criteria, patients who were then not treated at Month 6 experienced on average, a loss of visual acuity at Month 7, whereas patients who were treated at Month 6 did not. Patients should be treated monthly [see Clinical Studies (14.2)].
Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR)
LUCENTIS 0.3 mg (0.05 mL of 6 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).
Myopic Choroidal Neovascularization (mCNV)
LUCENTIS 0.5 mg (0.05 mL of 10 mg/mL LUCENTIS solution) is recommended to be initially administered by intravitreal injection once a month (approximately 28 days) for up to 3 months. Patients may be retreated if needed [see Clinical Studies (14.5)].
Preparation for Administration
Prefilled Syringe:
The prefilled syringe is sterile and is for single-dose only. Do not use the product if the packaging is damaged or has been tampered with.
To prepare LUCENTIS for intravitreal administration, please adhere to these instructions for use. Read all the instructions carefully before using the prefilled syringe.
The opening of the sealed tray and all subsequent steps should be done under aseptic conditions.
For the intravitreal injection, a 30-gauge × ½ inch sterile injection needle should be used (not provided).
Note: the dose must be set to 0.05 mL.
| Device description | |
LUCENTIS prefilled syringes are available in 2 dose strengths:
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| Check the labels on the LUCENTIS carton, syringe tray and prefilled syringe to make sure you have the correct dose strength.
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| Step 1: Prepare | |
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| Step 2: Inspect syringe | |
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| Step 3: Remove syringe cap | |
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| Step 4: Attach needle | |
Note: Do not wipe the needle at any time. | |
| Step 5: Dislodge air bubbles | |
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| Step 6: Expel air and adjust drug dose | |
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| Step 7: Inject | |
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Administration
The intravitreal injection procedure should be carried out under controlled aseptic conditions, which include the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide should be given prior to the injection.
Prior to and 30 minutes following the intravitreal injection, patients should be monitored for elevation in intraocular pressure using tonometry. Monitoring may also consist of a check for perfusion of the optic nerve head immediately after the injection [see Warnings and Precautions (5.2)]. Patients should also be monitored for and instructed to report any symptoms suggestive of endophthalmitis without delay following the injection [see Warnings and Precautions (5.1)].
Each prefilled syringe should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new prefilled syringe should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, and injection needle should be changed before LUCENTIS is administered to the other eye.
No special dosage modification is required for any of the populations that have been studied (e.g., gender, elderly).
Single-dose prefilled syringe designed to provide 0.05 mL for intravitreal injection.
- Colorless to pale yellow 10 mg/mL solution (LUCENTIS 0.5 mg)
- Colorless to pale yellow 6 mg/mL solution (LUCENTIS 0.3 mg)
Pregnancy
Risk Summary
There are no adequate and well-controlled studies of LUCENTIS administration in pregnant women.
Administration of ranibizumab to pregnant monkeys throughout the period of organogenesis resulted in a low incidence of skeletal abnormalities at intravitreal doses 13-times the predicted human exposure (based on maximal serum trough levels [Cmax]) after a single eye treatment at the recommended clinical dose. No skeletal abnormalities were observed at serum trough levels equivalent to the predicted human exposure after a single eye treatment at the recommended clinical dose [see Animal Data].
Animal reproduction studies are not always predictive of human response, and it is not known whether ranibizumab can cause fetal harm when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for ranibizumab [see Clinical Pharmacology (12.1)], treatment with LUCENTIS may pose a risk to human embryofetal development.
LUCENTIS should be given to a pregnant woman only if clearly needed.
Data
Animal Data
An embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received intravitreal injections of ranibizumab every 14 days starting on Day 20 of gestation, until Day 62 at doses of 0, 0.125, and 1 mg/eye. Skeletal abnormalities including incomplete and/or irregular ossification of bones in the skull, vertebral column, and hindlimbs and shortened supernumerary ribs were seen at a low incidence in fetuses from animals treated with 1 mg/eye of ranibizumab. The 1 mg/eye dose resulted in trough serum ranibizumab levels up to 13 times higher than predicted Cmax levels with single eye treatment in humans. No skeletal abnormalities were seen at the lower dose of 0.125 mg/eye, a dose which resulted in trough exposures equivalent to single eye treatment in humans. No effect on the weight or structure of the placenta, maternal toxicity, or embryotoxicity was observed.
Lactation
Risk Summary
There are no data available on the presence of ranibizumab in human milk, the effects of ranibizumab on the breastfed infant or the effects of ranibizumab on milk production/excretion.
Because many drugs are excreted in human milk, and because the potential for absorption and harm to infant growth and development exists, caution should be exercised when LUCENTIS is administered to a nursing woman.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LUCENTIS and any potential adverse effects on the breastfed child from ranibizumab.
Females and Males of Reproductive Potential
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 the anti-VEGF mechanism of action for ranibizumab, treatment with LUCENTIS may pose a risk to reproductive capacity.
Pediatric Use
The safety and effectiveness of LUCENTIS in pediatric patients have not been established.
Geriatric Use
In the clinical studies, approximately 76% (2449 of 3227) of patients randomized to treatment with LUCENTIS were ≥ 65 years of age and approximately 51% (1644 of 3227) were ≥ 75 years of age [see Clinical Studies (14)]. No notable differences in efficacy or safety were seen with increasing age in these studies. Age did not have a significant effect on systemic exposure.
Ocular or Periocular Infections
LUCENTIS is contraindicated in patients with ocular or periocular infections.
Hypersensitivity
LUCENTIS is contraindicated in patients with known hypersensitivity to ranibizumab or any of the excipients in LUCENTIS. Hypersensitivity reactions may manifest as severe intraocular inflammation.
Endophthalmitis and Retinal Detachments
Intravitreal injections, including those with LUCENTIS, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique should always be used when administering LUCENTIS. In addition, patients should be monitored following the injection to permit early treatment should an infection occur [see Dosage and Administration (2.6, 2.7) and Patient Counseling Information (17)].
Increases in Intraocular Pressure
Increases in intraocular pressure have been noted both pre-injection and post-injection (at 60 minutes) while being treated with LUCENTIS. Monitor intraocular pressure prior to and following intravitreal injection with LUCENTIS and manage appropriately [see Dosage and Administration (2.7)].
Thromboembolic Events
Although there was a low rate of arterial thromboembolic events (ATEs) observed in the LUCENTIS clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. Arterial thromboembolic events are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).
Neovascular (Wet) Age-Related Macular Degeneration
The ATE rate in the three controlled neovascular AMD studies (AMD-1, AMD-2, AMD-3) during the first year was 1.9% (17 of 874) in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS compared with 1.1% (5 of 441) in patients from the control arms [see Clinical Studies (14.1)]. In the second year of Studies AMD-1 and AMD-2, the ATE rate was 2.6% (19 of 721) in the combined group of LUCENTIS-treated patients compared with 2.9% (10 of 344) in patients from the control arms. In Study AMD-4, the ATE rates observed in the 0.5 mg arms during the first and second year were similar to rates observed in Studies AMD-1, AMD-2, and AMD-3.
In a pooled analysis of 2-year controlled studies [AMD-1, AMD-2, and a study of LUCENTIS used adjunctively with verteporfin photodynamic therapy (PDT)], the stroke rate (including both ischemic and hemorrhagic stroke) was 2.7% (13 of 484) in patients treated with 0.5 mg LUCENTIS compared to 1.1% (5 of 435) in patients in the control arms [odds ratio 2.2 (95% confidence interval (0.8-7.1)].
Macular Edema Following Retinal Vein Occlusion
The ATE rate in the two controlled RVO studies during the first 6 months was 0.8% in both the LUCENTIS and control arms of the studies (4 of 525 in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS and 2 of 260 in the control arms) [see Clinical Studies (14.2)]. The stroke rate was 0.2% (1 of 525) in the combined group of LUCENTIS-treated patients compared to 0.4% (1 of 260) in the control arms.
Diabetic Macular Edema and Diabetic Retinopathy
Safety data are derived from studies D-1 and D-2. All enrolled patients had DME and DR at baseline [see Clinical Studies (14.3, 14.4)].
In a pooled analysis of Studies D-1 and D-2 [see Clinical Studies (14.3)], the ATE rate at 2 years was 7.2% (18 of 250) with 0.5 mg LUCENTIS, 5.6% (14 of 250) with 0.3 mg LUCENTIS, and 5.2% (13 of 250) with control. The stroke rate at 2 years was 3.2% (8 of 250) with 0.5 mg LUCENTIS, 1.2% (3 of 250) with 0.3 mg LUCENTIS, and 1.6% (4 of 250) with control. At 3 years, the ATE rate was 10.4% (26 of 249) with 0.5 mg LUCENTIS and 10.8% (27 of 250) with 0.3 mg LUCENTIS; the stroke rate was 4.8% (12 of 249) with 0.5 mg LUCENTIS and 2.0% (5 of 250) with 0.3 mg LUCENTIS.
Fatal Events in Patients with Diabetic Macular Edema and Diabetic Retinopathy at Baseline
Diabetic Macular Edema and Diabetic Retinopathy
Safety data are derived from studies D-1 and D-2. All enrolled patients had DME and DR at baseline [see Clinical Studies (14.3, 14.4)].
A pooled analysis of Studies D-1 and D-2 [see Clinical Studies (14.3)], showed that fatalities in the first 2 years occurred in 4.4% (11 of 250) of patients treated with 0.5 mg LUCENTIS, in 2.8% (7 of 250) of patients treated with 0.3 mg LUCENTIS, and in 1.2% (3 of 250) of control patients. Over 3 years, fatalities occurred in 6.4% (16 of 249) of patients treated with 0.5 mg LUCENTIS and in 4.4% (11 of 250) of patients treated with 0.3 mg LUCENTIS. Although the rate of fatal events was low and included causes of death typical of patients with advanced diabetic complications, a potential relationship between these events and intravitreal use of VEGF inhibitors cannot be excluded.
Retinal Vasculitis with or without Occlusion
Retinal vasculitis with or without occlusion, typically in the presence of preexisting intraocular inflammation or post-treatment with other intravitreal agents, have been reported with the use of LUCENTIS. Discontinue treatment with LUCENTIS in patients who develop these events. Patients should be instructed to report any change in vision without delay [see Patient Counseling Information (17)].