Lucentis (ranibizumab injection) labeling
Genentech, Inc. Chambers
125156lbl HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use LUCENTIS safely and effectively. See full prescribing information for LUCENTIS.
LUCENTISTM (ranibizumab injection)
Initial U.S. Approval: 2006
-----------------INDICATIONS AND USAGE-------------------
LUCENTIS is indicated for the treatment of patients with neovascular (wet) age-related macular degeneration (1).
------------DOSAGE AND ADMINISTRATION---------------
· FOR OPHTHALMIC INTRAVITREAL INJECTION
ONLY (2.1)
· LUCENTIS 0.5 mg (0.05 mL) is recommended to be
administered by intravitreal injection once a month (2.2).
· Although less effective, treatment may be reduced to one
injection every three months after the first four injections if monthly injections are not feasible. Compared to continued monthly dosing, dosing every 3 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average, over the following 9 months. Patients should be evaluated regularly (2.2).
-------------DOSAGE FORMS AND STRENGTHS------------
· 10 mg/mL single-use vial (3)
---------------------CONTRAINDICATIONS--------------------
· Ocular or periocular infections (4.1) · Hypersensitivity (4.2)
--------------WARNINGS AND PRECAUTIONS--------------
· Endophthalmitis and retinal detachments may occur
following intravitreal injections. Patients should be monitored during the week following the injection (5.1).
· Increases in intraocular pressure have been noted within
60 minutes of intravitreal injection (5.2).
--------------------ADVERSE REACTIONS--------------------The most common adverse reactions (reported 6% higher in LUCENTIS-treated subjects than control subjects) are conjunctival hemorrhage, eye pain, vitreous floaters, increased intraocular pressure, and intraocular inflammation (6.2).
To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See Section 17 for PATIENT COUNSELING INFORMATION.
FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Information 2.2 Dosing 2.3 Preparation for Administration 2.4 Administration 2.5 Stability and Storage 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 4.1 Ocular or Periocular Infections 4.2 Hypersensitivity 5 WARNINGS AND PRECAUTIONS 5.1 Endophthalmitis and Retinal
Detachments 5.2 Increases in Intraocular Pressure 5.3 Thromboembolic Events 6 ADVERSE REACTIONS 6.1 Injection Procedure 6.2 Clinical Studies Experience Ocular
Events 6.3 Clinical Studies Experience Non-
Ocular Events 6.4 Immunogenicity 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Patients with Renal Impairment 8.7 Patients with Hepatic Dysfunction 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis,
Impairment of Fertility 14 CLINICAL STUDIES
14.1 Study 1 and Study 2 14.2 Study 3 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the Full Prescribing Information are not listed.
U.S. BLA (BL125156) Ranibizumab injection
Genentech, Inc.
FULL PRESCRIBING INFORMATION
1
INDICATIONS AND USAGE
LUCENTIS is indicated for the treatment of patients with
neovascular (wet) age-related macular degeneration.
2.5 Stability and Storage LUCENTIS should be refrigerated at 2º-8ºC (36º-46ºF). DO NOT FREEZE. Do not use beyond the date stamped on the label. LUCENTIS vials should be protected from light. Store in the original carton until time of use.
2
DOSAGE AND ADMINISTRATION
2.1 General Dosing Information FOR OPHTHALMIC INTRAVITREAL INJECTION ONLY.
2.2 Dosing LUCENTIS 0.5 mg (0.05 mL) is recommended to be administered by intravitreal injection once a month.
Although less effective, treatment may be reduced to one injection every three months after the first four injections if monthly injections are not feasible. Compared to continued monthly dosing, dosing every 3 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average, over the following 9 months. Patients should be evaluated regularly [see Clinical Studies (14.2)].
3
DOSAGE FORMS AND STRENGTHS
Single-use glass vial designed to deliver 0.05 mL of
10 mg/mL.
4
CONTRAINDICATIONS
4.1 Ocular or Periocular Infections LUCENTIS is contraindicated in patients with ocular or periocular infections.
4.2 Hypersensitivity LUCENTIS is contraindicated in patients with known hypersensitivity to ranibizumab or any of the excipients in LUCENTIS.
5
WARNINGS AND PRECAUTIONS
2.3 Preparation for Administration Using aseptic technique, all (0.2 mL) of the LUCENTIS vial contents are withdrawn through a 5-micron 19-gauge filter needle attached to a 1-cc tuberculin syringe. The filter needle should be discarded after withdrawal of the vial contents and should not be used for intravitreal injection. The filter needle should be replaced with a sterile 30-gauge × 1/2-inch needle for the intravitreal injection. The contents should be expelled until the plunger tip is aligned with the line that marks 0.05 mL on the syringe.
2.4 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.
Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. Monitoring may consist of a check for perfusion of the optic nerve head immediately after the injection, tonometry within 30 minutes following the injection, and biomicroscopy between two and seven days following the injection. Patients should be instructed to report any symptoms suggestive of endophthalmitis without delay.
Each vial should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles should be changed before LUCENTIS is administered to the other eye.
5.1 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 during the week following the injection to permit early treatment should an infection occur [see Dosage and Administration (2.3, 2.4) and Patient Counseling Information (17)].
5.2 Increases in Intraocular Pressure Increases in intraocular pressure have been noted within 60 minutes of intravitreal injection with LUCENTIS. Therefore, intraocular pressure as well as the perfusion of the optic nerve head should be monitored and managed appropriately [see Dosage and Administration (2.4)].
5.3 Thromboembolic Events Although there was a low rate (<4%) of arterial thromboembolic events observed in the LUCENTIS clinical trials, there is a theoretical risk of arterial thromboembolic events following intravitreal use of inhibitors of VEGF [see Adverse Reactions (6.3)].
6
ADVERSE REACTIONS
6.1 Injection Procedure Serious adverse events related to the injection procedure have occurred in < 0.1% of intravitreal injections, including endophthalmitis [see Warnings and Precautions (5.1)], rhegmatogenous retinal detachments, and iatrogenic traumatic cataracts.
No special dosage modification is required for any of the populations that have been studied (e.g., gender, elderly).
U.S. BLA (BL125156) Ranibizumab injection
6.2 Clinical Trials Experience Ocular Events Other serious ocular adverse events observed among LUCENTIS-treated patients occurring in <2% of patients
Genentech, Inc.
included intraocular inflammation and increased intraocular pressure [see Warnings and Precautions (5.1, 5.2)].
The available safety data include exposure to LUCENTIS in 874 patients with neovascular age-related macular degeneration in three double-masked, controlled studies with dosage regimens of 0.3 mg (375 patients) or 0.5 mg (379 patients) administered monthly by intravitreal injection (Studies 1 and 2) [see Clinical Studies (14.1)] and dosage regimens of 0.3 mg (59 patients) or 0.5 mg (61 patients) administered once a month for 3 consecutive doses followed by a dose administered once every 3 months (Study 3) [see Clinical Studies (14.2)].
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in one clinical trial of a drug cannot be directly compared with rates in the clinical trials of the same or another drug and may not reflect the rates observed in practice.
Table 1 shows the most frequently reported ocular adverse events that were reported with LUCENTIS treatment. The ranges represent the maximum and minimum rates across all three studies for control, and across all three studies and both dose groups for LUCENTIS.
Table 1
Adverse Event
LUCENTIS
Conjunctival hemorrhage
77%-43%
Eye pain
37%-17%
Vitreous floaters
32%-3%
Retinal hemorrhage
26%-15%
Intraocular pressure increased 24%-8%
Vitreous detachment
22%-7%
Intraocular inflammation
18%-5%
Eye irritation
19%-4%
Cataract
16%-5%
Foreign body sensation in eyes
19%-6%
Lacrimation increased
17%-3%
Eye pruritis
13%-0%
Visual disturbance
14%-0%
Blepharitis
13%-3%
Subretinal fibrosis
13%-0%
Ocular hyperemia
10%-5%
Maculopathy
10%-3%
Visual acuity blurred/decreased
17%-4%
Detachment of the retinal pigment epithelium
11%-1%
Dry eye
10%-3%
Ocular discomfort
8%-0%
Conjunctival hyperemia
9%-0%
Posterior capsule opacification
8%-0%
Retinal exudates
9%-1%
Control 66%-29% 33%-11% 10%-3% 56%-37% 7%-3% 18%-13% 11%-3% 20%-6% 16%-6%
14%-6%
16%-0% 12%-3% 9%-2% 9%-4% 19%-10% 10%-1% 11%-3%
24%-10%
15%-3%
8%-5% 5%-0% 7%-0%
5%-0%
11%-3%
6.3 Clinical Trials Experience Non-Ocular Events Table 2 shows the most frequently reported non-ocular adverse events with LUCENTIS treatment. The ranges represent the maximum and minimum rates across all three studies for control, and across all three studies and both dose groups for LUCENTIS.
Adverse Event Hypertension/elevated blood pressure Nasopharyngitis Arthralgia Headache Bronchitis Cough Anemia Nausea Sinusitis Upper respiratory tract infection Back pain Urinary tract infection Influenza Arthritis Dizziness Constipation
Table 2 LUCENTIS
23%-5%
16%-5% 11%-3% 15%-2% 10%-3% 10%-3% 8%-3% 9%-2% 8%-2% 15%-2%
10%-1% 9%-4% 10%-2% 8%-0% 8%-2% 7%-3%
Control 23%-8%
13%-5% 9%-0% 10%-3% 8%-2% 7%-2% 8%-0% 6%-4% 6%-4% 10%-4%
9%-0% 8%-5% 5%-1% 8%-2% 10%-2% 8%-2%
The rate of arterial thromboembolic events in the three studies in the first year was 2.1% of patients (18 out of 874) in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS compared with 1.1% of patients (5 out of 441) in the control arms of the studies. In the second year of Study 1, the rate of arterial thromboembolic events was 3.0% of patients (14 out of 466) in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS compared with 3.2% of patients (7 out of 216) in the control arm [see Warnings and Precautions (5.3)].
6.4 Immunogenicity The pre-treatment incidence of immunoreactivity to LUCENTIS was 0%-3% across treatment groups. After monthly dosing with LUCENTIS for 12 to 24 months, low titers of antibodies to LUCENTIS were detected in approximately 1%-6% of patients. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to LUCENTIS in an electrochemiluminescence assay and are highly dependent on the sensitivity and specificity of the assay. The clinical significance of immunoreactivity to LUCENTIS is unclear at this time, although some patients with the highest levels of immunoreactivity were noted to have iritis or vitritis.
7
DRUG INTERACTIONS
Drug interaction studies have not been conducted with
LUCENTIS.
U.S. BLA (BL125156) Ranibizumab injection
Genentech, Inc.
LUCENTIS intravitreal injection has been used adjunctively with verteporfin photodynamic therapy (PDT). Twelve of 105 (11%) patients developed serious intraocular inflammation; in 10 of the 12 patients, this occurred when LUCENTIS was administered 7 days (± 2 days) after verteporfin PDT.
8
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with ranibizumab. It is also not known whether ranibizumab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. LUCENTIS should be given to a pregnant woman only if clearly needed.
8.3 Nursing Mothers It is not known whether ranibizumab is excreted in human milk. 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.
injection 0.3 mg, doses as high as 2.0 mg were tolerated in 15 of 20 patients.
11
DESCRIPTION
LUCENTISTM (ranibizumab injection) is a recombinant
humanized IgG1 kappa isotype monoclonal antibody fragment
designed for intraocular use. Ranibizumab binds to and
inhibits the biologic activity of human vascular endothelial
growth factor A (VEGF-A). Ranibizumab has a molecular
weight of approximately 48 kilodaltons and is produced by an
E. coli expression system in a nutrient medium containing the
antibiotic tetracycline. Tetracycline is not detectable in the
final product.
LUCENTIS is a sterile, colorless to pale yellow solution in a single-use glass vial. LUCENTIS is supplied as a preservative-free, sterile solution in a single-use glass vial designed to deliver 0.05 mL of 10 mg/mL LUCENTIS aqueous solution with 10 mM histidine HCl, 10% , -trehalose dihydrate, 0.01% polysorbate 20, pH 5.5.
12 CLINICAL PHARMACOLOGY
8.4 Pediatric Use The safety and effectiveness of LUCENTIS in pediatric patients has not been established.
8.5 Geriatric Use In the controlled clinical studies, approximately 94% (822/879) of the patients randomized to treatment with LUCENTIS were 65 years of age and approximately 68% (601/879) were 75 years of age. No notable difference in treatment effect was seen with increasing age in any of the studies. Age did not have a significant effect on systemic exposure in a population pharmacokinetic analysis after correcting for creatinine clearance.
8.6 Patients with Renal Impairment No formal studies have been conducted to examine the pharmacokinetics of ranibizumab in patients with renal impairment. Sixty-eight percent of patients (136 of 200) in the population pharmacokinetic analysis had renal impairment (46.5% mild, 20% moderate, and 1.5% severe). Reduction in ranibizumab clearance is minimal in patients with renal impairment and is considered clinically insignificant. Dose adjustment is not expected to be needed for patients with renal impairment.
8.7 Patients with Hepatic Dysfunction No formal studies have been conducted to examine the pharmacokinetics of ranibizumab in patients with hepatic impairment. Dose adjustment is not expected to be needed for patients with hepatic dysfunction.
10
OVERDOSAGE
Planned initial single doses of ranibizumab injection 1.0 mg
were associated with clinically significant intraocular
inflammation in 2 of 2 patients injected. With an escalating
regimen of doses beginning with initial doses of ranibizumab
12.1 Mechanism of Action Ranibizumab binds to the receptor binding site of active forms of VEGF-A, including the biologically active, cleaved form of this molecule, VEGF110. VEGF-A has been shown to cause neovascularization and leakage in models of ocular angiogenesis and is thought to contribute to the progression of the neovascular form of age-related macular degeneration (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, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.
12.2 Pharmacodynamics Neovascular AMD is associated with foveal retinal thickening as assessed by optical coherence tomography (OCT) and leakage from CNV as assessed by fluorescein angiography.
In Study 3, foveal retinal thickness was assessed by OCT in 118/184 patients. OCT measurements were collected at baseline, Months 1, 2, 3, 5, 8, and 12. In patients treated with LUCENTIS, foveal retinal thickness decreased, on average, more than the sham group from baseline through Month 12. Retinal thickness decreased by Month 1 and decreased further at Month 3, on average. Foveal retinal thickness data did not provide information useful in influencing treatment decisions [see Clinical Studies (14.2)].
In patients treated with LUCENTIS, the area of vascular leakage, on average, decreased by Month 3 as assessed by fluorescein angiography. The area of vascular leakage for an individual patient was not correlated with visual acuity.
12.3 Pharmacokinetics In animal studies, following intravitreal injection, ranibizumab was cleared from the vitreous with a half-life of approximately 3 days. After reaching a maximum at approximately 1 day,
U.S. BLA (BL125156) Ranibizumab injection
Genentech, Inc.
the serum concentration of ranibizumab declined in parallel with the vitreous concentration. In these animal studies, systemic exposure of ranibizumab is more than 2000-fold lower than in the vitreous.
In patients with neovascular AMD, following monthly intravitreal administration, maximum ranibizumab serum concentrations were low (0.3 ng/mL to 2.36 ng/mL). These levels were below the concentration of ranibizumab (11 ng/mL to 27 ng/mL) thought to be necessary to inhibit the biological activity of VEGF-A by 50%, as measured in an in vitro cellular proliferation assay. The maximum observed serum concentration was dose proportional over the dose range of 0.05 to 1.0 mg/eye. Based on a population pharmacokinetic analysis, maximum serum concentrations of 1.5 ng/mL are predicted to be reached at approximately 1 day after monthly intravitreal administration of LUCENTIS 0.5 mg/eye. Based on the disappearance of ranibizumab from serum, the estimated average vitreous elimination half-life was approximately 9 days. Steady-state minimum concentration is predicted to be 0.22 ng/mL with a monthly dosing regimen. In humans, serum ranibizumab concentrations are predicted to be approximately 90,000-fold lower than vitreal concentrations.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity or mutagenicity data are available for ranibizumab injection in animals or humans.
No studies on the effects of ranibizumab on fertility have been conducted.
14 CLINICAL STUDIES The safety and efficacy of LUCENTIS were assessed in three randomized, double-masked, sham- or active-controlled studies in patients with neovascular AMD. A total of 1323 patients (LUCENTIS 879, Control 444) were enrolled in the three studies.
Study 2 received a mean of 12 total treatments out of a possible 13 from Day 0 through Month 12.
In both studies, the primary efficacy endpoint was the proportion of patients who maintained vision, defined as losing fewer than 15 letters of visual acuity at 12 months compared with baseline. Almost all LUCENTIS-treated patients (approximately 95%) maintained their visual acuity. 34%-40% of LUCENTIS-treated patients experienced a clinically significant improvement in vision, defined as gaining 15 or more letters at 12 months. The size of the lesion did not significantly affect the results. Detailed results are shown in the tables below.
Table 3
Outcomes at Month 12 and Month 24 in Study 1
LUCENTIS Estimated
Outcome Measure
Month
Sham n = 238
0.5 mg n = 240
Difference (95% CI)a
Loss of Month 12 62%
95%
32%
< 15
(26%, 39%)
letters in Month 24 53%
90%
37%
visual
(29%, 44%)
acuity (%)b
Gain of Month 12 5%
34%
29%
15
(22%, 35%)
letters in Month 24 4%
33%
29%
visual
(23%, 35%)
acuity (%)b
Mean
Month 12 -10.5 +7.2 (14.4)
17.5
change in
(16.6)
(14.8, 20.2)
visual
Month 24 -14.9 +6.6 (16.5)
21.1
acuity
(18.7)
(18.1, 24.2)
(letters) (SD)b
a Adjusted estimate based on the stratified model. b p < 0.01.
14.1 Study 1 and Study 2
In Study 1, patients with minimally classic or occult (without classic) CNV lesions received monthly LUCENTIS 0.3 mg or 0.5 mg intravitreal injections or monthly sham injections. Data are available through Month 24. Patients treated with LUCENTIS in Study 1 received a mean of 22 total treatments out of a possible 24 from Day 0 to Month 24.
In Study 2, patients with predominantly classic CNV lesions received one of the following: 1) monthly LUCENTIS 0.3 mg intravitreal injections and sham PDT; 2) monthly LUCENTIS 0.5 mg intravitreal injections and sham PDT; or 3) sham intravitreal injections and active verteporfin PDT. Sham PDT (or active verteporfin PDT) was given with the initial LUCENTIS (or sham) intravitreal injection and every 3 months thereafter if fluorescein angiography showed persistence or recurrence of leakage. Data are available through Month 12. Patients treated with LUCENTIS in
U.S. BLA (BL125156) Ranibizumab injection
Genentech, Inc.
Table 4
Outcomes at Month 12 in Study 2
Verteporfin LUCENTIS
Estimated
Outcome Measure
PDT n = 143
0.5 mg n = 140
Difference (95% CI)a
Loss of
64%
96%
33% (25%, 41%)
< 15 letters
in visual acuity (%)b
Gain of
6%
40%
35% (26%, 44%)
15
letters in
visual acuity (%)b
Mean
-9.5 (16.4) +11.3 (14.6) 21.1 (17.5, 24.6)
change in
visual
acuity
(letters) (SD)b a Adjusted estimate based on the stratified model.
b p < 0.01.
Figure 1 Mean Change in Visual Acuity from Baseline to Month 24 in Study 1 and to Month 12 in Study 2
Mean Change in Visual Acuity (letters)
Study 1
15
10
+6.6
5
0
-5
-10
-15
-14.9
0 2 4 6 8 10 12 14 16 18 20 22 24 Month
Study 2
15
+11.3
10
5
0
-5
-10
-9.5
-15
0 2 4 6 8 10 12 Month
Mean Change in Visual Acuity (letters)
Patients in the group treated with LUCENTIS had minimal observable CNV lesion growth, on average. At Month 12, the mean change in the total area of the CNV lesion was 0.1-0.3 DA for LUCENTIS versus 2.3-2.6 DA for the control arms.
The use of LUCENTIS beyond 24 months has not been studied.
14.2 Study 3 Study 3 was a randomized, double-masked, sham-controlled, two-year study designed to assess the safety and efficacy of LUCENTIS in patients with neovascular AMD (with or without a classic CNV component). Data are available through Month 12. Patients received LUCENTIS 0.3 mg or 0.5 mg intravitreal injections or sham injections once a month for 3 consecutive doses, followed by a dose administered once every 3 months. A total of 184 patients were enrolled in this study (LUCENTIS 0.3 mg, 60; LUCENTIS 0.5 mg, 61; sham, 63); 171 (93%) completed 12 months of this study. Patients treated with LUCENTIS in Study 3 received a mean of 6 total treatments out of possible 6 from Day 0 through Month 12.
In Study 3, the primary efficacy endpoint was mean change in visual acuity at 12 months compared with baseline (see Figure 2). After an initial increase in visual acuity (following monthly dosing), on average, patients dosed once every three months with LUCENTIS lost visual acuity, returning to baseline at Month 12. In Study 3, almost all LUCENTIS-treated patients (90%) maintained their visual acuity at Month 12.
Figure 2 Mean Change in Visual Acuity from Baseline to
Month 12 in Study 3
Mean Change in Visual Acuity (letters)
Study 3
10
5
0
-0.2
-5
-10
-15
-16.3
-20
0 2 4 6 8 10 12 Month
LUCENTIS 0.5 mg (n=61) Sham (n=63)
Study 1:
LUCENTIS 0.5 mg (n=240) Sham (n=238)
Study 2:
LUCENTIS 0.5 mg (n=139) Verteporfin PDT (n=143)
16
HOW SUPPLIED/STORAGE AND HANDLING
Each LUCENTIS carton, NDC 50242-080-01, contains one
2-cc glass vial of ranibizumab, one 5-micron,
19-gauge × 1-1/2-inch filter needle for withdrawal of the vial
.
contents, one 30-gauge × 1/2-inch injection needle for the intravitreal injection, and one package insert [see Dosage and
U.S. BLA (BL125156) Ranibizumab injection
Genentech, Inc.
Administration (2.4)]. VIALS ARE FOR SINGLE EYE USE ONLY. 17 PATIENT COUNSELING INFORMATION In the days following LUCENTIS administration, patients are at risk of developing endophthalmitis. If the eye becomes red, sensitive to light, painful, or develops a change in vision, the patient should seek immediate care from an ophthalmologist [see Warnings and Precautions (5.1)].
LUCENTISTM [ranibizumab injection] Manufactured by: Genentech, Inc. 1 DNA Way South San Francisco, CA 94080-4990
G#####-R0 Mmmmmm YYYY YYYY Genentech,
Inc.
U.S. BLA (BL125156) Ranibizumab injection
Genentech, Inc.
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