Lucentis

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

• eye pain or redness, swelling around your eyes;
• sudden vision problems;
• discharge or bleeding from the eye;
• eyes being more sensitive to light;
• seeing flashes of light or "floaters" in your vision;
• feeling like something is in your eye;
• sudden numbness or weakness, especially on one side of the body;
• sudden severe headache, confusion, problems with speech or balance; or
• pain or burning when you urinate.

Less serious side effects may include:

• itchy or watery eyes;
• dry eyes, swelling of the eyelids;
• blurred vision;
• sinus pain, sore throat, cough; or
• joint pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Dosage Forms & Strengths

intravitreal injectable preservative-free solution

• 6mg/mL (0.05mL [0.3mg/vial])
• 10mg/mL (0.05mL [0.5mg/vial])
• 10mg/mL (0.05mL [0.5mg/prefilled syringe])

Neovascular (Wet) Age-related Macular Degeneration

0.5 mg intravitreal qMonth (~q28 days)

May give q3month after 3 or 4 monthly injections (if continued monthly dosing not feasible) but is less effective than once monthly dosing

Macular Edema

Indicated for macular edema following retinal vein occlusion

0.5 mg intravitreal injection qMonth (~q28 days) x6 months

Diabetic Macular Edema

0.3 mg intravitreally qMonth (~q28 days)

Diabetic Retinopathy

Indicated for treatment of diabetic retinopathy in patients with or without diabetic macular edema (DME)

0.3 mg (0.05 mL of 6 mg/mL solution) intravitreally qMonth (~q28 days)

Myopic Choroidal Neovascularization

0.5 mg intravitreal injection qMonth initially, for up to 3 months

May retreat if needed, based on assessment of mean baseline change in visual acuity (BCVA)

Does not apply

Dosage Forms And Strengths

Single-use prefilled syringe designed to provide 0.05 mL for intravitreal injection.

• 10 mg/mL solution ( LUCENTIS 0.5 mg)

Single-use glass vial designed to provide 0.05 mL for intravitreal injection.

• 10 mg/mL solution (LUCENTIS 0.5 mg)
• 6 mg/mL solution (LUCENTIS 0.3 mg)

Storage And Handling

Each LUCENTIS 0.5 mg carton (NDC 50242-080-03) contains a single-use, prefilled syringe designed to deliver 0.05 mL of 10 mg/mL ranibizumab solution. The prefilled syringe has a non-retractable plunger stopper and a syringe cap consisting of a tamper-evident rigid seal with a rubber tip cap including a Luer lock adapter. The prefilled syringe has a plunger rod and a CLEAR finger grip. The prefilled syringe is sterile and is packed in a sealed tray.

Each LUCENTIS 0.5 mg carton (NDC 50242-080-02) contains a single-use, 2-mL glass vial with a BLUE CAP designed to deliver 0.05 mL of 10 mg/mL ranibizumab solution.

Each LUCENTIS 0.3 mg carton (NDC 50242-082-02) contains a single-use, 2-mL glass vial with a WHITE CAP designed to deliver 0.05 mL of 6 mg/mL ranibizumab solution.

EACH CARTON IS FOR SINGLE-EYE USE ONLY.

LUCENTIS should be refrigerated at 2°-8°C (36°-46°F). DO NOT FREEZE. Do not use beyond the date stamped on the label. Protect LUCENTIS prefilled syringe and vials from light and store in the original carton until time of use. Do not open LUCENTIS prefilled syringe sealed tray until time of use.

Manufactured by: Genentech, Inc. A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080-4990. Revised: Jan 2017

This medication may cause blurred vision. Be careful if you drive or do anything that requires you to be able to see clearly.

Neovascular Age-related Macular Degeneration

Treatment of neovascular (wet) age-related macular degeneration.1 4 5 6 14 19

Macular Edema Following Retinal Vein Occlusion

Treatment of macular edema following retinal vein occlusion.1 11 12 16 18

Diabetic Macular Edema

Treatment of diabetic macular edema.1 12 13 20

Diabetic Retinopathy in Patients with Diabetic Macular Edema

Treatment of diabetic retinopathy (proliferative or nonproliferative) in patients with diabetic macular edema.1 4 13 15

Contraindications

• Ocular or periocular infections.1

• Known hypersensitivity (e.g., severe intraocular inflammation) to ranibizumab or any ingredient in the formulation.1

Warnings/Precautions

Endophthalmitis and Other Serious Ocular Effects

Intravitreal injections, including those with ranibizumab, associated with endophthalmitis and retinal detachments.1 4 5 6 Always use proper aseptic injection technique.1 4 (See Ophthalmic Administration under Dosage and Administration.) Monitor patients closely for signs of endophthalmitis (e.g., redness, sensitivity to light, pain, changes in vision) during the week following injection to permit early treatment.1 4 (See Advice to Patients.)

Traumatic cataract and tearing of retinal pigment epithelium also reported.1 4 5

Increased IOP

Increased IOP observed both before and after (60 minutes after) intravitreal injection.1 4 6 Monitor IOP and perfusion of optic nerve head and manage appropriately.1 4

Thromboembolic Events

Potential risk of arterial thromboembolic events following intravitreal injection of VEGF antagonists.1 Arterial thromboembolic events (i.e., nonfatal stroke, nonfatal MI, vascular death [including deaths from unknown causes]) reported at low rates (0.8–10.8%).1 4 20 Patients with diabetic macular edema and diabetic retinopathy had higher rates, but were typical of this patient population.1 20

Potentially higher rate of stroke associated with the 0.5- versus 0.3-mg dose in patients with neovascular age-related macular degeneration; additional postmarketing surveillance and clinical studies are being conducted to further evaluate this finding.4 7 8 10 17

Fatal Events

In clinical studies in patients with diabetic macular edema and diabetic retinopathy, fatal events occurred more frequently with ranibizumab than sham treatment.1 4 Although the fatality rate was low and included causes typical of patients with advanced diabetic complications, a potential relationship to the drug cannot be excluded.1

Immunogenicity

Development of anti-ranibizumab antibodies reported.1 Clinical relevance unclear, but iritis or vitritis noted in some patients with neovascular age-related macular degeneration who had the highest levels of immunoreactivity.1

Specific Populations

Category C.1

Studies not conducted in pregnant women; it is not known whether ranibizumab can cause fetal harm when administered during pregnancy.1 Use only if potential benefits justify potential risk to fetus.1 Adverse effects on embryofetal development or reproductive capacity possible due to the drug's mechanism as a VEGF antagonist.1

Not known whether ranibizumab is distributed into milk.1 Caution if used in nursing women.1

Safety and efficacy not established.1

Safety and efficacy not established in adults <50 years of age.4

No substantial differences in efficacy or systemic exposure (after correcting for Clcr) relative to younger adults.1

Pharmacokinetics not studied; dosage adjustment not expected to be necessary.1

Increased ranibizumab exposure observed in patients with renal impairment; however, changes not considered to be clinically important.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Conjunctival hemorrhage,1 4 eye pain,1 4 vitreous floaters,1 4 increased IOP,1 4 intraocular inflammation.1 4

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Single-use prefilled syringe designed to provide 0.05 mL for intravitreal injection.

• Colorless to pale yellow 10 mg/mL solution ( Lucentis 0.5 mg)

Single-use glass vial 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)

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.

The following adverse reactions are discussed in greater detail in other sections of the label:

• Endophthalmitis and Retinal Detachments [see Warnings and Precautions (5.1)]
• Increases in Intraocular Pressure [see Warnings and Precautions (5.2)]
• Thromboembolic Events [see Warnings and Precautions (5.3)]
• Fatal Events in patients with DME and DR at baseline [see Warnings and Precautions (5.4)]

Injection Procedure

Serious adverse reactions related to the injection procedure have occurred in < 0.1% of intravitreal injections, including endophthalmitis [see Warnings and Precautions (5.1)], rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.

Clinical Studies Experience

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.

The data below reflect exposure to 0.5 mg Lucentis in 440 patients with neovascular AMD in Studies AMD-1, AMD-2, and AMD-3; in 259 patients with macular edema following RVO. The data also reflect exposure to 0.3 mg Lucentis in 250 patients with DME and DR at baseline [see Clinical Studies (14)].

Safety data observed in 224 patients with mCNV, as well as Studies AMD-4 and D-3, were consistent with these results. On average, the rates and types of adverse reactions in patients were not significantly affected by dosing regimen.

Ocular Reactions

Table 1 shows frequently reported ocular adverse reactions in Lucentis-treated patients compared with the control group.

Non-Ocular Reactions

Non-ocular adverse reactions with an incidence of ≥ 5% in patients receiving Lucentis for DR, DME, AMD, and/or RVO and which occurred at a ≥ 1% higher frequency in patients treated with Lucentis compared to control are shown in Table 2. Though less common, wound healing complications were also observed in some studies.

Immunogenicity

As with all therapeutic proteins, there is the potential for an immune response in patients treated with Lucentis. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to Lucentis in immunoassays and are highly dependent on the sensitivity and specificity of the assays.

The pre-treatment incidence of immunoreactivity to Lucentis was 0%-5% across treatment groups. After monthly dosing with Lucentis for 6 to 24 months, antibodies to Lucentis were detected in approximately 1%-9% of patients.

The clinical significance of immunoreactivity to Lucentis is unclear at this time. Among neovascular AMD patients with the highest levels of immunoreactivity, some were noted to have iritis or vitritis. Intraocular inflammation was not observed in patients with DME and DR at baseline, or RVO patients with the highest levels of immunoreactivity.

Postmarketing Experience

The following adverse reaction has been identified during post-approval use of Lucentis. Because this reaction was reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

• Ocular: Tear of retinal pigment epithelium among patients with neovascular AMD

More concentrated doses as high as 2 mg ranibizumab in 0.05 mL have been administered to patients. No additional unexpected adverse reactions were seen.