Scroll down to view complete indication and safety information

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

LUCENTIS® (ranibizumab injection) is indicated for the treatment of patients with:

  • Neovascular (wet) age-related macular degeneration (wAMD)
  • Macular edema following retinal vein occlusion (RVO)
  • Diabetic macular edema (DME)

IMPORTANT SAFETY INFORMATION

LUCENTIS is contraindicated in patients with ocular or periocular infections or hypersensitivity to ranibizumab or any of the excipients in LUCENTIS.

WARNINGS AND PRECAUTIONS

Intravitreal injections, including those with LUCENTIS, have been associated with endophthalmitis and retinal detachment. Proper aseptic injection technique should always be utilized when administering LUCENTIS. Patients should be monitored during the week following the injection to permit early treatment, should an infection occur.

Increases in intraocular pressure (IOP) have been noted both pre-injection and post-injection (at 60 minutes) with LUCENTIS. IOP and perfusion of the optic nerve head should be monitored and managed appropriately.

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. ATEs 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 3 controlled neovascular AMD studies during the first year was 1.9% in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS compared with 1.1% in patients from the control arms. In the second year of Studies AMD-1 and AMD-2, the ATE rate was 2.6% in the combined group of LUCENTIS-treated patients compared with 2.9% in patients from the control arms. In Study AMD-4, the ATE rates observed in the study during the first 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), the stroke rate (including both ischemic and hemorrhagic stroke) was 2.7% in patients treated with 0.5 mg LUCENTIS compared to 1.1% 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 2 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). The stroke rate was 0.2% in the combined group of LUCENTIS-treated patients compared to 0.4% in the control arms.

Diabetic macular edema

In a pooled analysis of Studies DME-1 and DME-2, the ATE rate at 2 years was 7.2% with 0.5 mg LUCENTIS, 5.6% with 0.3 mg LUCENTIS, and 5.2% with control. The stroke rate at 2 years was 3.2% with 0.5 mg LUCENTIS, 1.2% with 0.3 mg LUCENTIS, and 1.6% with control. At 3 years, the ATE rate was 10.4% with 0.5 mg LUCENTIS and 10.8% with 0.3 mg LUCENTIS; the stroke rate was 4.8% with 0.5 mg LUCENTIS and 2.0% with 0.3 mg LUCENTIS.

A pooled analysis of Studies DME-1 and DME-2 showed that fatalities in the first 2 years occurred in 4.4% of patients treated with 0.5 mg LUCENTIS, in 2.8% of patients treated with 0.3 mg LUCENTIS, and in 1.2% of control patients. Over 3 years, fatalities occurred in 6.4% of patients treated with 0.5 mg LUCENTIS and in 4.4% 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.

ADVERSE EVENTS

Serious adverse events related to the injection procedure that occurred in <0.1% of intravitreal injections included endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.

In clinical trials in neovascular (wet) age-related macular degeneration, the most common ocular side effects included conjunctival hemorrhage, eye pain, vitreous floaters, increased IOP, vitreous detachment, and intraocular inflammation. The most common non-ocular side effects included nasopharyngitis, headache, arthralgia, and bronchitis.

In clinical trials in macular edema following retinal vein occlusion, the most common ocular side effects included conjunctival hemorrhage, eye pain, and maculopathy. The most common non-ocular side effects included nasopharyngitis, headache, influenza, and sinusitis.

In clinical trials in diabetic macular edema, the most common ocular side effects included conjunctival hemorrhage, cataract, increased IOP, and vitreous detachment. The most common non-ocular side effects included nasopharyngitis, anemia, and nausea.

As with all therapeutic proteins, there is the potential for an immune response in patients treated with LUCENTIS. The clinical significance of immunoreactivity to LUCENTIS is unclear at this time.

For additional safety information, please see LUCENTIS full prescribing information.



ABOUT wAMD

wAMD Is a Chronic, VEGF-Mediated Disease That Primarily Affects an Older Population1-3

Typical risk factors
Common comorbidities
age, smoking, female, Caucasian, family history, cardiovascular disease, hypertension1
hyperlipidemia, hypertension, diabetes, myocardial infarction, renal dysfunction4

Elevated levels of VEGF lead to abnormal formation of CNV

  • In wAMD, VEGF plays a significant role in formation of blood vessels that grow abnormally and leak beneath the macula5,6
  • Overexpression of VEGF initiates abnormal growth of choroidal blood vessels5,6
  • These choroidal neovascular vessels leak blood and fluid, forming the characteristic lesions of wAMD5,6
  • wAMD is the leading cause of vision loss in people over 65 years of age7

Systemic VEGF plays multiple roles in cellular functions, including angiogenesis and vascularization8

  • Complications attributed to decreased systemic VEGF levels include hypertension, and arterial thromboembolic events9

Patients with wAMD may be at a higher risk for some of these conditions, including10,11:

  • Stroke
  • Myocardial infarction
CNV, choroidal neovascularization; RPE, retinal pigment epithelium; VEGF, vascular endothelial growth factor; wAMD, neovascular (wet) age-related macular degeneration.

References: 1.National Institutes of Health, National Eye Institute. Age-related macular degeneration. Available at: http://www.nei.nih.gov/health/maculardegen/armd_facts.asp. Accessed August 8, 2012.2. Ferrara N, Damico L, Shams N, Lowman H, Kim R. Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina. 2006;26:859-870. 3. Griffioen AW, Molema G. Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol Rev. 2000;52:237-268. 4. Alexander SL, Linde-Zwirble WT, Werther W, et al. Annual Rates of Arterial Thromboembolic Events in Medicare Neovascular Age- Related Macular Degeneration Patients. Ophthalmology 2007;114:2174–2178. 5. Ma W, Lee SE, Guo J, et al. RAGE ligand upregulation of VEGF secretion in ARPE-19 cells. Invest Ophthalmol Vis Sci. 2007;48:1355-1361. 6. Ikeda E, Achen MG, Breier G, Risau W. Hypoxia-induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells. J Biol Chem. 1995;270:19761-19766. 7. Quillen DA. Common Causes of Vision Loss in Elderly Patients. Am Fam Physician. 1999;60:99-108. 8. Wirostko B, Wong TY, Rafael Simo. Vascular endothelial growth factor and diabetic complications. Progress in Retinal and Eye Research. 2008;27:608–621. 9. Chen HX, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nat. Rev. Clin. Oncol. 2009;6:465–477. 10. Ikram MK et al. Age-Related Macular Degeneration and Long-Term Risk of Stroke Subtypes. Stroke. 2012;43:1-3. 11. Tan JSL et al. Age-related macular degeneration and mortality from cardiovascular disease or stroke. Br J Ophthalmol 2008;92:509–512.