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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 DME

Diabetes Is a Disease That May Affect the Eye and Other Parts of the Body1

Micro- and macrovascular comorbidities are common in diabetes patients

  • 25.6 million people in the US over the age of 20 have diabetes1

Various risk factors contribute to the development of DME:

  • Duration of diabetes: Patients who have had diabetes for ≥10 years are 11 times more likely to have DME3
  • Elevated HbA1C: Every 1% increase in HbA1C levels corresponds to a 50% increased risk of DME3

When left untreated, approximately half of DME patients will lose 2 or more lines of VA better
within 2 years6

Role of intraocular and systemic VEGF in DME

DME is associated with the overexpression of intraocular VEGF7

Elevated intraocular VEGF levels drive retinal neovascularization, leakage, and macular edema – which can result in vision loss8,9

Decreased levels of VEGF in the body may lead to systemic complications

  • VEGF plays a critical role in angiogenesis, which is needed for processes such as wound healing and tissue repair10
  • Decreased systemic VEGF can lead to arterial thromboembolic events (ATEs*), renal dysfunction, hypertension,
    and wound complications7

*ATEs are defined as a combination of cardiac ischemia (angina, myocardial infarction), cerebral ischemia (transient ischemic attack, cerebrovascular accident), and peripheral arterial or bowel ischemia.

ATE, arterial thromboembolic event; CV, cardiovascular; CVA, cerebrovascular accident; HbA1C, glycosylated hemoglobin; MI, myocardial infarction; DME, diabetic macular edema; VEGF, vascular endothelial growth factor.

Important Select Safety Information

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).

References: 1. Diabetes statistics. American Diabetes Association Web site. http://www.diabetes.org/diabetes-basics/statistics/?loc=db-slabnav. Published January 26, 2011. Accessed June 21, 2012. 2. Centers for Disease Control and Prevention. National diabetes fact sheet, 2011. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed June 21, 2012. 3. Centers for Disease Control and Prevention. Diabetes data & trends. http://www.cdc.gov/diabetes/statistics/cvd/fig2.htm. Accessed June 21, 2012. 4. United States Renal Data System. Atlas of chronic kidney disease in the United States: United States Renal Data System 2011 annual report. Volume 1. http://www.usrds.org/2011/slides/indiv/v1index.html. Accessed June 21, 2012. 5. Ferris FL, Patz A. Macular edema. A complication of diabetic retinopathy. Surv Ophthalmol. 1984:28;452-461. 6. Chen X, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nat Rev Clin Oncol. 2009:6;465-477. 7. Aiello LP, Wong JS. Role of vascular endothelial growth factor in diabetic vascular complications. Kidney Int Suppl. 2000;58:S113-S119. 8. Zhang W, Liu H, Rojas M, Caldwell RW, Caldwell RB. Anti-inflammatory therapy for diabetic retinopathy. Immunotherapy. 2011;3:609-628. 9. Funatsu H, Yamashita H, Noma H, et al. Aqueous humor levels of cytokines are related to vitreous levels and progression of diabetic retinopathy in diabetic patients. Graefes Arch Clin Exp Ophthalmol. 2005;243:3-8. 10. Nguyen-Khoa BA, Goehring EL, Werther W, et al. Hospitalized cardiovascular events in patients with diabetic macular edema [published online ahead of print May 30, 2012]. BMC Ophthalmology. doi:10.1186/1471-2415-12-11. 11. Simonson DC. Etiology and prevalence of hypertension in diabetic patients. Diabetes Care. 1988;11:821-827.