Pharmacology Update

Ranibizumab Intravitreal Injection (Lucentis™)

By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.

A new agent has been approved for the treatment of the neovascular (wet) form of age-related macular degeneration (AMD). Ranibizumab is a fragment of bevacizumab (Avastin), a monoclonal antibody that binds to vascular growth factor and has been used for the treatment of various cancers. Ranibizumab, produced by recombinant technology, is marketed by Genentech as Lucentis™.


Ranibizumab is indicated for the treatment of neovascular (wet) AMD.1


The recommended dose is 0.5 mg (0.05 mL) given by intravitreal injection monthly. The dose may be reduced to injections every 3 months after the first four doses, although this is less effective than monthly dosing.1 Ranibizumab is supplied as a single-dose vial (0.05 mL of 10 mg/mL).

Potential Advantages

Ranibizumab is more effective than photodynamic therapy with verteporfin in classic neovascular AMD.2 It also appears to be effective for the occult (minimally classic) form of AMD.3

Potential Disadvantages

Uveitis, endophthalmitis, and retinal detachment have been associated with ranibizumab. These appear to be rare (1% or less). The frequency of adverse events categorized as intraocular inflammation was 15%. Post injection, transient increase in intraocular pressure has been observed in about 9% of patients.2


In contrast to pegaptanib that binds to one isoform, ranibizumab, a fragment of bevacizumab, binds to the two key isoforms of vascular endothelial growth factor.4,5 Two pivotal phase III studies (Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab In the treatment of Neovascular AMD [MARINA] and Anti-VEGF Antibody for the treatment of Predominately Classic Choroidal Neovascularization in AMD [ANCHOR]) were the keys for FDA approval. In studies with minimally classic or occult AMD (n = 716), 94.6% of patients given monthly ranibizumab (0.5 mg) lost fewer than 15 letters at 1 year compared to 62.2% receiving sham injections.3 Visual acuity improved by 15 letters in 33.8% of patients compared to 5% for sham injections. The benefit appears to be maintained for 24 months. In patients with classic AMD, ranibizumab was more effective than photodynamic therapy (PDT) with verteporfin (n = 423). In patients receiving monthly ranibizumab (0.5 mg), 96.4% lost fewer than 15 letters in one year compared to 64.3% for PDT. Visual acuity improved by 15 letters in 40.3% compared to 5.6% for PDT. Trials are currently in progress to determine the effectiveness of less frequent injections.4 The combination of PDT and ranibizumab does not appear to improve effectiveness in predominately classic AMD. Ranibizumab is generally well tolerated. Rare serious adverse events include uveitis and endophthalmitis. Other more common less serious adverse events include conjunctival hemorrhage, eye pain, blurred vision, floaters, iris and uveal tract inflammation and transient increase in intraocular pressure.1,5 Nonocular adverse events include nasopharyngitis and a small increase in blood pressure. The cost of ranibizumab is $1,950 per monthly injection.

Clinical Implications

Due to the aging population, the prevalence of AMD is expected to increase in the upcoming years. It is the leading cause of vision loss or blindness in those 65 years of age and older. Wet AMD, the less common (10%) but more serious form, involves abnormal growth of blood vessels beneath the retina and leaks into the retina causing scarring and loss of central vision. AMD is categorized into different types based on the nature and location of the lesions and their location in the fovea. These categories include classic or occult and extrafoveal or subfoveal. In classic AMD (the more severe form), new blood vessel growth, and scarring have very clear, delineated outlines beneath the retina (ie, classic choroidal neovascularization). In occult AMD, new blood vessel growth is less pronounced and leakage is less evident. Currently there are 3 treatment modalities; laser photocoagulation, PDT with verteporfin, and pegaptanib intravitreal injection. Ranibizumab appears to be an improvement over current therapy. There are currently no published comparative trials between ranibizumab and pegaptanib. Intravitreal injection of bevacizumab has also been shown to be effective in AMD at a fraction of the cost ($20-$50) posing a dilemma for clinicians.4,6


1. Lucentis Product Information. Genentech, Inc. September 2006.

2. Brown DM, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-1444.

3. Rosenfeld PJ, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419-1431.

4. Rosenfeld PJ, et al. Ranibizumab: Phase III clinical trial results. Ophthalmol Clin N Am. 2006;19:361-372.

5. Chakravarthy U, et al. Evolving European guidance on the medical management of neovascular age related macular degeneration. Br J Ophthalmol. 2006;90:1188-1196.

6. Steinbrook R. The price of sight—ranibizumab, bevacizumab, and the treatment of macular degeneration. N Engl J Med. 2006;355:1409-1410.