Eyeworld

EW REFRACTIVE SURGERY 36 December 2015 RESTASIS ® (Cyclosporine Ophthalmic Emulsion) 0.05% BRIEF SUMMARY—PLEASE SEE THE RESTASIS ® PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION. INDICATION AND USAGE RESTASIS ® ophthalmic emulsion is indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular infl ammation associated with keratoconjunctivitis sicca. Increased tear production was not seen in patients currently taking topical anti-infl ammatory drugs or using punctal plugs. CONTRAINDICATIONS RESTASIS ® is contraindicated in patients with known or suspected hypersensitivity to any of the ingredients in the formulation. WARNINGS AND PRECAUTIONS Potential for Eye Injury and Contamination To avoid the potential for eye injury and contamination, be careful not to touch the vial tip to your eye or other surfaces. Use with Contact Lenses RESTASIS ® should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. If contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS ® ophthalmic emulsion. ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not refl ect the rates observed in practice. In clinical trials, the most common adverse reaction following the use of RESTASIS ® was ocular burning (17%). Other reactions reported in 1% to 5% of patients included conjunctival hyperemia, discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging, and visual disturbance (most often blurring). Post-marketing Experience The following adverse reactions have been identifi ed during post approval use of RESTASIS ® . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Reported reactions have included: hypersensitivity (including eye swelling, urticaria, rare cases of severe angioedema, face swelling, tongue swelling, pharyngeal edema, and dyspnea); and superfi cial injury of the eye (from the vial tip touching the eye during administration). USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects: Pregnancy Category C Adverse effects were seen in reproduction studies in rats and rabbits only at dose levels toxic to dams. At toxic doses (rats at 30 mg/kg/day and rabbits at 100 mg/kg/day), cyclosporine oral solution, USP, was embryo- and fetotoxic as indicated by increased pre- and postnatal mortality and reduced fetal weight together with related skeletal retardations. These doses are 5,000 and 32,000 times greater (normalized to body surface area), respectively, than the daily human dose of one drop (approximately 28 mcL) of 0.05% RESTASIS ® twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed. No evidence of embryofetal toxicity was observed in rats or rabbits receiving cyclosporine at oral doses up to 17 mg/kg/day or 30 mg/kg/day, respectively, during organogenesis. These doses in rats and rabbits are approximately 3,000 and 10,000 times greater (normalized to body surface area), respectively, than the daily human dose. Offspring of rats receiving a 45 mg/kg/day oral dose of cyclosporine from Day 15 of pregnancy until Day 21 postpartum, a maternally toxic level, exhibited an increase in postnatal mortality; this dose is 7,000 times greater than the daily human topical dose (0.001 mg/kg/day) normalized to body surface area assuming that the entire dose is absorbed. No adverse events were observed at oral doses up to 15 mg/kg/day (2,000 times greater than the daily human dose). There are no adequate and well-controlled studies of RESTASIS ® in pregnant women. RESTASIS ® should be administered to a pregnant woman only if clearly needed. Nursing Mothers Cyclosporine is known to be excreted in human milk following systemic administration, but excretion in human milk after topical treatment has not been investigated. Although blood concentrations are undetectable after topical administration of RESTASIS ® ophthalmic emulsion, caution should be exercised when RESTASIS ® is administered to a nursing woman. Pediatric Use The safety and effi cacy of RESTASIS ® ophthalmic emulsion have not been established in pediatric patients below the age of 16. Geriatric Use No overall difference in safety or effectiveness has been observed between elderly and younger patients. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: Systemic carcinogenicity studies were carried out in male and female mice and rats. In the 78-week oral (diet) mouse study, at doses of 1, 4, and 16 mg/kg/day, evidence of a statistically signifi cant trend was found for lymphocytic lymphomas in females, and the incidence of hepatocellular carcinomas in mid-dose males signifi cantly exceeded the control value. In the 24-month oral (diet) rat study, conducted at 0.5, 2, and 8 mg/kg/day, pancreatic islet cell adenomas signifi cantly exceeded the control rate in the low-dose level. The hepatocellular carcinomas and pancreatic islet cell adenomas were not dose related. The low doses in mice and rats are approximately 80 times greater (normalized to body surface area) than the daily human dose of one drop (approximately 28 mcL) of 0.05% RESTASIS ® twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed. Mutagenesis: Cyclosporine has not been found to be mutagenic/genotoxic in the Ames Test, the V79-HGPRT Test, the micronucleus test in mice and Chinese hamsters, the chromosome-aberration tests in Chinese hamster bone-marrow, the mouse dominant lethal assay, and the DNA- repair test in sperm from treated mice. A study analyzing sister chromatid exchange (SCE) induction by cyclosporine using human lymphocytes in vitro gave indication of a positive effect (i.e., induction of SCE). Impairment of Fertility: No impairment in fertility was demonstrated in studies in male and female rats receiving oral doses of cyclosporine up to 15 mg/kg/day (approximately 2,000 times the human daily dose of 0.001 mg/kg/day normalized to body surface area) for 9 weeks (male) and 2 weeks (female) prior to mating. PATIENT COUNSELING INFORMATION Handling the Container Advise patients to not allow the tip of the vial to touch the eye or any surface, as this may contaminate the emulsion. To avoid the potential for injury to the eye, advise patients to not touch the vial tip to their eye. Use with Contact Lenses RESTASIS ® should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. Advise patients that if contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS ® ophthalmic emulsion. Administration Advise patients that the emulsion from one individual single-use vial is to be used immediately after opening for administration to one or both eyes, and the remaining contents should be discarded immediately after administration. Rx Only Based on package insert 71876US18 © 2014 Allergan, Inc. Irvine, CA 92612, U.S.A. ® marks owned by Allergan, Inc. APC21XT14 Patented. See www.allergan.com/products/patent_notices Made in the U.S.A. Live: w 4.36" x h 9.25" NOTES: File is sized to Live Area. Bleed: few years, it has been about 600,000, and it has not been increasing." Additionally, he has found that there has been volatility in the number of patients. The number one reason that LASIK has decreased so dramatically is fear, according to Dr. Motwani. "Fear of the actual procedure is at an all-time high," he said. Although in the past physicians had a hard time getting patients to take the procedure seriously, patients are now more afraid of it. This fear also applies to the fear of spending mon- ey, which directly correlates to the economy. Finally, Dr. Motwani said, there is fear that is spread online, with information from websites and other sources preventing people from wanting LASIK. "The majority of information on the web is old and wrong, with too many sites hyping LASIK complications and disaster stories when they just don't happen in a good practice," he said. Marketing is key. Dr. Motwani said it's important to get your laser company to invest marketing money to directly advertise LASIK to the public. If there was a concerted advertising campaign from larger companies, he thinks this could help counter all of the negative informa- tion that is getting out to the pubic. "Doctors need to step away from the negative forces for short-term gain like massive price cutting [and] trashing other surgeons and make a team effort to counteract the myths out there," he said. Jonathan Rubenstein, MD, vice-chairman and Deutsch Family Professor, Rush University Medical Center, Chicago, thinks his LASIK volume may be down slightly, but his volume was not particularly high to begin with. "If there has been a drop, it is probably in the 5–10% range," he said. Dr. Rubenstein does not think this decrease is from patients decid- ing not to have the procedure. "Any fluctuations in LASIK volume seem to be tied more to the economy than anything else," he said. "I have not heard any negative opinions from patients about LASIK." There are a number of technol- ogies that help improve the LASIK procedure, including femtosecond lasers and excimer lasers. "As people feel more economic confidence, I think the LASIK numbers will in- crease," Dr. Rubenstein said. Surgeons themselves can help promote the procedure by con- tinuing to provide quality care and good results, he said. "The internal marketing that comes from a satis- fied patient is still the most effec- tive mechanism for attracting new patients." Steven Schallhorn, MD, San Diego, thinks LASIK numbers have fallen, both in the U.S. and in Europe. He attributes this decrease to several factors: the economy and cost factors, the knowledge and understanding factor, and the fear factor. "First, there's continued eco- nomic uncertainty," he said. Global economics definitely play a role. The economic factor also involves cost, and the most important cost element, Dr. Schallhorn said, is the perceived value of the procedure. Perceived value is affected by how we promote LASIK, he said. Surgeons need to be intimately aware of this; it would be much more beneficial to promote LASIK as a life-changing event rather than a commodity. "In the perceived value of the proce- dure, we can oftentimes be our worst enemy by the way we promote LASIK," he said. The second factor, knowledge and understanding, has to do with people's awareness of the procedure, Dr. Schallhorn said. This includes whether or not people are aware of the advances that have been made to better the procedure, including use of the femtosecond laser, cus- tomized treatments, etc. The last major factor that Dr. Schallhorn thinks is influencing LASIK is what he calls the "fear fac- tor." Despite millions of successful procedures, patients may see one or two negative reviews and become skeptical. The use of the Internet makes it easy for a small number of dissatisfied patients to broadcast their views to a very large audience. "It's understandable to have some apprehension about having surgery in general, especially on the eyes," he said. So what can be done? Dr. Schallhorn stressed the importance of having a sound and consistent message. The message should not be that one individual performs a safer procedure than other professionals, he said. To patients, this type of promotion implies that LASIK can be unsafe, and the end result is to needlessly elevate innate "fear" of the procedure, he said. "The outcomes of modern LASIK are incredible," he said, and they are unparalleled in terms of patient satisfaction and other metrics. However, he added that the fear factor and other issues still need to be tackled, and it's important to find a way of conveying the proper value that LASIK can provide, like its many visual benefits and improve- ments to quality of life. EW Editors' note: The sources have no financial interests related to their comments. Contact information Motwani: lasikdoc@drmotwani.com Rubenstein: Jonathan_Rubenstein@rush.edu Schallhorn: scschallhorn@yahoo.com Are LASIK continued from page 35

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