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EW CATARACT 32 February 2016 by Vanessa Caceres EyeWorld Contributing Writer value than branded ones. Only 10% of patients think that generic drugs cause more side effects. Yet if you ask physicians, 50% have a negative view of generics, and 27% would prefer not to use generic drugs for themselves or their family. Numbers like these show the debate over using brand versus generic medications continues. During the "Cataract Dilemmas and Controversies" symposium at the 2015 ASCRS•ASOA Symposium & Congress in San Diego, 2 ophthal- mologists shared their analysis and professional experience regarding why they are now leaning toward a specific side of the issue. The symposium was sponsored by the ASCRS Cataract Clinical Committee. In Wisconsin, as well as in many other states, pharmacists are allowed to dispense the generic version of a drug unless a doctor specifies oth- erwise, said presenter John Vukich, MD. In 2011, the Davis Duehr Dean Department of Ophthalmology made the decision to switch to all generic drops after cataract surgery, after what Dr. Vukich described as a lot of consternation and literature searches. The main reason for the switch was cost. "The increase in cost to the patient [with brand medications] was not a small factor. The number one reason we were contacted after hours was pharmacists asking if they could substitute a generic," he said. At the same time, ophthalmolo- gists within his multispecialty prac- tice were prescribing more branded drugs than other departments and they were identified as an outlier in cost containment efforts, Dr. Vukich said. Ophthalmologists began writing generic prescriptions for predniso- lone acetate (Pred Forte, Allergan, Dublin), ketorolac (Acular, Allergan), and ofloxacin (Ocuflox, Allergan). The practice then decided to review cases of post-surgical endoph- thalmitis before and after the generic switch. Although the surgeons at the practice were prescribing the same drugs, there were some differences in techniques, such as topical versus block, incision size and location, and type of intraocular lens used, Dr. Vukich said. However, the rate of endophthalmitis appeared to remain the same in the before versus after periods—1 per 2,000 cases. The practice then compared the cost of generics versus brand medications at area pharmacies for the drugs they prescribed. They found the additional cost for brand medications ranged from $277 to $319 more, as compared among 4 Motivations to use each one may differ among clinicians G eneric medications made up 71% of all prescriptions in the U.S. in 2010, and 80% of patients think that generic drugs are a better Brand vs. generic ophthalmic medications 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: Patient who developed corneal melt after using generic medications post-cataract surgery Source: John Wittpenn, MD continued on page 34

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