EyeWorld India March 2018 Issue

59 EWAP PHARMACEUTICALS March 2018 There are two compounding pharmacies that have put out a variety of formulations to try to address these issues. One of these companies, Ocular Science, has 503 A status and is a patient-specif- ic compounding pharmacy. Such pharmacies tend to be smaller. “They have voluntary inspections by the FDA and aren’t tightly regulated,” Dr. Radcliffe said. They have combinations of latanoprost and timolol in one bottle and they have all four glaucoma agents— timolol, brimonidine, dorzolamide, and latanoprost—in one bottle. Imprimis is a 503 B compound- ing pharmacy, which manufactures preservative-free glaucoma formu- lations. “With 503 B compounding pharmacies, because they’re mass producing, they do have some fairly frequent inspections,” Dr. Radcliffe said. “They have all of the combinations that you would want.” Possible downsides One potential downside is the un- certain status of some compound- ed medication. “It’s interesting because we’re in a gray zone legis- latively,” Dr. Radcliffe said, adding that replicating large quantities of these eye drops in combination may have legal implications. He pointed to an Allergan (Dublin, Ireland) lawsuit against Imprimis that’s challenging the legality of manufacturing and selling of these unapproved drops in mass quantities. “Allergan has taken the position that it is illegal for the compounding pharmacies to be mass-producing medications that haven’t been FDA approved,” Dr. Radcliffe said. It appears that the U.S. Food and Drug Administration (FDA) took action on Allergan’s complaint, sending a warning let- ter to Imprimis in December 2017. The FDA’s letter stated that on its website Imprimis violated the Fed- eral Food, Drug and Cosmetic Act by claiming “Simple Drops” were made with FDA-approved drugs and by omitting important safety information about its compounded formulations. Dr. Novack pointed out that drugs that have been FDA ap- proved and marketed meet good manufacturing practice standards for release and stability. “These criteria include the concentration of active (i.e. the named product molecule), as well as sterility, pH, and in the case of preserved prod- ucts, the ability to kill microbes,” Dr. Novack said. “Most products compounded by pharmacies are not tested, so this quality cannot be assured.” Preservative-free glaucoma formulations may bring addi- tional concerns. “While the active molecules are approved in indi- vidual or in some cases fixed-dose combinations, the non-preserved formulation has not undergone the chemical, preclinical and clinical evaluation, or benefit/risk evalu- ation of FDA-approved products,” Dr. Novack said. What’s more, some double and triple fixed-dose combinations have been evalu- ated in controlled studies, albeit in different formulations, and in some cases were judged by the FDA not to have a favorable benefit/risk ratio. There is also the question of in- fection with compounded medica- tions. In Dr. Radcliffe’s view, with the compounded drops, such con- cerns are not founded. “It needs to be said that any infections related to compounded medications have had to do with injected medica- tions,” he said. Topical medicines are much less likely to be associ- ated with ocular infections. Other questions, like how well the bottles do if they’re not refrigerated or how well they stay preserved, is something that practitioners need to think about, Dr. Radcliffe said. In addition to glaucoma medi- cation, compounded therapy has found its way into cataract surgery. “This can include combinations of antibiotic, steroid, and nonsteroi- dal anti-inflammatory that are dosed four times a day after cata- ract surgery. This can be particular- ly confusing and burdensome for glaucoma patients who are taking other medications as well,” Dr. Radcliffe said. “If our patients are taking glaucoma drops and they have cataract surgery, they can end up on six drops, and that gets confusing,” he said. “You may find that other things, such as dropless cataract surgery, can help.” Dr. Radcliffe has been using compounded Tri-Moxi (triamci- nolone/moxifloxacin, Imprimis) for cataract surgery. “When I perform a cataract surgery with MIGS, at the end of the cataract I inject the Tri-Moxi and often have patients who are completely off all glaucoma and cataract drops after cataract surgery,” Dr. Radcliffe said, adding that it is a great thing for a patient to come in for surgery on three drops, have the surgery, and end up on no drops. He finds that the patients are very grateful to have dropless cataract surgery and see the burden of their glaucoma drops reduced at the same time. Overall, Dr. Radcliffe views this as an exciting time, but acknowledges that the field is still very much evolving. “I think there are issues that still need to be resolved,” he said. “Some are financial, some have to do with safety and efficacy, and others have to do with practice dynam- ics.” Ultimately, it’s going to be a question of whether the majority of ophthalmologists embrace these therapies, he concluded. EWAP Editors’ note: Dr. Radcliffe had finan- cial interests with Aerie Pharmaceu- ticals (Irvine, California), Allergan, Bausch + Lomb (Bridgewater, New Jersey), Novartis (Basel, Switzerland), and Ocular Science. Dr. Novack has no financial interests related to his comments. Contact information Novack: gary_novack@pharmalogic.com Radcliffe: drradcliffe@gmail.com