EyeWorld Asia-Pacific March 2015 Issue

54 EWAP PHARMACEUTICALS March 2015 (dorzolamide/timolol, Akorn Pharmaceuticals, Lake Forest, Ill.), Combigan (brimonidine tartrate/ timolol maleate ophthalmic solution, Allergan, Irvine, Calif.), and Simbrinza (brinzolamide/ brimonidine tartrate, Alcon, Fort Worth, Texas). While Dr. Robin thinks the combined glaucoma agents have lived up to the promise of simplifying things for patients, a downside has been the cost, he finds. For example, timolol maleate and brimonidine tartrate, each an ingredient in Combigan, are inexpensive. “Timolol is a $4 drug at Walmart and Target, and brimonidine is almost as inexpensive,” he said. Combigan can be as high as $200. “Depending on someone’s pharmacy plan, sometimes it’s hard to rationalize the cost of a combination product compared with the two components separately,” Dr. Robin said. For patients for whom combination agents are feasible, deciding which of these to choose may rest on more than efficacy, said Reay H. Brown, MD , clinical professor, private practice, Atlanta. “To me, it’s a little bit about tolerance,” Dr. Brown said. For example, in choosing between Combigan and Cosopt, which both contain timolol, Dr. Brown considers how the brimonidine and the dorzolamide face off. “There may be a higher rate of side effects and intolerance with the brimonidine, but it’s a close call,” he said. Dr. Noecker also considers the pH factor. “There’s a fairly large difference in the pH and the environment that the drugs need to exist in the bottle,” he said. “Combigan has to have a higher, more neutral pH versus Cosopt, which is more acidic.” That lower pH for Cosopt, he finds, translates into stinging and, in the case of dry eye patients, may cause inflammation or breakdown of the ocular surface if enough is not washed away or neutralized. “In terms of relative efficacy, there are studies that show that Combigan is, on average, the more efficacious agent,” Dr. Noecker said. As for side effects, some patients may have a brimonidine allergy. For those for whom this is not an issue, they may find Combigan to be more tolerable. “I would say Combigan, having put it in my own eye, is a very comfortable eye drop. Simbrinza tends to be a comfortable eye drop as well,” Dr. Noecker said. “Cosopt is probably one of the least comfortable eye drops that we use.” This comfort factor makes a big difference in patient adherence to therapy, he thinks. Also available is Cosopt PF, which does not contain a preservative. “That makes it a more benign drug to the ocular surface, all other things being equal,” Dr. Noecker said. “It’s still a bit on the acidic side, which can be problematic for a dry eye patient. However, there are some patients who either have a BAK allergy, a preservative allergy, or just a tolerability problem with it. For someone who needs to be preservative free, that can be a nice way to go.” Dr. Brown remains a skeptic on the notion of preservative-free medication. He pointed out that the brand formulation of Xalatan (latanoprost, Pfizer, New York) tends to be the best tolerated even though it contains the most BAK of the prostaglandins, even when compared to Zioptan (tafluprost, Akorn Pharmaceuticals), the first preservative-free prostaglandin. The newest of the combination agents, Simbrinza, brings together two important medications— brinzolamide and brimonidine tartrate. “I use boatloads of [each of] them, so I think having them in one bottle is fabulous,” Dr. Brown said. “The convenience to the patient is important because instead of 2 drops twice a day, they’re taking just 1 drop twice a day.” Because this cuts the daily dosage in half, he think this will lead to a big improvement in compliance. However, he acknowledged that brimonidine on its own has about a 20% intolerance rate. With a second medication combined, tolerance should be monitored. “You have to warn people that they may experience some redness,” he said. Eye drop math Dr. Robin said practitioners should keep in mind that with all of the combination medicines, there is not as much of an additive effect for the second medication in the bottle. “In Cosopt or in Combigan, timolol is the major component, and in Simbrinza it’s brimonidine,” he said. “I think it’s important for most ophthalmologists to start out with just a major component, and if that isn’t enough don’t expect much more.” He urges practitioners to expect only 1 or 2 mm more of pressure lowering from adding the second agent. Dr. Brown agrees. He refers to this as “eye drop math.” “When you add 1 drop to another you do not get the full impact of the second drop—you get a fraction of what that drop does by itself,” Dr. Brown said. “Then if you use a third drop, you get a fraction of that.” Dr. Robin said it is an offshoot of this principle that has kept Xalacom (latanoprost and timolol, Pfizer), a combination of a prostaglandin and a beta blocker, out of the U.S. market. “It’s available in almost every other country except the U.S. and Japan,” Dr. Robin said. The U.S. Food and Drug Administration requires at least 2 mm of mean pressure difference at all time points between the combination and the single agent, something that was not attained with the prostaglandin timolol combination, he said. A new combination still in the pipeline that Dr. Robin thinks shows promise is Rhoclatan (Aerie Pharmaceuticals, Bedminster, NJ), which combines the Rho- kinase inhibitor Rhopressa with latanoprost. “The combination of a Rho-kinase inhibitor with a prostaglandin seems to be helpful,” he said. Overall, Dr. Brown views combination agents as an important, patient-centered innovation. “The more we can put in 1 bottle, the better,” he said. “Once a person is needing more than 1 drop a day, combinations make so much sense.” EWAP Editors’ note: Dr. Brown has no financial interests related to his comments. Dr. Noecker has financial interests with Alcon and Allergan. Dr. Robin has financial interests with Aerie Pharmaceuticals, Akorn Pharmaceuticals, and Teva Pharmaceutical Industries (Petah Tikvah, Israel). Contact information Brown: reaymary@comcast.net Noecker: noeckerrj@gmail.com Robin: arobin@glaucomaexpert.com The Latest - from page 53