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EW GLAUCOMA 36 December 2014 by Maxine Lipner EyeWorld Senior Contributing Writer 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 com- pared to Zioptan (tafluprost, Akorn Pharmaceuticals), the first preserva- tive-free prostaglandin. The newest of the combination agents, Simbrinza, brings together 2 important medications—brinzol- amide and brimonidine tartrate. "I use boatloads of [each of] them, so I think having them in 1 bottle is fabulous," Dr. Brown said. "The con- venience 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 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 com- fortable eye drop. Simbrinza tends to be a comfortable eye drop as well," Dr. Noecker said. "Cosopt is proba- bly one of the least comfortable eye drops that we use." This comfort fac- tor makes a big difference in patient adherence to therapy, he thinks. Also available is Cosopt PF, which does not contain a preserva- tive. "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 (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 simplify- ing things for patients, a downside has been the cost, he finds. For example, timolol maleate and brimonidine tartrate, each an ingredient in Combigan, are inex- pensive. "Timolol is a $4 drug at Walmart and Target, and brimoni- dine 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 separate- ly," Dr. Robin said. For patients for whom combi- nation 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 consid- ers 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 dif- ference in the pH and the environ- ment 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 acid- ic." 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 Eyeing this two-pronged approach T hese days about half of glaucoma patients are controlled by monotherapy, while the rest need more than one agent at a time, according to Robert J. Noecker, MD, clinical assistant professor, Yale University, and in private practice, Ophthalmic Consultants of Connecticut, Fairfield, Conn. One way to keep some patients from having to juggle more than one bottle is with the aid of combination medications. "I think we all acknowledge that the Achilles heel of medical glaucoma therapy is compliance," Dr. Noecker said. By making things simpler for patients, they are more likely to adhere to a regimen. "I think the messaging is much clearer when you have just 1 bottle. So the patient will have 1 copay and 1 thing to pick up versus 2." Also, patients only have to re- member 1 dosing regimen and keep 1 bottle on hand, he said. The pa- tient's side effect profile might also improve because the eye is exposed to fewer preservatives and variable pHs from other agents, Dr. Noecker said. In addition, the drop is more likely to get in the eye as expected. "You can also prevent a washout effect where [patients] put one drop in, and 5 seconds later they put a second drop in," he said. Alan L. Robin, MD, associate professor of ophthalmology and international health, Johns Hopkins University, Baltimore, agrees that streamlining the process with the use of combination agents is potentially attractive. "It simplifies patients' lives greatly and makes it easier for them to adhere to their prescribed treatment therapy," he said. Current options Currently, there are 3 combined glaucoma medications available in the U.S., Dr. Robin said. These include Cosopt (dorzolamide/ timolol, Akorn Pharmaceuticals, Lake Forest, Ill.), Combigan The latest on combined glaucoma agents continued on page 38 Combination agents can make it easier for patients to adhere to a glaucoma regimen with fewer drops to instill and potentially clearer messaging. Source: Robert J. Noecker, MD Pharmaceutical focus