Finding the sweet spot surrounding the number of anti-glaucoma medications translates to a balancing act with focus on individual patient needs.
Adding a medication
A few studies have provided positive evidence supporting the use of third and fourth drugs in the short term.
A small prospective Japanese study of ripasudil (Glanatec, Kowa Company, Ltd.), a rho kinase inhibitor with twice daily dosing, included 39 patients with a baseline of 3.6 medications; the study found that after 12 months of ripasudil treatment, there was an additional mean 15.5% decrease in IOP in more than two-thirds of patients.
A three-month retrospective study of netarsudil (Rhopressa, Aerie Pharmaceuticals) a rho kinase inhibitor approved in the United States, found an additional 3.9 mmHg IOP decrease in 172 eyes, that was similar in patients regardless of the number of baseline medications.
A retrospective evaluation of brimonidine (Alphagan, Allergan) in 53 eyes also showed an additional 20% IOP decrease in 53% of patients after 12 months who had been receiving a mean of three baseline medications.
Many prospective studies of latanoprost (Xalatan and Pharmacia, Upjohn) have shown a positive additive effect of the drug, with IOP decreases ranging from more than 20% to 36% in patients taking multiple baseline medications, Dr. Serle reported.
Fixed-dose combinations and co-drugs have changed the playing field in the past two years because, as Dr. Serle pointed out, they address all the caveats mentioned previously. To date, few studies of these drugs have been undertaken.
The question associated with these drugs, which include the co-drug nitric oxide-donating PGA latanoprostene bunod (Vyzulta, Bausch + Lomb), and the FDC netarsudil/latanoprost (Rocklatan, Aerie Pharmaceuticals), brinzolamide/brimonidine (Simbrinza, Alcon), topical CAI/beta-blocker (Cosopt, Merck Sharp & Dohme), and PGA/beta blocker (Xalacom, Pfizer), is whether the numbers of medications, bottles, or daily eyedrops should be counted, according to Dr. Serle.
Dr. Serle explained that when using the fixed-dose combinations, five medications can be instilled with four daily drop instillations, with only three bottles compared with previously when using pilocarpine alone, which was instilled four times daily. So, the consideration here is the level of individual patient tolerance for an ambitious regimen.
Patients can, she believes, instill three, four, or more topical medications daily, and in her practice some do so “reliably and comfortably.”
If issues arise, the options include simplification of regimens or moving on to laser or surgery, she noted and pointed to a few red flags indicating when something other than medical therapy may be entertained: the promise of better performance by the patient, IOP variability from visit to visit, running out of or not filling prescriptions, and poor visit compliance.
Medical therapy vs. surgery
All things considered, the waters can be murky when it comes to deciding the number of medications to use in individual patients to delay surgery, Dr. Serle explained. Some data indicate that adding more medications results in additional IOP lowering, which may delay surgery in some patients.
Regarding the question about how much medication is too much, unfortunately, there is no magic number of medications or daily drops.
“One patient’s sweet spot is another patient’s treatment burden,” she said, and the maximal number of medications that is effective, tolerated, and complied with varies markedly. The most efficacious and best-tolerated combinations of medications are unlikely to work for all patients. The bottom line seems to be highly individualized care.
“Make sure the target IOP is achieved, the disease is stable, and the patient is adhering to the regimen. These factors translate to the correct number of drop instillations daily,” Dr. Serle concluded.
Janet B. Serle, MD
E: [email protected]
Dr. Serle is a consultant to Aerie Pharmaceuticals, Inc., Allergan, and Bausch + Lomb, receives grant support from Ocular Therapeutix and Allergan, and receives lecture fees from Aerie Pharmaceuticals, and Bausch + Lomb. She reported equity ownership in Aerie Pharmaceuticals.