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Study: diclofenac may enhance efficacy of latanoprost
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A study conducted at the University of Ferrara in Ferrara, Italy, found that, in primary open-angle glaucoma patients, diclofenac significantly augmented the hypotensive effect of latanoprost, but demonstrated no change in timolol efficacy.
The study, authored by Ciro Costagliola, looked at the pressure-lowering effect of topical diclofenac when combined with glaucoma drugs.
“This raises interesting issues, because we have tended to use only glaucoma agents to lower IOP, using up to four medications at a time,” said Murray Fingeret, OD, a Primary Care Optometry News Editorial Bard member, in an interview. “The reduction observed was comparable to, if not greater than, adding a topical carbonic anhydrase inhibitor (CAI) or beta-blocker and may make the case that this area should be explored further.”
Details of the study
The study looked at 32 glaucomatous patients who were treated with 0.5% timolol and randomized into two study groups, A and B. Timolol was continued for the first 2 weeks in all patients. On day 15, it was switched to latanoprost.
This course of treatment was continued until the end of follow-up (8 weeks). At the beginning of the second week of the study, group A also began 5 weeks of therapy with topical 0.1% diclofenac. Group B received placebo eye drops during this time.
Intraocular pressure was measured and recorded at 5-day intervals during the first 5 weeks and at the 10th week. Neither the nonsteroidal anti-inflammatory drug (NSAID) nor the placebo changed the effect of timolol on IOP.
“After the first week of latanoprost administration, a significant decrease of IOP occurred in both groups,” the researchers stated. In placebo-treated patients, the decrease was less pronounced, they said.
After discontinuation of diclofenac, group A subjects showed a significant increase in IOP and remained at this level to the end of the study. In group B, no significant variations in IOP were observed.
Analyzing the study results
Dr. Fingeret said there are several ways to analyze this data. “The topical NSAID (diclofenac) was added at day 7, and there was no change in IOP, but the patients used the combination of an NSAID and timolol for only 7 days. One could ask if this was enough time to observe an additional IOP reduction.”
He added that the replacement of timolol with latanoprost could not necessarily be evaluated independent from the topical NSAID in terms of the IOP reduction. “At the end of 2 weeks, the timolol was stopped and latanoprost begun. The topical NSAID was continued for several more weeks,” he said. “Because the patients were already using a topical NSAID, there was no way to judge the IOP reduction with latanoprost alone.”
Dr. Fingeret also questioned the finding that there was little difference in the IOP reduction when timolol was switched to latanoprost.
Future recommendations
Dr. Fingeret said the paper raises several interesting issues, but he added that he is unsure of the full implications of the study. “One of the points the authors raise is that doctors should be aware of the systemic, and even ocular, medications a person is taking, because they can interact with topical eye drops and lead, in this case, to low IOP,” he said. “Still, I am not sure if you can compare a topical eye drop and the concentration achieved in the anterior chamber to a systemic medication.”
Primary Care Optometry News Editorial Board member Bruce E. Onofrey, OD, RPh, FAAO, also discussed the significance of this study. “Diclofenac does appear to enhance the IOP-reducing efficacy of latanoprost significantly in the short term, without producing significant side effects,” he said in an interview. “The proposed mechanism is increased numbers of prostanoid receptors by suppression of endogenous prostaglandin compounds.”
Dr. Onofrey added, however, that he would not necessarily recommend this treatment combination as a result of the study. “At this point in time, the authors do not recommend the use of long-term diclofenac therapy in glaucoma patients to enhance the effects of latanoprost,” he said. “I would certainly not recommend long-term use of diclofenac at this point.”
The study authors stated that systemic NSAIDS are commonly used for many conditions such as arthritis. Dr. Fingeret said the study’s use of a topical agent makes this point somewhat flawed. “This leap is not perfect, because they used a topical agent, not an oral one,” he said.
Dr. Onofrey said he would like to see this issue explored in a more long-term study. “I would very much like to see a dose-response, long-term study to resolve both safety and efficacy issues.”
For more information:
- Murray Fingeret, OD, can be reached at St. Albans VA Hospital, (718) 526-1000; e-mail: murrayf@optonline.net.
- Bruce E. Onofrey, OD, RPh, FAAO, can be reached at Lovelace at Journal Center, (505) 275-4226; e-mail: Eyedoc3@aol.com.
- Ciro Costagliola can be reached at the Department of Ophthalmology, University of Ferrara, Ferrara, Italy; e-mail: costaciro@libero.it.
Reference:
- Costagliola C., et al. The influence of diclofenac ophthalmic solution on the intraocular pressure-lowering effect of topical 0.5% timolol and 0.005% latanoprost in primary open-angle glaucoma patients. Experimental Eye Research. 2005;81:610-615.