A review of additivity to prostaglandin analogs: fixed and unfixed combinations

Prostaglandin analogs are currently the first-line agents in the medical treatment of glaucoma. Frequently, more than one drug is needed to control intraocular pressure. Beta-blockers, topical carbonic anhydrase inhibitors, and alpha-adrenergic agonists are commonly used in addition to prostaglandin analogs. Topical carbonic anhydrase inhibitors are more effective in lowering intraocular pressure at trough than alpha-adrenergic agonists. Although similarly effective as topical carbonic anhydrase inhibitors during the day, adequate nocturnal intraocular pressure reduction with beta-blockers is controversial. Three fixed combinations of prostaglandins with timolol (0.005% latanoprost with 0.5% timolol, 0.004% travoprost with 0.5% timolol, and 0.03% bimatoprost with 0.5% timolol) are available. Fixed-combination therapy has advantages over multi-drop, multi-bottle therapy in terms of patient convenience and adherence without sacrificing the additive effects of the unfixed combinations. In countries where they are available, fixed combinations of prostaglandins/beta-blockers may become second-line treatment. Fixed and unfixed adjunctive combinations with prostaglandin analogs have demonstrated, in multiple comparative studies, to be effective, but none has been shown to be an ideal combination.