Role of Fixed Combinations in the Management of Open-angle Glaucoma

Anton Hommer


Expert Rev Pharmacoeconomics Outcomes Res. 2011;11(1):91-99. 

In This Article

Abstract and Introduction


The first-line option for lowering intraocular pressure (IOP) is a single hypotensive agent, but patients frequently require additional IOP-lowering agents to reach their target pressures. Disadvantages of this multi-therapy approach include washout effect, inconvenience and poor adherence. Fixed combinations (FCs) combine two or more hypotensive agents in a single bottle, providing a convenient once-daily therapy, which tends to improve adherence. FCs generally offer equivalent efficacy to concomitant use of the individual components, with equivalent or superior tolerability. Studies also show that FCs can be more cost effective than nonfixed combinations. In terms of optimizing IOP control, minimizing visual field deterioration, preventing visual disability and minimizing associated healthcare costs, FCs are an important component of glaucoma management.


Glaucoma is a major cause of blindness worldwide.[1] Currently, the only modifiable risk factor for glaucoma is raised intraocular pressure (IOP), which can be treated by surgical or medical means.[2] Several large randomized clinical trials have shown that adequate control of IOP can reduce the risk of functional progression of glaucoma by as much as 10–19%.[3–6]

Newly diagnosed patients are usually prescribed a single IOP-lowering agent, whether visual field (VF) defects are present or not.[2] However, over time, many patients will require additional medications to avoid glaucomatous progression.[7,8] European Glaucoma Society (EGS) guidelines recommend that when a patient is responsive to initial monotherapy but does not attain their target IOP, a second agent should be added.[2] However, when dose frequency increases and/or the therapeutic regimen becomes complex, adherence to therapy tends to suffer, and is often overestimated by physicians.[9,10]

Fixed combinations (FCs) combine two or more agents in a single bottle. Most currently available FCs for the treatment of open-angle glaucoma consist of a β-blocker combined with either a prostaglandin (PG) analog, an α-2 agonist or a carbonic anhydrase inhibitor (CAI). Fixed combinations provide a convenient option for avoiding the poor adherence associated with complex therapeutic regimens.[11] A regimen consisting of one drop, once daily, from one bottle means fewer instillations and less opportunity for patient error. A single instillation also avoids the washout effect, whereby premature addition of a second drop can reduce the effect of the first.[12] Convenience is another important factor, and eliminating the need for a waiting period between instillations of multiple therapies is likely to improve adherence.[101] Other advantages of FCs include reduced exposure to excipients and preservatives, improved tolerability compared with the unfixed combinations and the potential for reduced costs.[13] A systematic review found that FCs generally offer equivalent efficacy and safety to unfixed combinations.[14]

Given all these considerations, FCs are an important addition to the management of glaucoma. They are of particular value in patients at high risk of visual disability, such as those who present with high IOP, pseudoexfoliative glaucoma or severe VF defects, or who subsequently exhibit a rate of functional progression that will lead to visual impairment during their expected lifetime.


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