Use of fixed-dose combination drugs for the treatment of glaucoma

Glaucoma is a leading cause of irreversible visual loss. This potentially blinding disease is a progressive optic neuropathy associated with elevated intraocular pressure (IOP). Initial therapy for glaucoma typically consists of topical medications or laser treatment to lower IOP. Frequently, more than one medication is required to achieve adequate control of IOP. However, more medications means more bottles and greater complexity for the patient. There are several potential benefits of fixed combination medications compared with using the individual components separately. These include a reduction in the total number of drops and preservative instilled per day, cost savings, improved tolerability and compliance and avoiding the washout effect resulting from rapid-sequence instillation of multiple drops. Attempts to develop effective fixed combinations of glaucoma medications date back several decades. In recent years, fixed combinations of commonly paired drugs have been approved by various regulatory bodies in different countries and have gained wide acceptance. Current commercially available, fixed combination drugs include the topical beta-adrenoceptor antagonist timolol 0.5% combined with a prostaglandin, a topical carbonic anhydrase inhibitor or an alpha-adrenoceptor agonist. Although there is no uniformity among registration trial designs, most published literature compares the efficacy of the fixed combination to the individual components and to concomitant use of both components. Various factors inherent to study design such as medication run-in, washout periods and peak and trough effects have to be taken into consideration when analysing the demonstrated efficacy of fixed combinations. Fixed combination treatments offer effective IOP control while reducing the washout effect and exposure to preservatives. They are also convenient. However, fixed combinations also remove the possibility of titrating the individual components both in terms of concentration and timing of administration. In addition, fixed combinations might not always provide the same efficacy as proper use of the individual components. The clinician must make individualised assessments when weighing the convenience of these medications against their limitations for specific patients.