The goal of treatment in glaucoma and ocular hypertension is to reduce intraocular pressure (IOP) to a target pressure sufficiently low to prevent glaucomatous progression. The most commonly used classes of IOP-lowering medications are the prostaglandin analogs, beta-adrenergic receptor antagonists (beta-blockers), alpha adrenergic receptor agonists (alpha agonists), and carbonic anhydrase inhibitors (CAIs). For many patients, a single medication is insufficient to reduce IOP to the target pressure, and the treatment regimen includes 2, 3, or more medications from different classes.
In recent years the number and use of fixed combinations of IOP-lowering medications for treatment in glaucoma and ocular hypertension has grown substantially. These fixed combinations contain 2 medications in a single bottle and offer several advantages over concomitant use of the medications from separate bottles. Most important is the increase in patient convenience that results from the use of fewer bottles and eyedrops of medication and sometimes from dosing fewer times each day. The improved convenience of a regimen containing a fixed combination rather than 2 separate medications is likely to lead to better adherence. Although few, if any, studies have directly evaluated adherence to IOP-lowering fixed combinations compared with the component medications used separately, there is evidence that adherence in glaucoma is better when regimens are simple rather than complex.1
A retrospective study using prescription data from a large national healthcare provider concluded that the rate of prescription refills was reduced when patients added a second prescription to their IOP-lowering regimen.2
In other disease states, studies have shown significantly better adherence with fixed combinations (1 pill) than with the separate components (2 pills). For example, in systemic hypertension, another chronic asymptomatic disease associated with low levels of long-term adherence to therapy,3
retrospective studies using pharmacy records showed that patients were more apt to refill a prescription for a fixed combination than 2 separate prescriptions for the component medications,4
and patients on a fixed combination had medication available for more days of therapy compared with patients on the separate component drugs.5
Because there is no possibility of a washout effect and no need to wait between instillation of the separate individual medications, both efficacy and adherence may be enhanced when a fixed combination is used rather than the separate component medications. Use of a fixed combination may also represent a safety improvement, because the patient’s overall daily exposure to preservative may be decreased. Finally, there are potential cost savings associated with the use of fixed combinations, especially for patients with prescription insurance who have 1 copay for a fixed combination rather than 2 for separate medications. Moreover, in the United States, the availability of a generic fixed combination of dorzolamide and timolol increases access for those patients who previously could not afford this therapeutic option.
A disadvantage that should be highlighted is that it is not possible to change the drug concentration or dosing schedule for one component medication independently of the other when using a fixed combination. However, if adherence is improved by simplifying the regimen, the advantages of using a fixed combination outweigh this disadvantage.