Switching within glaucoma medication class Simon K. Law Jules Stein Eye Institute, University of California, Los Purpose of review Angeles, California, USA In the current medical care environment, switching within class is often demanded by Correspondence to Simon K. Law, MD, 100 Stein cost consideration, medical insurance coverage, or formulary restriction. With many Plaza #2-235, Jules Stein Eye Institute, Los Angeles, CA 90095, USA choices of drugs available within a glaucoma medication class, questions exist whether Tel: +1 310 794 1477; fax: +1 310 206 7773; switching within class is beneficial. The purpose of this article is to provide a e-mail: [email protected] clinical update on the feasibility of switching among the frequently used drugs within Current Opinion in Ophthalmology 2009, glaucoma medication class. 20:110–115 Recent findings Although efficacies of medications within a therapeutic class are similar and significant differences are generally not observed in clinical trials, response to medication often varies among individual patients in a clinical practice. Such variation may be secondary to differences in drug–receptor interactions, patient’s compliance and tolerability to medical treatment, or bioavailability of the medication in individual ocular condition. In addition, switching within class is often necessary to minimize the systemic or local adverse reactions from the active or inactive ingredients of the medication. Summary In addition to keeping up-to-date with the efficacy and safety profiles of drugs within each glaucoma medication class, clinicians should familiarize themselves with the different formulations available, preservative systems used, generics availability and compatibility, and the local insurance formulary restriction to deliver an effective glaucoma management. Keywords class, glaucoma, medication, switch, therapy Curr Opin Ophthalmol 20:110–115 ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins 1040-8738 prostaglandin analogs for glaucoma management include Introduction latanoprost, travoprost, bimatoprost, and unoprostone. When the intraocular pressure (IOP) is not adequately The efficacies of latanoprost, travoprost, and bimatoprost controlled by one class of glaucoma medication or the are similar with IOP reduction of almost 30%; and dosed side-effect is not tolerable, the usual practice is to switch once daily, they have demonstrated superiority than to another class of glaucoma medication with a different timolol [1]. Unoprostone, however, is dosed twice daily mechanism of action. However, because there are many and with IOP reduction only comparable with betaxolol choices of drugs available within each glaucoma medi- but not timolol [2]. In a meta-analysis [1] of randomized cation class, switching within class is a reasonable con- clinical trials to estimate the IOP reduction achieved by sideration. In addition, switching within class is often the most frequently prescribed glaucoma drugs, includ- demanded by cost consideration, insurance coverage, or ing latanoprost, travoprost, and bimatoprost, IOP was formulary restriction, in the current medical care environ- reduced from baseline by 31–33% for the peak and ment. The purpose of this article is to provide a clinical 28–29% for the trough with topical prostaglandin analogs, update on the feasibility of switching within glaucoma and bimatoprost achieved the highest reduction of IOP at medication class with discussion focused on the fre- peak. There are studies showing that bimatoprost may be quently used drugs. slightly more effective than latanoprost and travoprost. For example, in a randomized, double-blinded crossover comparison [3] of bimatoprost and latanoprost, the Prostaglandin analogs 24-h diurnal IOP is statistically lower with bimatoprost Prostaglandin analogs are the most potent ocular hypo- than latanoprost. However, the difference was small tensive agent yet discovered. The primary mechanism of (0.5 mmHg) and may not be clinically meaningful. When action of prostaglandin analogs is believed to reduce IOP the three prostaglandin analogs were compared in a by increasing uveoscleral outflow, but they may have 12-week study [4], no statistical differences were effects on trabecular outflow also. Commercially available observed between them in mean IOP. Travoprost, which 1040-8738 ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/ICU.0b013e32831d1fc7 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Switching within glaucoma medication class Law 111 has the highest affinity to PGF2a (FP) receptor, has been iris pigmentation and eyelash changes associated with shown to significantly reduce the IOP below baseline even unoprostone was lower than latanoprost, and probably 60 h after the last dose of a 2-week once-daily therapy [5]. other prostaglandin analogs [4,17–22]. However, similar study has not yet been conducted for bimatoprost and latanoprost and the three prostaglandin Travoprost is available both with and without benzalk- analogs are supposed to be dosed once daily. onium chloride (BAK) as preservative. The travoprost BAK-free solution uses sofZia as the preservative system, Although the efficacies of the three prostaglandin analogs and is the only prostaglandin analog that does not contain are similar in the study populations of clinical trials, BAK. It may be worth switching a patient who developed variable response to prostaglandin analogs in individual allergic reaction to prostaglandin analogs with BAK or has patients is occasionally observed in clinical practice. In a ocular surface disease associated with BAK to travoprost retrospective review [6] of more than 300 patients in a BAK-free solution. However, the rates of adverse events, health management organization that had switched all hyperemia, and discontinuation were not found to be patients from latanoprost to bimatoprost, approximately different between travoprost with or without BAK in 13% of patients had a further IOP reduction of more than phase 3 trial [23]. Careful monitoring for adverse 3 mmHg after switching from latanoprost to bimatoprost reactions is necessary after switching. compared with 5% of patients who had a more than 3 mmHg reduction while using latanoprost before the switch. Variation in patient’s response with bimatoprost b-Adrenergic antagonists was suggested to be a result of the interaction of bimato- Because timolol was noted to markedly reduce IOP in prost with a receptor for prostamides instead of the FP glaucoma patients in the 70s, several b-adrenergic receptor for prostaglandins. Cantor et al. [7] noted that the antagonists were marketed, which include timolol, levo- level of bimatoprost acid, which can bind to FP receptor, bunolol, metipranolol, carteolol, and betaxolol. Efficacies detected in aqueous from cataract patients was too low for a of IOP reduction among the b-adrenergic antagonists are significant IOP reduction effect. Studies [8,9] showed equivalent except for betaxolol, which most studies have that the in-vitro effect of bimatoprost on trabecular mesh- shown to be slightly less effective in reducing aqueous work was blocked by prostamide-selective antagonist. flow and decreasing IOP than timolol [24–26]. When However, other studies [10,11,12] found that the contrac- patients are switched from timolol to betaxolol or tility effect of bimatoprost on the human ciliary muscle was randomized to one versus the other, IOP is often about blocked by FP-receptor antagonist, and none of the com- 2 mmHg higher in the timolol-treated eyes. Therefore, if mercially available topical prostaglandin analogs had effect a stronger IOP reduction is needed in patients taking on IOP in FP-receptor-deficient mice. In addition, a betaxolol, switching to timolol may be considered. How- receptor specifically for bimatoprost has not yet been ever, betaxolol is the only selective b-adrenergic anta- identified, and its existence remains controversial. Another gonist available for topical ophthalmic use. It is often possible mechanism of variation in response to prostaglan- termed cardioselective because of its relative affinity for din analogs is single-nucleotide polymorphisms in the the b1 (cardiac) over the b2 (pulmonary) adrenergic FP-receptor gene. Although prostaglandin analogs are receptor. In patients who had mild pulmonary distress generally effective in reducing the IOP, low responders with other nonselective b-adrenergic antagonists, switch- or nonresponders to latanoprost were identified from 4 ing to betaxolol may provide a relief [27–30]. However, to 32% in different populations [13,14]. In healthy caution is advised because it certainly can provoke volunteers, who were low responders to latanoprost, single- bronchospasm [31,32]. Betaxolol is available in either a nucleotide polymorphisms in the FP-receptor gene corre- suspension form or solution form. The suspension form lated to lower transcriptional activity of the FP-receptor has longer half-life, is dosed once a day, and has a lower gene were identified [15,16]. On the basis of the notion overall systemic absorption. that patient’s response to medication varies individually, switching to another prostaglandin analogs may be justified Carteolol, unlike the other topical b-adrenergic if the IOP response to a prostaglandin analog is deemed antagonists, also demonstrates weak intrinsic sympatho- suboptimum. mimetic activity (ISA), causing an early transient agonist response. This ISA theoretically reduces