Topical dorzolamide 2%/timolol 0.5%: a review of its use in the treatment of open-angle glaucoma.
The nonselective beta-blocker timolol and the carbonic anhydrase inhibitor dorzolamide both lower intraocular pressure (IOP). Timolol and dorzolamide have different mechanisms of action and their effects are additive when administered together. Therefore, the 2 drugs are frequently used concomitantly to treat patients with open-angle glaucoma who have not adequately responded to first-line therapy. A barrier to good compliance with concomitant therapy is the need to administer 5 or 6 drops of medication on 2 or 4 occasions during the day. Timolol 0.5% and dorzolamide 2.0% have therefore been combined in a single formulation, reducing the number of administrations required to 2 per day. Clinical trials in patients with glaucoma have demonstrated that dorzolamide 2%/timolol 0.5% (dorzolamide/timolol) is superior to monotherapy with the individual components. When dorzolamide/timolol administered twice daily was compared with concomitant treatment with dorzolamide 2% and timolol 0.5%, each administered twice daily for 90 days, both regimens resulted in marked lowering of trough IOP (measured just before the morning dose) compared with baseline (reduction in IOP = 4.2mm Hg). The effect of the 2 regimens on IOP at all time points, both before treatment and at peak effect (2 hours after treatment), were virtually indistinguishable. When the combined formulation was compared with a concomitant regimen that included dorzolamide 2% 3 times daily and timolol 0.5% twice daily the concomitant regimen was slightly more efficacious than the combined regimen at trough after 90 days: IOP was lowered by 3.6mm Hg in the combined group versus 4.1 mm Hg in the concomitant group. Dorzolamide/timolol has been compared with concomitant administration of timolol 0.5% and the IOP lowering miotic drug, pilocarpine 2.0%. This non-blind patient-preference study found that both regimens reduced IOP. However, the dorzolamide/timolol combination was preferred by the patients because of reduced frequency and severity of adverse effects and less frequent administration. Dorzolamide/timolol was well tolerated in clinical trials, the adverse effects reflected those of the individual components, and no additional tolerability issues were identified. However, the potential for timolol to cause cardiorespiratory effects must be considered when prescribing this combination. Furthermore, dorzolamide is a sulfonamide and can cause allergic reactions in those who are hypersensitive to this class of drug.


CONCLUSIONS
Dorzolamide/timolol is a well tolerated and effective fixed combination for lowering IOP in the treatment of open-angle glaucoma and is likely to be useful in those patients who do not respond adequately to first-line monotherapy. Compared with concomitant therapy with the same 2 drugs the primary advantage is convenience, which may lead to improved compliance. Studies of compliance and comparisons with other currently available combination therapies would be useful to fully define the value of the formulation. Nonetheless, dorzolamide combined with timolol in a single applicator system will be a useful addition to the treatment options for glaucoma, a leading cause of preventable blindness.
Ormrod
D
D
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
McClellan
K
K
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002257:Carbonic Anhydrase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology; D008297:Male; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013876:Thiophenes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013999:Timolol / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014785:Vision, Ocular / Q000187:drug effects* / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D002257:Carbonic Anhydrase Inhibitors; D004338:Drug Combinations; D013449:Sulfonamides; D013876:Thiophenes; D013999:Timolol; C062765:dorzolamide