Dorzolamide/timolol combination versus concomitant administration of brimonidine and timolol: six-month comparison of efficacy and tolerability

Ophthalmology. 2003 Mar;110(3):615-24. doi: 10.1016/S0161-6420(02)01900-0.

Abstract

Purpose: To compare the efficacy and tolerability of the 2% dorzolamide/0.5% timolol combination ophthalmic solution twice daily to the concomitant administration of 0.2% brimonidine ophthalmic solution twice daily and 0.5% timolol ophthalmic solution twice daily.

Design: Randomized, multicenter, observer-masked, parallel-group study.

Participants: Two hundred ninety-three patients with ocular hypertension or primary open-angle glaucoma participated.

Intervention: After an open-label 3-week 0.5% timolol run-in period, patients with an hour 2 intraocular pressure (IOP) of > or = 22 mmHg were randomly assigned to receive either the dorzolamide/timolol combination twice daily or the concomitant use of brimonidine twice daily and timolol twice daily (brimonidine + timolol) for 6 months.

Main outcome measures: The IOP-lowering effects at hour 0 and hour 2 were collected at 1, 3, and 6 months. We hypothesized that both treatment regimens would have comparable hour 2 IOP-lowering effects at month 3. The treatments were considered comparable if the two-sided 95% confidence interval of the treatment difference was within +/- 1.5 mmHg. Tolerability data were also collected at 1, 3, and 6 months.

Results: The primary efficacy analysis was based on the modified intent-to-treat population. At month 3, hour 2, the dorzolamide/timolol group had an adjusted mean (standard error) change in IOP of -5.04 (0.30) mmHg versus -5.41 (0.30) mmHg in the brimonidine + timolol group, with a treatment difference of 0.36 (0.40) mmHg (95% confidence interval [CI] of -0.42-1.14 mmHg). At month 3, hour 0, the dorzolamide/timolol group had a change in IOP of -3.66 (0.29) mmHg versus -4.15 (0.28) mmHg in the brimonidine + timolol group, with a treatment difference of 0.49 (0.39) mmHg (95% CI of -0.27-1.25 mmHg). Likewise, at all other observed time points, the 95% confidence interval of the treatment difference was within +/- 1.5 mmHg. Ninety-three patients (64%) in the dorzolamide/timolol group and 88 patients (60%) in the brimonidine + timolol group had adverse experiences that were deemed drug related by the investigator, for which 7 patients (5%) in the dorzolamide/timolol group and 8 patients (5%) in the brimonidine + timolol group were discontinued from the study.

Conclusions: The efficacy of the dorzolamide/timolol combination and the concomitant administration of brimonidine and timolol were comparable. The incidence of drug-related adverse experiences and the incidence of discontinuations caused by drug-related adverse experiences were similar between groups.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Brimonidine Tartrate
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glaucoma, Open-Angle / drug therapy*
  • Glaucoma, Open-Angle / physiopathology
  • Humans
  • Intraocular Pressure / drug effects*
  • Male
  • Middle Aged
  • Ocular Hypertension / drug therapy
  • Ocular Hypertension / physiopathology
  • Ophthalmic Solutions
  • Prospective Studies
  • Quinoxalines / adverse effects
  • Quinoxalines / therapeutic use*
  • Safety
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Thiophenes / adverse effects
  • Thiophenes / therapeutic use*
  • Timolol / adverse effects
  • Timolol / therapeutic use*
  • Visual Acuity
  • Visual Fields

Substances

  • Antihypertensive Agents
  • Ophthalmic Solutions
  • Quinoxalines
  • Sulfonamides
  • Thiophenes
  • Brimonidine Tartrate
  • Timolol
  • dorzolamide