Cardiovascular effects of timolol maleate, brimonidine or brimonidine/timolol maleate in concomitant therapy

To examine the influence on maximal exercise performance in young healthy volunteers of timolol 0.5%, brimonidine 0.2% or placebo versus brimonidine 0.2% and timolol 0.5% used concomitantly.

The subjects in this prospective, double-masked, crossover comparison were dosed 15 min prior to treadmill testing. A period of 1 week was allowed between tests.

The 20 subjects who completed the trials (average age 24.5 +/- 7.4) had a mean maximum exercise heart rate of 196 +/- 12 bpm for placebo, 182 +/- 13 bpm for timolol, 187 +/- 10 bpm for brimonidine, and 186 +/- 11 bpm for timolol/brimonidine concomitant therapy (p < 0.005). During recovery, the placebo group demonstrated a statistically higher systolic blood pressure (min 6) and pulse (mins 2 and 4) (p < 0.01). In addition, subjects treated with timolol/brimonidine demonstrated more premature contractions (atrial or ventricular) overall during exercise and recovery (p = 0.01). The brimonidine and concomitant treatment groups showed the greatest number of adverse events per subject, the most common of which were dizziness and fatigue (p = 0.031).

This study suggests that both timolol and brimonidine, used alone and concomitantly, cause cardiovascular effects consistent with their pharmacology.