Timoptol-XE Mechanism of Action

TIMOPTOL-XE (timolol maleate) is a formulation of TIMOPTOL (timolol maleate) containing a novel delivery vehicle. TIMOPTOL-XE reduces elevated and normal intraocular pressure whether or not associated with glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss. The higher the intraocular pressure, the greater the likelihood of glaucomatous visual field loss and optic nerve damage.
Clinical studies have shown that the intraocular pressure lowering effect of TIMOPTOL-XE administered once a day is equivalent to TIMOPTOL administered twice a day. The vehicle of TIMOPTOL-XE increases the contact time of the drug with the eye.
Gellan solution contains a highly purified anionic heteropolysaccharide derived from gellan gum. Aqueous solutions of gellan gum form a clear transparent gel at low polymer concentrations in the presence of cations. When TIMOPTOL-XE contacts the precorneal tear film, it becomes a gel.
Maximum reduction of intraocular pressure occurs in two to four hours with TIMOPTOL-XE. Significant lowering of intraocular pressure has been maintained for 24 hours with both 0.25% and 0.5% TIMOPTOL-XE.
TIMOPTOL-XE has a safety profile similar to that of TIMOPTOL, and both are generally well tolerated. Bradycardia was reported less frequently with TIMOPTOL-XE than with TIMOPTOL. In the three studies comparing TIMOPTOL-XE 0.5% once a day to TIMOPTOL 0.5% twice a day, TIMOPTOL-XE did not reduce mean heart rate as much as TIMOPTOL (see Precautions). At trough (24 hours post-dose TIMOPTOL-XE, 12 hours post-dose TIMOPTOL), the mean reduction was 0.8 beats/minute for TIMOPTOL-XE and 3.6 beats/minute for TIMOPTOL; whereas at two hours post-dose, the mean reduction in heart rate was comparable (3.8 beats/minute for TIMOPTOL-XE and 5 beats/minute for TIMOPTOL). There was a higher incidence of transient blurred vision following instillation in patients administered TIMOPTOL-XE.
Timolol maleate is a nonselective beta-adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane stabilizing) activity.
Onset of action of timolol maleate is usually rapid, occurring approximately 20 minutes after topical application to the eye. The precise mechanism of action of timolol maleate in lowering intraocular pressure is not clearly established. A fluorescein study and tonography studies indicate that the predominant action may be related to reduced aqueous formation. However, in some studies a slight increase in outflow facility was also observed.
In clinical studies timolol maleate was generally effective in more patients and produced fewer and less severe side effects than either pilocarpine or epinephrine.
Unlike miotics, timolol maleate reduces intraocular pressure with little or no effect on accommodation or pupil size. Thus, changes in visual acuity due to increased accommodation are uncommon, and the dim or blurred vision and night blindness produced by miotics are not evident. In addition, in patients with cataracts the inability to see around lenticular opacities when the pupil is constricted by miotics is avoided. When changing patients from miotics to TIMOPTOL-XE, refraction may be necessary after the effects of the miotic have passed.
As with other antiglaucoma drugs, diminished responsiveness to timolol maleate after prolonged therapy has been reported in some patients. However, in clinical studies of TIMOPTOL in which 164 patients were followed for at least 3 years, no significant difference in mean intraocular pressure was observed after initial stabilization. This indicates that the intraocular pressure-lowering effect of timolol maleate is well maintained.