Mechanism of Action
Timolol maleate is a beta1 and beta2 (non-selective) adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity.
TIMOPTIC‑XE, when applied topically on the eye, has the action of reducing elevated, as well as normal intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage.
The precise mechanism of the ocular hypotensive action of TIMOPTIC‑XE is not clearly established at this time. Tonography and fluorophotometry studies of TIMOPTIC (timolol maleate ophthalmic solution) in man suggest that its predominant action may be related to reduced aqueous formation. However, in some studies, a slight increase in outflow facility was also observed.
Beta-adrenergic receptor blockade reduces cardiac output in both healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor blockade may inhibit the stimulatory effect of the sympathetic nervous system necessary to maintain adequate cardiac function.
Beta-adrenergic receptor blockade in the bronchi and bronchioles results in increased airway resistance from unopposed parasympathetic activity. Such an effect in patients with asthma or other bronchospastic conditions is potentially dangerous.
In a study of plasma drug concentration in six subjects, the systemic exposure to timolol was determined following once daily administration of TIMOPTIC‑XE 0.5% in the morning. The mean peak plasma concentration following this morning dose was 0.28 ng/mL.
In controlled, double-masked, multicenter clinical studies, comparing TIMOPTIC‑XE 0.25% to TIMOPTIC 0.25% and TIMOPTIC‑XE 0.5% to TIMOPTIC 0.5%, TIMOPTIC‑XE administered once a day was shown to be equally effective in lowering intraocular pressure as the equivalent concentration of TIMOPTIC administered twice a day. The effect of timolol in lowering intraocular pressure was evident for 24 hours with a single dose of TIMOPTIC‑XE. Repeated observations over a period of six months indicate that the intraocular pressure-lowering effect of TIMOPTIC‑XE was consistent. The results from the largest U.S. and international clinical trials comparing TIMOPTIC‑XE 0.5% to TIMOPTIC 0.5% are shown in Figure 1.
Figure 1: Mean IOP and Std Deviation (mm Hg) by Treatment Group
TIMOPTIC‑XE administered once daily had a safety profile similar to that of an equivalent concentration of TIMOPTIC administered twice daily. Due to the physical characteristics of the formulation, there was a higher incidence of transient blurred vision in patients administered TIMOPTIC‑XE. A slight reduction in resting heart rate was observed in some patients receiving TIMOPTIC‑XE 0.5% (mean reduction 24 hours post-dose 0.8 beats/minute, mean reduction 2 hours post-dose 3.8 beats/minute). (See ADVERSE REACTIONS.)
TIMOPTIC‑XE has not been studied in patients wearing contact lenses.