Timolol

Additional information

Pharmacokinetics and dosing

No studies with a clinically relevant sex analysis regarding the pharmacokinetics or dosing of timolol have been found.

Effects

Studies show conflicting results regarding sex differences in response to timolol treatment.

In two double-blind controlled trials of reduction of intraocular pressure patients were randomized to treatment with latanoprost or timolol (one study with 82 men, 101 women treated with latanoprost, 34 men, 50 women treated with timolol, and another with 101 men, 97 women) during 6 months. In both studies, the intraocular pressure was reduced similarly in men and women regardless of treatment [10, 11]. In contrast, a double-blind controlled trial randomizing patients with elevated intraocular pressure to treatment with latanoprost or timolol (191 men, 103 women, half in each group treated with timolol) showed that timolol reduced the intraocular pressure more in men than in women (pressure reduction 9.4 and 7.1 mmHg, respectively) [12]. In a pooled analysis of these three studies (183 men, 186 women treated with timolol) comparing latanoprost to timolol treatment in patients with ocular hypertension or primary open angle glaucoma, the intraocular pressure was lowered more (0.7 mmHg, 11%) in men [13]. In another pooled analysis of the same material but only including the patients with ocular hypertension (around half of the patients) no sex differences were found [14].

A prospective, open label, multicenter, phase III study in patients with open angle glaucoma or ocular hypertension (182 men, 209 women) showed no difference in effect between men and women when treating non-responders to mono-therapy with a combination of latanoprost/timolol [15].

A prospective open-label study during six months where 119 glaucoma patients (56 men, 63 women) were switched from timolol to brinzolamide/timolol fixed combination showed that the median intraocular pressure decreased from 20 to 16 mmHg similarly in men and women [16].

Adverse effects

No studies with a clinically relevant sex analysis regarding the adverse effects of timolol have been found.

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

A study of out-patients using topical glaucoma drugs > 3 months (113 male eyes, 103 female eyes) showed that men and women developed conjunctival metaplasia to the same extent while the control group without medication did not. The authors suggest that the presence of the preservative benzalkonium chloride in the medications caused this side effect [17]. In a population-based survey study including a medical examination in 4744 Australians, 2.3% were previously diagnosed with ocular hypertension or open angle glaucoma (52 male, 56 female). The proportion reporting a history of glaucoma surgery or treatment with glaucoma medication was similar in men and women [1].

In a study from the US nearly half of the individuals who had filled one glaucoma prescription discontinued the treatment within six months. Among glaucoma patients aged 40-49 years, living in the Southeast region of the US and being a woman were factors associated with discontinuation [2].

General differences between men and women with glaucomaIn a randomized clinical trial of normal-tension glaucoma patients, an untreated subset of patients (61 men, 99 women) was analyzed regarding risk factors for (a high) progression rate of visual field loss. The time to measurable decrease in visual field was shorter in women than in men (1849 vs. 2356 days and the speed of deterioration was higher in women than in men (0.47 vs. 0.23 decibels per year). Migraine and optic disk hemorrhage were other risk factors for an increased progression rate (OR 2.58 and 2.72, respectively). According to the authors, it could be wise to treat women with migraine or optic disk hemorrhage aggressively as they are at a higher risk of faster progression than others [3].An eye examination of a West Greenland Eskimos population > 40 years old (162 men, 182 women) aimed at detecting primary angle-closure glaucoma (PACG) showed a higher prevalence in women than in men (age-group 60-69: 5% in men, 15% in women and age-group 70+: 3% in men, 27% in women) [4]. Measurements of the right eyes (155 men, 156 women) showed that the limbal chamber depth (LCD), as well as the axial chamber depth (ACD) was lower in women than in men [5].In a population based study in the Netherlands it was noted that women who were postmenopausal before the age of 45 had a higher risk of open-angle glaucoma (odds ratio 2.6) compared to those who were older at menopause (odds ratio for open angle glaucoma of 1.1) [6]. A study of endothelial nitric oxide synthase gene variants found an association with open angle glaucoma which might explain this [7]. Studies on the effect of hormonal replacement therapy (HRT) are lacking [8].In a retrospective study, glaucoma patients (64 men, 59 women) underwent selective laser trabeculoplasty (SLT). The intra ocular pressure (IOP) lowering efficacy of SLT was equal in men and women and regardless of type, or absence of glaucoma medication at 6 months post-laser [9].