Drug products: Amelocare, AZARGA, Bimatoprost/Timolol STADA, Bimatoprost/Timolol Zentiva, Blocadren Depot, Blocadren®, Blocadren® Depot, Brinzolamide/Timolol Abacus Medicine, Brinzolamide/Timolol Accord, Brinzolamide/Timolol STADA, Combigan, Combigan®, Cosopt, Cosopt sine, Cosopt®, Costad, Dorlatim, Dorzolamid/Timolol Abacus Medicine, Dorzolamid/Timolol Actavis, Dorzolamid/Timolol Ebb, Dorzolamid/Timolol Medical Valley, Dorzolamid/Timolol Sandoz, Dorzolamide/Timolol Teva, Duokopt, DuoTrav, Fixopost, Fotil, Fotil forte, GANFORT, Latacomp, Latanoprost/Timolol 2care4, Latanoprost/Timolol Upjohn, Latiotim, Optimol, Taniost, Taptiqom, Taptiqom sine, Timolol Alcon, Timolol CCS, Timoptol LA, Timosan, Torzkom, Travoprost/Timolol Medical Valley, Travoprost/Timolol STADA, Xalcom, Xalcom®, Xatabloc
ATC code: S01ED01, S01ED51
Substances: timolol, timolol maleate, timolol maleate, r-enantiomer
No difference between men and women in the ocular pressure lowering effect of timolol has been shown in most studies. However, an old pooled analysis found slightly less lowering of ocular pressure in women
Pharmacokinetics and dosing
No studies with a clinically relevant sex analysis regarding the pharmacokinetics or dosing of timolol have been found.
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) . 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 . 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 .
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 .
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 .
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 Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
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 . 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 .
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 .
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 .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) . 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 .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) . A study of endothelial nitric oxide synthase gene variants found an association with open angle glaucoma which might explain this . Studies on the effect of hormonal replacement therapy (HRT) are lacking .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 .
Date of litterature search: 2015-12-02
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- Kang JH, Wiggs JL, Rosner BA, Hankinson SE, Abdrabou W, Fan BJ et al. Endothelial nitric oxide synthase gene variants and primary open-angle glaucoma: interactions with sex and postmenopausal hormone use. Invest Ophthalmol Vis Sci. 2010;51:971-9. PubMed
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- Singh D, Coote MA, O'Hare F, Walland MJ, Ghosh S, Xie J et al. Topical prostaglandin analogues do not affect selective laser trabeculoplasty outcomes. Eye (Lond). 2009;23:2194-9. PubMed
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- Rossi GC, Tinelli C, Pasinetti GM, Fusetti M, Pallavicini C, Stringa M et al. Signs and symptoms of ocular surface status in glaucoma patients switched from timolol 05% to brinzolamide 1%/timolol 05% fixed combination: a 6-month efficacy and tolerability, multicenter, open-label prospective study. Expert Opin Pharmacother. 2011;12:685-90. PubMed
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- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson