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Timolol

Klassificering: A

Preparat: Aquanil®, AZARGA, Blocadren Depot, Blocadren®, Blocadren® Depot, Combigan, Combigan®, Cosopt, Cosopt sine, Cosopt®, Costad, Dorzolamid/Timolol Actavis, Dorzolamid/Timolol Ebb, Dorzolamid/Timolol Sandoz, Dorzolamide/Timolol Teva, Duokopt, DuoTrav, Fotil, Fotil forte, Ganfort, Latacomp, Latanoprost/Timolol 2care4, Latanoprost/Timolol Pfizer, Latiotim, Optimol, Taptiqom, Timolol Alcon, Timolol CCS, Timoptol LA, Timosan, Timpilo®, Timpilo® forte, Travoprost/Timolol Medical Valley, Travoprost/Timolol STADA, Xalcom, Xalcom®, Xatabloc

ATC kod: S01ED01, S01ED51

Substanser: timolol, timololmaleat

Sammanfattning

Ingen skillnad mellan kvinnor och män avseende intraockulär trycksänknig har påvisats i de flesta studier. Det finns dock en äldre, poolad analys där något större reduktion av intraockulärt tryck påvisats hos män.
 
Kunskapsunderlaget avseende skillnader mellan kvinnor och män är begränsat och motiverar inte olika dosering eller behandling.

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].

Försäljning på recept

Fler kvinnor än män hämtade ut ögondroppar innehållande timolol (ATC-kod S01ED01) på recept i Sverige år 2015, totalt 21 586 kvinnor och 16 487 män. Det motsvarar 4,4 respektive 3,4 personer per tusen invånare. Andelen som hämtat ut läkemedel ökade med stigande ålder hos båda könen. Totalt sett var ögondroppar innehållande timolol 1,3 gånger vanligare hos kvinnor [18].

Fler kvinnor än män hämtade ut ögondroppar innehållande timolol i kombination (ATC-kod S01ED51) på recept i Sverige år 2015, totalt 38 434 kvinnor och 33 818 män. Det motsvarar 7,9 respektive 6,9 personer per tusen invånare. Andelen som hämtat ut läkemedel ökade med stigande ålder hos båda könen. ATC-koden innehåller timololkombinationer med bimatoprost, brinzolamid, brimonidin, dorzolamid, latanoprost, pilokarpin, travoprost, tafluprost [18].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2015-12-02

Referenser

  1. Weih LM, Van Newkirk M, McCarty CA, Taylor HR. Patterns of glaucoma medication use in urban and rural Victoria. Aust N Z J Ophthalmol. 1998;26 Suppl 1:S12-5. PubMed
  2. Nordstrom BL, Friedman DS, Mozaffari E, Quigley HA, Walker AM. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol. 2005;140:598-606. PubMed
  3. Drance S, Anderson DR, Schulzer M, Collaborative Normal-Tension Glaucoma Study Group. Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol. 2001;131:699-708. PubMed
  4. Alsbirk PH. Early detection of primary angle-closure glaucoma Limbal and axial chamber depth screening in a high risk population (Greenland Eskimos). Acta Ophthalmol (Copenh). 1988;66:556-64. PubMed
  5. Alsbirk PH. Limbal and axial chamber depth variations A population study in Eskimos. Acta Ophthalmol (Copenh). 1986;64:593-600. PubMed
  6. Higginbotham EJ. Does sex matter in glaucoma?. Arch Ophthalmol. 2004;122:374-5. PubMed
  7. 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
  8. Vajaranant TS, Nayak S, Wilensky JT, Joslin CE. Gender and glaucoma: what we know and what we need to know. Curr Opin Ophthalmol. 2010;21:91-9. PubMed
  9. 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
  10. Alm A, Stjernschantz J. Effects on intraocular pressure and side effects of 0005% latanoprost applied once daily, evening or morning A comparison with timolol Scandinavian Latanoprost Study Group. Ophthalmology. 1995;102:1743-52. PubMed
  11. Camras CB, Alm A, Watson P, Stjernschantz J. Latanoprost, a prostaglandin analog, for glaucoma therapy Efficacy and safety after 1 year of treatment in 198 patients Latanoprost Study Groups. Ophthalmology. 1996;103:1916-24. PubMed
  12. Watson P, Stjernschantz J. A six-month, randomized, double-masked study comparing latanoprost with timolol in open-angle glaucoma and ocular hypertension The Latanoprost Study Group. Ophthalmology. 1996;103:126-37. PubMed
  13. Hedman K, Alm A. A pooled-data analysis of three randomized, double-masked, six-month clinical studies comparing the intraocular pressure reducing effect of latanoprost and timolol. Eur J Ophthalmol. 2000;10:95-104. PubMed
  14. Hedman K, Alm A, Gross RL. Pooled-data analysis of three randomized, double-masked, six-month studies comparing intraocular pressure-reducing effects of latanoprost and timolol in patients with ocular hypertension. J Glaucoma. 2003;12:463-5. PubMed
  15. Sellem E, Rouland JF, Baudouin C, Bron A, Denis P, Nordmann JP et al. Predictors of additional intraocular pressure reduction in patients changed to latanoprost/timolol fixed combination. BMC Ophthalmol. 2010;10:10. PubMed
  16. 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
  17. Turaçli E, Budak K, Kaur A, Mizrak B, Ekinci C. The effects of long-term topical glaucoma medication on conjunctival impression cytology. Int Ophthalmol. 1997;21:27-33. PubMed
  18. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Författare: Maria Enghag, Desirée Loikas

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson