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Bimatoprost/Timolol

A Review of Its Use in Glaucoma and Ocular Hypertension

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Summary

Abstract

Topically administered bimatoprost 0.03%/timolol 0.5% ophthalmic solution (bimatoprost/timolol: Ganfort®) comprises the synthetic prostamide bimatoprost (structurally related to prostaglandin F2α) and the β-adrenergic receptor antagonist timolol.

Bimatoprost/timolol (one drop administered in the affected eye[s] once daily in the morning or evening) is an effective and well tolerated fixed combination for lowering intra-ocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension (OHT), including individuals uncontrolled on monotherapy with a β-adrenergic receptor antagonist or prostaglandin analogue/prostamide.

Pharmacological Properties

Bimatoprost is a synthetic prostamide (structurally related to prostaglandin F2α) that reduces IOP by increasing the outflow of aqueous humour through the trabecular network and uveoscleral routes. Timolol is a non-selective β-adrenergic receptor antagonist that reduces IOP by reducing aqueous humour production. Timolol has no significant intrinsic sympathomimetic, direct myocardial depressant or local anaesthetic (membrane-stabilizing) activity.

Penetration of bimatoprost of the eye is mainly via the sciera and cornea. After topical administration, systemic absorption of both components of the bimatoprost/timolol fixed combination was minimal; peak blood concentrations of bimatoprost and timolol were reached rapidly, with bimatoprost blood concentrations rapidly declining to below the lower limit of detection within 20 minutes of administration. There was no accumulation of either bimatoprost or timolol in 12-month studies. The elimination half-life of bimatoprost was ≈45 minutes and of timolol was ≈11 hours. Bimatoprost is excreted via the urine and faeces; timolol is largely excreted via the urine.

Therapeutic Efficacy

Topical bimatoprost 0.03%/timolol 0.5% once daily was effective in lowering IOP in patients with OHT or open-angle glaucoma, according to data from three 3-month, phase III studies. The patient population in these studies included those previously untreated and those unresponsive to previous monotherapy with prostaglandins/prostamides or β-adrenergic receptor antagonists. One of these studies was preceded by a run-in period on timolol twice daily and patients previously treated with ocular hypotensive medication underwent a washout period in the other two studies.

In these three studies, the mean reduction from baseline in mean diurnal IOP at 3 months was significantly greater with once-daily bimatoprost/timolol than with twice-daily timolol. According to a combined analysis of two of the studies, the mean reduction from baseline in IOP was significantly greater with bimatoprost/timolol than with timolol monotherapy at all assessed timepoints (hours 0, 2 and 8 at weeks 2, 6 and 12) and significantly greater with bimatoprost/timolol than with bimatoprost monotherapy in six of the nine timepoints. The percentage of patients with a mean reduction in diurnal IOP of >20% across all visits and the percentage of patients achieving a target IOP <18 mmHg at all timepoints was significantly greater with bimatoprost/timolol than with timolol (all three studies) or with bimatoprost (two of three studies).

Bimatoprost/timolol was noninferior (according to generally accepted criteria) to the non-fixed concomitant administration of bimatoprost and timolol in reducing IOP in a randomized, double-blind, 3-week study in patients with glaucoma or OHT who were naive to IOP-lowering therapy.

Bimatoprost/timolol was significantly more effective than the fixed combination of latanoprost/timolol in reducing the mean diurnal IOP versus baseline in 4- and 12-week, randomized, investigator-masked studies in patients with open-angle glaucoma. Patients in these studies had elevated IOP that was insufficiently responsive to monotherapy with either prostaglandin analogues/prostamides or timolol.

Bimatoprost/timolol was predicted to be a cost-effective therapy option in five European countries relative to two other IOP-lowering fixed combinations (travoprost/timolol and latanoprost/timolol) in patients with primary open-angle glaucoma, according to a 3-month pharmacoeconomic model conducted from a health service perspective. The incremental cost (year 2007) per 1% reduction in IOP of bimatoprost/timolol compared with travoprost/timolol ranged from −€0.45 to −€2.35 and compared with latanoprost/timolol ranged from −€12.11 to −€69.30.

Tolerability

Bimatoprost/timolol was generally well tolerated, with most adverse events being ocular, mild in severity and similar in nature to those reported with bimatoprost or timolol monotherapy. The incidence of treatment-related adverse events with bimatoprost/timolol was significantly lower than that with bimatoprost monotherapy, but significantly higher than that with timolol monotherapy, in a combined analysis of two 3-month studies in patients with OHT or glaucoma. The most commonly reported treatment-related adverse event was conjunctival hyperaemia and was reported in significantly fewer patients treated with bimatoprost/timolol than with bimatoprost monotherapy. The tolerability profile of bimatoprost/timolol was similar to that of latanoprost/timolol in 12-week trials.

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Authors and Affiliations

  1. Wolters Kluwer Health | Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Monique P. Curran & Jennifer S. Orman

  2. Wolters Kluwer Health, Conshohocken, Pennsylvania, USA

    Monique P. Curran & Jennifer S. Orman

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  1. Monique P. Curran
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Correspondence to Monique P. Curran.

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Curran, M.P., Orman, J.S. Bimatoprost/Timolol. Drugs Aging 26, 169–184 (2009). https://doi.org/10.2165/0002512-200926020-00008

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