Cardiac safety of ophthalmic timolol

ABSTRACT

Introduction: It is generally believed that topical administration of eye drops safeguards against harmful systemic effects. However, about 80% of the drug in the ophthalmic products is systemically absorbed and the first-pass metabolism is avoided. Ophthalmic timolol is widely prescribed in the treatment of glaucoma either alone or in the combination eye drop products, many of which have been launched fairly recently. Ophthalmic timolol may cause serious adverse effects such as symptomatic bradycardia, various conduction disorders in the heart, orthostatic hypotension, syncope and falls.

Areas covered: In this review we document a number of factors associated with the properties of ophthalmic timolol and specific features of a patient, which may jeopardize patient’s cardiac safety even after topical treatment.

Expert opinion: Plasma timolol levels are correlated with cardiovascular adverse effects in patients, since timolol is mainly metabolized by cytochrome P450 2D6 (CYP2D6) enzyme in the liver. Patients who are lacking the functional CYP2D6 or who are concomitantly using potent CYP2D6 inhibitor drugs (e.g. paroxetine or fluoxetine) or verapamil or other beta-blockers are at risk of getting serious cardiac adverse effects. Prior to treatment initiation, ECG should be always performed and CYP2D6 genotyping should be considered, if routinely available.

KEYWORDS:

• Beta-blocker
• bradycardia
• CYP2D6
• poor metabolizer
• selective serotonin reuptake inhibitors
• timolol
• eye drops
• glaucoma

Acknowledgements

The authors thank Dr Christer Gottfridsson for valuable comments.

Declaration of interest

J Mäenpää is an employee of AstraZeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.