Severe systemic Adverse Reactions to Ophthalmic Timolol in a CYP2D6 Homozygous *4 Allele Carrier: A Case Report

Abstract

A woman with ocular hypertension suffered from severe bradycardia, hypotension and syncope attacks in temporal relation with ophthalmic timolol application. Topically applied timolol is nasally absorbed and has been shown to reach potentially relevant systemic concentrations. Timolol is mainly metabolized by CYP2D6, which exhibits interindividual metabolic capacity due to genetic variations. A reactive pharmacogenetic panel test identified the patient as a CYP2D6 homozygous *4 allele carrier, which has been associated with a poor metabolizer phenotype and lacking enzyme activity. Thus, the adverse drug reactions possibly resulted from increased systemic timolol exposure. This case report highlights that pharmacogenetic panel testing can contribute to safe and effective pharmacotherapy, even for topically applied drugs.

Keywords::

• drug safety
• glaucoma
• pharmaceutical care
• pharmacogenetics
• pharmacy

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/pgs-2023-0122

Author contributions

C Jeiziner, H Meyer zu Schwabedissen, K Hersberger and C Stäuble: conceptualization and study design. A Bollinger and C Jeiziner: investigation and interpretation of genotyping data. A Bollinger: writing original draft preparation. C Jeiziner, H Meyer zu Schwabedissen, K Hersberger, S Allemann and C Stäuble: critical review and editing. C Stäuble: supervision. All authors have read and agreed to the published version of the manuscript.

Financial disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The case was collected within the observational study ‘Pharmacogenetic Testing of Patients with unwanted Adverse Drug Reactions or Therapy Failure’, which was conducted according to the guidelines of the Declaration of Helsinki and approved by the local ethics committee of ‘Ethikkommission Nordwest- und Zentralschweiz’ (2019-01452, 31.10.2019). The patient provided written informed consent to use the data for research purposes, as well as for publishing this case report.

Data sharing statement/data availability statement

The genetic data presented in this study are available on request from the corresponding author. The data are not publicly available for ethical and privacy reasons.