Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and Historical Review of Adverse Events
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REVIEW ARTICLE
Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and Historical Review of Adverse Events Daniel J. Yoon1,2 · Ramanjot Kaur2 · Anthony Gallegos1 · Kaitlyn West2 · Hsinya Yang1 · Saul Schaefer3 · Catherine Tchanque‑Fossuo2 · Sara E. Dahle1,4 · R. Rivkah Isseroff1,2 Accepted: 10 October 2020 © This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection 2020
Abstract Ophthalmic timolol solution is increasingly being repurposed as a topical therapeutic for a variety of dermatologic diseases, including pyogenic granulomas, infantile hemangiomas, and chronic wounds. There are no published guidelines or protocols for use in these indications in adults, and the dermatologic community may not be familiar with adverse events that have been extensively documented relating to its ophthalmic use. We review the evidence available relating to adverse events to topical timolol use to evaluate its safety in dermatologic applications and to alert clinicians to screening and monitoring that is needed when repurposing this drug for dermatologic use. The majority of serious adverse events associated with ophthalmic timolol were reported in the first 7 years of use, between 1978 and 1985, of which most common were cardiovascular and respiratory events, but also included 32 deaths. The available evidence suggests that ophthalmic timolol safety profiling may have been incomplete prior to widespread use. Recent clinical trials for dermatologic indications have focused on documenting efficacy and have not had rigorous monitoring for potential adverse events. Topical timolol may be safe and effective for the treatment of various dermatologic conditions in patients whose medical histories have been carefully reviewed for evidence of pre-existing cardiac or pulmonary disease and are monitored for potential adverse events. Despite the wide use of timolol in ophthalmologic practice, safe dermatologic repurposing requires recognition of the potential for facilitated systemic absorption though the skin and appreciation of its history of adverse events.
1 Introduction Timolol is a non-selective beta-adrenergic receptor antagonist that was first approved by the US Food and Drug Administration in 1978 for topical application to the surface of the eye for the treatment of wide-angle glaucoma Daniel J. Yoon and Ramanjot Kaur contributed equally to the article. * R. Rivkah Isseroff [email protected] 1
Department of Dermatology, University of California Davis School of Medicine, Institute for Regenerative Cures, 2921 Stockton Blvd, Ste 1630, Sacramento, CA 95817, USA
2
Dermatology Service, VA Northern California Health Care System, Mather, CA, USA
3
Department of Internal Medicine, University of California School of Medicine, Davis, CA, USA
4
Podiatry Section, VA Northern California Health Care System, Mather, CA, USA
Key Points Timolol solution, formulated as an ophthalmic medication, is in
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