(A-243) Ethambutol Under Scrutiny: Surge in Serious Eye Disorders

Background: Optic neuropathy, as an adverse drug reaction of Ethambutol is fairly well-documented. The recent dose-frequency modification in the Ethambutol regimen from thrice-weekly regimen to daily-dose regimen in India seems to have resulted in increasing cases of eye disorders due to increased drug toxicity.

Objectives: To quantify the extent of ocular toxicity and the consequent eye disorders precipitated by Ethambutol drug toxicity, particularly in the South-East Asian Region.

Methods:

Design: Retrospective, post-market observational study;
Setting: VigiBase database, an International signal detection and management tool maintained by Uppsala Monitoring Centre (UMC), Sweden;
Exposure: Ethambutol used to treat Tuberculosis;
Main outcome measures: Vision loss, field of view, permanence of vision loss;
Statistical Analysis: Categorical data were expressed as percentages (%) and calculated for all necessary parameters.

Results: Of the 3, 88, 30,824 reports of adverse reactions totally stored in VigiBase as of June 2024, 43,863 reports were related to the antitubercular drug Ethambutol. Among countries in the South-East Asian Region (SEAR), cases related to the drug were reported by India (n=7780, 17.5%), Thailand (n=2157, 4.9%) and Indonesia (n=668, 1.5%), and data reported under the System Organ Class (SOC) Eye Disorders, revealed 4,212 cases globally, with cases reported from India (n=666, 15.8%), followed by Thailand (n=128, 3.0%) and Indonesia (n=26, 3.89%). In India, the Preferred Terms (PT) commonly reported include blindness (n=36, 5.5%), vision blurred (n=294, 44.9%), visual impairment (n=188, 27.9%), optic neuropathy (n=36, 5.5%), diplopia (n=11, 1.6%), eye pain (n=11, 1.6%), eye disorder (n=10, 1.5%), optic atrophy (n=9, 1.3%) and ocular toxicity (n=9, 1.3%).In Thailand, they included visual impairment (n=42, 32.8%), vision blurred (n=26, 20.3%) , amblyopia (n=15, 11.7%), optic ischemic neuropathy (n=9, 7%) , eye disorder (n=7, 5.5%) and periorbital oedema (n=6,4.7%) among others. In Indonesia, the preferred terms included visual impairment (n=12, 46.2%), vision blurred (n=9, 34.6%), eye disorder (n=3, 11.5%), presbyopia (n=1, 3.8%), retinal disorder (n=1, 3.8%) and conjunctival disorder (n=1, 3.8%).

Conclusions: Ocular disorders as an adverse event of Ethambutol may result from dose-related toxicity or imbalance in trace elements like zinc, crucial for optic nerve function. Monitoring and potential dose adjustments, increasing the number of vision centres and trained staff, and exploring newer antibiotics with fewer risks is warranted.