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  • Reconsidering Oral and Topical Carbonic Anhydrase Inhibitors

    By Jean Shaw
    Selected and reviewed by Neil M. Bressler, MD, and Deputy Editors
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    Journal Highlights

    JAMA Ophthalmology, March 2022

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    Popovic et al. evaluated the safety of oral and topical carbonic anhydrase inhibitors (CAIs) in clinical care. They found a low risk of severe adverse reactions.

    This population-based matched cohort study took place in Ontario, Canada. The researchers identified 128,942 patients older than 65 years of age (mean, 75 years) who were pre­scribed an oral or topical CAI between Jan. 1, 1995, and Jan.1, 2020. The pri­mary endpoint was the occurrence of Stevens-Johnson syndrome, toxic epi­dermal necrolysis, or aplastic anemia. All told, 71,958 of the patients (55.8%) were women, and 25,057 (19.4%) had a diagnosis of diabetes. The patients were not required to be under the care of an ophthalmologist or to have a diagnosis of glaucoma.

    For this analysis, the category of oral CAIs comprised acetazolamide or methazolamide, while that of topical CAIs comprised dorzolamide, brinzol­amide, or a combination agent. Zoni­samide and topiramate were excluded. Acetazolamide was the most commonly prescribed oral CAI, for a mean initial duration of 8.4 days. Dorzolamide—in a single-agent or combination formula—was the most common topical CAI and was prescribed for a mean initial duration of 23 days.

    The researchers identified 321 serious adverse events. Of these, 187 occurred in patients on an oral CAI (absolute risk, 2.90/1,000 patients; number needed to harm, 1/345 patients). The remaining 134 serious adverse events occurred in patients on a topical CAI (absolute risk, 2.08/1,000 patients; number needed to harm, 1/481 patients). These findings were replicated across a diverse set of patient subgroups. The researchers also observed a directly proportional asso­ciation in the risk of serious adverse events over time, contrary to the stan­dard hypothesis that these events tend to occur soon after therapy is initiated.

    In their discussion, the researchers reminded clinicians that appropriate informed consent discussions must take place if CAIs are under consider­ation. At the same time, they said, the results of this study support taking a second look at the general reluctance to prescribe oral CAIs, in particular, given the low risk of serious adverse events.

    The original article can be found here.