[Comprehensive Monograph: Acetazolamide (DB00819)]

[1.0 Executive Summary]

Acetazolamide is a first-generation, non-competitive inhibitor of the enzyme carbonic anhydrase, a small molecule drug with a remarkably diverse and enduring clinical profile spanning over seven decades.[1] Initially approved by the U.S. Food and Drug Administration (FDA) in the early 1950s, it has long been a cornerstone therapy for a distinct set of conditions, including various forms of glaucoma, certain types of epilepsy (particularly as adjunctive therapy), and the prevention and treatment of acute mountain sickness.[1][ Its therapeutic utility stems from a single, potent mechanism—the inhibition of a fundamental physiological enzyme—which produces a cascade of effects across multiple organ systems, including the kidneys, eyes, and central nervous system.]

Recently, this septuagenarian drug has experienced a significant clinical renaissance, driven by new, high-quality evidence for its use in a major public health challenge: acute decompensated heart failure (ADHF). The landmark ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial demonstrated that adding intravenous acetazolamide to standard loop diuretic therapy significantly improves the rate of successful decongestion and shortens hospital stays for patients with ADHF, repositioning the drug from a niche therapeutic to a potentially vital tool in acute cardiology.[5]

The pharmacological profile of acetazolamide is unique. It is not metabolized in the body and is excreted unchanged by the kidneys, a property that simplifies its interaction profile but necessitates caution in patients with renal impairment.[8] It exhibits avid binding to its target enzyme, leading to high concentrations in tissues rich in carbonic anhydrase, such as red blood cells and the renal cortex.[8]