By Marcello Cherchi, MD PhD
For patients
Acetazolamide is a diuretic (“water pill”). This medication is sometimes used to treat forms of episodic ataxia, altitude sickness or (less commonly) Ménière’s disease.
For clinicians
Practical summary
Acetazolamide is a carbonic anhydrase inhibitor used off-label in otoneurology in the management of episodic ataxia (mostly type 2), altitude sickness or (less commonly) Ménière’s disease.
Introduction
Acetazolamide, originally developed as a diuretic, is a carbonic anhydrase inhibitor that inhibits hydrogen io secretion in the proximal renal tubule, which enhances renal excretion of sodium, potassium, bicarbonate and water, and thus can be used in the treatment of metabolic alkalosis. Acetazolamide also has effects in other organ systems, including the eye (reducing the production of aqueous humor) and central nervous system (reducing neuronal discharge). In otoneurology it is sometimes used off-label for management of episodic ataxia (mostly type 2), altitude sickness or (less commonly) Ménière’s disease. The safety of acetazolamide in pregnancy and lactation has not been established.
Pharmacology
Acetazolamide reversibly inhibits carbonic anhydrase, which exerts a diuretic effect by reducing hydrogen ion secretion at the proximal renal tubule, thereby increasing renal excretion of sodium, potassium, bicarbonate and water. Because this enhances the excretion of bicarbonate, acetazolamide can be helpful in managing edema in a patient with metabolic alkalosis.
Inhibition of carbonic anhydrase also has effects in other organs, such as the eye (reducing the production of aqueous humor) and central nervous system (reducing neuronal discharge).
Though originally developed as a diuretic, the multiple physiologic effects of acetazolamide have led to a variety of off-label uses, including management of glaucoma, certain forms of epilepsy and intracranial hypertension (Van Berkel and Elefritz 2018).
Adverse effects
The most common adverse effect of acetazolamide is paresthesias. It has also been reported to cause gustatory disturbances (Joyce 1990; Martinez-Mir et al. 1997) and fatigue (Schmickl et al. 2020).
Cautions and contraindications
There are rare reports of apparent teratogenicity of acetazolamide (Al-Saleem and Al-Jobair 2016). Acetazolamide has been classified as pregnancy category C (safety not established).
Relevance in otoneurology
Acetazolamide has several off-label uses in otoneurology, including:
- Treatment of episodic ataxia type 2 (Calandriello et al. 1997; Muth et al. 2021; Scoggan et al. 2006; Strupp et al. 2011; Strupp et al. 2007), and perhaps types 1, 3 and 5 (Kotagal 2012)
- Treatment of altitude sickness (Gonzalez Garay et al. 2018; Kayser et al. 2012; Swenson 2016) at doses of 250 mg to 750 mg (Low et al. 2012).
- There is an older literature regarding the use of acetazolamide in the treatment of Ménière’s disease (Brookes and Booth 1984; Brookes et al. 1982; Corvera and Corvera 1989; Muftic 1957; Varga 1958; Varga et al. 1966; Varga and Ribari 1958), but it is seldom used for this purpose in clinical practice today.
References
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