Safety and Tolerability of Acetazolamide in the Idiopathic Intracranial Hypertension Treatment Trial

• Published in: Journal of neuro-ophthalmology Vol. 36; no. 1; pp. 13 - 19
• Main Authors: ten Hove, Martin W, Friedman, Deborah I, Patel, Anil D, Irrcher, Isabella, Wall, Michael, McDermott, Michael P
• Format: Journal Article
• Language: English
• Published: United States by North American Neuro-Ophthalmology Society 01-03-2016
• Subjects: Acetazolamide - adverse effects; Acetazolamide - therapeutic use; Adolescent; Adult; Carbonic Anhydrase Inhibitors - adverse effects; Carbonic Anhydrase Inhibitors - therapeutic use; Combined Modality Therapy; Diet, Sodium-Restricted; Double-Blind Method; Female; Humans; Intracranial Pressure - drug effects; Male; Maximum Tolerated Dose; Middle Aged; Papilledema - physiopathology; Pseudotumor Cerebri - diet therapy; Pseudotumor Cerebri - drug therapy; Pseudotumor Cerebri - physiopathology; Quality of Life; Vision Disorders - drug therapy; Vision Disorders - physiopathology; Visual Fields - drug effects; Visual Fields - physiology
• ISSN: 1070-8022; 1536-5166
• DOI: 10.1097/WNO.0000000000000322

OBJECTIVE:To examine the tolerability and adverse events reported in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).
METHODS:Randomized, double-masked, placebo-controlled clinical trial. Trial participants (n = 165) with mild visual loss concurrently receiving low-sodium weight-reduction diet plus the maximally tolerated dosage of acetazolamide (up to 4 g/d) or placebo for 6 months. Main outcomes measuresadverse events (AEs), assessment of clinical and laboratory findings at study visits.
RESULTS:Thirty-eight of 86 participants randomized to the acetazolamide group (44.1%) tolerated the maximum allowed dosage of 4 g/d. The average time to achieve maximum study dosage in the acetazolamide group was 13 weeks (median 12 weeks; range 10–24 weeks). A total of 676 AEs (acetazolamide, n = 480; placebo, n = 196) and 9 serious AEs (acetazolamide, n = 6; placebo, n = 3) were reported. Notably, the percentages of participants reporting at least 1 AE in the nervous, gastrointestinal, metabolic, and renal organ systems were significantly higher in the acetazolamide group (P < 0.05). The odds of paresthesia (OR 9.82; 95% CI 3.87–27.82), dysgeusia (OR ∞; 95% CI 3.99–∞), vomiting and diarrhea (OR 4.11; 95% CI 1.04–23.41), nausea (OR 2.99; 95% CI 1.26–7.49) and fatigue (OR 16.48; 95% CI 2.39–702.40) were higher in the acetazolamide group than in the placebo group.
CONCLUSION:Acetazolamide appears to have an acceptable safety profile at dosages up to 4 g/d in the treatment of idiopathic intracranial hypertension. The majority of participants in the Idiopathic Intracranial Hypertension Treatment Trial were able to tolerate acetazolamide above 1 g/d for 6 months.