Acetazolamide Side Effects
Acetazolamide causes common and dose-dependent side effects, with paraesthesias occurring in nearly half of patients (number needed to harm: 2.3), along with dysgeusia, polyuria, fatigue, and potentially serious electrolyte imbalances that require monitoring. 1, 2
Most Common Side Effects (Well-Recognized)
Neurological and Sensory
- Paraesthesias (tingling/numbness) are the most frequent side effect, affecting approximately 1 in 2-3 patients, with risk increasing significantly at higher doses 1, 2
- Dysgeusia (taste disturbances) occurs in approximately 1 in 18 patients, with dose-dependent risk 1, 2
- Tinnitus is a recognized adverse effect 1
- Cognitive slowing and depression can occur, particularly concerning for patients requiring mental acuity 1
- Vertigo has been reported 3
- Confusion and drowsiness may develop, though can be reduced with sustained-release formulations 4
Gastrointestinal
Genitourinary
- Polyuria affects approximately 1 in 17 patients 2
Constitutional
Serious Adverse Effects Requiring Monitoring
Electrolyte Imbalances
- Hypokalemia is a serious adverse effect requiring mandatory monitoring, particularly when acetazolamide is combined with medications containing licorice or other potassium-depleting agents 3, 5, 6
- Hyperchloremia develops with chronic use, correlating with erythrocyte acetazolamide concentrations above 20 mcg/mL 7
- Serum electrolyte levels, particularly potassium, should be monitored periodically 8, 7
Metabolic Complications
- Renal stones occur rarely but are a recognized complication 1
- Development of acidotic state can occur, particularly in overdose situations 8
Hepatic Effects
Dose-Dependent Relationships
The risk of side effects correlates with total daily dose, particularly for paraesthesias and dysgeusia 2:
- Lower doses (<400 mg/day) have reduced side effect burden
- Moderate doses (400-600 mg/day) show intermediate risk
- Higher doses (>600 mg/day) significantly increase risk of paraesthesias (beta=1.8) and dysgeusia (beta=3.1) 2
In clinical practice, 48% of patients discontinue acetazolamide at mean doses of 1.5 g/day due to side effects, while only 44% tolerate the maximum 4 g/day dose 1
Special Populations and Contraindications
Absolute Contraindications
- Sulfonamide allergy (acetazolamide is a non-bacteriostatic sulfonamide) 9, 8
- Severe liver disease 9
- Impaired renal function 9
- Pregnancy due to potential teratogenic risks 1, 9
High-Risk Situations
- Elderly patients on chronic therapy require periodic monitoring of erythrocyte acetazolamide concentrations and plasma chloride to prevent overdosage 7
- Diabetic patients need careful consideration of potential metabolic effects 5
Strategies to Minimize Side Effects
Dosing Adjustments
- Start low (250-500 mg twice daily) and titrate gradually to minimize initial side effect burden 1
- Use the lowest effective dose as side effects are dose-dependent 2
- Consider switching to methazolamide if acetazolamide is not tolerated—50% of patients with severe acetazolamide side effects tolerate methazolamide better 10
Formulation Considerations
- Sustained-release formulations (GITS 15/125) reduce plasma concentration fluctuations and substantially decrease incidence of drowsiness, tingling, and confusion compared to conventional tablets 4
Monitoring Requirements
- Periodic electrolyte panels (particularly potassium) 3, 5, 8
- Liver function tests 9, 6
- Renal function assessment 9
- Erythrocyte acetazolamide concentrations in elderly patients on chronic therapy (maintain <20 mcg/mL) 7
Clinical Pitfalls
High discontinuation rates (80% experience numbness/tingling; 33% discontinue after initial prescription in some series) mean patients require detailed counseling about expected side effects before starting therapy 6. The combination with licorice-containing medications dramatically increases hypokalemia risk and should be avoided 6. Despite theoretical benefits, acetazolamide has not been shown effective for headache treatment alone in conditions like idiopathic intracranial hypertension 1.