Side Effects of Diamox (Acetazolamide)
Diamox (acetazolamide) has numerous well-documented side effects including paresthesia, dysgeusia, fatigue, gastrointestinal disturbances, and metabolic acidosis, with many side effects showing dose-dependent relationships. 1
Common Side Effects
- Neurological effects: Paresthesia (numbness and tingling) is the most common side effect, with a number needed to harm of only 2.3, meaning approximately 1 in every 2-3 patients will experience this symptom 1
- Sensory disturbances: Dysgeusia (taste disturbances, often described as metallic taste) occurs frequently with a number needed to harm of 18 1
- Gastrointestinal effects: Nausea, vomiting, diarrhea, and abdominal cramps are common, particularly at higher doses 2, 1
- Urinary effects: Polyuria (increased urination) is common with a number needed to harm of 17 1
- Fatigue and malaise: Significant fatigue occurs in many patients with a number needed to harm of 11 1, 3
Dose-Dependent Side Effects
- The risk of paresthesia increases significantly with higher doses (beta=1.8, p=0.01) 1
- Taste disturbances show strong dose dependence (beta=3.1, p=0.02) 1
- Fatigue also tends to increase with higher doses, though this relationship is not as statistically significant (beta=2.6, p=0.14) 1
- In clinical trials, only 44% of participants could tolerate the maximum dose of 4g daily, with 48% discontinuing at mean doses of 1.5g due to side effects 2, 3
Less Common but Serious Side Effects
- Metabolic effects: Electrolyte imbalances, particularly hypokalemia and development of metabolic acidosis 4, 5
- Hematologic effects: Blood dyscrasias including aplastic anemia and thrombocytopenia in rare cases 2
- Renal effects: Increased risk of kidney stones 2
- Dermatologic reactions: Allergic dermatitis, Stevens-Johnson syndrome (rare but serious) 2
- Central nervous system effects: Confusion, depression, and cognitive slowing 2, 6
Special Considerations
- Renal impairment: Acetazolamide should be used with extreme caution in patients with impaired renal function as it can accumulate and lead to toxicity 7, 8
- Pregnancy: Classified as FDA Pregnancy Category C, indicating potential risks to the fetus based on animal studies 2
- Drug interactions: May interact with other medications affecting electrolyte balance 4
- Overdose risk: While generally considered to have low toxicity in overdose, monitoring of electrolytes and pH is essential, with bicarbonate administration often needed to correct acidosis 4
Tolerability Strategies
- Starting at lower doses (250-500mg twice daily) and gradually titrating upward improves tolerability 2, 6
- Modified-release formulations may reduce plasma concentration fluctuations and decrease the incidence of side effects like drowsiness and paresthesia 9
- Monitoring electrolytes and renal function is recommended, especially at higher doses or with prolonged use 4
- Gastric protection may be needed when used with NSAIDs due to potential additive gastrointestinal effects 2
Contraindications
- Sulfonamide allergy 2
- Severe kidney or liver disease 7
- Adrenal gland failure 2
- Hyperchloremic acidosis 2
Understanding these side effects is crucial for appropriate patient counseling and monitoring, particularly when higher doses are required for conditions like idiopathic intracranial hypertension or altitude sickness.