Can Diamox (acetazolamide) cause metabolic acidosis?

Acetazolamide (Diamox) and Metabolic Acidosis

Yes, Diamox (acetazolamide) does cause metabolic acidosis as a direct pharmacological effect of its mechanism of action as a carbonic anhydrase inhibitor.

Mechanism of Acetazolamide-Induced Acidosis

• Acetazolamide inhibits carbonic anhydrase, which produces a metabolic acidosis by increasing bicarbonate excretion in the kidneys 1
• This metabolic acidosis is non-anion gap in nature and is a direct pharmacological effect, not an adverse reaction 2
• The inhibition of carbonic anhydrase V in mitochondria can impair the tricarboxylic acid cycle, potentially worsening acidosis by affecting pyruvate carboxylase function 3

Severity and Prevalence

• In a study of elderly patients receiving acetazolamide for glaucoma, 37% developed moderate metabolic acidosis (pH 7.20-7.29) and 3.7% developed severe acidosis (pH <7.20) 4
• The acidosis can range from mild and transient to severe and clinically significant 5
• Metabolic acidosis is common enough that it's mentioned in the FDA drug label as an expected pharmacological effect 2

Risk Factors for Severe Acidosis

• Patients with renal impairment are at higher risk for developing significant acidosis 2, 6
• Concomitant use with high-dose aspirin significantly increases the risk of severe metabolic acidosis 2, 6
• Patients with chronic obstructive pulmonary disease (COPD) or other respiratory conditions are at increased risk due to impaired respiratory compensation 5
• Elderly patients appear to be more susceptible to clinically significant acidosis 4
• Patients who have undergone nephrectomy or have other forms of reduced renal function are at higher risk 5

Monitoring and Management

• The FDA recommends periodic monitoring of serum electrolytes for patients on acetazolamide therapy 2
• The acidotic state can usually be corrected by the administration of bicarbonate if clinically necessary 2
• In severe cases, discontinuation of acetazolamide may be required 6
• Blood pH levels and serum electrolytes (particularly potassium) should be monitored in patients at risk 2

Clinical Applications and Considerations

• In some clinical contexts, the acidosis induced by acetazolamide is actually therapeutically beneficial, such as in the treatment of acute mountain sickness where it helps offset respiratory alkalosis 7
• For management of edema in nephrotic syndrome, acetazolamide may be used as part of combination diuretic therapy, but with awareness of its effect on acid-base balance 1
• Acetazolamide has no role in the routine management of obstructive sleep apnea due to limited efficacy and poor tolerability, with metabolic acidosis being one of the limiting factors 1

Special Precautions

• Acetazolamide should be avoided in patients with severely impaired renal function or those undergoing dialysis 6
• It should be used with caution in patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, as it may precipitate or aggravate acidosis 2
• Patients receiving concomitant high-dose aspirin and acetazolamide require close monitoring due to reports of severe acidosis, anorexia, tachypnea, lethargy, and even death 2, 6