Physician's Sheet: Acetazolamide Drug Interactions

Acetazolamide (aka Diamox) is frequently prescribed as therapy for the periodic paralyses. While most patients take this drug without incident it can interact with other drugs. Physicians should be aware of potential problems which might arise.

Acetazolamide can decrease excretion of dextroamphetamine, anticholinergics, mecamylamine, ephedrine, mexiletine, or quinidine because carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption. The effects of these drugs can be prolonged or enhanced.

Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. Concurrent use of methenamine and acetazolamide is not recommended. Acetazolamide produces alkaline urine and can increase the rate of excretion of weakly acidic drugs including barbiturates and salicylates. Large or regular dosing with aspirin and other salicylates should be avoided as acetazolamide can potentiate salicylate toxicity by causing metabolic acidosis and enhancing the penetration of the salicylate into tissues. In addition, salicylates decrease the elimination of acetazolamide, which could result in CNS toxicity.

Acetazolamide can induce osteomalacia in patients being concomitantly treated with carbamazepine, primidone, or phenytoin. Potential mechanisms for this interaction include an acetazolamide-induced increase in the urinary excretion of calcium and effects resulting from metabolic acidosis.

Acetazolamide can enhance the effect of other diuretics, such as thiazides, when used concurrently. The hypokalemic and hyperuricemic effects, however, also can be potentiated. Acetazolamide can potentiate the hypokalemia caused by corticosteroids, amphotericin B, or corticotropin, ACTH. In addition, patients receiving digoxin and acetazolamide concurrently are at an increased risk for digoxin toxicity if hypokalemia develops during treatment.

A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If acetazolamide is used concomitantly, the solubility of ciprofloxacin can be decreased because of alkaline urine. Patients should be monitored for crystalluria and nephrotoxicity.

Adverse Reactions:

The inhibition of carbonic anhydrase affects excretion of electrolytes. Hyperchloremia and/or metabolic acidosis can result from an increase in plasma chloride concentrations. Acetazolamide increases the excretion of bicarbonate and sodium, decreasing the extracellular fluid concentration of bicarbonate and causing mild metabolic acidosis. Increased excretion of potassium is most likely to occur and can result in hypokalemia.

Carbonic anhydrase inhibitors are sulfonamide derivatives and have caused crystalluria and sulfonamide-like nephrotoxicity characterized by renal intratubular obstruction, hematuria, dysuria, and oliguria. An increase in calcium excretion can cause nephrolithiasis. Patients with preexisting hypercalcemia develop renal calculi most frequently. There has also been a report of fatal anaphylactic shock occurring in a patient who had a sulphonamide allergy. Before prescribing acetazolamide, the physician should inquire about sulphonamide allergy because of the related chemical structure of the substances. Such an allergy should be regarded as a contraindication. 1

1: Ned Tijdschr Geneeskd 2000 Jun 17;144(25):1228-30, Fatal anaphylactic reaction after oral acetazolamide (diamox) for glaucoma; Gerhards LJ, van Arnhem AC, Holman ND, Nossent GD Afd. Cardiologie, Martini Ziekenhuis, Groningen. PMID: 10897303, UI: 20355494 

 

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