Side effects
Common adverse effects of acetazolamide include the following: paraesthesia, fatigue, drowsiness, depression, decreased libido, bitter or metallic taste, nausea, vomiting, abdominal cramps, diarrhea, black stool, polyuria, kidney stones, metabolic acidosis and electrolyte changes (hypokalemia, hyponatremia). Whereas less common adverse effects include Stevens–Johnson syndrome, anaphylaxis and blood dyscrasias. Contraindications
Contraindications include:
Hyperchloremic acidosis
Hypokalemia (low blood potassium)
Hyponatremia (low blood sodium)
Adrenal insufficiency
Impaired kidney function
Hypersensitivity to acetazolamide or other sulphonamides. Marked liver disease or impairment of liver function, including cirrhosis because of the risk of development of hepatic encephalopathy. Acetazolamide decreases ammonia clearance. Interactions
It is possible that it might interact with:
Amphetamines, because it increases the pH of the renal tubular urine, hence reducing the clearance of amphetamines. Other carbonic anhydrase inhibitors — potential for additive inhibitory effects on carbonic anhydrase and hence potential for toxicity. Ciclosporin, may increase plasma levels of ciclosporin. Antifolates such as trimethoprim, methotrexate, pemetrexed and raltitrexed. Hypoglycemics, acetazolamide can both increase or decrease blood glucose levels. Lithium, increases excretion, hence reducing therapeutic effect. Methenamine compounds, reduces the urinary excretion of methenamines. Phenytoin, reduces phenytoin excretion, hence increasing the potential for toxicity. Primidone, reduces plasma levels of primidone. Hence reducing anticonvulsant effect. Quinidine, reduces urinary excretion of quinidine, hence increasing the potential for toxicity. Salicylates, potential for severe toxicity. Sodium bicarbonate, potential for kidney stone formation. Anticoagulants, cardiac glycosides, may have their effects potentiated by acetazolamide. Mechanism of action
Acetazolamide is a carbonic anhydrase inhibitor, hence causing the accumulation of carbonic acid.
Because the body senses CO2 concentration indirectly via blood pH (increase in CO2 causes a decrease in pH), acidifying the blood through decreased renal reabsorption of bicarbonate is sensed as an increase in CO2. This, in turn, causes the body to increase minute ventilation (the amount of air breathed per minute) in order to "breathe off" CO2, which in turn increases the amount of oxygen in the blood. Acetazolamide is not an immediate cure for acute mountain sickness; rather, it speeds up (or, when taking before traveling, forces the body to early start) part of the acclimatization process which in turn helps to relieve symptoms. Acetazolamide is still effective if started early in the course of mountain sickness. As prevention, it is started one day before travel to altitude and continued for the first 2 days at altitude. Pregnancy and lactation
Acetazolamide is pregnancy category B3 in Australia, which means that studies in rats, mice and rabbits in which acetazolamide was given intravenously or orally caused an increased risk of fetal malformations, including defects of the limbs. Despite this, there is insufficient evidence from studies in humans to either support or discount this evidence.Limited data are available on the effects of nursing mothers taking acetazolamide. Therapeutic doses create low levels in breast milk and are not expected to cause problems in infants.