Acetazolamide: Indications, Mechanism of Action, Administration, Adverse Effects and Toxicity

It is a diuretic drug and carbonic anhydrase inhibitor that is used to treat various diseases.

Acetazolamide indications

FDA approved indications

  • Glaucoma.
  • Idiopathic intracranial hypertension.
  • Congestive heart failure
  • Vertigo.
  • Periodic paralysis
  • Epilepsy.

Indications not approved by the FDA

  • Central sleep apnea.
  • Dural ectasia in Marfan syndrome.
  • Methotrexate- induced kidney damage .

It is a classic treatment option for glaucoma, as it causes a reduction in aqueous humor. In addition, it is used for the treatment of altitude sickness given its basic mechanism of action. The medication works to excrete bicarbonate.

By doing so, it alkalizes the urine, as there is more bicarbonate in the urine. As a result, the blood is more acidic since the bicarbonate has been excreted. There are mechanisms that equate the levels of carbon dioxide in the body with the level of acidity.

This results in an artificial compensatory mechanism for what the body believes to be excess carbon dioxide. This results in faster and deeper breathing.

The result of this is higher oxygen levels in the body. This improves the body’s ability to adjust to higher altitude levels.

Common side effects seen with this drug include fatigue, abdominal pain, nausea, vomiting, and also paresthesia.

There are also rare side effects like Stevens-Johnson syndrome. The drug is used orally and intravascularly. It should not be used by people with impaired kidney or liver function.

The drug is also known to interact with certain antibiotics, baking soda, amphetamines, and salicylates.

The recommended dose range for treating glaucoma is 250 mg per day to 1000 mg per day. Typically the dose will be 250 to 500 mg per day. The range of 500 to 1000 mg per day is used to treat altitude sickness.

Lower doses are recommended to treat edema, epilepsy, and urine output in congestive heart failure. The range used for those conditions is typically 250 to 375 mg. However, epilepsy may require higher doses up to 1000 mg per day.

Mechanism of action of acetazolamide

Acetazolamide is a carbonic anhydrase inhibitor. That means that this drug works to cause a build-up of carbonic acid by preventing its breakdown.

The result is a lower pH in the blood due to the increase in carbonic acid, which has a reversible reaction to bicarbonate and a hydrogen ion.

Carbonic anhydrase is found in red blood cells and also in the proximal tubule of the kidney. It works to reabsorb sodium, bicarbonate, and chloride.

Once acetazolamide inhibits carbonic anhydrase, sodium, bicarbonate, and chloride are excreted rather than reabsorbed. This also leads to the excretion of excess water.

The clinical outcome is a decrease in blood pressure, a decrease in intracranial pressure, and also a decrease in intraocular pressure. The excretion of bicarbonate also increases the acidity of the blood.

Aqueous humor levels decrease in the eyes, and there are compensatory mechanisms for increased acidity of the blood, for example (eg, hyperventilation).

The entire excretion process that is inhibited by carbonic anhydrase is essentially working to acidify the urine and reabsorb the bicarbonate.

Acetazolamide will disrupt the entire process by increasing sodium in the urine and increasing bicarbonate in the urine which alkalizes the urine. Diuresis is the other result.

Acetazolamide Administration

Acetazolamide is taken by mouth. It can be taken with or without food, and the patient must drink plenty of fluids with the medication. The available doses are 125 mg, 250 mg and 500 mg tablets.

These are also available in instant and extended release form.

Intravenous (IV) administration of acetazolamide is available. However, intramuscular (IM) administration of acetazolamide is not recommended.

Acetazolamide adverse effects

There is a wide range of general and specific adverse effects that can be induced by the use of acetazolamide:

  • Fatigue.
  • Nausea
  • Vomiting
  • Abdominal pain
  • Diarrhea is frequently observed in patients.

Some other patients will experience:

  • Paraesthesia
  • Black stools
  • Decreased libido
  • Tinnitus.
  • Taste alteration

There are also reports of patients developing depression while using acetazolamide or developing a bitter or metallic taste. Less commonly, there is a risk of developing metabolic acidosis, as well as hyponatremia and hypokalemia.

Kidney stones can also be seen, but they are rare. Rarely, patients develop Stevens-Johnson syndrome, aplastic anemia, agranulocytosis, toxic epidermal necrolysis, or fulminant liver necrosis.

Contraindications of acetazolamide

Since acetazolamide decreases the elimination of ammonia, patients who have decreased liver function or liver disease should not use acetazolamide. Use can precipitate the development of hepatic encephalopathy.

Acetazolamide can induce electrolyte abnormalities. As such, people with hypokalemia or hyponatremia should not use it. Similarly, it can decrease kidney function and should be avoided by anyone with kidney disease or decreased kidney function.

Patients with hyperchloremic acidosis should not use acetazolamide.

Although acetazolamide does not cause QT prolongation; people with long QT should use it with caution and monitor their potassium levels, given the drug’s ability to cause hypokalemia.

Patients with an allergy to sulfonamides should not use acetazolamide.

Acetazolamide is known to interact with several classes of medications. If a patient takes amphetamines, they are likely to develop reduced amphetamine clearance. This is because acetazolamide increases the pH of the urine.

On the contrary, the excretion of lithium is increased, and therefore the efficacy of lithium may be reduced. Acetazolamide also decreases the excretion of phenytoin, primidone, and quinidine.

Patients taking these medications can develop toxicity if they also use acetazolamide.

Patients taking salicylates can develop toxicity if they start taking acetazolamide. Also, patients taking baking soda increase their risk of kidney stone formation if acetazolamide is used at the same time.

Any patient using anti-folates, including methotrexate and trimethoprim, should not use acetazolamide. Also, any patient taking any other carbonic anhydrase inhibitor should also avoid this drug.

Patients with a history of developing a severe rash should avoid the use of acetazolamide, as it can induce Stevens-Johnson syndrome.

Acetazolamide is a Category C drug and should only be used in pregnancy if the benefits outweigh the risks to the unborn baby. There are reports of teratogenicity in animal studies. Similarly, it should only be used in nursing mothers if the benefits outweigh the risks.


There have been reports of central nervous system (CNS) toxicity with positive symptoms including fatigue, lethargy, and confusion. Symptoms resolve on their own after discontinuation of acetazolamide treatment.

There is no specific antidote for an acetazolamide overdose.

Acetazolamide is not a commonly used drug in clinical medicine, but it is important for healthcare workers (eg, nurses, primary care physicians, emergency rooms) to know the adverse effects and contraindications of the drug.

Patients should be educated by the team, including the clinician, nurse and pharmacist, on the dosage and indications of the drug and to report any side effects.

Because there is no antidote to acetazolamide, it is important to emphasize that the patient seek immediate care if there is an overdose.