Acetazolamide Side Effects
Not all side effects for acetazolamide may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.
For the Consumer
Applies to acetazolamide: oral capsules, oral tablets, parenteral powder for injection
Side effects include:
Paresthesias, hearing dysfunction or tinnitus, anorexia, altered taste, nausea, vomiting, diarrhea, polyuria, drowsiness, confusion.
For Healthcare Professionals
Applies to acetazolamide: compounding powder, injectable powder for injection, oral capsule extended release, oral tablet
Because it inhibits carbonic anhydrase in the renal proximal tubule, acetazolamide can cause a bicarbonate diuresis and metabolic acidosis. The following case is illustrative:
A 61-year-old man with a history of glaucoma, diabetic ketoacidosis, myocardial infarction, and renal insufficiency developed mental lethargy and disorientation while taking acetazolamide 250 mg four times a day. He was also taking furosemide, potassium, metoclopramide, and eye drops (timolol, atropine, and pilocarpine). The most remarkable associated findings included an anion gap of 15, serum glucose of 97 mg/dl, and arterial blood gas values of pH = 7.23, p02 = 68 mm Hg, bicarbonate 6 mEq/L, and paC02 = 14 mm Hg. Serum ketones were absent; other pertinent laboratory values, including serum calcium, spinal tap findings, ECG, head CT and cultures were negative. An EEG revealed findings consistent with a metabolic encephalopathy. The patient recovered after acetazolamide was withheld and a total of 140 mEq of sodium bicarbonate was infused over a 12-day period. A follow-up analysis revealed type IV renal tubular acidosis when acetazolamide, potassium and bicarbonate were withheld.
Metabolic side effects have included metabolic acidosis and electrolyte imbalance (hypokalemia). Rare cases of severe metabolic acidosis, hypocalcemia, or hypophosphatemia have been reported. Many patients who have developed metabolic acidosis have either had renal insufficiency, diabetes mellitus, or both. Metabolic derangements may be more likely and more severe in patients with renal dysfunction.
Ocular side effects have included rare reports of local paresthesias, transient myopia, and choroidal detachment.
Dysgeusia following ingestion of some foods, particularly carbonated beverages, has been associated with use of acetazolamide.
While acetazolamide has been used to successfully alleviate myotonia in patients with hypokalemic or hyperkalemic periodic paralysis, it has also been associated with reversible quadriparesis in rare cases.
A small series of patients who developed spastic craniofacial syndromes associated with some diuretics, including acetazolamide, has been reported. The serum calcium levels were not reported in this series.
Nervous system side effects have included weakness, lethargy, drowsiness, and paresthesias. A "tingling" feeling in the extremities has been reported in up to 20% of patients. Rare nervous system side effects have included tinnitus or hearing dysfunction and alteration of taste (dysgeusia). Profound muscle weakness has been associated with the use of acetazolamide in patients with periodic paralysis.
Psychiatric side effects have included rare reports of delirium associated with acetazolamide-induced metabolic acidosis. A single case of major depression has been associated with the use of this drug.
Acetazolamide increases the urinary excretion of bicarbonate. The resulting increase in the pH of the urine decreases the excretion of titratable acid and of ammonia. Urinary alkalinization in effect diverts ammonia from the renal tubules into the systemic circulation. This can be detrimental to patients with liver disease.
A single case of major depression associated with the use of acetazolamide eye drops has been reported. The patient's depression was refractory to drug therapy, and resolved upon discontinuation of acetazolamide. A rechallenge was not attempted.
Renal side effects have included rare reports of new or worsened renal insufficiency, nephrolithiasis, or nephrocalcinosis. The drug can cause alkalinization of the urine, decreased citrate excretion, and mild hypercalciuria. As a non-bacteriostatic sulfonamide, the drug can cause sulfonamide crystalluria. Rare cases of acute renal failure without evidence of obstruction have been associated with the use of acetazolamide.
A 33-year-old woman with hypertension, pseudotumor cerebri, status post-renal transplant developed progressive renal dysfunction within 3 days of starting acetazolamide 750 mg/day. Her antihypertensive and immunosuppressive medications remained unchanged, and there was no evidence of dehydration, hypotension, infection, obstruction, or transplant rejection. The possible catabolic influence of high-dose corticosteroids was excluded by a normal BUN to creatinine ratio and by the fact that her renal function began to improve during high-dose corticosteroid therapy. Arterial blood gases showed a mild metabolic acidosis. The patient's renal function returned to baseline within four days after stopping acetazolamide.
A 66-year-old woman with glaucoma developed laryngeal edema and severe respiratory distress after the first dose of acetazolamide 250 mg. The patient died despite intensive care. She had previously taken topical timolol and dipivefrin without adverse consequences. There was no history of allergy or hypersensitivity.
A 54-year-old man with glaucoma developed progressive weakness, anorexia, rash, abdominal pain, nausea, vomiting, diarrhea, and delirium within days after beginning acetazolamide 500 mg/day. Physical examination was remarkable for a diffuse erythematous rash, signs of peripheral circulatory failure, jaundice, a flapping tremor, hiccups, and extreme tenderness in the right hypochondrium. Laboratory examination was mostly remarkable for a serum bicarbonate of 7 mEq/L and an anion gap of 23. The patient developed acute renal failure and died. Autopsy revealed marked hepatic cholestasis with widespread fatty infiltration, compatible with drug intoxication, and an anterior mediastinal Hodgkin's lymphoma.
Hypersensitivity reactions have included rare reports of toxic epidermal necrolysis, Stevens-Johnson syndrome, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Two cases of fatal anaphylaxis have been associated with the use of this drug.
Hematologic side effects have included rare reports of myelosuppression. Thrombocytopenia, leukopenia, and even pancytopenia and aplastic anemia have been reported.
Idiosyncratic aplastic anemia has been associated with the use of sulfonamides. Acetazolamide is a sulfonamide derivative.
A retrospective Swedish study revealed 11 cases of acetazolamide-associated aplastic anemia during a 17-year period. Given the rate of acetazolamide use during that period, the reported incidence was one in 17,800 patient-years, and the calculated relative risk was 13.3.
Genitourinary side effects have included rare reports of decreased libido or impotence.
Musculoskeletal side effects have included a single case of gouty arthritis, which was believed to be related to hyperuricemia secondary to acetazolamide-induced decreased renal excretion of uric acid.
Gastrointestinal side effects have included nausea, vomiting, and diarrhea. A single case each of erosive gastritis and hypersensitivity hepatitis has been associated with the use of acetazolamide.
A 65-year-old man with glaucoma developed anorexia, dyspnea on exertion, upper abdominal pain, and weight loss within two months after starting acetazolamide. Physical and biochemical examinations were basically unremarkable except for a gastroscopy which showed small superficial ulcerations in the antrum and pylorus. After switching from acetazolamide to timolol for intraocular pressure reduction, the patient's symptoms resolved. A repeat gastroscopy was normal.
Drugs like acetazolamide which act as peripheral vasodilators (e.g., nitrates and calcium channel blockers) have been known to exacerbate rosacea.
Dermatologic side effects have included a single case of exacerbation of rosacea after oral administration. Intravenous administration has been complicated by extravasation and rare cases of skin ulceration.
Other side effects have included confusion and stupor.
General side effects have included fever.
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