ACETAZOLAMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACETAZOLAMIDE (ACETAZOLAMIDE).
Reversible inhibition of carbonic anhydrase, primarily in the proximal renal tubule, reducing hydrogen ion secretion and increasing bicarbonate, sodium, potassium, and water excretion. Also reduces aqueous humor formation via ocular carbonic anhydrase inhibition.
| Metabolism | Primarily excreted unchanged in urine (70-100%). Minor metabolism via hydrolysis of acetyl group (possibly by plasma esterases) to acetazolamide, and glucuronide conjugation. |
| Excretion | Renal: ~90% unchanged drug via tubular secretion and glomerular filtration; minor biliary/fecal (<2%). |
| Half-life | Terminal half-life approximately 10–15 hours; prolonged in renal impairment (up to 30+ hours). |
| Protein binding | ~70–90% bound primarily to carbonic anhydrase in erythrocytes and plasma proteins (albumin). |
| Volume of Distribution | 0.2–0.3 L/kg; concentrates in tissues with high carbonic anhydrase content (RBCs, kidneys, eyes). |
| Bioavailability | Oral: ~100% (well absorbed); IV: 100%. |
| Onset of Action | Oral: 1–1.5 hours; IV: within minutes; peak effect 2–4 hours. |
| Duration of Action | Oral: 8–12 hours; IV: 4–6 hours; extended with sustained-release formulations. |
250-500 mg orally twice daily or 250 mg intravenously twice daily; for edema, 250-375 mg orally once daily; for altitude sickness, 250 mg orally every 8-12 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: administer every 12 hours; CrCl <10 mL/min: avoid use (ineffective). |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B-C: caution, reduce dose by 50% and monitor for encephalopathy. |
| Pediatric use | Children: 5-10 mg/kg/dose orally or IV every 8-12 hours; maximum 500 mg/dose. |
| Geriatric use | Initiate at lowest effective dose (250 mg daily) due to increased risk of electrolyte disturbances and renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACETAZOLAMIDE (ACETAZOLAMIDE).
| Breastfeeding | Excreted into breast milk (M/P ratio approximately 0.25). Not recommended due to risk of sulfonamide-related adverse effects (e.g., kernicterus in jaundiced infants, hemolytic anemia in G6PD deficiency). |
| Teratogenic Risk | First trimester: Avoid; associated with increased risk of congenital malformations (limb defects, hypospadias). Second and third trimesters: Use only if clearly needed; may cause fetal metabolic acidosis, electrolyte disturbances, and growth retardation. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: Metabolically induced acidosis. Use with caution in patients with hepatic cirrhosis to avoid precipitation of hepatic encephalopathy. Not recommended for long-term use in patients with chronic noncongestive angle-closure glaucoma due to risk of increased intraocular pressure with lens displacement.
| Common Effects | Nausea Taste change Vomiting Diarrhea Constipation Cough Dizziness Weakness Headache Cold extremities Slow heart rate Numbness of extremity Increased potassium level in blood Decreased blood pressure |
| Serious Effects |
["Hypersensitivity to acetazolamide or any sulfonamide derivative","Severe hepatic cirrhosis or hepatic impairment","Severe renal impairment (CrCl <10 mL/min) or anuria","Hyponatremia or hypokalemia","Adrenocortical insufficiency (Addison's disease)","Long-term use in chronic noncongestive angle-closure glaucoma","Metabolic acidosis"]
| Precautions | ["Sulfonamide hypersensitivity reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) - discontinue at first sign of rash","Metabolic acidosis - monitor electrolytes, use with caution in patients with respiratory acidosis or those at risk","Hepatic impairment - contraindicated in cirrhosis; may precipitate hepatic encephalopathy","Renal impairment (CrCl <10 mL/min) - ineffective and may cause metabolic acidosis","Hematologic reactions (agranulocytosis, aplastic anemia) - monitor CBC","Hypercalciuria and renal stone formation - ensure adequate hydration","Drowsiness, confusion, fatigue - impaired ability to drive/operate machinery","Use in pregnancy - potential risk; cross-sensitivity with sulfonamides"] |
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| Maternal: Serum electrolytes, renal function, complete blood count, blood pH; fetal: Ultrasound for growth and anatomy, fetal heart rate monitoring if used in third trimester. |
| Fertility Effects | No known direct effect on fertility, but may cause metabolic acidosis, which could theoretically impair conception. |
| Food/Dietary | Avoid high doses of vitamin C or cranberry juice as they may acidify urine and decrease drug effectiveness. Maintain adequate hydration; no specific food restrictions. |
| Clinical Pearls | Acetazolamide is a carbonic anhydrase inhibitor used for glaucoma, altitude sickness, and as a diuretic. Monitor serum electrolytes (especially potassium and bicarbonate) due to metabolic acidosis risk. Avoid in severe hepatic or renal impairment. Can cause paresthesias, especially in hands and feet. Use with caution in patients with sulfonamide allergy as cross-reactivity is possible but rare. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly. · May cause tingling or numbness in fingers, toes, or mouth; this is usually temporary. · Drink plenty of fluids unless otherwise directed; avoid excessive alcohol. · Report unusual fatigue, muscle cramps, or rapid breathing to your doctor. · Avoid prolonged sun exposure; use sunscreen as photosensitivity may occur. · If used for altitude sickness, start 1-2 days before ascent and continue during climb. |