ACETAZOLAMIDE SODIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACETAZOLAMIDE SODIUM (ACETAZOLAMIDE SODIUM).
Acetazolamide is a carbonic anhydrase inhibitor. It reversibly inhibits the enzyme carbonic anhydrase, which catalyzes the reversible hydration of carbon dioxide and dehydration of carbonic acid. This results in increased excretion of bicarbonate, sodium, potassium, and water in the urine, leading to metabolic acidosis. Additionally, it reduces aqueous humor secretion in the eye, lowering intraocular pressure, and can decrease cerebrospinal fluid production.
| Metabolism | Acetazolamide is minimally metabolized in the liver, with the majority of the drug excreted unchanged in the urine. The primary metabolic pathway involves oxidation of the thiadiazole ring, but this is a minor route. The drug is not extensively biotransformed; hepatic metabolism accounts for less than 10% of elimination. |
| Excretion | Primarily renal (90% unchanged via tubular secretion). <2% biliary/fecal. |
| Half-life | 10-15 hours (prolonged in renal impairment; cirrhosis increases t1/2 to 20-30 h). |
| Protein binding | 70-90% (mainly carbonic anhydrase in RBCs; low affinity for albumin). |
| Volume of Distribution | Approximately 0.2-0.3 L/kg; mainly confined to extracellular fluid and highly perfused tissues. |
| Bioavailability | Oral: ~90-100% (rapidly absorbed; food may delay). Intramuscular: not recommended (acidic pH). |
| Onset of Action | IV: 2-3 minutes; oral: 60-90 minutes (diuresis); oral: 1-2 hours (glaucoma). |
| Duration of Action | IV diuresis: 4-6 hours; oral diuresis: 8-12 hours; IOP reduction: 4-6 hours (single dose), up to 12-24 h with sustained-release. |
| Molecular Weight | 222.25 |
Adult: 250-500 mg IV or IM every 12-24 hours; for edema, 250-375 mg IV once daily in morning. For glaucoma, 250-1000 mg IV or IM daily in divided doses.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 10-50 mL/min: administer every 12 hours. GFR <10 mL/min: avoid or use with extreme caution. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% or extend interval to 24-48 hours. Child-Pugh C: avoid use. |
| Pediatric use | For edema: 5 mg/kg IV or IM once daily. For glaucoma: 10-15 mg/kg/day IV or IM in divided doses every 6-8 hours. |
| Geriatric use | Initiate at lowest adult dose; monitor renal function and electrolytes; adjust based on creatinine clearance. |
| 1st trimester | Avoid unless essential; associated with increased risk of congenital malformations including limb defects, hypospadias, and neural tube defects due to inhibition of carbonic anhydrase and folate metabolism. |
| 2nd trimester | Use only if clearly needed; may cause fetal acidosis, electrolyte disturbances, and potential growth retardation. |
| 3rd trimester | Avoid due to risk of neonatal metabolic acidosis, hyperbilirubinemia, and hypoglycemia; may precipitate premature labor via diuretic effect. |
Clinical note
Comprehensive clinical and safety monograph for ACETAZOLAMIDE SODIUM (ACETAZOLAMIDE SODIUM).
| Placental transfer | Readily crosses the placental barrier; achieves fetal concentrations similar to maternal plasma. |
| Breastfeeding | Excreted into breast milk in low amounts; use with caution due to potential for neonatal hyperbilirubinemia, metabolic acidosis, and sulfonamide-related adverse effects. Monitor infant for jaundice, drowsiness, and oral sulcus. |
■ FDA Black Box Warning
None
| 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 sulfonamidesSevere hepatic cirrhosis with impaired hepatic function (risk of hepatic encephalopathy)Severe renal insufficiency (e.g., anuria, CrCl < 10 mL/min)Adrenal gland failure (e.g., Addison's disease)Hyperchloremic acidosisHypokalemia or hyponatremiaUremia
| Precautions | Use with caution in patients with hepatic cirrhosis, as acetazolamide can precipitate hepatic encephalopathy due to increased ammonia levels, May cause metabolic acidosis, which can be severe with prolonged use; monitor serum electrolytes and bicarbonate levels, Can precipitate renal calculi due to decreased urinary citrate excretion; ensure adequate hydration, May cause drowsiness, confusion, or ataxia; caution when operating machinery or driving, Use with caution in patients with respiratory acidosis or chronic obstructive pulmonary disease, as metabolic acidosis may worsen respiratory function, Monitor for signs of hypersensitivity reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, May cause hematologic reactions such as agranulocytosis, aplastic anemia, and thrombocytopenia; monitor blood counts |
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| Lactation Rating | L3 (Moderately Safe) or 'Moderately Safe' |
| Teratogenic Risk | Acetazolamide is contraindicated in pregnancy (FDA category C). First trimester: associated with increased risk of neural tube defects and limb anomalies in animal studies; human data limited but suggests potential teratogenicity. Second and third trimesters: may cause fetal metabolic acidosis, electrolyte disturbances, and growth restriction due to carbonic anhydrase inhibition. |
| Fetal Monitoring | Monitor maternal serum electrolytes (especially potassium and bicarbonate), renal function, and acid-base status. Fetal ultrasound for growth and amniotic fluid volume assessment. In neonate, monitor for metabolic acidosis and electrolyte imbalances. |
| Fertility Effects | Acetazolamide may cause reversible decreases in sperm motility and count in males. In females, animal studies suggest possible interference with ovulation; human reproductive effects are not well established. Use with caution in patients attempting conception. |
| Food/Dietary | No specific food interactions reported. However, high-sodium foods may counteract the diuretic effect. Maintain adequate fluid intake to prevent kidney stones. Avoid large amounts of caffeine as it may increase diuresis and electrolyte loss. |
| Clinical Pearls | Acetazolamide is a carbonic anhydrase inhibitor used for altitude sickness prophylaxis, glaucoma, and as a diuretic. Monitor for metabolic acidosis, especially in elderly or renal impairment. Can cause hypokalemia; check serum potassium. Contraindicated in hepatic cirrhosis due to risk of hepatic encephalopathy. May cause paresthesias, especially in hands and feet, which are harmless but can be distressing. |
| Patient Advice | Take with food to reduce gastrointestinal upset. · May cause tingling in fingers, toes, or face; this is usually temporary and not harmful. · Drink plenty of fluids unless otherwise instructed to prevent kidney stones. · Avoid alcohol as it may increase side effects like dizziness. · Do not drive or operate machinery until you know how this medication affects you, as it may cause drowsiness or blurred vision. · Report any signs of unusual bleeding, bruising, or signs of infection to your healthcare provider. · Take exactly as prescribed; do not stop suddenly without consulting your doctor. · If used for altitude sickness, start 24-48 hours before ascent and continue for 48 hours at high altitude. |