ETHAMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ETHAMIDE (ETHAMIDE).
Ethamide is a carbonic anhydrase inhibitor that reduces aqueous humor production in the eye, lowering intraocular pressure. It also has diuretic effects by inhibiting carbonic anhydrase in the proximal renal tubule, leading to bicarbonate excretion and metabolic acidosis.
| Metabolism | Hepatic metabolism via acetylation; undergoes enterohepatic circulation. |
| Excretion | Primarily renal (80-90%) as unchanged drug via glomerular filtration and tubular secretion; minor biliary/fecal (<5%) and metabolic (5-10%) elimination. |
| Half-life | Terminal elimination half-life is 4-6 hours in normal renal function; prolonged to 12-24 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 70-80% bound to serum albumin. |
| Volume of Distribution | 0.3-0.5 L/kg, indicating distribution primarily within extracellular fluid. |
| Bioavailability | Oral: 90-100%; bioavailability is high with minimal first-pass metabolism. |
| Onset of Action | IV: immediate (within 1-2 minutes); Oral: 30-60 minutes following administration. |
| Duration of Action | 6-8 hours for oral dose; 2-4 hours for IV bolus; duration extended in renal impairment. |
| Molecular Weight | 284.29 |
15-25 mg/kg orally once daily (max 1.5 g/day).
| Dosage form | TABLET |
| Renal impairment | CrCl 30-60 mL/min: 50% dose reduction. CrCl <30 mL/min: avoid use. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 50% dose reduction. Child-Pugh C: avoid use. |
| Pediatric use | 10-20 mg/kg orally once daily (max 800 mg/day). |
| Geriatric use | Start at 10 mg/kg orally once daily; titrate based on renal function. |
| 1st trimester | Avoid due to teratogenic potential; associated with neural tube defects and cleft palate in animal studies. |
| 2nd trimester | Use only if benefit outweighs risk; may cause fetal growth restriction and oligohydramnios. |
| 3rd trimester | Avoid near term due to risk of neonatal hemorrhage and persistent pulmonary hypertension. |
Clinical note
Comprehensive clinical and safety monograph for ETHAMIDE (ETHAMIDE).
| Placental transfer | Crosses placenta readily; fetal plasma concentrations reach 50-100% of maternal levels. |
| Breastfeeding | Excreted into human milk in small amounts; potential for serious adverse reactions in nursing infants, including kernicterus in jaundiced infants. Discontinue breastfeeding or drug, considering importance of drug to mother. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to ethamide or sulfonamidesSevere hepatic impairmentPorphyriaUrinary tract obstruction
| Precautions | Sulfonamide allergy (cross-sensitivity possible), Hepatic insufficiency, Renal insufficiency or calculi, Electrolyte imbalance (hypokalemia, hyponatremia), Metabolic acidosis, Use with caution in diabetes mellitus, May cause drowsiness or confusion |
| Food/Dietary | Avoid high-purine foods (e.g., organ meats, anchovies, sardines, beer) as they can increase uric acid levels. Limit alcohol intake, especially beer and spirits. Maintain adequate fluid intake. |
| Clinical Pearls |
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| Lactation Rating |
| L4 - Possibly Hazardous |
| Teratogenic Risk | Ethamide is a carbonic anhydrase inhibitor. Human data are limited. Animal studies have shown teratogenic effects, including increased incidence of fetal malformations (e.g., limb defects, cleft palate) at doses similar to human therapeutic doses. In the first trimester, risk cannot be excluded. During the second and third trimesters, use may cause fetal metabolic acidosis and electrolyte disturbances. There is potential for adverse effects on fetal growth and development, but specific trimester-based risks are not well characterized due to lack of adequate human studies. |
| Fetal Monitoring | Monitor maternal renal function, serum electrolytes (sodium, potassium, bicarbonate, chloride), complete blood count, and signs of metabolic acidosis. In fetus, monitor fetal growth via ultrasound and amniotic fluid index (risk of oligohydramnios). Consider nonstress test or biophysical profile in third trimester. Neonatal monitoring after delivery for electrolyte disturbances and metabolic acidosis. |
| Fertility Effects | No specific human studies on fertility. In animal studies, high doses caused testicular atrophy and decreased spermatogenesis in males; effects on female reproduction are unknown. Potential for reversible impairment of spermatogenesis and sperm motility. Relevance to human fertility is uncertain. |
| Monitor serum uric acid levels regularly; ethamide is a uricosuric agent and may precipitate gout flares upon initiation. Adjust dose in renal impairment (CrCl <50 mL/min avoid). Ensure adequate hydration to prevent urate nephropathy. Discontinue if symptoms of hypersensitivity or hepatitis occur. |
| Patient Advice | Take ethamide with food or milk to reduce gastrointestinal upset. · Drink plenty of fluids (at least 2 liters daily) to prevent kidney stones. · Report any new joint pain, swelling, or redness immediately. · Avoid excessive alcohol consumption as it may increase uric acid levels. · Do not drive or operate heavy machinery if dizziness occurs. |