ETHAMIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ETHAMIDE (ETHAMIDE).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ETHAMIDE (ETHAMIDE).

Breastfeeding

Ethamide is excreted into breast milk. The milk-to-plasma ratio is unknown. Based on limited data, the relative infant dose is estimated to be low, but potential for accumulation in preterm infants or sensitive individuals exists. Effects on the nursing infant are unknown. Caution is advised; use only if clearly needed, and monitor infant for signs of metabolic acidosis, electrolyte imbalance, or growth effects.

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.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to sulfonamides","Severe renal or hepatic disease","Adrenal insufficiency","Hyponatremia or hypokalemia","Metabolic acidosis","History of urinary calculi"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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ETHAMIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ETHAMIDE (ETHAMIDE).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ETHAMIDE (ETHAMIDE).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to sulfonamides","Severe renal or hepatic disease","Adrenal insufficiency","Hyponatremia or hypokalemia","Metabolic acidosis","History of urinary calculi"]