ETHACRYNATE SODIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ETHACRYNATE SODIUM (ETHACRYNATE SODIUM).
Ethacrynate sodium inhibits the Na-K-2Cl cotransporter (NKCC2) in the thick ascending limb of the loop of Henle, reducing reabsorption of sodium, chloride, and potassium, leading to increased diuresis.
| Metabolism | Primarily metabolized by hepatic glutathione S-transferase (GST) to a cysteine conjugate; minor metabolism via oxidation. Excreted in urine and bile. |
| Excretion | Renal: approximately 30% unchanged; biliary/fecal: minor (less than 10%); majority metabolized to cysteine adducts excreted in urine. |
| Half-life | Terminal elimination half-life: 2-4 hours in normal renal function; prolonged to 20-30 hours in end-stage renal disease. |
| Protein binding | Approximately 95% bound, primarily to albumin. |
| Volume of Distribution | 0.1-0.2 L/kg (small Vd, consistent with high protein binding and limited extravascular distribution). |
| Bioavailability | Oral: approximately 100% (well absorbed, no significant first-pass metabolism). |
| Onset of Action | Intravenous: 5-15 minutes; oral: 30 minutes. |
| Duration of Action | Intravenous: 2 hours; oral: 6-8 hours (note: shorter duration than furosemide, often requires more frequent dosing). |
50 mg intravenously once daily; may increase in increments of 25-50 mg as needed, maximum 200 mg/day.
| Dosage form | INJECTABLE |
| Renal impairment | eGFR 30-59 mL/min: reduce dose by 50%; eGFR <30 mL/min: avoid use or use with extreme caution. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use. |
| Pediatric use | 1 mg/kg intravenously once daily; maximum 50 mg/day. Not recommended in neonates. |
| Geriatric use | Start at 25 mg intravenously once daily; increase slowly due to increased risk of electrolyte disturbances and hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ETHACRYNATE SODIUM (ETHACRYNATE SODIUM).
| Breastfeeding | Excreted into breast milk in low concentrations; M/P ratio not determined. Potential for adverse effects in nursing infants (e.g., electrolyte imbalance, diuresis). Weigh benefits against risks; consider alternative diuretics. |
| Teratogenic Risk | Ethacrynate sodium crosses the placenta. First trimester: Limited human data; animal studies not available. Second and third trimesters: Potential for electrolyte disturbances, ototoxicity, and oligohydramnios in the fetus due to diuretic effect. Avoid use in pregnancy unless clearly needed. |
■ FDA Black Box Warning
Ethacrynic acid (ethacrynate) can cause profound diuresis with water and electrolyte depletion; close medical supervision and dose titration are required.
| Serious Effects |
["Anuria","Hypersensitivity to ethacrynic acid or any component","Severe electrolyte depletion (hypokalemia, hyponatremia, hypochloremia)","Hepatic coma or precoma"]
| Precautions | ["May cause severe electrolyte disturbances (hypokalemia, hyponatremia, hypochloremia) and volume depletion","Ototoxicity, especially with rapid IV administration or in patients with renal impairment; may be irreversible","Hyperuricemia and gout","Hepatic coma can be precipitated in patients with cirrhosis or ascites","May increase risk of digoxin toxicity due to hypokalemia","Photosensitivity reaction possible"] |
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| Fetal Monitoring |
| Monitor maternal fluid status, serum electrolytes (especially potassium, sodium, chloride), and renal function. Assess fetal growth and amniotic fluid volume via ultrasound if prolonged use. |
| Fertility Effects | No specific data on fertility effects in humans. In animals, no adverse reproductive effects reported at therapeutic doses. |