ETHACRYNIC ACID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ETHACRYNIC ACID (ETHACRYNIC ACID).
Inhibits sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle, leading to increased excretion of sodium, chloride, potassium, and water. Also inhibits prostaglandin degradation.
| Metabolism | Primarily metabolized by conjugation with glutathione; also undergoes hepatic metabolism via CYP450 enzymes (minor). |
| Excretion | Primarily renal (approximately 60-70% as unchanged drug and metabolites) with some biliary/fecal excretion (approximately 30-40%). |
| Half-life | Terminal elimination half-life is approximately 2-4 hours in patients with normal renal function; may be prolonged in renal impairment. |
| Protein binding | Approximately 90-98% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.1-0.2 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 100%. |
| Onset of Action | Onset of diuresis: within 30 minutes after oral administration; within 5 minutes after intravenous administration. |
| Duration of Action | Duration of diuresis: approximately 6-8 hours after oral administration; approximately 2-4 hours after intravenous administration. |
| Molecular Weight | 303.14 |
50 to 100 mg orally once daily; may increase by 25 to 50 mg increments at intervals of 2 to 3 days up to 400 mg/day. IV: 0.5 to 1 mg/kg slowly (over several minutes); usual initial dose 50 mg.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: no adjustment; eGFR <30 mL/min: avoid use due to risk of ototoxicity and decreased efficacy. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Oral: 1 mg/kg/dose once daily; may increase by 1 mg/kg/dose at intervals of 2-3 days up to 3 mg/kg/day. IV: 1 mg/kg/dose slow IV; maximum 50 mg/dose. |
| Geriatric use | Initiate at lower doses (25 mg orally once daily) due to increased risk of electrolyte disturbances and renal impairment; monitor closely. |
| 1st trimester | Ethacrynic acid is not recommended during the first trimester due to potential teratogenic effects; animal studies have shown fetal harm. |
| 2nd trimester | Use only if clearly needed; may cause adverse fetal effects including electrolyte disturbances and reduced placental perfusion. |
| 3rd trimester | Avoid use in third trimester; may cause electrolyte imbalance in the fetus and neonate, and has been associated with premature ductal closure and other adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for ETHACRYNIC ACID (ETHACRYNIC ACID).
| Placental transfer | Ethacrynic acid crosses the placenta; studies have demonstrated detectable levels in fetal plasma and amniotic fluid. |
| Breastfeeding | Ethacrynic acid is excreted into breast milk in small amounts; however, due to potential adverse effects on the infant, such as electrolyte imbalance, it is generally recommended to avoid use during breastfeeding or to monitor the infant closely. |
■ FDA Black Box Warning
This drug is a potent diuretic which, if given in excessive amounts, can lead to profound diuresis with water and electrolyte depletion. Close medical supervision and dose adjustment are required.
| Serious Effects |
AnuriaSevere renal impairment (creatinine clearance <10 mL/min)Hypersensitivity to ethacrynic acid or any component of the formulationSevere electrolyte depletion (hypokalemia, hyponatremia)Concomitant use with lithium
| Precautions | Risk of excessive diuresis leading to dehydration, electrolyte imbalance, and hypovolemia, May cause ototoxicity, especially with rapid IV administration or in patients with renal impairment, Can worsen azotemia or precipitate hepatic encephalopathy in cirrhotic patients, Monitor serum electrolytes, CO2, BUN, and creatinine regularly, Use with caution in patients with diabetes mellitus (may increase blood glucose), May cause hyperuricemia and gout |
| Food/Dietary | Avoid licorice, which can worsen hypokalemia. Limit salt intake as directed. No specific food interactions; maintain a balanced diet. |
Loading safety data…
| Lactation Rating | L4 |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity but fetal toxicity at high doses. Second trimester: Theoretical risk of electrolyte imbalances affecting fetal development. Third trimester: Risk of premature ductus arteriosus closure due to prostaglandin inhibition (theoretical), neonatal ototoxicity, and thrombocytopenia. |
| Fetal Monitoring | Monitor maternal serum electrolytes (especially potassium), BUN, creatinine, and uric acid. Fetal monitoring: Ultrasound for amniotic fluid volume and fetal growth. Neonatal: Hearing test after delivery. |
| Fertility Effects | No specific human data; animal studies show no adverse effects on fertility. May theoretically affect ovulation due to electrolyte/volume changes. |
| Clinical Pearls | Ethacrynic acid is a loop diuretic used for patients with sulfonamide allergy, as it is not a sulfonamide derivative. Monitor for ototoxicity, especially when given with aminoglycosides or in renal impairment. Rapid diuresis may cause hypokalemia, hypomagnesemia, and metabolic alkalosis. Use cautiously in hepatic cirrhosis to avoid electrolyte-induced coma. |
| Patient Advice | Take exactly as prescribed, usually once or twice daily. · Expect increased urination; take in the morning to avoid nighttime trips. · Weigh yourself daily and report rapid weight gain or loss. · Avoid alcohol and medications that may cause dizziness. · This drug may cause hearing loss or ringing in the ears; report immediately. · Do not take with aspirin or other NSAIDs without doctor approval. · Inform your doctor if you have gout, diabetes, or kidney disease. · Stay adequately hydrated but avoid excessive fluid intake. |