ETHACRYNIC ACID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ETHACRYNIC ACID (ETHACRYNIC ACID).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ETHACRYNIC ACID (ETHACRYNIC ACID).

Breastfeeding	Safety not established. Drug excreted in breast milk; M/P ratio unknown. Avoid breastfeeding or use with caution due to potential for ototoxicity and electrolyte disturbances in the infant.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Anuria","Hypersensitivity to ethacrynic acid or any component of the formulation","Severe electrolyte depletion (hypokalemia, hyponatremia) until corrected","Concurrent use with other ototoxic drugs (e.g., aminoglycosides) may increase risk"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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ETHACRYNIC ACID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ETHACRYNIC ACID (ETHACRYNIC ACID).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ETHACRYNIC ACID (ETHACRYNIC ACID).

Breastfeeding	Safety not established. Drug excreted in breast milk; M/P ratio unknown. Avoid breastfeeding or use with caution due to potential for ototoxicity and electrolyte disturbances in the infant.
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.

Warnings & precautions

■ 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.