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CARDIOVASCULAR SYSTEM › DIURETICS › HIGH-CEILING DIURETICS › Aryloxyacetic acid derivatives
etacrynic acid
C03CC01
Forms & Strengths
- Oral tablets: 25 mg
- Intravenous powder for injection: 50 mg (as sodium etacrynate)
Adult Dosing
- Oral (Edema): Initial 50 mg once daily after a meal; may increase by 25 mg increments cautiously; maintenance typically 50-200 mg daily.
- Intravenous (Acute pulmonary edema/Emergency): 50 mg (0.5 to 1 mg/kg) administered slowly over several minutes.
Pediatric Dosing
- Oral (infants and children): Initial 25 mg; titrate cautiously in increments of 25 mg; not routinely recommended in neonates.
- Intravenous (pediatric emergency): 1 mg/kg administered cautiously; limited safety and efficacy data.
Indications
- Treatment of severe fluid retention (edema) associated with congestive heart failure, cirrhosis, and renal disease (including nephrotic syndrome)
- Short-term management of ascites due to malignancy, idiopathic edema, or lymphedema
- Used when greater diuresis is required than can be achieved with other agents, or in patients allergic to sulfonamide-derived diuretics
Mechanism of Action
- Loop diuretic that inhibits the reabsorption of sodium and chloride in the thick ascending limb of the loop of Henle
- Inhibits the luminal Na+-K+-2Cl- cotransporter (NKCC2)
- Decreases urinary concentrating and diluting capacity, leading to significant excretion of water, sodium, chloride, potassium, and calcium
Contraindications
- Anuria or severe renal failure unresponsive to test doses
- Severe watery diarrhea or electrolyte depletion states
- History of severe hypersensitivity to etacrynic acid
- Infants (neonates) due to risk of ototoxicity and jaundice
Adverse Reactions
- Electrolyte disturbances (hyponatremia, hypokalemia, hypomagnesemia, hypocalcemia)
- Ototoxicity (transient or permanent deafness, tinnitus, vertigo) - uniquely higher risk compared to other loop diuretics
- Gastrointestinal toxicity (severe watery diarrhea, anorexia, GI bleeding)
- Hyperuricemia, gout, hyperglycemia
- Orthostatic hypotension, dizziness, dehydration
Drug Interactions
- Aminoglycoside antibiotics and vancomycin: Increased risk of ototoxicity and nephrotoxicity
- Lithium: Decreased renal clearance, increasing risk of lithium toxicity
- Antihypertensives and diuretics: Potentiation of hypotensive effects
- NSAIDs: Reduced diuretic, natriuretic, and antihypertensive efficacy; increased risk of renal impairment
- Warfarin: Enhanced anticoagulant effect due to displacement from plasma protein binding sites
Curated Content: Needs Vetting Before Put to Clinical Use