Drug reference

ethacrynic acid

Loop Diuretic · Diuretic

Loop DiureticDiuretic

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

4 major

SEVERE in our sources

PREGNANCY

—

not curated

Top interactionssee all 12 →

AminoglycosidesSevereTextbookG&G 14e
AmikacinSevereDatabase
NetilmicinSevereDatabase
TobramycinSevereDatabase

Mechanism

Ethacrynic acid inhibits the activity of the Na+-K+-2Cl− symporter in the thick ascending limb (TAL) of the loop of Henle, blocking salt transport. This abolishes the transepithelial potential difference, inhibiting Ca2+ and Mg2+ reabsorption. Ethacrynic acid also has weak carbonic anhydrase–inhibiting activity.

Indications

acute pulmonary edemachronic congestive heart failurehypertension (in patients with GFR <30 mL/min or resistant hypertension)edema of nephrotic syndromeedema of liver cirrhosisascites of liver cirrhosisdrug overdose (to induce forced diuresis)hypercalcemia (with isotonic saline)life-threatening hyponatremia (with hypertonic saline)edema associated with chronic kidney diseaseacute pulmonary edema (intravenous)edema associated with congestive heart failureliver cirrhosischronic kidney diseasenephrotic syndromehyponatremiahypercalcemiahypertension with renal insufficiency

Pharmacokinetics

Half-life

Bioavailability

~100%

Metabolism

~33% metabolism

Excretion

~67% renal excretion of intact drug

Contraindications

severe Na+ depletion
severe volume depletion
anuria unresponsive to a trial dose of loop diuretic

Side effects

Common

asymptomatic hyperuricemiatinnitushearing impairmentvertigosense of fullness in the earshyperglycemia (infrequently precipitating diabetes mellitus)increased plasma LDL cholesterolincreased plasma triglyceridesdecreased plasma HDL cholesterolskin rashesphotosensitivityparesthesiasGI disturbanceshypokalemiahyponatremiahypomagnesemiahyperuricemiahypocalcemiaglucose intolerancehypotensionreduction in GFRelectrolyte disturbance

Serious

depletion of total-body Na+
hyponatremia
extracellular fluid volume depletion
hypotension
reduced GFR
circulatory collapse
thromboembolic episodes
hepatic encephalopathy (in liver disease)
hypochloremic alkalosis
hypokalemia
cardiac arrhythmias (particularly with cardiac glycosides)
hypomagnesemia
hypocalcemia (rarely leading to tetany)
ototoxicity (more often than other loop diuretics, usually reversible, most frequently with rapid intravenous administration)
gout (rarely)
bone marrow depression
nephrotoxicity
ototoxicity

Drug interactions

Aminoglycosides

Severe

Textbook

Increased risk and severity of aminoglycoside-induced ototoxicity.

Not explicitly stated, but implies careful monitoring and cautious co-administration due to the severe, potentially irreversible nature of ototoxicity.

Source: G&G 14e

Amikacin

Severe

Database

Increased risk of ototoxicity (hearing loss, tinnitus, vertigo)

Avoid concomitant use. Ethacrynic acid has a higher ototoxic potential than furosemide. If a loop diuretic is required, consider furosemide with extreme caution and close monitoring.

Netilmicin

Severe

Database

Significantly increased risk of irreversible ototoxicity (hearing loss, vestibular dysfunction) and nephrotoxicity. Ethacrynic acid is particularly potent in this interaction.

Avoid concomitant use. If no alternative is available, extreme caution is warranted with very close monitoring of renal function and audiometry. Consider alternative diuretics or antibiotics.

Tobramycin

Severe

Database

Significantly increased risk of irreversible ototoxicity (hearing loss, tinnitus, vertigo) and nephrotoxicity. Ethacrynic acid is particularly potent in causing ototoxicity.

CONTRAINDICATED due to high risk of irreversible ototoxicity. Use alternative diuretics or antibiotics.

Aceclofenac + Paracetamol

Moderate

Textbook

Reduce the antihypertensive effects of diuretics (and all other antihypertensives).

Be aware of reduced efficacy of loop diuretics when combined with NSAIDs.

Source: G&G 14e

Aceclofenac

Moderate

Textbook

Reduce the antihypertensive effects of diuretics (and all other antihypertensives).

Be aware of reduced efficacy of loop diuretics when combined with NSAIDs.