ethacrynate sodium

ethacrynic acid
Edecrin

Available forms
Available by prescription only
Injectable: 50 mg (with 62.5 mg mannitol and 0.1 mg thimerosal)
Tablets: 25 mg, 50 mg

Indications and dosages
 Acute pulmonary edema. Adults: 50 mg or 0.5 to 1 mg/kg I.V. to a maximum dose of 100 mg of ethacrynate sodium I.V. slowly over several minutes.
 Edema. Adults: 50 to 200 mg P.O. daily. Refractory cases may require up to 200 mg b.i.d.
Children: Initially, 25 mg P.O., given cautiously and increased in 25-mg increments daily until desired effect is achieved.
 Hypertension ◇. Adults: Initially, 25 mg P.O. daily. Adjust dose, as needed. Maximum maintenance dosage is 200 mg P.O. daily in two divided doses.

Pharmacodynamics
Diuretic action: Ethacrynic acid inhibits sodium and chloride reabsorption in the proximal part of the ascending loop of Henle, promoting the excretion of sodium, water, chloride, and potassium.

Pharmacokinetics
Absorption: Absorbed rapidly from the GI tract.
Distribution: Ethacrynic acid accumulates in the liver of animals. Ethacrynic acid doesn’t enter the CSF, and its distribution into breast milk or the placenta is unknown.
Metabolism: Metabolized by the liver to a potentially active metabolite.
Excretion: 30% to 65% is excreted in urine and 35% to 40% is excreted in bile as the metabolite. Duration of action is 6 to 8 hours after oral administration and about 2 hours after I.V. administration.

Contraindications and precautions
Contraindicated in infants, patients hypersensitive to drug, and patients with anuria, hypotension, dehydration with hyponatremia, and metabolic alkalosis with hypokalemia. Also contraindicated if azotemia, oliguria, electrolyte imbalance, or severe watery diarrhea occurs during therapy.
 Use cautiously in patients with electrolyte abnormalities or impaired hepatic function.

Interactions
Drug-drug. Aminoglycosides, some cephalosporins, or other ototoxic drugs, such as cisplatin: May increase risk of hearing loss. Avoid use together.
Antihypertensives: Increases antihypertensive effect. Reduce dosage if needed.
Cardiac glycosides: Increases risk of digitalis toxicity from ethacrynate-induced hypokalemia. Monitor digitalis and potassium levels.
Diuretics, such as metolazone: May increase diuretic effect. Reduce dosage when adding ethacrynic acid to a diuretic regimen.
Insulin, oral antidiabetics: Increases blood glucose levels. Increased dosage if needed.
Lithium: Reduces renal clearance of lithium. Monitor lithium levels. Dosage adjustment may be necessary.
NSAIDs: Decreases diuretic effectiveness and possible risk of renal failure. Use together cautiously.
Potassium-depleting drugs: May cause severe potassium loss. Monitor patient closely.
Potassium-sparing diuretics, such as amiloride, spironolactone, and triamterene: Decreases potassium loss induced by ethacrynic acid. May be used as a therapeutic advantage.
Warfarin: May potentiate anticoagulant effects. Use together cautiously.
Drug-herb. Dandelion: May interfere with diuretic activity. Discourage use together.

Adverse reactions
CNS: confusion, fatigue, vertigo, headache, malaise, fever.
CV: volume depletion and dehydration, orthostatic hypotension.
EENT: transient deafness (with too-rapid I.V. injection), blurred vision, tinnitus, hearing loss.
GI: diarrhea, anorexia, nausea, vomiting, GI bleeding, pancreatitis.
GU: oliguria, hematuria, nocturia, polyuria, azotemia.
Hematologic: agranulocytosis, neutropenia, thrombocytopenia.
Metabolic: hypokalemia; hypochloremic alkalosis; asymptomatic hyperuricemia; dilutional hyponatremia, hypocalcemia, hypomagnesemia; hyperglycemia; impaired glucose tolerance.
Other: chills.

Effects on lab test results
• May increase glucose and uric acid levels. May decrease potassium, sodium, calcium, and magnesium levels.
• May decrease granulocyte, neutrophil, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include profound electrolyte and volume depletion, which may precipitate circulatory collapse.
 Treatment of ethacrynic acid overdose is primarily supportive; empty stomach by inducing emesis or gastric lavage. Replace fluid and electrolytes as needed.

Special considerations
• Give drug slowly over 20 to 30 minutes, by I.V. infusion or by direct I.V. injection over several minutes; rapid injection may cause hypotension.
• Don’t give drug with whole blood or blood products; hemolysis may occur.
• I.V. ethacrynate sodium has been used to treat hypercalcemia and to manage ethylene glycol poisoning and bromide intoxication.
• Periodically assess hearing function in patients receiving high-dose therapy. Ethacrynic acid may potentiate ototoxicity of other drugs.
Pregnant patients
• Use drug only when clearly indicated.
Breast-feeding patients
• Don’t use drug in breast-feeding women.
Pediatric patients
• Ethacrynate sodium and ethacrynic acid shouldn’t be administered to infants. Safety in children hasn’t been established.
Geriatric patients
• Elderly and debilitated patients need close observation because they’re more susceptible to drug-induced diuresis. Excessive diuresis promotes rapid dehydration, leading to hypovolemia, hypokalemia, hyponatremia, and circulatory collapse. Reduced dosages may be indicated.

Patient education
• Advise patient receiving I.V. form of drug to immediately report pain or irritation at I.V. site.
• Caution patient with diabetes that antidiabetic dosage may need to be increased.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use