No

Diuretic, Loop

Management of edema associated with congestive heart failure; hepatic cirrhosis or renal disease; short-term management of ascites due to malignancy, idiopathic edema, and lymphedema

B

Clinical effects on the fetus: No data available. Generally, use of diuretics during pregnancy is avoided due to risk of decreased placental perfusion.

Breast-feeding/lactation: No data available

Hypersensitivity to ethacrynic acid or any component; anuria; history of severe watery diarrhea caused by this product; infants

Adjust dose to avoid dehydration. In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Ototoxicity is associated with rapid I.V. administration, renal impairment, excessive doses, and concurrent use of other ototoxins. Has been associated with a higher incidence of ototoxicity than other loop diuretics. Hypersensitivity reactions can rarely occur. Monitor fluid status and renal function in an attempt to prevent oliguria, azotemia, and reversible increases in BUN and creatinine. Close medical supervision of aggressive diuresis required. Watch for and correct electrolyte disturbances. Coadministration of antihypertensives may increase the risk of hypotension. Increased risk of gastric hemorrhage associated with corticosteroid therapy.

Incidence of adverse events is not reported.

Endocrine & metabolic: Hyponatremia, hyperglycemia, variations in phosphorus, CO₂ content, bicarbonate, and calcium

Gastrointestinal: Anorexia, malaise, abdominal discomfort or pain, dysphagia, nausea, vomiting, and diarrhea, gastrointestinal bleeding, acute pancreatitis (rare)

Renal: Increased serum creatinine

<1% (Limited to important or life-threatening symptoms): Reversible hyperuricemia, gout, hyperglycemia, hypoglycemia (occurred in two uremic patients who received doses above those recommended), jaundice, abnormal liver function tests, agranulocytosis, severe neutropenia, thrombocytopenia, Henoch-Schönlein purpura (in patient with rheumatic heart disease), deafness, tinnitus, temporary or permanent deafness, vertigo, blurred vision, headache, fatigue, apprehension, confusion, skin rash, fever, chills, hematuria, local irritation and pain, thrombophlebitis (with intravenous use), encephalopathy (patients with pre-existing liver disease)

Symptoms of overdose include electrolyte depletion, volume depletion, dehydration, circulatory collapse

Following GI decontamination, treatment is supportive; hypotension responds to fluids and Trendelenburg position

ACE inhibitors: Hypotensive effects and/or renal effects are potentiated by hypovolemia.

Antidiabetic agents: Glucose tolerance may be decreased.

Antihypertensive agents: Hypotensive effects may be enhanced.

Cephaloridine or cephalexin: Nephrotoxicity may occur.

Cholestyramine or colestipol may reduce bioavailability of ethacrynic acid.

Clofibrate: Protein binding may be altered in hypoalbuminemic patients receiving ethacrynic acid, potentially increasing toxicity.

Digoxin: Ethacrynic acid-induced hypokalemia may predispose to digoxin toxicity; monitor potassium.

Indomethacin (and other NSAIDs) may reduce natriuretic and hypotensive effects of diuretics.

Lithium: Renal clearance may be reduced. Isolated reports of lithium toxicity have occurred; monitor lithium levels.

NSAIDs: Risk of renal impairment may increase when used in conjunction with diuretics.

Ototoxic drugs (aminoglycosides, cis-platinum): Concomitant use of ethacrynic acid may increase risk of ototoxicity, especially in patients with renal dysfunction.

Peripheral adrenergic-blocking drugs or ganglionic blockers: Effects may be increased.

Salicylates (high-dose) with diuretics may predispose patients to salicylate toxicity due to reduced renal excretion or alter renal function.

Sparfloxacin, gatifloxicin, and moxifloxacin: Risk of cardiotoxicity may be increased; avoid use.

Thiazides: Synergistic diuretic effects occur.

Inhibits reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule, interfering with the chloride-binding cotransport system, thus causing increased excretion of water, sodium, chloride, magnesium, and calcium

Onset of diuretic effect: Oral: Within 30 minutes; I.V.: 5 minutes

Peak effect: Oral: 2 hours; I.V.: 30 minutes

Duration of action: Oral: 12 hours; I.V.: 2 hours

Absorption: Oral: Rapid

Metabolism: In the liver to active cysteine conjugate (35% to 40%)

Protein binding: >90%

Half-life: Normal renal function: 2-4 hours

Elimination: 30% to 60% excreted unchanged in bile and urine

I.V. formulation should be diluted in D₅W or NS (1 mg/mL) and infused over several minutes.

Adults:

Oral: 50-200 mg/day in 1-2 divided doses; may increase in increments of 25-50 mg at intervals of several days; doses up to 200 mg twice daily may be required with severe, refractory edema.

I.V.: 0.5-1 mg/kg/dose (maximum: 100 mg/dose); repeat doses not routinely recommended; however, if indicated, repeat doses every 8-12 hours.

Dosing adjustment/comments in renal impairment: Cl_cr <10 mL/minute: Avoid use.

Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.

This product may cause a potassium loss; your physician may prescribe a potassium supplement, another medication to help prevent the potassium loss, or recommend that you eat foods high in potassium, especially citrus fruits; do not change your diet on your own while taking this medication, especially if you are taking potassium supplements or medications to reduce potassium loss; too much potassium can be as harmful as too little

Blood pressure, renal function, serum electrolytes, and fluid status closely, including weight and I & O daily; hearing

Limited use over other loop diuretics because of increased risk of ototoxicity. Hypotensive effect of ethacrynic acid may be more pronounced in patients previously on a diuretic therapy or who have volume depletion.

May cause dizziness; may rarely cause drowsiness, nervousness, or confusion

Rare reports of agranulocytosis; use caution with clozapine and carbamazepine; may increase serum lithium levels, however, more likely with thiazide diuretic

No information available to require special precautions

No effects or complications reported

Take prescribed dose with food early in day. Include orange juice or bananas (or other potassium-rich foods) in your diet, but do not take potassium supplements without consulting prescriber. You may experience postural hypotension (use caution when rising from lying or sitting position, when climbing stairs, or when driving); lightheadedness, dizziness, or drowsiness (use caution driving or when engaging in hazardous activities); diarrhea (buttermilk, boiled milk, or yogurt may help); or decreased accommodation to heat (avoid excessive exercise in hot weather). Diabetics should monitor serum glucose closely (this medication may interfere with antidiabetic medications). Report changes in hearing or ringing in ears, persistent headache, unusual confusion or nervousness, abdominal pain or blood stool (black stool), palpitations, chest pain, rapid heartbeat, joint or muscle soreness or weakness, flu-like symptoms, skin rash or itching, or blurred vision. Report swelling of ankles or feet, weight changes of more than 3 lb/day, increased fatigue, or muscle cramping or trembling. Breast-feeding precautions: Do not breast-feed.

Tissue irritant; not to be administered I.M. or S.C.; dilute injection with 50 mL dextrose 5% or normal saline (1 mg/mL concentration resulting); may be injected without further dilution over a period of several minutes or infused over 20-30 minutes

Monitor blood pressure, serum electrolytes, renal function, hearing

Powder for injection, as ethacrynate sodium: 50 mg (50 mL)

Tablet: 25 mg, 50 mg

To make a 1 mg/mL suspension: Dissolve 120 mg ethacrynic acid powder in a small amount of 10% alcohol. Add a small amount of 50% sorbitol solution and stir. Adjust pH to 7 with 0.1N sodium hydroxide solution. Add sufficient 50% sorbitol solution to make a final volume of 120 mL. (Methylparaben 6 mg and propylparaben 2.4 mg are added as preservatives.) Stable 220 days at room temperature.

Cowley AJ and Elkeles RS, "Diabetes and Therapy With Potent Diuretics," Lancet, 1978, 1(8056):154.

Gomolin IH and Garschick E, "Ethacrynic Acid-Induced Deafness Accompanied by Nystagmus," N Engl J Med, 1980, 303(12):702.

Lant A, "Diuretics: Clinical Pharmacology and Therapeutic Use," Drugs, 1985, 29(1):57-87.