nce or hepatic encephalopathy. like other diuretics it may precipitate hepatic coma and death. too vigorous a diuresis, as evidenced by rapid and excessive weight loss, may induce an acute hypotensive episode. in elderly cardiac patients, rapid contraction of plasma volume and the resultant hemoconcentration should be avoided to prevent the development of thromboembolic episodes, such as cerebral vascular thromboses and pulmonary emboli which may be fatal. excessive loss of potassium in patients receiving digitalis glycosides may precipitate digitalis toxicity. care should also be exercised in patients receiving potassium-depleting steroids. a number of possibly drug-related deaths have occurred in critically ill patients refractory to other diuretics. these generally have fallen into two categories: (1) patients with severe myocardial disease who have been receiving digitalis and presumably developed acute hypokalemia with fatal arrhythmia; (2) patients with severely decompensated hepatic cirrhosis with ascites, with or without accompanying encephalopathy, who were in electrolyte imbalance and died because of intensification of the electrolyte defect. deafness, tinnitus, and vertigo with a sense of fullness in the ears have occurred, most frequently in patients with severe impairment of renal function. these symptoms have been associated most often with intravenous administration and with doses in excess of those recommended. the deafness has usually been reversible and of short duration (one to 24 hours). however, in some patients the hearing loss has been permanent. a number of these patients were also receiving drugs known to be ototoxic. ethacrynic acid may increase the ototoxic potential of other drugs (see precautions, drug interactions ). lithium generally should not be given with diuretics (see precautions, drug interactions ).

other antihypertensive agents when given ethacrynic acid. ethacrynic acid has little or no effect on glomerular filtration or on renal blood flow, except following pronounced reductions in plasma volume when associated with rapid diuresis. a transient increase in serum urea nitrogen may occur. usually, this is readily reversible when the drug is discontinued. as with other diuretics used in the treatment of renal edema, hypoproteinemia may reduce responsiveness to ethacrynic acid and the use of salt-poor albumin should be considered. a number of drugs, including ethacrynic acid, have been shown to displace warfarin from plasma protein; a reduction in the usual anticoagulant dosage may be required in patients receiving both drugs. ethacrynic acid may increase the risk of gastric hemorrhage associated with corticosteroid treatment.

standard conditions before and during the institution of diuretic therapy with this compound. small alterations in dose should effectively prevent a massive diuretic response. the following schedule may be helpful in determining the smallest effective dose. day 1 — 50 mg once daily after a meal day 2 — 50 mg twice daily after meals, if necessary day 3 — 100 mg in the morning and 50 to 100 mg following the afternoon or evening meal, depending upon response to the morning dose. a few patients may require initial and maintenance doses as high as 200 mg twice daily. these higher doses, which should be achieved gradually, are most often required in patients with severe, refractory edema. in pediatric patients (excluding infants, see contraindications ): the initial dose should be 25 mg. careful stepwise increments in dosage of 25 mg should be made to achieve effective maintenance. maintenance therapy it is usually possible to reduce the dosage and frequency of administration once dry weight has been achieved. ethacrynic acid tablets may be given intermittently after an effective diuresis is obtained with the regimen outlined above. dosage may be on an alternate daily schedule or more prolonged periods of diuretic therapy may be interspersed with rest periods. such an intermittent dosage schedule allows time for correction of any electrolyte imbalance and may provide a more efficient diuretic response. the chloruretic effect of this agent may give rise to retention of bicarbonate and a metabolic alkalosis. this may be corrected by giving chloride (ammonium chloride or arginine chloride). ammonium chloride should not be given to cirrhotic patients. ethacrynic acid tablets, has additive effects when used with other diuretics. for example, a patient who is on maintenance dosage of an oral diuretic may require additional intermittent diuretic therapy, such as an organomercurial, for the maintenance of basal weight. the intermittent use of ethacrynic acid tablets orally may eliminate the need for injections of organomercurials. small doses of ethacrynic acid tablets may be added to existing diuretic regimens to maintain basal weight. this drug may potentiate the action of carbonic anhydrase inhibitors, with augmentation of natriuresis and kaliuresis. therefore, when adding ethacrynic acid tablets the initial dose and changes of dose should be in 25 mg increments, to avoid electrolyte depletion. rarely, patients who failed to respond to ethacrynic acid have responded to older established agents. while many patients do not require supplemental potassium, the use of potassium chloride or potassium-sparing agents, or both, during treatment with ethacrynic acid tablets is advisable, especially in cirrhotic or nephrotic patients and in patients receiving digitalis. salt liberalization usually prevents the development of hyponatremia and hypochloremia. during treatment with ethacrynic acid tablets, salt may be liberalized to a greater extent than with other diuretics. cirrhotic patients, however, usually require at least moderate salt restriction concomitant with diuretic therapy. intravenous use intravenous ethacrynate sodium is for intravenous use when oral intake is impractical or in urgent conditions, such as acute pulmonary edema.

e this effect. thrombocytopenia has been reported rarely. henoch-schönlein purpura has been reported rarely in patients with rheumatic heart disease receiving multiple drug therapy, including ethacrynic acid. special senses (see warnings ) deafness, tinnitus and vertigo with a sense of fullness in the ears, and blurred vision have occurred. central nervous system headache, fatigue, apprehension, confusion. miscellaneous skin rash, fever, chills, hematuria. to report suspected adverse reactions, contact amneal pharmaceuticals at 1-877-835-5472 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

exceeds that of sodium. with prolonged administration, chloride excretion declines, and potassium and hydrogen ion excretion may increase. ethacrynic acid is effective whether or not there is clinical acidosis or alkalosis. although ethacrynic acid, in carefully controlled studies in animals and experimental subjects, produces a more favorable sodium/potassium excretion ratio than the thiazides, in patients with increased diuresis excessive amounts of potassium may be excreted. onset of action is rapid, usually within 30 minutes after an oral dose of ethacrynic acid. after oral use, diuresis peaks in about 2 hours and lasts about 6 to 8 hours. the sulfhydryl binding propensity of ethacrynic acid differs somewhat from that of the organomercurials. its mode of action is not by carbonic anhydrase inhibition. ethacrynic acid does not cross the blood-brain barrier.

m. with prolonged administration, chloride excretion declines, and potassium and hydrogen ion excretion may increase. ethacrynic acid is effective whether or not there is clinical acidosis or alkalosis. although ethacrynic acid, in carefully controlled studies in animals and experimental subjects, produces a more favorable sodium/potassium excretion ratio than the thiazides, in patients with increased diuresis excessive amounts of potassium may be excreted. onset of action is rapid, usually within 30 minutes after an oral dose of ethacrynic acid. after oral use, diuresis peaks in about 2 hours and lasts about 6 to 8 hours. the sulfhydryl binding propensity of ethacrynic acid differs somewhat from that of the organomercurials. its mode of action is not by carbonic anhydrase inhibition. ethacrynic acid does not cross the blood-brain barrier.