ETHACRYNIC ACID

ETHACRYNIC ACID (eth-a-krin'ik) Edecrin ETHACRYNATE SODIUM Sodium Edecrin Classifications: electrolytic and water balance agent; loop diuretic; antihypertensive; Therapeutic: loop diuretic; antihypertensive Prototype: Furosemide Pregnancy Category: B

Availability

25 mg, 50 mg tablet; 50 mg injection

Action

Inhibits sodium and chloride reabsorption in proximal tubule and most segments of loop of Henle, promotes potassium and hydrogen ion excretion, and decreases urinary ammonium ion concentration as well as pH of the blood. Promotes calcium elimination in hypercalcemia and nephrogenic diabetes insipidus. Hypotensive effect may be due to hypovolemia secondary to diuresis and in part to decreased vascular resistance.

Therapeutic Effect

Rapid and potent diuretic effect resulting in hypotensive effect. Fluid and electrolyte loss may exceed that caused by thiazides.

Uses

Severe edema associated with CHF, hepatic cirrhosis, ascites of malignancy, kidney disease, nephrotic syndrome, lymphedema.

Unlabeled Uses

Treatment of nephrogenic diabetes insipidus, hypercalcemia, mild to moderate hypertension, and as adjunct in therapy of hypertensive crisis complicated by pulmonary edema.

Contraindications

History of hypersensitivity to ethacrynic acid; increasing azotemia, anuria; hepatic coma; severe diarrhea, dehydration, electrolyte imbalance, hypotension; lactation, infants, and neonates; parenteral use in pediatric patients.

Cautious Use

Hepatic cirrhosis; older adult cardiac patients; diabetes mellitus; history of gout; pulmonary edema associated with acute MI; hyperaldosteronism; nephrotic syndrome; history of pancreatitis; pregnancy (category B).

Route & Dosage

Edema Adult: PO 50–100 mg 1–2 times/d, may increase by 25–50 mg prn up to 400 mg/d IV 0.5–1 mg/kg or 50 mg up to 100 mg, may repeat if necessary Child: PO 1 mg/kg q.d., may increase to 3 mg/kg/d

Administration

Oral

• Give after a meal or food to prevent gastric irritation.
• Schedule doses to avoid nocturia and thus sleep interference. Avoid administration within at least 4 h of bedtime, if possible. This recommendation may not apply to the patient who accumulates fluid and develops respiratory symptoms during sleep.

Intravenous PREPARE: Direct/Intermittent: Reconstitute by adding 50 mL of D5W or NS to vial. Use solution within 24 h. Vials reconstituted with D5W may turn cloudy; if so, discard the vial.   ADMINISTER: Direct: Give at a rate of 10 mg/min.  Intermittent: Give over 15–30 min. If a second IV dose is required, a new site should be selected to prevent thrombophlebitis.   INCOMPATIBILITIES Solution/additive: Hydralazine, procainamide, ranitidine, tolazoline, triflupromazine.

• Store oral and parenteral form at 15°–30° C (59°–86° F) unless otherwise directed.

Adverse Effects (≥1%)

CNS: Headache, fatigue, apprehension, confusion. CV: Postural hypotension (dizziness, light-headedness). Metabolic: Hyponatremia, hypokalemia, hypochloremic alkalosis, hypomagnesemia, hypocalcemia, hypercalciuria, hyperuricemia, hypovolemia, hematuria, glycosuria, hyperglycemia, gynecomastia, elevated BUN, creatinine, and urate levels. Special Senses: Vertigo, tinnitus, sense of fullness in ears, temporary or permanent deafness. GI: Anorexia, diarrhea, nausea, vomiting, dysphagia, abdominal discomfort or pain, GI bleeding (IV use), abnormal liver function tests. Hematologic: Thrombocytopenia, agranulocytosis (rare), severe neutropenia (rare). Skin: Skin rash, pruritus. Body as a Whole: Fever, chills, acute gout; local irritation and thrombophlebitis with IV injection.

Interactions

Drug: thiazide diuretics increase potassium loss; increased risk of digoxin toxicity from hypokalemia; corticosteroids, amphotericin B increase risk of hypokalemia; decreased lithium clearance, so increased risk of lithium toxicity; sulfonylurea effect may be blunted, causing hyperglycemia; antihypertensive agents increase risk of orthostatic hypotension; aminoglycosides may increase risk of ototoxicity; warfarin potentiates hypoprothrombinemia.

Pharmacokinetics

Absorption: Rapidly absorbed from GI tract. Onset: 30 min PO; 5 min IV. Peak: 2 h PO; 15–30 min IV. Duration: 6–8 h PO; 2 h IV. Distribution: Does not cross CSF. Metabolism: Metabolized to cysteine conjugate. Elimination: 30–65% in urine; 35–40% in bile. Half-Life: 30–70 min.

Nursing Implications

Assessment & Drug Effects

• Observe closely when receiving the drug by IV infusion. Rapid, copious diuresis following IV administration can produce hypotension.
• Monitor IV site closely. Extravasation of IV drug causes local pain and tissue irritation from dehydration and blood volume depletion.
• Monitor BP during initial therapy. Because orthostatic hypotension can occur, supervise ambulation.
• Monitor BP and pulse throughout therapy in patients with impaired cardiac function. Diuretic-induced hypovolemia may reduce cardiac output, and electrolyte loss promotes cardiotoxicity in those receiving digitalis (cardiac) glycosides.
• Establish baseline weight prior to start of therapy; weigh patient under standard conditions. Keep physician informed of weight loss or gain in excess of 1 kg (2 lb)/d.
• Monitor I&O ratio. Drug should be discontinued if excessive diuresis, oliguria, hematuria, or sudden profuse diarrhea occurs. Report signs to physician.
• Lab tests: Determine baseline and periodic blood count, serum electrolytes, CO₂, BUN, creatinine, blood glucose, uric acid, and liver function.
• Observe for and report S&S of electrolyte imbalance: Anorexia, nausea, vomiting, thirst, dry mouth, polyuria, oliguria, weakness, fatigue, dizziness, faintness, headache, muscle cramps, paresthesias, drowsiness, mental confusion. Instruct patient to report these symptoms promptly to physician.
• Report immediately possible signs of thromboembolic complications (see Appendix F).
• Impaired glucose tolerance with hyperglycemia and glycosuria has occurred in patients receiving doses in excess of 200 mg/d.

Patient & Family Education

• Learn S&S of hypokalemia and hyponatremia (see Appendix F), and report any of these promptly to physician.
• Make position changes slowly, particularly from lying to upright posture.
• Report GI adverse effects to physician; they occur most frequently after 1–3 mo of PO therapy or in patients on high dosage. The onset of loose stools or other GI symptoms at any time during therapy indicates possible need for dosage adjustment or discontinuation of drug.
• Notify physician immediately of any evidence of impaired hearing. Hearing loss may be preceded by vertigo, tinnitus, or fullness in ears; it may be transient, lasting 1–24 h, or it may be permanent.

---

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug