Adult: For rapid onset of diuresis or when oral treatment is not feasible: As etacrynate Na (equivalent to 50 mg etacrynic acid): 50 mg or 0.5-1 mg/kg via slow direct inj or into the tubing of a running infusion over 5-20 minutes. Max single dose: 100 mg. A single IV dose is usually sufficient; if needed, a 2nd dose may be given at a new inj site to avoid thrombophlebitis.
Oral Oedema
Adult: For cases associated with CHF, hepatic cirrhosis, or renal disease: As etacrynic acid: Initially, 50 mg once daily in the morning, may be increased by 25-50 mg daily increments according to response and tolerability. Usual effective dose: 50-200 mg daily in 1-2 divided doses. Maintenance doses may be taken daily or intermittently. In severe refractory oedema, gradually titrating the dose up to Max of 200 mg bid may be required. Use the smallest effective dose.
Administration
Should be taken with food.
Reconstitution
IV: Reconstitute vial with 50 mL of dextrose 5% in water or NaCl 0.9% inj to make a final concentration of 1 mg/mL.
Incompatibility
IV: Incompatible with solutions that have pH <5.
Contraindications
Anuria, history of etacrynic acid-induced severe watery diarrhoea.
Special Precautions
Patient with advanced hepatic cirrhosis, particularly those with a history of episodes of electrolyte imbalance or hepatic encephalopathy; diabetes; history of gout or elevated serum uric acid levels. Patients undergoing surgery. Renal and hepatic impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Profound diuresis with fluid and electrolyte loss (especially with high doses); nephrotoxicity; ototoxicity (e.g. tinnitus, temporary or permanent deafness, vertigo), particularly with high doses or rapid IV administration. Rarely, hypersensitivity reactions. Blood and lymphatic system disorders: Rarely, thrombocytopenia. Eye disorders: Blurred vision. Gastrointestinal disorders: Diarrhoea, abdominal pain or discomfort, nausea, vomiting, dysphagia. General disorders and administration site conditions: Malaise, fever, fatigue, chills; inj or infusion site pain or irritation (IV). Investigations: Transient increases in BUN. Metabolism and nutrition disorders: Anorexia, gout, reversible hyperuricaemia. Nervous system disorders: Headache. Psychiatric disorders: Apprehension, confusion. Renal and urinary disorders: Rarely, haematuria. Skin and subcutaneous tissue disorders: Skin rash.
Monitor renal function, blood pressure, serum electrolytes, BUN, CO2, daily weight, and fluid status, including input and output during treatment. Assess hearing and for signs of hypovolaemia and electrolyte imbalance (e.g. hypokalaemia, hyponatraemia, hypocalcaemia, hypomagnesaemia).
Overdosage
Symptoms: Excessive diuresis with dehydration and electrolyte depletion. Management: Symptomatic and supportive treatment. May induce emesis or perform gastric lavage. For respiratory impairment, oxygen or artificial respiration may be necessary.
Drug Interactions
Additive effects with other diuretics (e.g. spironolactone, triamterene). May increase the risk of ototoxicity with other ototoxic agents (e.g. aminoglycosides, certain cephalosporins). May result in orthostatic hypotension with antihypertensive agents. May decrease the diuretic and natriuretic effects with NSAIDs. May displace warfarin from plasma proteins. May increase the risk of gastrointestinal bleeding with corticosteroids. Toxic effects of cardiac glycosides may be increased by the hypokalaemic and hypomagnesaemic effects of etacrynic acid. May reduce the renal clearance of lithium which may lead to toxicity. May interfere with the hypoglycaemic effects of insulin or other antidiabetic agents. May potentiate the natriuretic and kaliuretic effects of carbonic anhydrase inhibitors (e.g. acetazolamide, dichlorphenamide).
Lab Interference
May result in false-negative aldosterone/renin ratio (ARR). May alter glucose tolerance tests.
Action
Description: Mechanism of Action: Etacrynic acid is a potent loop diuretic that inhibits the reabsorption of Na and chloride in the ascending loop of Henle and distal renal tubules. It also interferes with the chloride-binding cotransport system, thereby increasing the excretion of water, Na, K, Ca, Mg, and chloride ions. Synonym(s): Ethacrynic acid. Onset: Diuresis: Approx 30 minutes (oral); 5 minutes (IV). Duration: 12 hours (oral); 2-4 hours (IV). Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 100%. Distribution: Plasma protein binding: >90%. Metabolism: Metabolised in the liver to form active cysteine conjugate. Excretion: Via urine (30-65%); faeces (35-40%). Elimination half-life: 2-4 hours.
Chemical Structure
Etacrynic acid Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3278, Ethacrynic acid. https://pubchem.ncbi.nlm.nih.gov/compound/Ethacrynic-acid. Accessed Oct. 25, 2024.
C03CC01 - etacrynic acid ; Belongs to the class of high-ceiling aryloxyacetic acid derivative diuretics.
References
Anon. Ethacrynic Acid, Ethacrynate Sodium. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/10/2024.Brayfield A, Cadart C (eds). Etacrynic Acid. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/10/2024.Etacrynic Acid [Ethacrynic Acid]. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 02/10/2024.Ethacrynic Acid. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 02/10/2024.Ethacrynic Sodium Powder, for Solution and Ethacrynic Acid Tablet (Oceanside Pharmaceuticals). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/10/2024.
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