Ethacrynic Acid

Ethacrynic acid is a loop diuretic that is not a sulphonamide, so it can be used in patients with a true sulphonamide allergy who need a strong diuretic. Its action is similar to furosemide, but it causes more ototoxicity and gastrointestinal upset, and it is less often used. It is not stocked in most East African pharmacies and is mainly imported for specific patients.

Classification. Loop diuretic (phenoxyacetic acid derivative; non sulphonamide).

Mechanism. Blocks the sodium potassium 2 chloride cotransporter in the thick ascending limb of the loop of Henle by binding sulphydryl groups, causing sodium, chloride, potassium and water loss.

Pharmacodynamics. Oral onset within 30 minutes, peak at 2 hours, duration 6 to 8 hours. IV onset within 5 minutes, peak at 15 to 30 minutes, duration 2 hours.

Pharmacokinetics. Well absorbed orally. Half life about 1 hour. Metabolised in the liver to an active cysteine conjugate; excreted in urine and bile.

Oedema, adult (oral).

• Start 50 mg once daily after a meal.

• Increase by 25 to 50 mg every few days as needed.

• Usual maintenance 50 to 200 mg daily, in 1 to 2 doses; maximum 400 mg daily.

• In resistant oedema, use alternate day dosing to reduce electrolyte loss.

Acute pulmonary oedema or urgent diuresis, adult (IV, as ethacrynate sodium).

• 50 mg or 0.5 to 1 mg/kg slowly IV (over 5 to 10 minutes).

• Maximum single dose 100 mg; do not exceed 100 mg a day by repeated doses in most patients.

• Use a fresh solution for each dose.

Children (specialist). Oral: start 25 mg once daily, increased in 25 mg steps; IV: 1 mg/kg once. Avoid in infants.

Contraindications. Anuria; infants; severe diarrhoea; severe hypovolaemia; severe hypokalaemia; hepatic coma and precoma; hypersensitivity.

Warnings. Ototoxicity (tinnitus, deafness, may be permanent), more than with furosemide; severe electrolyte loss and alkalosis; gastrointestinal bleeding and diarrhoea; hypovolaemia; hyperuricaemia; hyperglycaemia; thrombocytopenia.

Adverse effects. Nausea, vomiting, diarrhoea, abdominal pain, tinnitus, hearing loss, dehydration, hypokalaemia, hyponatraemia, hypotension, rash.

Interactions. Warfarin: displaced from protein binding, raising the INR. Aminoglycosides and cisplatin: ototoxicity. Digoxin: hypokalaemia raises toxicity. Lithium: raised levels. Non steroidal anti-inflammatory drugs: reduced effect. Corticosteroids and amphotericin B: more potassium loss. Cephalosporins: possible nephrotoxicity.

Special groups.

• Pregnancy: avoid.

• Breastfeeding: avoid; no data.

• Patients of African ancestry: no change.

• Older adults: lower doses; check hearing and electrolytes.

• Kidney impairment: raise the dose for effect, but monitor hearing; avoid rapid IV bolus.

• Liver impairment: start low; risk of encephalopathy from electrolyte shifts.

Formulations. Tablets 25 and 50 mg; powder for injection 50 mg (as ethacrynate sodium).

Administration. Oral after meals. IV: reconstitute with 50 mL of 5% glucose or 0.9% sodium chloride; do not use if the solution is cloudy; inject slowly into a vein (not into muscle or under the skin because it causes tissue damage).

Baseline. Weight, blood pressure, volume status, sodium, potassium, magnesium, creatinine, hearing history, INR if on warfarin.

Monitoring. Daily weight in hospital. Sodium, potassium, magnesium and creatinine 1 to 2 weeks after starting or each dose increase, then every 3 to 6 months. Replace potassium when below 3.5 mmol/L. Ask about tinnitus and hearing at each visit. INR more often when used with warfarin.

Stopping. Taper to the lowest effective dose. Stop at the first sign of hearing change.

Common prescribing errors. Using it without a clear sulphonamide allergy when furosemide would do; giving a fast IV bolus; missing the warfarin interaction; ignoring early tinnitus; extravasation during IV injection.