Amiloride

Amiloride is a weak potassium sparing diuretic that blocks the epithelial sodium channel in the distal tubule. It is mainly used to prevent hypokalaemia when given with a thiazide or loop diuretic, as an add-on in resistant hypertension, and to treat lithium induced nephrogenic diabetes insipidus and Liddle syndrome. It is not stocked in many East African pharmacies, but combinations with a thiazide exist.

Classification. Potassium sparing diuretic; epithelial sodium channel blocker (not an aldosterone antagonist).

Mechanism. Blocks the epithelial sodium channel in the late distal tubule and collecting duct, reducing sodium reabsorption and the lumen negative potential that drives potassium and hydrogen ion secretion.

Pharmacodynamics. Onset within 2 hours, peak at 6 to 10 hours, duration about 24 hours. Weak natriuretic effect; blood pressure effect builds over 2 to 4 weeks.

Pharmacokinetics. Oral absorption about 50%. Half life 6 to 9 hours (longer in kidney impairment, up to 100 hours). Not metabolised; excreted unchanged in urine.

Adjunct to a thiazide or loop diuretic (oedema, hypertension, heart failure), adult. Start 5 mg once daily; usual maintenance 5 to 10 mg once daily; maximum 20 mg daily in 1 or 2 doses.

Resistant hypertension, adult. 5 to 10 mg once daily added to the regimen; maximum 20 mg daily.

Lithium induced nephrogenic diabetes insipidus, adult (specialist). Start 5 mg twice daily; titrate to the lowest effective dose; maximum 20 mg daily; monitor lithium levels.

Liddle syndrome, adult (specialist). 5 to 20 mg daily in 1 or 2 doses.

Children. Not established; specialist use of 0.4 to 0.625 mg/kg once daily has been described (maximum 20 mg).

Contraindications. Hyperkalaemia (above 5.5 mmol/L); Addison disease; anuria; severe kidney impairment (eGFR under 30 mL/min); concurrent potassium supplements or other potassium sparing diuretics; hypersensitivity.

Warnings. Hyperkalaemia, which can be fatal, especially in diabetes, older age, dehydration and kidney impairment; hyponatraemia; metabolic acidosis; kidney function decline. Stop in dehydrating illness.

Adverse effects. Hyperkalaemia, nausea, abdominal pain, diarrhoea, headache, dizziness, muscle cramp, hyponatraemia, rash, impotence.

Interactions. Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, potassium supplements, trimethoprim, spironolactone, ciclosporin and tacrolimus: hyperkalaemia. Non steroidal anti-inflammatory drugs: kidney injury and hyperkalaemia. Lithium: levels rise. Digoxin: reduced clearance.

Special groups.

• Pregnancy: avoid unless essential.

• Breastfeeding: no data; avoid.

• Patients of African ancestry: useful in low renin hypertension; monitor potassium.

• Older adults: start 2.5 to 5 mg; high risk of hyperkalaemia.

• Kidney impairment: avoid with eGFR under 30 mL/min; use half doses at eGFR 30 to 50 mL/min.

• Liver impairment: use with care; risk of electrolyte disturbance.

Formulations. Tablets 5 mg; oral solution 5 mg/5 mL; fixed combination tablets with hydrochlorothiazide (2.5/25 mg or 5/50 mg) or furosemide.

Administration. Oral with food, in the morning.

Baseline. Potassium, sodium, creatinine and eGFR, blood pressure.

Monitoring. Potassium and creatinine at 1 week and 4 weeks after starting or any dose increase, then every 3 to 6 months. Halve the dose if potassium is above 5.5 mmol/L; stop if above 6.0 mmol/L.

Stopping. No taper. Hold on sick days.

Common prescribing errors. Giving with potassium supplements or an angiotensin converting enzyme inhibitor without monitoring; using the fixed combination tablet and adding another thiazide; starting at 10 mg or more in older adults; omitting potassium checks.