Torsemide

Torsemide (torasemide) is a loop diuretic with excellent oral absorption, a longer duration than furosemide, and some potassium sparing effect through mild anti-aldosterone activity. It is used in oedema from heart failure, liver and kidney disease, and at low doses for hypertension. Its predictable absorption makes it useful in chronic heart failure with gut oedema. It is not stocked in many East African pharmacies.

Classification. Loop diuretic (pyridine sulphonylurea).

Mechanism. Blocks the sodium potassium 2 chloride cotransporter in the thick ascending limb of the loop of Henle; also antagonises aldosterone at the receptor level, and may reduce cardiac fibrosis.

Pharmacodynamics. Oral onset within 1 hour, peak at 1 to 2 hours, duration 6 to 8 hours (longer than furosemide). IV onset within 10 minutes. At low doses (2.5 to 5 mg) the diuretic effect is small and the antihypertensive effect remains.

Pharmacokinetics. Oral bioavailability 80 to 90% regardless of food or gut oedema. Half life about 3 to 4 hours (not much changed in kidney impairment, longer in liver disease). Metabolised by CYP2C9 in the liver; about 20% excreted unchanged in urine. Protein bound over 99%.

Oedema in heart failure, adult.

• Start 10 to 20 mg once daily in the morning.

• Double the dose every few days until the target weight is reached.

• Usual maintenance 10 to 40 mg daily; maximum 200 mg daily under specialist supervision.

Oedema in chronic kidney disease, adult. Start 20 mg once daily; increase by doubling to a maximum 200 mg daily.

Oedema in cirrhosis, adult. Start 5 to 10 mg once daily with spironolactone 100 mg to 200 mg daily; maximum 40 mg daily.

Hypertension, adult. 2.5 mg once daily; increase to 5 mg after 4 to 6 weeks; some labels allow up to 10 mg daily. Doses above 5 mg add little blood pressure effect.

Acute pulmonary oedema or fluid overload, adult (IV). 10 to 20 mg IV slowly over at least 2 minutes; repeat after 30 to 60 minutes if poor response; maximum 200 mg in 24 hours in specialist care.

Children. Not established.

Contraindications. Anuria; severe hypovolaemia; severe hypokalaemia or hyponatraemia; hepatic coma and precoma; hypersensitivity; sulphonylurea hypersensitivity (possible cross reaction); concurrent aminoglycosides in high dose.

Warnings. Hypokalaemia (less than furosemide), hyponatraemia, hypomagnesaemia, hypochloraemic alkalosis, hyperuricaemia, hyperglycaemia. Hypovolaemia and kidney injury. Ototoxicity (rare). Hepatic encephalopathy may be triggered. Urinary retention in prostate enlargement.

Adverse effects. Dizziness, headache, hypotension, cramps, hypokalaemia, hyponatraemia, nausea, rash, tinnitus (rare), gout.

Interactions. Aminoglycosides and cisplatin: ototoxicity and nephrotoxicity. Digoxin: hypokalaemia raises toxicity. Lithium: raised levels. Non steroidal anti-inflammatory drugs: blunt effect and kidney injury. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers: first dose hypotension. Rifampicin: lowers torsemide levels (CYP2C9 induction). Corticosteroids and amphotericin B: more potassium loss. Colestyramine and other bile acid resins reduce absorption.

Special groups.

• Pregnancy: avoid unless essential; no good data.

• Breastfeeding: no data; avoid.

• Patients of African ancestry: no dose change.

• Older adults: start at 5 mg; risk of dehydration and falls.

• Kidney impairment: no dose reduction because elimination is hepatic; higher doses are needed for effect.

• Liver impairment: half life is longer; start low and monitor potassium.

Formulations. Tablets 2.5, 5, 10, 20 mg; injection 10 mg/mL.

Administration. Oral once daily in the morning with or without food. IV: slow injection over at least 2 minutes.

Baseline. Weight, blood pressure, volume status, sodium, potassium, magnesium, creatinine and eGFR, urate, glucose.

Monitoring. Daily weight and fluid balance 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. Stop or reduce if symptomatic hypotension, creatinine rise over 30%, or sodium below 125 mmol/L.

Stopping. Taper to the lowest effective dose. Hold on sick days with vomiting or diarrhoea.

Common prescribing errors. Treating a 20 mg dose as equal to 20 mg of furosemide (20 mg of torsemide is about 40 mg of furosemide); omitting potassium checks; giving with rifampicin and not adjusting the dose; using more than 5 mg for hypertension.