Bendroflumethiazide

Bendroflumethiazide is a thiazide diuretic used in hypertension and in oedema from heart failure, liver or kidney disease. In hypertension, 2.5 mg daily is as effective as larger doses with fewer metabolic effects. It is cheap and still common in East African formularies, although hydrochlorothiazide and chlorthalidone are more often used in other settings.

Classification. Thiazide diuretic (benzothiadiazine).

Mechanism. Blocks the sodium chloride cotransporter in the distal convoluted tubule, increasing sodium, chloride and water excretion; potassium and magnesium are lost; calcium excretion falls.

Pharmacodynamics. Diuresis begins within 2 hours, peaks at 4 to 6 hours, and lasts 12 to 18 hours. Blood pressure effect builds over 2 to 4 weeks.

Pharmacokinetics. Well absorbed; about 70% is bound to plasma protein. Half life 3 to 4 hours (effect lasts longer). Metabolised in the liver; about 30% excreted unchanged in urine.

Hypertension, adult. 2.5 mg once daily in the morning; maximum 2.5 mg daily (higher doses add metabolic harm without extra blood pressure effect).

Oedema, adult.

• Start 5 to 10 mg once daily in the morning, or on alternate days.

• Maintenance 5 to 10 mg once to 3 times a week.

• Maximum 10 mg daily.

Children (oedema, specialist). Maintenance 50 to 100 micrograms/kg daily as a single morning dose; maximum 10 mg daily.

Contraindications. Refractory hyponatraemia, hypokalaemia or hypercalcaemia; symptomatic hyperuricaemia; Addison disease; anuria; severe hepatic impairment; hypersensitivity to sulphonamide derived drugs.

Warnings. Hyponatraemia, hypokalaemia, hypomagnesaemia, hyperuricaemia and gout, raised glucose and lipids; hypercalcaemia; non melanoma skin cancer risk with long use; acute angle closure glaucoma; may worsen hepatic encephalopathy.

Adverse effects. Dizziness, postural hypotension, hypokalaemia, hyponatraemia, erectile dysfunction, photosensitivity, gout, rarely pancreatitis.

Interactions. Lithium: toxicity. Digoxin: hypokalaemia raises toxicity. Non steroidal anti-inflammatory drugs: reduced effect and kidney injury. QT prolonging drugs: hypokalaemia raises arrhythmia risk. Corticosteroids and loop diuretics: more potassium loss. Antidiabetic drugs: may need higher doses.

Special groups.

• Pregnancy: avoid for hypertension; may reduce placental perfusion.

• Breastfeeding: small amounts enter milk; large doses can suppress lactation.

• Patients of African ancestry: good blood pressure response; first line with a calcium channel blocker.

• Older adults: use 2.5 mg or less; high risk of hyponatraemia.

• Kidney impairment: little effect at eGFR under 30 mL/min; use a loop diuretic.

• Liver impairment: use with care; watch electrolytes.

Formulations. Tablets 2.5 mg and 5 mg.

Administration. Oral, in the morning, with or without food.

Baseline. Blood pressure, sodium, potassium, calcium, creatinine and eGFR, glucose, urate.

Monitoring. Sodium, potassium and creatinine 1 to 2 weeks after starting or each dose increase, then every 6 to 12 months. Stop or reduce if sodium falls below 130 mmol/L or potassium below 3.0 mmol/L; correct potassium below 3.5 mmol/L. Weight in oedema.

Stopping. No taper. Hold on sick days with vomiting or diarrhoea.

Common prescribing errors. Using 5 to 10 mg for hypertension; giving at night; omitting early sodium and potassium checks; combining with lithium; using it when eGFR is under 30 mL/min.