bendroflumethiazide
Thiazide diuretic· Brands: AprinoxPO
Mechanism of action
Bendroflumethiazide inhibits the sodium-chloride cotransporter in the distal convoluted tubule of the kidney, thereby increasing urinary excretion of sodium and water. This reduces plasma volume and cardiac output initially, and with long-term use may reduce peripheral vascular resistance, contributing to its antihypertensive effect. It also enhances excretion of potassium and magnesium.
Pharmacokinetics
Orally administered bendroflumethiazide is well absorbed from the gastrointestinal tract. It is extensively bound to plasma proteins, undergoes hepatic metabolism, and is excreted primarily in the urine. The diuretic effect usually begins within 2 hours, peaks at 4 to 6 hours, and can persist up to 24 hours, allowing once-daily dosing. Elimination half-life is approximately 6 to 9 hours.
Indications & dosing
Hypertension
Starting dose 2.5 mg once daily; adjust as needed.
- adult · PO: 2.5–5 mg once daily · Starting dose 2.5 mg once daily; adjust as needed.
Oedema
For oedema, give in the morning; may be increased to 20 mg daily if needed.
- adult · PO: 5–10 mg once daily · For oedema, give in the morning; may be increased to 20 mg daily if needed.
Heart failure (mild to moderate)off-label
Used as an adjunct in mild heart failure; monitor renal function and electrolytes.
- adult · PO: 2.5–5 mg once daily · Used as an adjunct in mild heart failure; monitor renal function and electrolytes.
Contraindications & precautions
- Anuria · Thiazide diuretics are ineffective and potentially harmful.
- Hypersensitivity to bendroflumethiazide or other thiazides/sulfonamides · Cross-sensitivity with sulfonamides.
- Severe hepatic impairment or hepatic coma · May precipitate hepatic encephalopathy.
- Severe renal impairment (creatinine clearance <30 mL/min) · Thiazides are ineffective; loop diuretics preferred.
- Gout · Thiazides increase serum uric acid and may precipitate gout attacks.
- Diabetes mellitus · Thiazides may worsen glycaemic control.
- Monitor serum potassium and renal function regularly.
- Use with caution in patients with gout or diabetes; may worsen these conditions.
- Avoid in pregnancy unless essential; thiazides may reduce placental perfusion.
- Caution in hepatic impairment; may precipitate hepatic encephalopathy.
- Ensure adequate hydration to prevent dehydration and electrolyte disturbances.
- Caution when used with other drugs that prolong the QT interval due to hypokalaemia.
Adverse effects
- Hypokalaemia
- Hyponatraemia
- Hyperuricaemia
- Hyperglycaemia
- Hypercalcaemia
- Postural hypotension
- Pancreatitisserious
- Blood dyscrasias (e.g. thrombocytopenia, leucopenia)serious
- Photosensitivity
Interactions
- lithiummajorAvoid this combination if possible. If co-prescription is necessary, monitor serum lithium levels frequently, for example every 3 to 5 days initially and then weekly until stable. Reduce the lithium dose as needed and monitor for signs of toxicity, including neurological and gastrointestinal symptoms. Advise the patient to maintain adequate fluid intake and to seek medical attention if symptoms develop. Consider alternative diuretics, such as loop diuretics, which have a smaller effect on lithium clearance, but regular monitoring is still advised.
Renal & hepatic adjustment
- eGFR 0–29: Thiazide diuretics are ineffective in severe renal impairment; consider a loop diuretic instead. (avoid)
- eGFR 30–300: No dosage adjustment required, but monitor renal function and electrolytes periodically.
- Hepatic impairment (mild): No dosage adjustment required; monitor electrolytes and liver function as clinically indicated.
- Hepatic impairment (moderate): Use with caution; monitor fluid balance, electrolytes and signs of hepatic encephalopathy.
- Hepatic impairment (severe): Avoid use; thiazides can precipitate hepatic encephalopathy due to electrolyte disturbances. (avoid)
Monitoring, pregnancy & toxicity
- Blood pressure · Regularly during dose titration and then at routine intervals.
- Serum potassium · Baseline and periodically, especially in patients at risk of hypokalaemia.
- Serum sodium · Baseline and periodically.
- Renal function (serum creatinine, eGFR) · Baseline and periodically.
- Plasma glucose · Baseline and periodically in patients with diabetes.
- Serum uric acid · Baseline and periodically in patients with a history of gout.
- Pregnancy: Avoid use in pregnancy; thiazides reduce placental perfusion and are not first-line for hypertension in pregnancy. Consider alternatives such as labetalol or nifedipine.
- Toxicity: Hypokalaemia and other electrolyte disturbances (e.g. hyponatraemia) · Replace potassium and correct other electrolyte imbalances; monitor serum electrolytes closely.
- Toxicity: Hypotension · Fluid resuscitation with intravenous saline; use vasopressors if hypotension persists.
- Toxicity: Dehydration · Provide oral or intravenous rehydration; monitor fluid balance and renal function.
- Toxicity: Metabolic alkalosis · Correct fluid and electrolyte deficits; monitor acid-base balance and adjust therapy accordingly.
Clinical notes
Bendroflumethiazide is used to treat hypertension, heart failure, and oedema associated with renal or hepatic disease. It is often a first-line thiazide diuretic for uncomplicated hypertension. Electrolyte imbalances, particularly hypokalaemia and hyponatraemia, should be monitored, and caution is advised in patients with gout, diabetes, or renal impairment. It may be used in fixed-dose combinations with other antihypertensives. Dose in hypertension is typically 2.5 mg once daily; in oedema, up to 10 mg daily. Prescribers should check local guidelines and formulary.
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BNF; local formulary