Thiazide diuretics (thiazides).

Bendrofluazide [bendroflumethiazide]

Each Aprinox Tablet 2.5 mg contains bendroflumethiazide 2.5 mg Each Aprinox Tablet 5 mg contains bendroflumethiazide 5 mg

White tablets

For the treatment of oedema and hypertension. Aprinox may also be used to suppress lactation

For oral administration.

Adults:

Oedema

Initially, 5-10 mg in the morning, daily or on alternate days; maintenance dose 5-10 mg one to three times weekly.

Hypertension

The usual dose is 2.5 mg taken in the morning. Higher doses are rarely necessary

Suppression of lactation

5 mg in the morning and 5 mg at midday for about five days.

Dosage in children may be up to 400 mcg/kg bodyweight initially, reducing to 50-100 mcg/kg bodyweight daily for maintenance.

The dosage of thiazide diuretics may need to be reduced in the elderly, particularly when renal function is impaired, because of the possibility of electrolyte imbalance.

Aprinox is contra-indicated in patients with known hypersensitivity to thiazides; refractory hypokalaemia, hyponatraemia, hypercalcaemia; severe renal and hepatic impairment; symptomatic hyperuricaemia and Addison's disease

Bendroflumethiazide should be used with caution in patients with mild to moderate hepatic or renal impairment (avoid if severe). Renal function should be continuously monitored during thiazide therapy. Thiazide diuretics may exacerbate or activate systemic lupus erythematosus in susceptible patients.

All thiazide diuretics can produce a degree of electrolyte imbalance, especially in patients with renal or hepatic impairment or when dosage is high or prolonged. Serum electrolytes should be checked for abnormalities, particularly hypokalaemia, and the latter corrected by the addition of a potassium supplement to the regimen. Aggravates diabetes and gout; increased risk of hypomagnesaemia in alcoholic cirrhosis.

Regular ongoing monitoring and blood tests are to be performed in elderly patients and patients who are on long term treatment with bendroflumethiazide.

This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malsorption should not take this medicine.

Sensitivity to digitalis glycosides may be increased by the hypokalaemic effect of concurrent bendroflumethiazide. Patients should be observed for signs of digitalis intoxication, in particular arrhythmias, and if these appear, the dosage of the digitalis glycoside should be temporarily reduced and a potassium supplement given to restore stability.

Serum lithium concentrations may be increased by concurrent use of thiazide diuretics.

Non-steroidal anti-inflammatory agents may blunt the diuretic and antihypertensive effects of thiazide diuretics. Diuretics may increase the risk of nephrotoxicity of NSAIDs.

Xanthines, beta-agonists, ACTH, corticosteroids, acetazolamide and carbenoxolone may exacerbate the hypokalaemia associated with thiazide use. Thiazide diuretics may enhance the neuromuscular blocking effects of the non-depolarising muscle relaxants, e.g. tubocurarine.

Thiazides may enhance the effects of antihypertensive agents, while postural hypotension associated with therapy may be enhanced by concomitant ingestion of alcohol, barbiturates or opioids.

Concomitant use of carbamazepine may increase the risk of hyponatraemia.

There is an increased risk of hyponatraemia if thiazides are given with amphotericin.

The risk of hypercalcaemia is increased by the concomitant intake of calcium salts or vitamin D preparations.

Concomitant use with cisplatin can lead to an increased risk of nephrotoxicity and ototoxicity.

The cardiac toxicity of disopyramide, amiodarone, flecainide and quinidine is increased if hypokalaemia occurs. The action of lidocaine and mexiletine is antagonised by hypokalaemia.

There is an increased risk of hyponatraemia when thiazides are used concomitantly with aminoglutethimide. Thiazides can cause an increased risk of hypercalcaemia with toremifene.

Colestipol and colestyramine may reduce the absorption of thiazide diuretics and should therefore be given 2 hours prior to, or after the ingestion of bendroflumethiazide.

Calcium-channel blockers and moxisylyte can cause an enhanced hypotensive effect.

There is an increased risk of postural hypotension with tricyclic antidepressants. There may also be an increased risk of hypokalaemia if thiazides are given with reboxetine. Concomitant use with monoamine oxidase inhibitors (MAOIs), baclofen or tizanidine may also give an increased hypotensive effect.

Oestrogens and combined oral contraceptives may antagonise the diuretic effect of thiazides.

There is an increased risk of first-dose hypotensive effect of post-synaptic alpha-blockers such as prazosin.

Hypokalaemia increases the risk of ventricular arrhythmias with pimozide or thioridazine, therefore, concomitant use should be avoided. Hypokalaemia or other electrolyte imbalance also increases the risk of ventricular arrhythmias with terfenadine.

Bendroflumethiazide may interfere with a number of laboratory tests, including estimation of serum protein-bound iodine and tests of parathyroid function.

All thiazide diuretics can produce a degree of electrolyte imbalance, e.g. hypokalaemia.

Thiazide diuretics may raise the serum uric acid levels with subsequent exacerbation of gout in susceptible subjects.

Thiazide diuretics sometimes lower carbohydrate tolerance and the insulin dosage of the diabetic patient may require adjustment. Care is necessary when bendroflumethiazide is administered to those with a known predisposition to diabetes.

Postural hypotension and mild gastro-intestinal effects; hypokalaemia, hypomagnesaemia, hyponatraemia, hypercalcaemia, hypochloraemic alkalosis, hyperuricaemia, gout, hyperglycaemia, and altered plasma lipid concentration.

Less commonly, rashes, photosensitivity; blood disorders (including neutropenia and thrombocytopenia – when given in late pregnancy neonatal thrombocytopenia has been reported); pancreatitis, intrahepatic cholestasis, and hypersensitivity reactions (including pneumonitis, pulmonary oedema, severe skin reactions) also reported.

Rarely, blood dyscrasias, including agranulocytosis, aplastic anaemia, thrombocytopenia and leucopenia, and pancreatitis have been reported with long term therapy. Skin rashes and impotence (reversible on withdrawal of treatment) have occasionally been reported.

Sovereign

(POM)

30 June 2009