Potassium-sparing diuretics (K+- sparing diuretics) / thiazide diuretics (thiazides).

Each tablet contains 25mg spironolactone BP and 25mg hydroflumethiazide BP Each tablet contains 50mg spironolactone BP and 50mg hydroflumethiazide BP

Buff, film coated tablets engraved “SEARLE 101” on one side. Buff, film coated tablets engraved “SEARLE 180” on one side.

Congestive cardiac failure.

Administration of Aldactide once daily with a meal is recommended.

Most patients will require an initial dosage of 100mg spironolactone daily. The dosage should be adjusted as necessary and may range from 25mg to 200mg spironolactone daily.

Although clinical trials using Aldactide have not been carried out in children, as a guide, a daily dosage providing 1.5 to 3mg of spironolactone per kilogram body weight given in divided doses, may be employed.

It is recommended that treatment is started with the lowest dose and titrated upwards as required to achieve maximum benefit. Care should be taken with severe hepatic and renal impairment which may alter drug metabolism and excretion.

Aldactide is contraindicated in patients with anuria, acute renal insufficiency, rapidly deteriorating or severe impairment of renal function, hyperkalaemia, significant hypercalcaemia, Addison's disease and in patients who are hypersensitive to spironolactone, thiazide diuretics or to other sulphonamide derived drugs.

Aldactide should not be administered with other potassium conserving diuretics and potassium supplements should not be given routinely with Aldactide as hyperkalemia may be induced.

Warnings

Sulphonamide derivatives including thiazides have been reported to exacerbate or activate systemic lupus erythematosus.

Precautions

Fluid and electrolyte balance: Fluid and electrolyte status should be regularly monitored particularly in the elderly, in those with significant renal and hepatic impairment, and in patients receiving digoxin and drugs with pro-arrhythmic effects.

Hyperkalaemia may occur in patients with impaired renal function or excessive potassium intake and can cause cardiac irregularities which may be fatal. Should hyperkalaemia develop Aldactide should be discontinued, and if necessary, active measures taken to reduce the serum potassium to normal. . (See 4.3 Contraindications)

Hypokalaemia may develop as a result of profound diuresis, particularly when Aldactide is used concomitantly with loop diuretics, glucocorticoids or ACTH.

Hyponatraemia may be induced especially when Aldactide is administered in combination with other diuretics.

Hepatic impairment: Caution should be observed in patients with acute or severe liver impairment as vigorous diuretic therapy may precipitate encephalopathy in susceptible patients. Regular estimation of serum electrolytes is essential in such patients.

Reversible hyperchloraemic metabolic acidosis usually in association with hyperkalaemia has been reported to occur in some patients with decompensated hepatic cirrhosis, even in the presence of normal renal function.

Urea and uric acid: Reversible increases in blood urea have been reported, particularly accompanying vigorous diuresis or in the presence of impaired renal function.

Thiazides may cause hyperuricaemia and precipitate attacks of gout in some patients.

Diabetes mellitus: Thiazides may aggravate existing diabetes and the insulin requirements may alter. Diabetes mellitus which has been latent may become manifest during thiazide administration.

Hyperlipidaemia: Caution should be observed as thiazides may raise serum lipids.

Spironolactone has been reported to increase serum digoxin concentration and to interfere with certain serum digoxin assays. In patients receiving digoxin and spironolactone the digoxin response should be monitored by means other than serum digoxin concentrations, unless the digoxin assay used has been proven not to be affected by spironolactone therapy. If it proves necessary to adjust the dose of digoxin, patients should be carefully monitored for evidence of enhanced or reduced digoxin effect. Potentiation of the effect of antihypertensive drugs occurs and their dosage may need to be reduced when Aldactide is added to the treatment regime and then adjusted as necessary. Since ACE inhibitors decrease aldosterone production they should not routinely be used with Aldactide, particularly in patients with marked renal impairment.

As carbenoxolone may cause sodium retention and thus decrease the effectiveness of Aldactide , concurrent use should be avoided.

Non-steroidal anti-inflammatory drugs may attentuate the natriuretic efficacy of diuretics due to inhibition of intrarenal synthesis of prostaglandins.

Concurrent use of lithium and thiazides may reduce lithium clearance leading to intoxication.

Spironolactone and thiazides may reduce vascular responsiveness to noradrenaline. Caution should be exercised in the management of patients subjected to regional or general anaesthesia while they are being treated with Aldactide.

Concomitant use of aldactide with other potassium-sparing diuretics, ACE inhibitors, angiotensin II antagonists, aldosterone blockers, potassium supplements, a diet rich in potassium, or salt substitutes containing potassium, may lead to severe hyperkalaemia.

In fluorimetric assays, spironolactone may interfere with the estimation of compounds with similar flourescence characteristics.

Spironolactone has been shown to increase the half-life of digoxin.

Aspirin, indometacin, and mefanamic acid have been shown to attenuate the diuretic effect of spironolactone.

Spironolactone enhances the metabolism of antipyrine.

Spironolactone can interfere with assays for plasma digoxin concentrations

The absorption of a number of drugs including thiazides is decreased when co-administered with colestyramine and colestipol.

Thiazide co-administered with calcium and/or vitamin D may increase the risk of hypercalcaemia. Thiazides may delay the elimination of quinidine.

Gynaecomastia may develop in association with the use of spironolactone. Development appears to be related to both dosage level and duration of therapy and is normally reversible when the drug is discontinued. In rare instances some breast enlargement may persist.

The following adverse events have been reported in association with spironolactone therapy:

Body as a Whole: malaise

Endocrine Disorders: benign breast neoplasm, breast pain

Gastrointestinal Disorders: gastrointestinal disturbances, nausea

Hematologic Disorders: leukopenia (including agranulocytosis), thrombocytopenia

Liver Disorders: hepatic function abnormal

Metabolic and Nutritional Disorders: electrolyte disturbances, hyperkalemia

Musculoskeletal Disorders: leg cramps

Nervous System Disorders: dizziness

Psychiatric Disorders: changes in libido, confusion

Reproductive Disorders: menstrual disorders

Skin and Appendages: alopecia, hypertrichosis, pruritus, rash, urticaria,

Urinary System Disorders: acute renal failure

The following isolated adverse event has been reported in association with spironolactone therapy:

Skin and Appendages: Stevens Johnson Syndrome

Adverse reactions reported in association with thiazides include: gastrointestinal upsets, skin rashes, photosensitivity, blood dyscrasias, raised serum lipids, aplastic anaemia, purpura muscle cramps, weakness, restlessness, headache, dizziness, vertigo, jaundice, orthostatic hypotension, impotence, paraesthesia, and rarely pancreatitis, necrotising vasculitis and xanthopsia. Rarely hypercalcaemia has been reported in association with thiazides, usually in patients with pre-existing metabolic bone disease or parathyroid dysfunction.

Pharmacia Limited

(POM)

12 March 2009