competitive aldosterone antagonist

Spironolactone

Each tablet contains 25mg, 50mg or 100mg spironolactone BP

Aldactone 25mg tablets are buff, film coated tablets engraved “SEARLE 39” on one side. Aldactone 50mg tablets are white, film coated tablets engraved “SEARLE 916” on one side. Aldactone 100 mg tablets are buff, film coated tablets engraved “SEARLE 134” on one side.

• Congestive cardiac failure

• Hepatic cirrhosis with ascites and oedema.

• Malignant ascites

• Nephrotic syndrome.

• Diagnosis and treatment of primary aldosteronism.

Administration of Aldactone once daily with a meal is recommended.

Adults

Congestive cardiac failure with oedema

For management of oedema an initial dose of 100mg/day Of spironolactone administered in either a single or divided doses is recommended, but may range from 25 to 200 mg daily. Maintenance dose should be individually determined.

Patients with severe heart failure (NYHA Class III-IV): Based on the Randomized Aldactone Evaluation Study, treatment in conjunction with standard therapy should be initiated at a dose of spironolactone 25 mg once daily if serum is potassium 5.0 mEq/L and serum creatinine is 2.5 mg/dL. Patients who tolerate 25 mg once daily may have their dose increased to 50 mg once daily as clinically indicated. Patients who do not tolerate 25 mg once daily may have their dose reduced to 25 mg every other day. 

Hepatic cirrhosis with ascites and oedema.

If urinary Na+/K+ ratio is greater than 1.0, 100mg/day. If the ratio is less than 1.0, 200-400mg/day. Maintenance dosage should be individually determined.

Malignant ascites

Initial dose usually 100-200mg/day. In severe cases the dosage may be gradually increased up to 400mg/day. When oedema is controlled, maintenance dosage should be individually determined.

Nephrotic syndrome

Usual dose 100-200mg/day. Spironolactone has not been shown to be anti-inflammatory, nor to affect the basic pathological process. Its use is only advised if glucocorticoids by themselves are insufficiently effective.

Diagnosis and treatment of primary aldosteronism.

Aldactone may be employed as an initial diagnostic measure to provide presumptive evidence of primary hyperaldosteronism while patients are on normal diets.

Long test: Aldactone is administered at a daily dosage of 400mg for three to four weeks. Correction of hypokalaemia and of hypertension provides presumptive evidence for the diagnosis of primary hyperaldosteronism.

Short test: Aldactone is administered at a daily dosage of 400mg for four days. If serum potassium increases during Aldactone administration but drops when Aldactone is discontinued, a presumptive diagnosis of primary hyperaldosteronism should be considered.

After the diagnosis of hyperaldosteronism has been established by more definitive testing procedures, Aldactone may be administered at doses of 100mg-400mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, Aldactone may be employed for long-term maintenance therapy at the lowest effective dosage determined for the individual patient.

Initial daily dosage should provide 3mg of spironolactone per kilogram body weight given in divided doses. Dosage should be adjusted on the basis of response and tolerance. If necessary a suspension may be prepared by crushing Aldactone tablets.

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.

Spironolactone is contraindicated in patients with the following:

• acute renal insufficiency, significant renal compromise, anuria

• Addison's disease

• hyperkalemia

• hypersensitivity to spironolactone or to any of its excipients

• concomitant use of eplerenone or other potassium sparing diuretics

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

Fluid and electrolyte balance: Fluid and electrolyte status should be regularly monitored particularly in the elderly, in those with significant renal and hepatic impairment

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 Aldactone should be discontinued, and if necessary, active measures taken to reduce the serum potassium to normal.

Hyponatremia may be induced, especially when Aldactone is administered in combination with other diuretics.

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.

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

Urea: Reversible increases in blood urea have been reported in association with Aldactone therapy, particularly in the presence of impaired renal function.

Hyperkalemia in Patients with Severe Heart Failure

Hyperkalemia may be fatal. It is critical to monitor and manage serum potassium in patients with severe heart failure receiving spironolactone. Avoid using other potassium-sparing diuretics. Avoid using oral potassium supplements in patients with serum potassium > 3.5 mEq/L. The recommended monitoring for potassium and creatinine is one week after initiation or increase in dose of spironolactone, monthly for the first 3 months, then quarterly for a year, and then every 6 months. Discontinue or interrupt treatment for serum potassium > 5 mEq/L or for serum creatinine > 4 mg/dL.

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 Aldactone is added to the treatment regime and then adjusted as necessary. Since ACE inhibitors decrease aldosterone production they should not routinely be used with Aldactone, particularly in patients with marked renal impairment.

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

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

Spironolactone reduces 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 Aldactone.

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

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 & Appendages: Stevens Johnson Syndrome

Pharmacia Limited

(POM)

28 March 2012