| Composition |
| Each tablet contains 25mg, 50mg or 100mg spironolactone |
| Pharmacodynamics properties |
| Spironolactone, as a competitive aldosterone antagonist, increases sodium excretion whilst reducing potassium loss at the distal renal tubule. It has a gradual and prolonged action. |
| Therapeutic indications |
• Congestive cardiac failure
• Hepatic cirrhosis with ascites and oedema.
• Malignant ascites
• Nephrotic syndrome.
• Diagnosis and treatment of primary aldosteronism. |
| Side effect |
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:
Malaise, benign breast neoplasm, breast pain, gastrointestinal disturbances, nausea, leukopenia, hepatic function abnormal, electrolyte disturbances, hyperkalemia, leg cramps, dizziness, menstrual disorders, alopecia, hypertrichosis, pruritus, rash, urticaria, acute renal failure |
| Contraindication |
Spironolactone is contraindicated in patients with the following:
• acute renal insufficiency, anuria
• Addison's disease
• hyperkalemia
• hypersensitivity to spironolactone or to any of its excipients
• concomitant use of eplerenone or other potassium sparing diuretics
Spironolactone should not be administered concurrently with other potassium conserving diuretics and potassium supplements should not be given routinely with Spironolactone as hyperkalemia may be induced. |
| Warnings and 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 Hyperkalaemia may occur in patients with impaired renal function or excessive potassium intake and can cause cardiac irregularities.
Should hyperkalaemia develop Spironolactone should be discontinued, and if necessary, active measures taken to reduce the serum potassium to normal.
Hyponatremia may be induced, especially when Spironolactone 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 spironolactone 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 Spironolactone therapy, particularly in the presence of impaired renal function. |
| Pregnancy and lactation |
Pregnancy
Spironolactone or its metabolites may cross the placental barrier.
The use of Spironolactone in pregnant women requires that the anticipated benefit be weighed against the possible hazards to the mother and foetus.
Lactation
Metabolites of spironolactone have been detected in breast milk. If use of Spironolactone is considered essential, an alternative method of infant feeding should be instituted. |
| Drug interactions |
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.
Potentiation of the effect of antihypertensive drugs occurs and their dosage may need to be reduced when Spironolactone is added to the treatment regime and then adjusted as necessary. Since ACE inhibitors decrease aldosterone production they should not routinely be used with Spironolactone , particularly in patients with marked renal impairment.
As carbenoxolone may cause sodium retention and thus decrease the effectiveness of Spironolactone 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 Spironolactone .
Aspirin, indometacin, and mefanamic acid have been shown to attenuate the diuretic effect of spironolactone.
Spironolactone enhances the metabolism of antipyrine. |
| DOSAGE & ADMINISTRATION |
Administration of Spironolactone 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): 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.
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.
Spironolactone may be employed as an initial diagnostic measure to provide presumptive evidence of primary hyperaldosteronism while patients are on normal diets.
Long test: Spironolactone 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: Spironolactone is administered at a daily dosage of 400mg for four days. If serum potassium increases during Spironolactone
administration but drops when Spironolactone is discontinued, a presumptive diagnosis of primary hyperaldosteronism should be considered.
After the diagnosis of hyperaldosteronism has been established by more definitive testing procedures, Spironolactone may be administered at doses of 100mg-400mg daily in preparation for surgery. For patients who are considered unsuitable for surgery,
Spironolactone may be employed for long-term maintenance therapy at the lowest effective dosage determined for the individual patient.
Elderly
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.
Children
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 Spironolactone tablets. |
| Overdose |
| Acute overdosage may be manifested by drowsiness, mental confusion, nausea, vomiting, dizziness or diarrhoea. Hyponatraemia, or hyperkalaemia may be induced , but these effects are unlikely to be associated with acute overdosage. Symptoms of hyperkalaemia may manifest as paraesthesia, weakness, flaccid paralysis or muscle spasm and may be difficult to distinguish clinically from hypokalaemia. Electrocardiographic changes are the earliest specific signs of potassium disturbances. No specific antidote has been identified. Improvement may be expected after withdrawal of the drug. General supportive measures including replacement of fluids and electrolytes may be indicated. For hyperkalaemia, reduce potassium intake, administer potassium-excreting diuretics, intravenous glucose with regular insulin or oral ion-exchange resins. |
