- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
- 11. Legal status
Congestive cardiac failure with oedemaFor management of oedema an initial daily dose of 100 mg of spironolactone administered in either single or divided doses is recommended, but may range from 25 mg to 200 mg daily. Maintenance dose should be individually determined.
Severe heart failure (New York Heart Association Class III-IV)Based on the Randomized Aldactone Evaluation Study (RALES: see also section 5.1), treatment in conjunction with standard therapy should be initiated at a dose of spironolactone 25 mg once daily if serum potassium is ≤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. See section 4.4 for advice on monitoring serum potassium and serum creatinine.
Hepatic cirrhosis with ascites and oedemaIf urinary Na+/K+ ratio is greater than 1.0, 100 mg/day. If the ratio is less than 1.0, 200 mg/day to 400 mg/day. Maintenance dosage should be individually determined.
Malignant ascitesInitial dose usually 100 mg/day to 200 mg/day. In severe cases the dosage may be gradually increased up to 400 mg/day. When oedema is controlled, maintenance dosage should be individually determined.
Nephrotic syndromeUsual dose 100 mg/day to 200 mg/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 aldosteronismAldactone 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 400 mg for 3 to 4 weeks. Correction of hypokalaemia and hypertension provides presumptive evidence for the diagnosis of primary hyperaldosteronism.Short test: Aldactone is administered at a daily dosage of 400 mg for 4 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 100 mg to 400 mg 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.
ElderlyIt 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.
Paediatric populationInitial daily dosage should provide 1-3 mg of spironolactone per kilogram body weight given in divided doses. Dosage should be adjusted on the basis of response and tolerance (see sections 4.3 and 4.4). Children should only be treated under guidance of a paediatric specialist. There is limited paediatric data available (see sections 5.1 and 5.2).
Fluid and electrolyte balanceFluid 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 (see section 4.3).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, angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs, angiotensin II antagonists, aldosterone blockers, heparin, low molecular weight heparin or other drugs or conditions known to cause hyperkalaemia, potassium supplements, a diet rich in potassium or salt substitutes containing potassium, may lead to severe hyperkalaemia.
UreaReversible increases in blood urea have been reported in association with Aldactone therapy, particularly in the presence of impaired renal function.
Hyperkalaemia in Patients with Severe Heart FailureHyperkalaemia 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 1 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 (see section 4.2).
Paediatric populationPotassium-sparing diuretics should be used with caution in hypertensive paediatric patients with mild renal insufficiency because of the risk of hyperkalaemia. (Spironolactone is contraindicated for use in paediatric patients with moderate or severe renal impairment; see section 4.3).
PregnancySpironolactone or its metabolites may cross the placental barrier. With spironolactone, feminisation has been observed in male rat foetuses. The use of Aldactone in pregnant women requires that the anticipated benefit be weighed against the possible hazards to the mother and foetus.
Breast-feedingMetabolites of spironolactone have been detected in breast milk. If use of Aldactone is considered essential, an alternative method of infant feeding should be instituted.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
Mechanism of actionSpironolactone, as a competitive aldosterone antagonist, increases sodium excretion whilst reducing potassium loss at the distal renal tubule. It has a gradual and prolonged action.
Severe Heart FailureRALES was a multinational, double-blind study in 1663 patients with an ejection fraction of ≤35%, a history of NYHA Class IV heart failure within 6 months, and Class III-IV heart failure at the time of randomization. All patients were taking a loop diuretic, 97% were taking an ACE inhibitor and 78% were on digoxin (at the time this trial was conducted, b-blockers were not widely used to treat heart failure and only 15% were treated with a b-blocker). Patients with a baseline serum creatinine of >2.5 mg/dL or a recent increase of 25% or with a baseline serum potassium of >5.0 mEq/L were excluded. Patients were randomized 1:1 to spironolactone 25 mg orally once daily or matching placebo. Patients who tolerated 25 mg once daily had their dose increased to 50 mg once daily as clinically indicated. Patients who did not tolerate 25 mg once daily had their dosage reduced to 25 mg every other day. The primary endpoint for RALES was time to all-cause mortality. RALES was terminated early, after a mean follow-up of 24 months, because of significant mortality benefit detected on a planned interim analysis. Spironolactone reduced the risk of death by 30% compared to placebo (p<0.001; 95% confidence interval 18% - 40%). Spironolactone also significantly reduced the risk of cardiac death, primarily sudden death and death from progressive heart failure as well as the risk of hospitalization for cardiac causes. Changes in NYHA class were more favorable with spironolactone. Gynaecomastia or breast pain was reported in 10% of men who were treated with spironolactone, as compared with 1% of men in the placebo group (p<0.001). The incidence of serious hyperkalaemia was low in both groups of patients.
Paediatric populationThere is a lack of substantive information from clinical studies on spironolactone in children. This is a result of several factors: the few trials that have been performed in the paediatric population, the use of spironolactone in combination with other agents, the small numbers of patients evaluated in each trial and the different indications studied. The dosage recommendations for paediatrics are based upon clinical experience and case studies documented in the scientific literature.
Paediatric populationThere are no pharmacokinetic data available in respect of use in paediatric population. The dosage recommendations for paediatrics are based upon clinical experience and case studies documented in the scientific literature.
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