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Aldactone 25mg Tablets

Last Updated on eMC 06-Oct-2014 View changes  | Pfizer Limited Contact details

1. Name of the medicinal product

Aldactone 25mg

2. Qualitative and quantitative composition

Each tablet contains 25mg spironolactone BP

3. Pharmaceutical form

Aldactone 25mg tablets are buff, film coated tablets engraved “SEARLE 39” on one side.

4. Clinical particulars
4.1 Therapeutic indications

• Congestive cardiac failure

• Hepatic cirrhosis with ascites and oedema.

• Malignant ascites

• Nephrotic syndrome.

• Diagnosis and treatment of primary aldosteronism.

4.2 Posology and method of administration

Administration of Aldactone once daily with a meal is recommended.

Adults

Congestive cardiac failure with oedema

For 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 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 (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 Hyperkalemia in Patients with Severe Heart Failure for advice on monitoring serum potassium and serum creatinine.

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.

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 Aldactone tablets.

4.3 Contraindications

Spironolactone is contraindicated in patients with the following:

• acute renal insufficiency, significant renal compromise, anuria

• Addison's disease or other conditions associated with hyperkalaemia

• hyperkalaemia

• 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 hyperkalaemia may be induced.

4.4 Special warnings and precautions for use

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.(See 4.3 Contraindications)

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 other drugs known to cause hyperkalaemia, 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.

Hyperkalaemia in Patients with Severe Heart Failure

Hyperkalaemia 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. (See section 4.2 Posology and method of administration; Severe heart failure).

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant use of drugs known to cause hyperkalaemia with spironolactone may result in severe hyperkalaemia.

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

4.6 Pregnancy and lactation

Pregnancy

Spironolactone 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.

Lactation

Metabolites of spironolactone have been detected in breast milk. If use of Aldactone is considered essential, an alternative method of infant feeding should be instituted.

4.7 Effects on ability to drive and use machines

Somnolence and dizziness have been reported to occur in some patients. Caution is advised when driving or operating machinery until the response to initial treatment has been determined.

4.8 Undesirable effects

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:

General disorders and administration site conditions: malaise

Neoplasms benign, malignant and unspecified (including cysts and polyps): benign breast neoplasm

Gastrointestinal disorders: gastrointestinal disturbances, nausea

Blood and lymphatic system disorders: leukopenia (including agranulocytosis), thrombocytopenia

Hepatobiliary disorders: hepatic function abnormal

Metabolism and nutrition disorders: electrolyte disturbances, hyperkalaemia

Musculoskeletal disorders: leg cramps

Nervous system disorders: dizziness

Psychiatric disorders: changes in libido, confusion

Reproductive system and breast disorders: menstrual disorders, breast pain

Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), alopecia, hypertrichosis, pruritus, rash, urticaria,

Renal and urinary disorders: acute renal failure

4.9 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.

5. Pharmacological properties
5.1 Pharmacodynamic 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.

Severe heart failure: The Randomized Aldactone Evaluation Study (RALES) was a multinational, double-blind study in 1663 patients with an ejection fraction of ≤ 35%, a history of New York Heart Association (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% to 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.

5.2 Pharmacokinetic properties

Spironolactone is well absorbed orally and is principally metabolised to active metabolites: sulphur containing metabolites (80%) and partly canrenone (20%). Although the plasma half life of spironolactone itself is short (1.3 hours) the half lives of the active metabolites are longer (ranging from 2.8 to 11.2 hours). Elimination of metabolites occurs primarily in the urine and secondarily through biliary excretion in the faeces.

Following the administration of 100 mg of spironolactone daily for 15 days in non-fasted healthy volunteers, time to peak plasma concentration (tmax), peak plasma concentration (Cmax), and elimination half-life (t1/2) for spironolactone is 2.6 hr., 80 ng/ml, and approximately 1.4 hr., respectively. For the 7-alpha-(thiomethyl) spironolactone and canrenone metabolites, tmax was 3.2 hr. and 4.3 hr., Cmax was 391 ng/ml and 181 ng/ml, and t1/2 was 13.8 hr. and 16.5 hr., respectively.

The renal action of a single dose of spironolactone reaches its peak after 7 hours, and activity persists for at least 24 hours

5.3 Preclinical safety data

Carcinogenicity : Spironolactone has been shown to produce tumours in rats when administered at high doses over a long period of time. The significance of these findings with respect to clinical use is not certain. However the long term use of spironolactone in young patients requires careful consideration of the benefits and the potential hazard involved. Spironolactone 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.

6. Pharmaceutical particulars
6.1 List of excipients

Aldactone 25mg contain:

Calcium sulphate dihydrate, corn starch, polyvinyl pyrrolidone, magnesium stearate, felocofix peppermint, hypromellose, polyethylene glycol and opaspray yellow (contains E171 and E172).

6.2 Incompatibilities

None stated.

6.3 Shelf life

The shelf life of Aldactone tablets is 5 years.

6.4 Special precautions for storage

Store in a dry place below 30°C.

6.5 Nature and contents of container

Aldactone 25mg tablets may be packaged in the following containers:

Amber glass or plastic bottles containing 100 or 500 tablets.

HDPE containers of 50 or 1,000 tablets.

PVC/foil blister packs containing 100 or 500 tablets.

6.6 Special precautions for disposal and other handling

None

7. Marketing authorisation holder

Pfizer Limited

Ramsgate Road

Sandwich

Kent, CT13 9NJ

United Kingdom

8. Marketing authorisation number(s)

PL 00057/0928

9. Date of first authorisation/renewal of the authorisation

Aldactone 25mg tablets: 10 February 2002

10. Date of revision of the text

07/2014

11. Legal status

POM

AN 8_0

Company contact details

Pfizer Limited

Company image
Address

Ramsgate Road, Sandwich, Kent, CT13 9NJ

Fax

+44 (0)1304 656 221

Telephone

+44 (0)1304 616 161

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Active ingredients

spironolactone

Legal categories

POM - Prescription Only Medicine

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