SPIRONOLACTONE

Posology Adults The dosage should be determined individually depending on the condition and the degree of diuresis required. Dosage up to100 mg daily may be administered as a single dose or in divided doses. Oedema associated with congestive heart failure 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. 5 mg/dL (221 μmol/L). 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.

4 for advice on monitoring serum potassium and serum creatinine. Resistent Hypertension The starting dose for spironolactone should be 25mg daily in a single dose; the lowest effective dose should be found, very gradually titrating upwards to a dose of 100mg daily or more.

Nephrotic syndrome Usual dose is 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.

g. based on Na+/K+ ratio. If the response to 200 mg spironolactone within the first two weeks is not sufficient, furosemide is added and if necessary, the spironolactone dose is increased stepwise up to 400 mg per day. Maintenance dosage should be individually determined.

Diagnosis and treatment of primary aldosteronism If primary hyperaldosteronism is suspected, spironolactone is given at a dose of 100 – 150 mg, or up to 400 mg daily. In the event of rapid onset of a strong diuretic and antihypertensive effect, this is a clear indication of elevated aldosterone production.

In this case, 100 – 150 mg daily is administered for 3 – 5 weeks prior to surgery. If surgery is not an option, this dose is often sufficient to maintain blood pressure and potassium concentration at normal levels. In exceptional cases, higher doses are necessary, but the lowest possible dosage should be found.

Paediatric population Initial daily dosage should provide 1-3 mg of spironolactone per kilogram body weight, given in divided doses. 4). The tablet may be ground or crushed and then suspended in water to make it easier to take. Children should only be treated under guidance of a paediatric specialist.

2). The Elderly It is recommended that treatment is started at the lowest possible dose, then titrated with higher doses until the optimum effect is achieved. Caution is required, in particular in renal dysfunction. Method of administration The tablets should be taken with meals.

Daily dosages in excess of 100 mg should be given in several divided doses.

The undesirable effects are dependent on dose and duration of treatment. The most common adverse effects are hyperkalaemia (9%), disorders of the reproductive system and breasts, including gynaecomastia, reported in 13% of patients (at a dose of less than 100 mg).

Gynaecomastia appears to be related to both dosage level and duration of therapy and is usually reversible once treatment stops. Other very common undesirable effects include headache, digestive system disorders, diarrhoea, fatigue and drowsiness.

The undesirable effects below are classified in accordance with the following frequencies: Very common (≥1/10), Common (1/100, < 1/10), Uncommon ( ≥1/ 1,000, <1/100), Rare ( ≥1/10,000, <1/1,000), Very rare (< 1/10,000), not known (cannot be estimated from the available data) Neoplasms benign, malignant and unspecified (including cysts and polyps) Very rare: breast cancer Blood and lymphatic system disorders Rare: thrombocytopenia, eosinophilia, leukopenia (including agranulocytosis) Immune system disorders Rare: eczema (type 1 allergic reaction), hypersensitivity Endocrine disorders Not known: slight androgenic effects, including hirsutism.

4) Common: hyponatraemia (in particular during combined intensive therapy with thiazide diuretics), hyperkalaemia in (1) patients with severe renal dysfunction, (2) patients receiving treatment with ACE inhibitors or potassium chloride, (3) the elderly, and (4) diabetic patients Uncommon: acidity of the blood (acidosis) in patients with liver problems Rare: insufficient fluid in the tissues (dehydration), porphyria, temporary increase in nitrogen levels in the blood and urine, hyperuricemia (may lead to gout in predisposed patients) Not known: reversible hyperchloraemic metabolic acidosis – usually accompanied by hyperkalaemia has been reported in some patients with decompensated hepatic cirrhosis, even where renal function was normal.

Psychiatric disorders Uncommon: confusion Nervous system disorders Very common: headache Common: weakness, lethargy in patients with cirrhosis, tingling (paraesthesia) Rare: paralysis, paraplegia of the limbs due to hyperkalaemia Not known: dizziness, ataxia Vascular disorders Very rare: inflammation of the vessel walls (vasculitis) Not known: mild hypotension Gastrointestinal disorders Very common: indigestion, diarrhoea Common: nausea and vomiting Very rare: gastric inflammation, gastric ulcers, intestinal haemorrhage, cramps Hepatobiliary disorders Very rare: hepatitis Skin and subcutaneous tissue disorders Uncommon: skin rash, urticaria, erythema, chloasma, pruritus, exanthema Very rare: alopecia, eczema, erythema annulare centrifugum (EAC), hypertrichosis Not known: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), Pemihigoid Musculoskeletal and connective tissue disorders Uncommon: muscle spasms, leg cramps Very rare: systemic lupus erythematosus (SLE), Osteomalacia Renal and urinary disorders Uncommon: elevated serum creatinine levels Very rare: acute renal failure Reproductive system and breast disorders Very common: Men: reduced libido, erectile dysfunction, impotence, enlargement of the mammary glands (gynaecomastia); Women: breast disorders, tenderness of the breasts, menstrual disorders, deepening of the voice (in many cases irreversible) Common: Women: changes in vaginal secretions, reduced libido, absence of periods (amenorrhoea), post-menopausal bleeding General disorders and administration site conditions Very common: fatigue, drowsiness common: malaise Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

Fluid and electrolyte balance During long-term therapy with spironolactone, fluid and and electrolyte status should be regularly monitored, especially in elderly patients. 3). During treatment with spironolactone, severe hyperkalaemia can occur, which may result in cardiac arrest (sometimes fatal) in patients with severe renal dysfunction who are receiving concomitant treatment with potassium supplements.

Hyperkalaemia may be accompanied by paraesthesia, weakness, mild paralysis or muscle spasms and is difficult to distinguish clinically from hypokalaemia. ECG changes may be the first sign of disturbed potassium balance, although hyperkalaemia is not always accompanied by an abnormal ECG.

Combination with potent potassium-sparing diuretics such as triamterene and amiloride is contra-indicated in order to prevent hyperkalaemia and care should be taken to avoid administration of extra potassium Concomitant use of medicinal products known to cause hyperkalaemia with spironolactone may result in severe hyperkalaemia.

Impaired renal function Potassium levels should be monitored regularly in patients with impaired renal function, including diabetic microalbuminuria. The risk of hyperkalaemia increases with decreasing renal function. Therefore, these patients should be treated with caution.

Severe hepatic insufficiency Caution is required in patients with hepatic disorders due to the risk of hepatic coma. Carcinogenicity Animal studies have shown that at high doses and after long-term use, spironolactone induces tumours.

The significance of these data for clinical application is unclear. However, the benefits of therapy should be weighed against the possible long-term harm before initiating long-term use of spironolactone in young patients. Lactose This medicine contains lactose.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Paediatric population Potassium-sparing diuretics should be used with caution in hypertensive paediatric patients with mild renal insufficiency because of the risk of hyperkalaemia.

3).

1. 0 mmol/L) at initiation • Concomitant use of potassium-sparing diuretics (including eplerenone) or potassium-supplements, or dual-RAAS blockade with the combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB) Spironolactone is contraindicated in paediatric patients with moderate to severe renal impairment.