This information is intended for use by health professionals
AdultsThe 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 failureFor 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.
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 potassium is ≤ 5.0 mEq/L and serum creatinine is ≤ 2.5 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. See Section 4.4 for advice on monitoring serum potassium and serum creatinine.
Resistent HypertensionThe 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 syndromeUsual 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.
Hepatic cirrhosis with ascites and oedemaThe starting dose is 100-200 mg per day, e.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 aldosteronismIf 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 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). 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. There is limited paediatric data available (see sections 5.1 and 5.2).
The ElderlyIt 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 administrationThe tablets should be taken with meals. Daily dosages in excess of 100 mg should be given in several divided doses.
Fluid and electrolyte balanceDuring long-term therapy with spironolactone, fluid and and electrolyte status should be regularly monitored, especially in elderly patients. Administration of spironolactone is not recommended if plasma potassium levels are elevated and contra-indicated in severe renal insufficiency (See Section 4.3) 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
Impaired renal functionPotassium 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 insufficiencyCaution is required in patients with hepatic disorders due to the risk of hepatic coma.
CarcinogenicityAnimal 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.
LactoseThis 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 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). Concomitant use of medicinal products known to cause hyperkalaemia with spironolactone may result in severe hyperkalaemia.
Interactions affecting spironolactone
Combinations causing hyperkalaemiaConcomitant 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) is contraindicated because of the risk of hyperkalaemia (see Section 4.3).The use of ACE inhibitors in combination with spironolactone may be accompanied by hyperkalaemia, especially in patients with impaired renal function. Concomitant use requires careful dosing and close monitoring of the electrolyte balance.Spironolactone and ciclosporin coadministration not recomended, as both increase serum potassium level and possible serious life-threatening interactions.
Heparin, low molecular weight heparin:Concomitant use of spironolactone with heparin or low molecular weight heparin may lead to severe hyperkalemia. Increased diuresis has been observed during concomitant use of spironolactone and heparin.
Non-Steroidal Anti-Inflammatory DrugsAcetyl salicylic acid and indomethacin may attenuate the diuretic action of spironolactone due to inhibition of intrarenal synthesis of prostaglandins. Hyperkalemia has been associated with the use of indomethacin in combination with potassium-sparing diuretics.
Interactions affecting other medicinal products
Anti-coagulantsSpironolactone reduces the effect of anticoagulants.
NoradrenalinSpironolactone reduces the vasoconstrictive effects of noradrenaline.
Anti-hypertensivesSpironolactone can potentiate the effect of antihypertensive agents. The dosage of such drugs, in particular ganglion-blocking drugs, can often be halved when spironolactone is added to the therapy.
LithiumDiuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.
DigoxinSpironolactone has been shown to increase the half-life of digoxin. This may result in increased serum digoxin levels and subsequent digitalis toxicity.
Alcohol, barbiturates or narcoticsPotentiation of orthostatic hypotension may occur.
CholestyramineHyperchloremic metabolic acidosis, frequently associated with hyperkalemia, has been reported in patients given spironolactone concurrently with cholestyramine.
Corticosteroids, ACTHIntensified electrolyte depletion, particularly hypokalemia, may occur.
Other forms of interaction
Ammonium ChlorideHyperchloremic metabolic acidosis, frequently associated with hyperkalemia, has been reported in patients given spironolactone concurrently with ammonium chloride (e.g. in liquorice).
Plasma Cortisone levelsSpironolactone interferes with Mattingly's fluorimetric method for determination of plasma cortisone levels. In addition to other medicinal products known to cause hyperkalaemia concomitant use of trimethoprim / sulfamethoxazole (co-trimoxazole) with spironolactone may result in clinically relevant hyperkalaemia.
Spironolactone binds to the androgen receptor and may increase prostate specific antigen (PSA) levels in abiraterone-treated prostate cancer patients. Use with abiraterone is not recommended.
PregnancyThere are very limited data on the use of spironolactone during pregnancy in humans.Experimental animal studies have shown reproductive toxicity associated with the anti-androgenic effect of spironolactone (see section 5.3). Spironolactone should not be used during pregnancy.Diuretics can lead to reduced perfusion of the placenta and thus to impairment of intrauterine growth and are therefore not recommended for the standard therapy for hypertension and edema during pregnancy.
BreastfeedingCanrenone, the principal and active metabolite of spironolactone, appears in small quantities in human breast milk. Spironolactone should not be used during breast-feeding. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from spironolactone-therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the women.
FertilitySpironolactone may induce impotence and menstrual irregularities (see section 4.8).
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 cancerBlood and lymphatic system disordersRare: thrombocytopenia, eosinophilia, leukopenia (including agranulocytosis)Immune system disordersRare: eczema (type 1 allergic reaction), hypersensitivityEndocrine disordersNot known: slight androgenic effects, including hirsutism.Metabolism and nutrition disordersVery common: hyperkalaemia in patients with severe renal dysfunction who are receiving concomitant treatment with potassium supplements (see also section 4.4)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 patientsUncommon: acidity of the blood (acidosis) in patients with liver problemsRare: 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 disordersUncommon: confusionNervous system disordersVery common: headacheCommon: weakness, lethargy in patients with cirrhosis, tingling (paraesthesia)Rare: paralysis, paraplegia of the limbs due to hyperkalaemiaNot known: dizziness, ataxiaVascular disordersVery rare: inflammation of the vessel walls (vasculitis)Not known: mild hypotensionGastrointestinal disordersVery common: indigestion, diarrhoeaCommon: nausea and vomitingVery rare: gastric inflammation, gastric ulcers, intestinal haemorrhage, crampsHepatobiliary disordersVery rare: hepatitisSkin and subcutaneous tissue disordersUncommon: skin rash, urticaria, erythema, chloasma, pruritus, exanthemaVery rare: alopecia, eczema, erythema annulare centrifugum (EAC), hypertrichosisNot known: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), Pemhigoid Musculoskeletal and connective tissue disordersUncommon: muscle spasms, leg crampsVery rare: systemic lupus erythematosus (SLE), OsteomalaciaRenal and urinary disordersUncommon: elevated serum creatinine levelsVery rare: acute renal failureReproductive system and breast disordersVery 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 bleedingGeneral disorders and administration site conditionsVery common: fatigue, drowsinesscommon: malaiseReporting 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 Yellow Card SchemeWebsite: www.mhra.gov.uk/yellowcard.
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 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.
Blister pack: 3 years
Bottles: 24 months
in-use shelf-life after first opening: 3 months.
Tablets are packed in PVC-Aluminium blister pack & HDPE bottle pack
Blister pack: 20, 28, 30, 50, 60, 90 and 100 tablets in blister.
HDPE bottle: 250, 500 and 1000 tablets (for hospital or dose dispensing use only)
Not all pack sizes may be marketed.
Date of Renewal: 31/05/2022