URACTONUM Tablet Ref.[28219] Active ingredients: Spironolactone

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 Uractonum 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 medicinal products known to cause hyperkalaemia with spironolactone may result in severe hyperkalaemia.

Concomitant use of spironolactone 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.

Urea

Reversible increases in blood urea have been reported in association with spironolactone 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 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 population

Potassium-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).

Uractonum contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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

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 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 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 such as aspirin, indomethacin and mefanamic acid may attenuate the natriuretic efficacy of diuretics due to inhibition of intrarenal synthesis of prostaglandins and have been shown to attenuate the diuretic effect of spironolactone.

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 Uractonum.

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.

Spironolactone enhances the metabolism of antipyrine.

Spironolactone can interfere with assays for plasma digoxin concentrations.

Pregnancy

Spironolactone or its metabolites may cross the placental barrier. With spironolactone, feminisation has been observed in male rat foetuses. The use of spironolactone in pregnant women requires that the anticipated benefit be weighed against the possible hazards to the mother and foetus.

Breast-feeding

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.

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.

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:

Frequency not known (cannot be be estimated from the available data)

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 and connective tissue 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, pemphigoid.

Renal and urinary disorders: acute renal failure.

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. Healthcare professionals are asked to report any suspected adverse reactions via Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.

None stated.