QAIALDO Oral suspension Ref.[51071] Active ingredients: Spironolactone

Monitoring fluid and electrolyte state

Patients who are being treated with this preparation require regular supervision with monitoring of fluid and electrolyte state. Periodic estimation of serum electrolytes is recommended due to the possibility of hyperkalaemia, hyponatremia and possible transient blood urea nitrogen (BUN) elevation, especially in the elderly and/or in patients with pre-existing impaired renal or hepatic function. The preparation should only be used with particular caution in elderly patients or those with potential obstruction of the urinary tract, or with disorders rendering their electrolyte balance precarious.

Concomitant use of spironolactone with other potassium sparing diuretics, angiotensin- converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory medicinal products, angiotensin II antagonists, aldosterone blockers, heparin, low molecular weight heparin or other medicinal products or conditions known to cause hyperkalaemia, potassium supplements, a diet rich in potassium, or salt substitutes containing potassium, may lead to severe hyperkalaemia (see section 4.5).

Hyperkalaemia may also occur in patients with impaired renal function. Cardiac dysrhythmias, occasionally fatal, may result.

Reversible hyperchloraemic metabolic acidosis, usually in association with hyperkalaemia, has been reported to occur in some patients with decompensated hepatic cirrhosis, even when renal function is normal.

Dilution hyponatraemia may occur in combination with other diuretics (see section 4.5).

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).

Concomitant use with cardiac glycosides or hypotensive agents

The concomitant administration of this preparation with cardiac glycosides or hypotensive agents may necessitate adjustment of those medicinal products (see section 4.5).

Urea

Reversible increases in blood urea may occur during use of spironolactone especially in the presence of impaired renal function.

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).

Excipients with known effect

Sodium benzoate

This medicinal product contains 0.75 mg sodium benzoate in each 1 ml which is equivalent to 112.5 mg/150 ml. Increase in bilirubinaemia following its displacement from albumin may increase neonatal jaundice which may develop into kernicterus (non-conjugated bilirubin deposits in the brain tissue).

Sodium

This medicinal product contains less than 1 mmol (23 mg) sodium within the recommended dose range, that is to say essentially ‘sodium-free’.

Sucrose

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. As this medicinal product contains 400 mg sucrose per ml, this has to be taken into consideration in terms of daily intake. This should be taken into account in patients with diabetes mellitus. Qaialdo 10 mg/ml may be harmful to the teeth.

Interactions affecting the use of this medicinal product

Interactions affecting the potassium homeostasis

Concomitant use of medicinal products known to cause hyperkalaemia (such as lisinopril, valsartan, indomethacin) with spironolactone may result in severe hyperkalaemia. In addition, concomitant use of trimethoprim/sulfamethoxazole (co-trimoxazole) with spironolactone may result in clinically relevant hyperkalaemia.

Since ACE inhibitors decrease aldosterone production, they should not routinely be used with spironolactone, particularly in patients with marked renal impairment.

Hyperkalaemic metabolic acidosis has been reported in patients given spironolactone concurrently with ammonium chloride or colestyramine.

Interactions attenuating the natriuretic effect of spironolactone

Non-steroidal anti-inflammatory medicinal products such as acetylsalicylic acid, indomethacin and mefenamic acid may attenuate the natriuretic efficacy of diuretics due to the inhibition of intra-renal synthesis of prostaglandins and have been shown to attenuate the diuretic effect of spironolactone.

Interactions affecting the use of other medicinal products

Concurrent use with carbenoxolone or lithium salts should be avoided.

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.

Potentiation of the effect of other diuretics and antihypertensive medicinal products occurs and their dose may need to be reduced by about 50% when spironolactone is added to the treatment regime, and then adjusted as necessary. Concomitant administration with cardiac glycosides may necessitate adjustment of the doses of these medicinal products.

Spironolactone has been shown to increase the half-life of digoxin. 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.

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 spironolactone.

Spironolactone enhances the metabolism of antipyrine.

In fluorimetric assays, spironolactone may interfere with the estimation of compounds with similar fluorescence characteristics.

Pregnancy

There are no studies of spironolactone in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Qaialdo is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

Canrenone is excreted in human milk. Qaialdo should not be used during breast-feeding.

Fertility

Studies in animals suggest spironolactone may impair fertility (see section 5.3).

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.

Summary of the safety profile

The most frequent adverse reactions of spironolactone include: hyperkalaemia, reported in 17.5% of patients, particularly in patients with renal impairment or if receiving ACE-inhibitors or angiotensin II

antagonists concomitantly; gynaecomastia and breast pain, reported in 9% of males. The following undesirable effects have been observed in clinical trials and reported during treatment with spironolactone with the following frequencies: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000); not known (cannot be estimated from the available data). Table 2 presented below is according to the MedDRA system organ classification and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 2. Tabulated list of adverse reactions:

^* Gynaecomastia may develop in association with the use of spironolactone. Development appears to be related to both dose level and duration of therapy and is normally reversible when the medicinal product is discontinued. In rare instances some breast enlargement may persist.
^** In clinical trials, breast pain was reported more commonly in males than in females.
^*** Arrhythmia, chest pain, nausea, diarrhoea, 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 disturbance.

Paediatric population

Frequency, type and severity of adverse reactions in children are expected to be similar to adults.

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 the national reporting system listed in Appendix V.

Not applicable.