Spironolactone

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.

Non-steroidal anti-inflammatory drugs such as aspirin, indomethacin, and mefenamic 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.

As carbenoxolone may cause sodium retention and thus decrease the effectiveness of spironolactone concurrent use should be avoided.

Concomitant administration of spironolactone with ciclosporin and tacrolimus is not recommended.

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

Co-administration of spironolactone with lithium causes an increase in the level of lithium in the blood.

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.

Concomitant use of trimethoprim/sulfamethoxazole (co-trimoxazole) with spironolactone may result in clinically relevant hyperkalaemia.

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.

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:

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, Frequency Not Known (cannot be estimated from the available data).

Neoplasms benign, malignant and unspecified (including cysts and polyps)

Uncommon: Benign breast neoplasm (male)

Blood and lymphatic system disorders

Frequency Not Known: Agranulocytosis, Leukopenia, Thrombocytopenia

Metabolism and nutrition disorders

Very Common: Hyperkalaemia

Uncommon: Electrolyte imbalance

Psychiatric disorders

Common: Confusional state

Frequency Not Known: Libido disorder

Nervous system disorders

Common: Dizziness

Gastrointestinal disorders

Common: Nausea

Frequency Not Known: Gastrointestinal disorder

Hepatobiliary disorders

Uncommon: Hepatic function abnormal

Skin and subcutaneous tissue disorders

Common: Pruritus, Rash

Uncommon: Urticaria

Frequency Not Known: Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, Drug reaction with eosinophilia and systemic symptoms (DRESS), Alopecia, Hypertrichosis, Pemphigoid

Musculoskeletal and connective tissue disorders

Common: Muscle spasms

Renal and urinary disorders

Common: Acute kidney injury

Reproductive system and breast disorders

Common: Gynaecomastia, Breast pain (male)^a

Uncommon: Menstrual disorder, Breast pain (female)^b

General disorders and administration site conditions

Common: Malaise

Abbreviations: CDS = Core Data Sheet; F = female; LLT = lower level term; M = male; PT = preferred term; WHO-ART = World Health Organization Adverse Drug Reaction Terminology.
^a The term Breast pain is mapped from CDS and the frequency is derived from WHO-ART term Breast pain (M); however, Breast pain male is the LLT.
^b Breast pain is the PT from CDS, and the frequency is derived from WHO-ART term Breast pain (F).