Trade name Aldactone; Spiractin Presentation

Dose can be divided into different intervals.

Renal impairment – Refer to precautions section.

Hepatic impairment – Refer to precautions section.

Significant renal impairment.

Anuria.

Adrenal insufficiency.

Monitor more frequently if infant is also given potassium.

Antiandrogenic effects include reduced hirsutism and gynecomastia.

There is one case report of an ovarian cyst in a neonate on spironolactone.

Spironolactone interferes with 17-hydroxyprogesterone measurement, which is used to screen neonates for congenital adrenal hyperplasia.

Reduces clearance of digoxin.

Spironolactone is a non-selective mineralocorticoid receptor antagonist with moderate affinity for both progesterone and androgen receptors. Pharmacokinetics and pharmacodynamics have not been evaluated in newborn infants. In adults, absorption is estimated to be 80–90%. The onset of action for spironolactone is typically very slow, with a peak response sometimes occurring 48 hours or more after the first dose. Spironolactone is rapidly metabolised hepatically into a number of metabolites. The predominant metabolite, 7α-methylspironolactone, accounts for around 80% of the K⁺-sparing effect of spironolactone. Spironolactone (88%) and its canrenone metabolite (99%) are extensively bound to plasma protein at therapeutic concentrations. In normal volunteers, the mean t_½ of spironolactone, canrenone, 7α-TMS and 6ß-hydroxy-7α-TMS were 1.4, 16.5, 13.8 and 15 hours, respectively. In cirrhotic patients, the t_½ of spironolactone and its metabolites are increased. The pharmacokinetics of spironolactone and its metabolites have not been specifically studied in the setting of renal insufficiency or end-stage renal disease.^8,9

Preterm infants receiving hydrochlorothiazide in combination with spironolactone may have an increased need for sodium and potassium supplementation.³ (LOE II GOR B) The addition of spironolactone to a thiazide diuretic did not reduce the requirement for supplemental electrolytes over 2 weeks in a small trial.¹⁰ (LOE II GOR C) Use of spironolactone in adults increases creatinine and the incidence of hyperkalaemia.⁵ (LOE I GOR C) Spironolactone reduced digoxin clearance in infants.¹¹ (LOE IV GOR C)

2. Stewart A, Brion LP, Ambrosio-Perez I. Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev. 2011:CD001817.

3. Albersheim SG, Solimano AJ, Sharma AK, Smyth JA, Rotschild A, Wood BJ, Sheps SB. Randomized, double-blind, controlled trial of long-term diuretic therapy for bronchopulmonary dysplasia. J Pediatr. 1989;115:615-20.

4. Hobbins SM, Fowler RS, Rowe RD, Korey AG. Spironolactone therapy in infants with congestive heart failure secondary to congenital heart disease. Arch Dis Child. 1981;56:934-8.

5. Hu LJ, Chen YQ, Deng SB, Du JL, She Q. Additional use of an aldosterone antagonist in patients with mild to moderate chronic heart failure: a systematic review and meta-analysis. Br J Clin Pharmacol. 2013;75:1202-12.

6. Anonymous. Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (the Randomized Aldactone Evaluation Study [RALES]). Am J Cardiol. 1996;78:902-7.

7. Fremont OT, Chan JC. Understanding Bartter syndrome and Gitelman syndrome. World J Pediatr. 2012;8:25-30.

8. Sica DA. Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis. Heart Fail Rev. 2005;10:23-9.

9. Karim A. Spironolactone: disposition, metabolism, pharmacodynamics, and bioavailability. Drug Metab Rev. 1978;8:151-88.

10. Hoffman DJ, Gerdes JS, Abbasi S. Pulmonary function and electrolyte balance following spironolactone treatment in preterm infants with chronic lung disease: a double-blind, placebo-controlled, randomized trial. J Perinatol. 2000;20:41-5.

11. Suematsu F, Minemoto M, Yukawa E, Higuchi S. Population analysis for the optimization of digoxin treatment in Japanese paediatric patients. J Clin Pharm Ther. 1999;24:203-8.