There have not been enough studies addressing the course of action for a patient who accidentally took an extra dose of spironolactone.
The manufacturer’s prescribing information gives no guidance about the effect of a single extra dose of spironolactone.1 They do report that possible effects of overdose may include drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea.
Spironolactone is currently prescribed at levels that range from up to 50 mg/day for heart failure, 100 mg/day for hypertension, up to 200 mg/day for edema, and up to 400 mg/day for primary hyperaldosteronism.1 Historically it has been given at therapeutic doses up to 500 mg/day.2
The elimination half-life of spironolactone and its various metabolites ranges from 10 to 35 hours.3–5 These half-lives are even longer in patient with cirrhosis.6 The effects of spironolactone and its metabolites persist for several days after discontinuation.7
It might be inferred that the effects of a single extra dose will depend on the amount taken (the dosage in a single pill) and the liver and kidney function of the individual.1 Spironolactone may remain in the body longer in people with impaired kidney function, because the drug is excreted in the kidney. Schohn et al studied the cardiovascular effects of spironolactone on five patients undergoing dialysis for chronic renal failure.8 Compared with placebo, 25 mg/day of spironolactone produced statistically significant changes in blood pressure without compensatory increase in cardiac output. Higher doses (up to 75 mg/day) produced a more pronounced and dose-dependent effect that was not statistically significant. It might be inferred that added dosing of spironolactone could increase the antihypertensive effect of the drug to cause low blood pressure, particularly in patients with impaired kidney function.
The effects of added spironolactone may be felt more strongly in patients with impaired liver function.1 The alterations in fluid and electrolyte balance may worsen hepatic encephalopathy and coma in these patients.
References
- Aldactone-spironolactone [package insert], New York, NY: Pfizer, Inc; 2016.
- Batterink J, Sn S, Am T, et al. Spironolactone for hypertension (review). Cochrane Database Syst Rev 2010;(8): 8-10.
- ClinicalKey drug monograph: spironolactone. Elsevier; 2018. https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-572. Accessed September 4, 2018.
- Yang J, Young MJ. Mineralocorticoid receptor antagonists - pharmacodynamics and pharmacokinetic differences. Curr Opin Pharmacol 2016; 27 : 78-85.
- Kolkhof P, Borden SA. Molecular pharmacology of the mineralocorticoid receptor: Prospects for novel therapeutics. Mol Cell Endocrinol 2012; 350 (2): 310-317.
- Sungaila I, Bartle WR, Walker SE, et al. Spironolactone pharmacokinetics and pharmacodynamics in patients with cirrhotic ascites. Gastroenterology 1992; 102 (5): 1680-1685.
- Sica DA. Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis. Heart Fail Rev 2005; 10 (1): 23-29.
- Schohn DC, Jahn HA, Pelletier BC. Dose-related cardiovascular effects of spironolactone. Am J Cardiol 1993; 71 (3).
