Spironolactone

Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood pressure, low blood potassium that does not improve with supplementation, early puberty in boys, acne and excessive hair growth in women, and as a part of feminizing hormone therapy in transgender women. Spironolactone is taken by mouth. Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood pressure, low blood potassium that does not improve with supplementation, early puberty in boys, acne and excessive hair growth in women, and as a part of feminizing hormone therapy in transgender women. Spironolactone is taken by mouth. Common side effects include electrolyte abnormalities, particularly high blood potassium, nausea, vomiting, headache, rashes, and a decreased desire for sex. In those with liver or kidney problems, extra care should be taken. Spironolactone has not been well studied in pregnancy and should not be used to treat high blood pressure of pregnancy. It is a steroid that blocks the effects of the hormones aldosterone and testosterone and has some estrogen-like effects. Spironolactone belongs to a class of medications known as potassium-sparing diuretics. Spironolactone was discovered in 1957 and was introduced in 1959. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world as of 2014 is between US$0.02 and US$0.12 per day. In the United States it costs about US$0.50 per day. Spironolactone is used primarily to treat heart failure, edematous conditions such as nephrotic syndrome or ascites in people with liver disease, essential hypertension, low blood levels of potassium, secondary hyperaldosteronism (such as occurs with liver cirrhosis), and Conn's syndrome (primary hyperaldosteronism). The most common use of spironolactone is in the treatment of heart failure. On its own, spironolactone is only a weak diuretic because it primarily targets the distal nephron (collecting tubule), where only small amounts of sodium are reabsorbed, but it can be combined with other diuretics to increase efficacy. The classification of spironolactone as a 'potassium-sparing diuretic' has been described as obsolete. Spironolactone is also used to treat Bartter's syndrome due to its ability to raise potassium levels. Spironolactone has antiandrogenic activity. For this reason, it is frequently used to treat a variety of dermatological conditions in which androgens play a role. Some of these uses include acne, seborrhea, hirsutism, and pattern hair loss in women. Spironolactone is the most commonly used medication in the treatment of hirsutism in the United States. High doses of spironolactone, which are needed for considerable antiandrogenic effects, are not recommended for men due to the high risk of feminization and other side effects. Spironolactone is also commonly used to treat symptoms of hyperandrogenism, such as due to polycystic ovary syndrome, in women. While loop diuretics remain first-line for most people with heart failure, spironolactone has shown to reduce both morbidity and mortality in numerous studies and remains an important agent for treating fluid retention, edema, and symptoms of heart failure. Current recommendations from the American Heart Association are to use spironolactone in patients with NYHA Class II-IV heart failure who have a left ventricular ejection fraction of less than 35%. In a randomized evaluation which studied people with severe congestive heart failure, people treated with spironolactone were found to have a relative risk of death of 0.70 or an overall 30% relative risk reduction compared to the placebo group, indicating a significant death and morbidity benefit of the medication. People in the study's intervention arm also had fewer symptoms of heart failure and were hospitalized less frequently. Likewise, it has shown benefit for and is recommended in patients who recently suffered a heart attack and have an ejection fraction less than 40%, who develop symptoms consistent with heart failure, or have a history of diabetes mellitus. Spironolactone should be considered a good add-on agent, particularly in those patients 'not' yet optimized on ACE inhibitors and beta-blockers. Of note, a recent randomized, double-blinded study of spironolactone in patients with symptomatic heart failure with 'preserved' ejection fraction (i.e. >45%) found no reduction in death from cardiovascular events, aborted cardiac arrest, or hospitalizations when spironolactone was compared to placebo. It is recommended that alternatives to spironolactone be considered if serum creatinine is greater than 2.5 mg/dL (221 µmol/L) in males or greater than 2 mg/dL (176.8 µmol/L) in females, if glomerular filtration rate is below 30 mL/min or with a serum potassium of greater than 5.0 mEq/L given the potential for adverse events detailed elsewhere in this article. Doses should be adjusted according to the degree of kidney function as well. According to systematic review, in heart failure with preserved ejection fraction, treatment with spironolactone did not improve patient outcomes. This is based on the TOPCAT Trial examining this issue, which found that of those treated with placebo had a 20.4% incidence of negative outcome vs 18.6% incidence of negative outcome with spironolactone. However, because the p-value of the study was 0.14, and the unadjusted hazard ratio was 0.89 with a 95% confidence interval of 0.77 to 1.04, it is determined the finding had no statistical significance. Hence the finding that patient outcomes are not improved with use of spironolactone. More recently, when blood samples from 366 patients in the TOPCAT study were analyzed for presence of canrenone (an active metabolite of spironolactone), 30% of blood samples from Russia lacked detectable residues of canrenone. This led to the conclusion that the TOPCAT trial results in Russia do not reflect actual clinical experience with spironolactone in patients with preserved ejection fraction. The TOPCAT study results are now considered to have been invalidated. The study's prime investigator and other prominent research cardiologists are now advising physicians treating heart failure with preserved ejection fraction to consider prescribing spironolactone pending outcome of two multicenter trials of newer medications.