SPIRONOLACTONE

Spironolactone (INN, BAN, USAN) (pronounced /spɪˌrɒnɵˈlæktoʊn/), commonly referred to simply as “spiro”, and marketed primarily under the brand name Aldactone in most countries, is a synthetic, steroidal antimineralocorticoid agent with additional antiandrogen and weak progestogen properties, as well as some indirect estrogen and glucocorticoid effects. It is used primarily as a diuretic and antihypertensive, but may also be employed for the purpose of reducing elevated or unwanted androgen activity in the body. It acts predominantly as a competitive antagonist of the aldosterone (or mineralocorticoid) receptor, and belongs to a class of pharmaceutical drugs known as potassium-sparing diuretics.

Spironolactone is a relatively old drug, having been introduced clinically in 1959. Some have predicted that spironolactone will be less commonly used in cardiovascular conditions (e.g., heart failure and hypertension) as the newer agents like the structurally-related compound eplerenone (also an aldosterone antagonist) are more selective and lack many of the side effects and actions of spironolactone that are undesirable in that particular patient population. However, spironolactone remains more widely used as an antiandrogen than eplerenone for patients in whom this effect is a main goal.

It is on the World Health Organization’s List of Essential Medicines, a list of the most important medication needed in a basic health system.

Side effects

The most common side effect of spironolactone is urinary frequency. Other general side effects include ataxia, drowsiness, dry skin, and rashes. Because it also affects the androgen receptors, spironolactone can cause gynecomastia and feminization in general, testicular atrophy, and sexual dysfunction consisting of loss of libido and erectile dysfunction, and in females it can cause menstrual irregularities and breast tenderness and enlargement.

Spironolactone may put patients at a heightened risk for gastrointestinal issues like nausea, vomiting, diarrhea, cramping, and gastritis. Additionally, there has been some evidence suggesting an association between use of the drug and bleeding from the stomach and duodenum, though a causal relationship between the two has not been established. Also, it has been shown to be immunosuppressive in the treatment of sarcoidosis.

Spironolactone may rarely cause more severe side effects such as anaphylaxis, renal failure, hepatotoxicity, agranulocytosis, DRESS syndrome, Stevens-Johnson Syndrome or toxic epidermal necrolysis.

Interactions

Spironolactone often increases serum potassium levels and can cause hyperkalemia, a very serious condition. Therefore, it is recommended that people using this drug avoid potassium supplements and salt substitutes containing potassium. Doctors usually recommend periodic screening of serum potassium levels and some patients may be advised to limit dietary consumption of potassium-rich foods.

Research has also shown spironolactone can interfere with the effectiveness of antidepressant treatment. As the drug acts as on antagonist on the mineralocorticoid receptor, among others, it is presumed that it reduces the effectiveness of certain antidepressants by interfering with normalization of the hypothalamic-pituitary-adrenal axis in patients receiving antidepressant therapy.Spironolactone can also have numerous other interactions, most commonly with other cardiac and blood pressure medications.

Contraindications

Spironolactone is considered Pregnancy Category C by the FDA and should not be taken by pregnant women due to the high risk of birth defects and feminization of male fetuses. Likewise, it has been found to be present in the breast milk of lactating mothers and, while the effects of spironolactone or its metabolites have not been extensively studied in breast-feeding infants, it is generally recommended that women also not take the drug while nursing.

It should also be used with caution in patients with some neurological disorders, anuria, acute kidney injury, or significant impairment of renal excretory function with risk of hyperkalemia.