Fludrocortisone was approved by the FDA in 1954. Fludrocortisone mimics the actions of aldosterone, an endogenous mineralocorticoid. Mineralocorticoids alter electrolyte and fluid balance by facilitating sodium resorption and hydrogen and potassium excretion at the level of the distal renal tubule, resulting in edema and hypertension. The circulating drug binds extensively to the plasma proteins albumin and transcortin, and only the unbound portion of a dose is active. Systemic fludrocortisone is quickly distributed into the kidneys, intestines, skin, liver, and muscle.
Corticosteroids distribute into breast milk and cross the placenta.
Fludrocortisone is metabolized by the liver to inactive metabolites. These inactive metabolites, as well as a small portion of unchanged drug, are excreted in the urine. Because of the high sodium-retaining activity of fludrocortisone, the drug should be used with extreme caution in patients with congestive heart failure, hypertension, renal disease, or cardiac disease. Therapy should be discontinued if significant weight gain, cardiac enlargement, blood pressure increase, or edema occurs. Adequate glucocorticoid therapy should be used concomitantly with fludrocortisone therapy in treating adrenal insufficiency or salt-losing adrenogenital syndrome.