What is fludrocortisone?

What is Fludrocortisone?

Fludrocortisone is a synthetic mineralocorticoid medication used as replacement therapy for aldosterone deficiency in primary adrenal insufficiency (Addison's disease) and salt-losing forms of congenital adrenal hyperplasia. 1

Pharmacology and Mechanism

Fludrocortisone acetate (also known as 9-fluorohydrocortisone) is a potent synthetic steroid with strong mineralocorticoid activity—approximately equal to aldosterone in potency—but with a longer duration of action, making it more practical for clinical use 1, 2. It works by:

• Maintaining water and electrolyte homeostasis through sodium retention and potassium excretion
• Supporting blood pressure by increasing blood volume
• Acting primarily on renal mineralocorticoid receptors 3, 4

The medication also possesses some glucocorticoid activity, though it is prescribed specifically for its mineralocorticoid effects 1.

Clinical Indications

Primary Uses (FDA-Approved)

Fludrocortisone is indicated for:

• Primary adrenal insufficiency (Addison's disease) as partial replacement therapy
• Secondary adrenocortical insufficiency
• Salt-losing adrenogenital syndrome (congenital adrenal hyperplasia) 1

Key Clinical Context

All patients with confirmed aldosterone deficiency should receive mineralocorticoid replacement 3. However, there is one critical exception: fludrocortisone should NOT be used in glucocorticoid-induced adrenal insufficiency 5. This is because glucocorticoid-induced adrenal insufficiency represents secondary adrenal insufficiency where the renin-angiotensin-aldosterone system remains intact, so mineralocorticoid replacement is unnecessary and potentially harmful.

Dosing and Administration

Standard Dosing

• Adults and adolescents: 0.05-0.2 mg once daily, typically taken in the morning 3
• Children and newborns: Higher doses often required due to lower mineralocorticoid sensitivity 3
• The morning timing mimics the natural circadian rhythm of aldosterone secretion 3

Dose Adjustments

• Hot climates or excessive sweating: Increase dose by 50-100% or increase salt intake 3
• Patients on prednisolone: May require higher fludrocortisone doses (prednisolone has less mineralocorticoid activity) 3
• Patients on dexamethasone: Require full mineralocorticoid replacement (dexamethasone has no mineralocorticoid activity) 3

Monitoring

Monitor replacement primarily through clinical assessment 3:

Signs of Adequate Replacement

• Normal blood pressure without postural hypotension
• Absence of salt craving or lightheadedness
• Normal electrolytes (sodium and potassium)
• General sense of well-being
• Plasma renin activity in the upper reference range 3

Signs of Over-Replacement

• Hypertension
• Peripheral edema
• Hypokalemia
• Hypernatremia 4

Signs of Under-Replacement

• Postural hypotension
• Salt craving
• Lightheadedness when standing
• Hyperkalemia

Important Drug Interactions and Precautions

Avoid these substances as they potentiate mineralocorticoid effects:

• Licorice
• Grapefruit juice 3

Phenytoin increases fludrocortisone metabolism, potentially requiring higher replacement doses 3.

Management of Hypertension on Fludrocortisone

If hypertension develops while on fludrocortisone 3:

1. First: Reduce the fludrocortisone dose
2. Second: If blood pressure remains uncontrolled, initiate antihypertensive treatment while continuing fludrocortisone
3. Preferred antihypertensives: Angiotensin II receptor blockers or ACE inhibitors (to counter vasoconstrictive effects of elevated angiotensin II)
4. Second-line: Dihydropyridine calcium channel blockers
5. Avoid: Diuretics and aldosterone receptor blockers (spironolactone, eplerenone are contraindicated) 3

Common Pitfalls

• Do not use fludrocortisone in glucocorticoid-induced adrenal insufficiency—this is the most important contraindication 5
• Evaluate both glucocorticoid AND mineralocorticoid doses when assessing hypertension in patients with primary adrenal insufficiency, as over-replacement with either can cause elevated blood pressure 3
• Long-term use requires monitoring for hypernatremia, hypokalemia, hyperglycemia, and congestive heart failure 4