fludrocortisone

mineralocorticoid· Brands: FlorinefPO

Mechanism of action

Fludrocortisone is a synthetic mineralocorticoid that binds to the mineralocorticoid receptor in the distal tubules and collecting ducts of the kidney, promoting sodium reabsorption and potassium and hydrogen ion excretion, thereby increasing blood volume and blood pressure.

Pharmacokinetics

Fludrocortisone is readily absorbed after oral administration and binds extensively to plasma proteins. It is metabolised in the liver and excreted mainly in the urine. The half-life is around 3 to 4 hours.

Indications & dosing

Adrenal insufficiency (Addison's disease) as adjunct to glucocorticoid replacement

Dose adjusted based on blood pressure, electrolyte balance, and renin levels. Typically 0.1 mg daily.

adult · PO: 0.05–0.2 mg once daily · Dose adjusted based on blood pressure, electrolyte balance, and renin levels. Typically 0.1 mg daily.

Salt-losing congenital adrenal hyperplasia (CAH)

Dose titrated to maintain normal electrolytes and blood pressure. Often given with hydrocortisone.

pediatric · PO: 0.05–0.2 mg once daily · Dose titrated to maintain normal electrolytes and blood pressure. Often given with hydrocortisone.

Orthostatic hypotension (autonomic dysfunction)off-label

Off-label use; monitor for supine hypertension and electrolyte disturbances.

adult · PO: 0.05–0.2 mg once daily · Off-label use; monitor for supine hypertension and electrolyte disturbances.

Contraindications & precautions

Systemic fungal infection · Fludrocortisone may worsen systemic fungal infections.
Known hypersensitivity to fludrocortisone or other corticosteroids · Cross-sensitivity may occur.
Severe hepatic impairment · Corticosteroid metabolism is reduced; dose reduction may be required.
Monitor blood pressure, serum electrolytes, and weight regularly.
Use with caution in patients with hypertension, heart failure, renal impairment, or oedema.
Consider potassium supplementation or increased dietary potassium intake.
Adjust dose in patients with liver disease as metabolism may be impaired.

Adverse effects

Hypertensionserious
Hypokalaemiaserious
Fluid retention (oedema)serious
Hyperglycaemia
Increased susceptibility to infectionsserious
Muscle weakness
Mood changes

Renal & hepatic adjustment

eGFR 0+: No specific dose adjustment based on eGFR; caution in severe renal impairment due to risk of fluid retention and hypertension.
Hepatic impairment (moderate): Use with caution; monitor for signs of excess mineralocorticoid effect (hypertension, hypokalemia).
Hepatic impairment (severe): Consider dose reduction; increased risk of adverse effects due to reduced hepatic metabolism.

Monitoring, pregnancy & toxicity

Blood pressure · Regularly, especially during initial titration
Serum potassium · Periodically; more frequently if on diuretics or in renal impairment
Serum sodium · Periodically
Weight and appearance of oedema · Monitor for fluid retention
Clinical signs of corticosteroid excess or deficiency · At each review
Pregnancy: Can be used if clinically indicated. There is no evidence of harm in human pregnancy, but monitor for hypertension and electrolyte disturbances. Doses may need to be increased in the third trimester.
Toxicity: Hypertension, hypernatraemia, hypokalaemia, fluid overload (oedema, weight gain), and in severe cases cardiac failure. · Stop the drug, correct electrolyte imbalances, restrict sodium and monitor fluid status.
Toxicity: Chronic overdose may cause signs of Cushing's syndrome, including weight gain, glucose intolerance, and osteoporosis. · Reduce the dose or discontinue under specialist supervision; treat complications.

Clinical notes

Fludrocortisone is used for the treatment of adrenocortical insufficiency and salt-losing forms of congenital adrenal hyperplasia. Monitor for signs of fluid retention, hypertension, and hypokalaemia, and adjust doses according to serum electrolytes and blood pressure. Use with caution in patients with heart failure or hepatic impairment.

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BNF; local formulary