How Florinef (Fludrocortisone) Works in POTS
Fludrocortisone works in POTS by acting as a mineralocorticoid that stimulates renal sodium retention and expands plasma volume, thereby improving orthostatic tolerance and reducing symptoms of orthostatic intolerance. 1, 2
Mechanism of Action
Fludrocortisone acts on the distal tubules of the kidney to enhance sodium reabsorption from tubular fluid into plasma, while simultaneously increasing urinary excretion of both potassium and hydrogen ions. 2 This mineralocorticoid effect directly addresses one of the key pathophysiologic mechanisms in POTS: hypovolemia and reduced plasma volume. 3, 4
The expanded fluid volume from sodium retention helps counteract the excessive venous pooling that occurs in POTS patients upon standing, which contributes to the compensatory tachycardia. 4 By increasing circulating blood volume, fludrocortisone reduces the need for excessive heart rate increases to maintain cardiac output and cerebral perfusion in the upright position. 1
Dosing and Administration
The recommended dose is 0.1-0.2 mg taken once daily at night (up to 0.3 mg maximum). 1 The American College of Cardiology specifically recommends up to 0.2 mg taken at night for orthostatic intolerance in POTS. 1
The drug has a plasma half-life of approximately 3.5 hours but a biological half-life of 18-36 hours, allowing for once-daily dosing. 2
Essential Adjunctive Measures
Fludrocortisone should always be used in conjunction with salt loading for optimal effect. 1 The combination therapy works synergistically:
- Salt intake: 5-10 g (1-2 teaspoons) of table salt per day through liberalized dietary sodium (avoid salt tablets to minimize nausea). 1, 5
- Fluid intake: 2-3 liters of water or electrolyte-balanced fluids daily. 1, 5
- Head-up tilt sleeping: Elevate the head of the bed 4-6 inches (10-15 cm) to prevent nocturnal polyuria and maintain favorable fluid distribution. 1
Critical Monitoring Requirements
Careful monitoring for hypokalemia is critical when using fludrocortisone, as the drug increases urinary potassium excretion. 1, 2 Regular electrolyte monitoring is essential to prevent this potentially serious side effect.
Important Caveats and Limitations
Supine hypertension is a major limiting factor. 1 When supine hypertension is present, other medications should be used before fludrocortisone. 1 This is particularly important because POTS patients may already have abnormal blood pressure regulation.
Additional side effects include edema, headache, and with doses exceeding 0.3 mg daily, more serious adverse reactions such as adrenal suppression and immunosuppression can occur. 1
Fludrocortisone may not be beneficial in patients with history of hypertension, renal disease, heart failure, or cardiac dysfunction due to the volume expansion effects. 1
Evidence Quality and Clinical Context
The evidence supporting fludrocortisone in POTS comes from small observational studies and one double-blind trial in 60 patients showing symptomatic improvement and higher blood pressures. 1 While the evidence base is limited compared to other interventions, fludrocortisone remains a guideline-recommended option when used appropriately as part of comprehensive management. 1, 4
The drug is most appropriate for POTS patients with the hypovolemic phenotype, though many patients exhibit overlapping pathophysiologic mechanisms. 3, 4