What is the typical dosage and treatment goal of Fludrocortisone (mineralocorticoid) for patients with primary adrenal insufficiency, such as Addison's disease?

Fludrocortisone Dosing in Primary Adrenal Insufficiency

Most patients with primary adrenal insufficiency should take 50-200 μg of fludrocortisone as a single daily dose in the morning, with the dose adjusted based on blood pressure, serum electrolytes (sodium and potassium), and plasma renin activity to achieve normotension, normokalemia, and upper-normal range renin levels. 1, 2, 3

Standard Dosing Protocol

Initial Dosing

• Start with 100 μg (0.1 mg) daily as a single morning dose 3
• The FDA-approved dosing range is 50-200 μg daily, though some patients may require 100 μg three times weekly up to 200 μg daily 3
• Children and younger adults typically require higher doses, potentially up to 500 μg daily 2

Treatment Goals

The primary objectives of fludrocortisone therapy are: 1, 2, 4

• Maintain normal blood pressure (both supine and standing positions)
• Achieve normokalemia (normal potassium levels)
• Maintain normal sodium levels
• Keep plasma renin activity in the upper normal range 5
• Eliminate salt cravings and orthostatic symptoms

Dose Adjustment Algorithm

When to INCREASE the dose: 2

• Persistent orthostatic hypotension despite adequate salt intake
• Ongoing salt cravings despite liberal salt consumption
• Hyponatremia (low sodium)
• Hyperkalemia (elevated potassium)
• Elevated plasma renin activity above normal range

When to DECREASE the dose: 1, 2

• Development of hypertension (reduce dose but never stop completely)
• Peripheral edema develops
• Hypernatremia (elevated sodium)
• Hypokalemia (low potassium)
• Suppressed plasma renin activity

Monitoring Parameters

At Each Visit (Minimum Annually): 1, 6

• Blood pressure in both supine and standing positions 2
• Serum sodium and potassium 1, 6
• Body weight 1, 6
• Clinical symptoms: salt cravings, lightheadedness, edema 2
• Plasma renin activity (optional but helpful for fine-tuning) 4, 5

Recent research demonstrates that renin and electrolytes correlate with mineralocorticoid activity of fludrocortisone in a dose-dependent manner, with higher doses associated with increased sodium and decreased potassium and renin levels 4

Special Clinical Situations

Pregnancy: 1, 2

• Increase fludrocortisone dose during the third trimester due to progesterone's anti-mineralocorticoid effects
• Monitor blood pressure, electrolytes, and salt cravings rather than plasma renin (which normally increases in pregnancy)
• Plasma renin activity is not reliable for dose adjustment during pregnancy 1

Long-term Management: 4

• Fludrocortisone dose may be reduced over time in long-term follow-up (>60 months)
• Approximately half of patients maintain stable doses of 50-75 μg daily 4

Medication Interactions Requiring Adjustment: 2

• Drospirenone-containing contraceptives may require higher fludrocortisone doses
• Avoid diuretics, acetazolamide, carbenoxolone, and NSAIDs as they interact with fludrocortisone
• Avoid liquorice and grapefruit juice as they potentiate mineralocorticoid effects 1, 2

Critical Pitfalls to Avoid

Never Stop Fludrocortisone Abruptly: 2

• If hypertension develops, reduce the dose but do not discontinue 1, 2
• Abrupt discontinuation can trigger adrenal crisis with hypotension, hyponatremia, hyperkalemia, and cardiovascular collapse 2
• If discontinuation is necessary, taper over at least 1-3 days under medical supervision 2

Under-replacement is Common: 2

• Under-dosing with fludrocortisone predisposes patients to recurrent adrenal crises
• Patients should be advised to consume salt and salty foods liberally 1, 2
• Avoid potassium-containing salt substitutes marketed as "healthy" alternatives 2

Combination Therapy

Fludrocortisone must always be given with glucocorticoid replacement: 3, 7

• Hydrocortisone 15-25 mg daily in divided doses, OR 1, 6, 7
• Prednisone 3-5 mg daily 7
• The combination provides complete substitution therapy approximating normal adrenal activity 3

Patient Education Requirements

All patients on fludrocortisone should: 1, 6

• Wear Medic Alert identification jewelry and carry a steroid alert card
• Receive education on managing daily medications and minor illnesses
• Have supplies for self-injection of parenteral hydrocortisone for emergencies
• Understand the signs of both under-replacement (salt cravings, dizziness) and over-replacement (hypertension, edema)