What is the typical dosage and management of Fludocortisone for a patient with primary adrenal insufficiency, such as Addison's disease?

Fludrocortisone Management in Primary Adrenal Insufficiency

For patients with primary adrenal insufficiency such as Addison's disease, start fludrocortisone at 100 μg (0.1 mg) once daily in the morning, with a typical therapeutic range of 50-200 μg daily, titrated based on blood pressure (both supine and standing), serum electrolytes, and clinical symptoms like salt cravings or edema. 1, 2, 3

Standard Dosing Protocol

• Initial dose: 100 μg (0.1 mg) once daily, taken in the morning upon awakening 1, 3
• Therapeutic range: 50-200 μg daily for most adults 1, 2, 3
• Higher doses: Children and younger adults may require up to 500 μg daily due to increased metabolic demands 1
• Combination therapy: Always prescribe with glucocorticoid replacement (hydrocortisone 15-25 mg daily or cortisone acetate 10-37.5 mg daily in divided doses) 2, 3, 4

Dose Titration Algorithm

Increase fludrocortisone when:

• Serum sodium is low (hyponatremia) 1, 5
• Serum potassium is high (hyperkalemia) 1, 5
• Orthostatic hypotension persists despite adequate sodium intake 1, 5
• Patient reports persistent salt cravings 6, 1
• Lightheadedness or postural symptoms occur 1

Decrease fludrocortisone when:

• Hypertension develops (reduce dose but never stop completely) 6, 1, 5
• Peripheral edema appears 6, 1, 5
• Supine hypertension occurs 5

Critical pitfall: If hypertension develops, reduce the fludrocortisone dose rather than stopping it entirely—complete cessation can trigger life-threatening adrenal crisis with hypotension, hyponatremia, and hyperkalemia. 1, 5 Instead, add a vasodilator if blood pressure control remains inadequate. 6

Monitoring Parameters

At each visit, assess:

• Blood pressure in both supine and standing positions 6, 1, 5
• Serum sodium and potassium levels 1, 2, 5
• Body weight 2, 5
• Clinical symptoms: salt cravings, lightheadedness, peripheral edema 6, 1

Follow-up schedule:

• Review patients at least annually 1, 2, 5
• More frequent monitoring during dose adjustments or special circumstances 2, 5

Note on renin monitoring: While plasma renin activity (PRA) can indicate mineralocorticoid activity, recent evidence shows renin correlates negatively with fludrocortisone dose (r = -0.131), and electrolytes plus blood pressure remain the most practical monitoring tools. 7 PRA is particularly unreliable during pregnancy when levels normally increase. 6

Drug and Dietary Interactions

Avoid these medications:

• Diuretics 6, 2, 5
• Acetazolamide 6, 2, 5
• NSAIDs 6, 2, 5
• Carbenoxolone 6, 2, 5

May require dose increase:

• Drospirenone-containing contraceptives (due to anti-mineralocorticoid effects) 6, 1, 5

Dietary recommendations:

• Encourage salt and salty foods ad libitum 1, 2, 5
• Avoid potassium-containing salt substitutes 1, 5
• Avoid liquorice and grapefruit juice (both potentiate mineralocorticoid effects) 6, 5

Special Clinical Situations

Pregnancy:

• Fludrocortisone dose often needs to increase during late pregnancy, particularly the third trimester, due to progesterone's anti-mineralocorticoid effects 6, 2, 5
• Monitor using salt cravings, blood pressure, and serum electrolytes rather than PRA (which normally rises in pregnancy) 6
• Also increase hydrocortisone by 2.5-10 mg daily during third trimester 6, 2

Surgery:

• Focus on stress-dose hydrocortisone (100 mg IV/IM before anesthesia, then every 6 hours) 6, 2
• Resume fludrocortisone once oral intake is established 5
• For major surgery: continue 100 mg hydrocortisone every 6 hours until able to eat and drink, then double oral dose for 48+ hours 6, 2

Physical activity:

• Regular, accustomed exercise does not require dose adjustment 6
• Intense or prolonged exercise (e.g., marathon): add 5 mg hydrocortisone before activity and increase salt/fluid intake 6

Common Clinical Pitfalls

Under-replacement is more common than over-replacement and may predispose patients to recurrent adrenal crises—sometimes clinicians compensate by over-replacing glucocorticoids instead of appropriately increasing fludrocortisone. 6, 1

Never abruptly discontinue fludrocortisone: This can trigger adrenal crisis with hypotension, hyponatremia, hyperkalemia, and potentially fatal cardiovascular collapse. 1 If discontinuation is necessary, taper over at least 1-3 days under medical supervision. 1

Don't be overly conservative with dosing: Recent long-term data shows fludrocortisone doses can often be reduced after 60+ months of treatment, but initial adequate replacement is critical to prevent crises. 7