How should fludrocortisone be dosed, titrated, and monitored in a patient with primary adrenal insufficiency (Addison disease) or orthostatic hypotension due to autonomic failure, and what are its contraindications and alternative therapies?

Fludrocortisone Dosing and Management

Primary Adrenal Insufficiency (Addison Disease)

Start fludrocortisone at 0.1 mg once daily upon awakening, with a typical dosing range of 0.05-0.2 mg daily, though doses up to 0.5 mg may be required in children, younger adults, or during the third trimester of pregnancy. 1, 2

Initial Dosing

• Standard starting dose: 0.1 mg once daily taken upon awakening 1, 2
• Dosing range: 0.05-0.2 mg daily for most adults 1, 3, 2
• Higher doses (up to 0.5 mg daily) may be necessary in:
  • Children and younger adults 1
  • Third trimester of pregnancy when progesterone counteracts mineralocorticoids 1
• If transient hypertension develops, reduce to 0.05 mg daily 2

Titration Strategy

• Adjust dose based on clinical parameters, not laboratory values alone 1
• Increase dose if patient reports:
  • Salt cravings 1
  • Lightheadedness or orthostatic symptoms 1
  • Postural hypotension on blood pressure measurement 1
• Decrease dose if patient develops:
  • Peripheral edema 1
  • Hypertension 1
  • Hypokalemia 3

Monitoring Parameters

• Clinical assessment at each visit:
  • Ask specifically about salt cravings 1
  • Measure blood pressure in both supine and standing positions 1
  • Examine for peripheral edema 1
• Laboratory monitoring:
  • Serum sodium and potassium levels 3, 4
  • Plasma renin activity (target upper normal range) 5, 4
  • Recent evidence shows renin and electrolytes correlate with fludrocortisone dose and indicate mineralocorticoid activity 4

Critical Drug Interactions and Contraindications

Avoid the following medications entirely: 1

• Diuretics 1
• Acetazolamide 1
• Carbenoxolone and liquorice 1
• NSAIDs 1

May require dose adjustment:

• Drospirenone-containing contraceptives (may need more fludrocortisone) 1
• ACE inhibitors or ARBs (monitor potassium and creatinine closely) 3

Dietary considerations:

• Advise patients to consume sodium salt and salty foods without restriction 1, 3
• Avoid potassium-containing salts 1
• Avoid liquorice and grapefruit juice, which potentiate mineralocorticoid effects 1, 3

Special Populations

Pregnancy:

• Fludrocortisone dose often needs to be increased during late pregnancy due to progesterone's anti-mineralocorticoid effects 1
• Plasma renin activity is not reliable for dose adjustment during pregnancy; rely on salt cravings, blood pressure, and serum electrolytes 1

Essential hypertension in PAI patients:

• Treat with a vasodilator rather than stopping mineralocorticoid replacement 1
• Consider dose reduction but do not discontinue 1

Common Pitfalls

• Under-replacement is common and may be compensated for by over-replacement of glucocorticoids, predisposing patients to recurrent adrenal crises 1
• Recent data shows fludrocortisone prescription appears independent of glucocorticoid dose, suggesting clinicians should evaluate mineralocorticoid needs separately 6
• Storage: While formulation instructions require refrigeration, actual decay rate is only 0.1% in the first 6 months at room temperature 1

Orthostatic Hypotension Due to Autonomic Failure

For orthostatic hypotension, use fludrocortisone 0.05-0.2 mg daily (or 0.1-0.3 mg once daily per European Society of Cardiology guidelines) as adjunctive therapy when salt and fluid intake alone are inadequate. 3

Dosing for Orthostatic Hypotension

• Standard dose: 0.05-0.2 mg daily 3
• Alternative range: 0.1-0.3 mg once daily per European Society of Cardiology 3
• Blood pressure effects may be more pronounced in older adults and those prone to polypharmacy effects 3

Mechanism of Action in Orthostatic Hypotension

Fludrocortisone works through three mechanisms: 3

• Causes sodium retention and water expansion, directly increasing intravascular volume 3
• Has a direct constricting effect on partially denervated blood vessels 3
• Increases water content of vessel walls, reducing their distensibility 3

Monitoring for Orthostatic Hypotension

• Monitor serum potassium levels regularly, as hypokalemia is a common side effect that may require potassium supplementation 3
• Measure blood pressure in supine and standing positions 1

Alternative Therapies

For primary adrenal insufficiency, there is no alternative to mineralocorticoid replacement—fludrocortisone is essential for maintaining blood pressure and electrolyte homeostasis. 1

Glucocorticoid Component (PAI only)

While not an alternative to fludrocortisone, glucocorticoid replacement must be optimized: 1

• Hydrocortisone 15-25 mg daily in divided doses (preferred) 1
• Cortisone acetate 25-37.5 mg daily in divided doses 1
• Modified-release hydrocortisone formulations are available but their role is still being evaluated 1

Adjunctive Therapy for Women with PAI

• DHEA 25 mg daily may be considered for women with persistent fatigue, low libido, or low energy despite optimized glucocorticoid and mineralocorticoid replacement 1, 7
• Offer a 6-month trial and continue only if clinically effective 1, 7
• Long-term effects are unknown; use with caution 1

For Vasovagal Syncope

• The American Heart Association suggests fludrocortisone might be reasonable for patients with recurrent vasovagal syncope who have inadequate response to salt and fluid intake 3