What is the appropriate dosing, monitoring, contraindications, and adverse effects of fludrocortisone acetate 0.1 mg oral tablet for primary adrenal insufficiency and orthostatic hypotension?

Fludrocortisone Acetate 0.1 mg Oral Tablet: Dosing, Monitoring, and Management

Standard Dosing

Most patients with primary adrenal insufficiency should take 50–200 µg (0.05–0.2 mg) fludrocortisone as a single daily dose taken upon awakening, with 100 µg (0.1 mg) daily being the most common starting dose. 1, 2

Dosing by Population:

• Adults with PAI: 50–200 µg daily, typically starting at 100 µg 1, 2
• Children and younger adults: Often require higher doses, up to 500 µg daily due to physiological differences 1, 3
• Pregnancy (third trimester): May require up to 500 µg daily due to progesterone's anti-mineralocorticoid effects 1
• Salt-losing congenital adrenal hyperplasia: 100–200 µg daily 2

Critical Administration Details:

• Take as a single morning dose upon awakening—never use alternate-day dosing 1, 3
• Tablets may be kept at room temperature despite package labeling requiring refrigeration (decay rate only 0.1% in 6 months at room temperature) 1
• Must be taken daily without interruption to prevent dangerous electrolyte fluctuations and adrenal crisis 3

---

Monitoring Parameters

Clinical Assessment (at every visit):

• Blood pressure in both supine AND standing positions: Orthostatic hypotension indicates under-replacement; hypertension indicates over-replacement 1, 4, 3
• Salt craving or lightheadedness: Suggests under-replacement 1, 4
• Peripheral edema: Suggests over-replacement 1, 4
• Weight monitoring: Assess for fluid retention 1

Laboratory Monitoring:

• Serum sodium and potassium: Low sodium or high potassium warrant dose increases by 0.05 mg increments 4, 2, 5
• Plasma renin activity (PRA): Target the upper half of normal range; low-normal PRA suggests over-replacement, elevated PRA suggests under-replacement 4, 5, 6
• Monitor at baseline, then at least annually 1, 4

Follow-up Schedule:

• Annual minimum review with assessment of health, well-being, weight, blood pressure, and serum electrolytes 1, 4
• Screen periodically for new autoimmune disorders (particularly hypothyroidism) 1
• Bone mineral density every 3–5 years to assess for glucocorticoid-related complications 1

---

Contraindications and Drug Interactions

Absolute Contraindications:

• Systemic fungal infections (general corticosteroid contraindication) 2

Medications to AVOID (interact dangerously with fludrocortisone):

• Diuretics (all types, including thiazides, loop diuretics) 1, 4, 3
• Acetazolamide 1, 4
• NSAIDs 1, 4, 3
• Carbenoxolone and licorice (potentiate mineralocorticoid effects, causing hypertension) 1, 4, 3
• Grapefruit juice (potentiates mineralocorticoid effects) 1, 4, 3

Medications Requiring Dose Adjustment:

• Drospirenone-containing contraceptives: May require increased fludrocortisone dose 1
• Digitalis glycosides: Enhanced risk of arrhythmias due to hypokalemia; monitor potassium closely 2
• Potassium-depleting diuretics and amphotericin B: Enhanced hypokalemia risk; check potassium frequently 2
• Oral anticoagulants: Decreased prothrombin time response 2

Use with Caution:

• Hypothyroidism or cirrhosis: Enhanced corticosteroid effects 2
• Ocular herpes simplex: Risk of corneal perforation 2
• Nonspecific ulcerative colitis, diverticulitis, peptic ulcer disease: Risk of perforation 2
• Renal insufficiency, hypertension, osteoporosis, myasthenia gravis: Requires careful monitoring 2

---

Adverse Effects and Management

Common Adverse Effects:

• Hypertension: Reduce dose by 0.05 mg but never discontinue completely (risk of adrenal crisis) 1, 4, 3
• Peripheral edema: Indicates over-replacement; reduce dose 1, 4
• Hypokalemia: Enhanced with concurrent potassium-depleting drugs; supplement potassium if needed 2
• Hypernatremia: Monitor electrolytes regularly 7

Serious Adverse Effects:

• Congestive heart failure: Especially with chronic use or over-replacement 7
• Hyperglycemia: Monitor in diabetic patients 7
• Arrhythmias: Particularly with concurrent digitalis use and hypokalemia 2
• Psychic derangements: Range from euphoria to severe depression or psychosis 2

Signs of Under-Replacement (Common Pitfall):

• Under-replacement is more common than over-replacement and predisposes to recurrent adrenal crises 1, 3
• Persistent salt craving, orthostatic hypotension, lightheadedness, elevated PRA, hyponatremia, hyperkalemia 1, 4, 5
• Do not compensate for mineralocorticoid under-replacement by increasing glucocorticoid doses 1

---

Special Situations and Dose Adjustments

Pregnancy:

• Small dose adjustments may be needed, particularly in the third trimester (up to 500 µg daily) due to progesterone's anti-mineralocorticoid activity 1
• Parenteral hydrocortisone required during delivery 1

Surgery and Invasive Procedures:

• Continue fludrocortisone at usual dose 1
• Increase glucocorticoid (hydrocortisone) coverage as needed 1

Hypertension Management:

• If essential hypertension develops, reduce fludrocortisone dose but never stop completely 1
• Add vasodilator therapy if needed rather than discontinuing mineralocorticoid 1
• Monitor for hyperkalemia with dose reduction 4

High Ambient Temperature:

• May require dose adjustments to avoid sodium depletion 6

---

Patient Education Essentials

Critical Safety Information:

• Wear medical alert identification jewelry and carry a steroid alert card at all times 1
• Carry emergency injectable hydrocortisone (100 mg IM) and know how to self-administer 1, 4
• Never skip doses or attempt alternate-day dosing (risk of adrenal crisis) 3

Dietary Recommendations:

• Consume salt and salty foods ad libitum (without restriction) 1, 3
• Avoid potassium-containing salt substitutes (often marketed as "healthy salts") 1, 3
• Avoid licorice and grapefruit juice completely 1, 4, 3

Stress Dose Protocols:

• Double or triple hydrocortisone dose during febrile illness, gastroenteritis, or significant physical stress 4
• Use emergency injectable hydrocortisone (100 mg IM) if unable to take oral medications or during severe illness 4
• Seek immediate medical attention for signs of adrenal crisis 1

Missed Dose Instructions:

• Take as soon as remembered unless almost time for next dose 2
• Never double the next dose 2

---

Algorithm for Dose Titration

Starting dose: 100 µg (0.1 mg) daily upon awakening 2

If Under-Replacement Signs Present (salt craving, orthostatic hypotension, elevated PRA, hyponatremia, hyperkalemia):

1. Increase by 50 µg (0.05 mg) increments 4, 2
2. Reassess in 2–4 weeks with blood pressure (supine/standing), electrolytes, and PRA 4
3. Continue titrating until symptoms resolve and PRA in upper normal range 4, 6

If Over-Replacement Signs Present (hypertension, edema, suppressed PRA):

1. Decrease by 50 µg (0.05 mg) but never discontinue completely 1, 4, 2
2. Monitor for rebound hyperkalemia 4
3. Consider adding vasodilator if hypertension persists despite dose reduction 1

Long-Term Follow-Up:

• Fludrocortisone dose may be reduced over time (>60 months follow-up) as patients stabilize 5
• Continue annual monitoring indefinitely 1, 4