What is the use and dosage of Fludrocortisone (a synthetic corticosteroid) in treating primary adrenocortical insufficiency and orthostatic hypotension?

Fludrocortisone: Clinical Use and Dosing

Fludrocortisone is a synthetic mineralocorticoid used at 50-200 μg daily as a single morning dose for mineralocorticoid replacement in primary adrenal insufficiency, with dose adjustments based on blood pressure, serum electrolytes, and clinical symptoms such as salt cravings or orthostatic hypotension. 1

Primary Indication

• Fludrocortisone is indicated for partial replacement therapy in primary adrenocortical insufficiency (Addison's disease) and salt-losing adrenogenital syndrome 2
• It is NOT required in secondary adrenal insufficiency, where only glucocorticoid replacement is needed 3
• Primary adrenal insufficiency requires both glucocorticoid AND mineralocorticoid replacement, as all adrenocortical hormones are deficient 3

Standard Dosing Protocol

Initial Dosing

• Most adults with primary adrenal insufficiency should receive 50-200 μg fludrocortisone as a single daily dose taken upon awakening 1
• The FDA-approved starting dose is typically 0.1 mg (100 μg) daily 2
• Children and younger adults may require higher doses, up to 500 μg daily 1
• For salt-losing adrenogenital syndrome, the recommended dose is 0.1-0.2 mg daily 2

Timing

• Administer as a single dose in the morning upon awakening 1
• Fludrocortisone is preferably given in conjunction with hydrocortisone (10-30 mg daily in divided doses) or cortisone acetate (10-37.5 mg daily in divided doses) 2

Dose Adjustment Algorithm

Indicators to INCREASE Dose

• Orthostatic hypotension despite adequate sodium intake 4
• Persistent salt cravings 1, 4
• Hyponatremia 4, 5
• Hyperkalemia 4, 5
• Elevated plasma renin activity 5
• Lightheadedness or postural symptoms 1

Indicators to DECREASE Dose

• Development of hypertension (reduce dose but do NOT stop completely) 1, 4
• Peripheral edema 1, 4
• Hypernatremia 5
• Hypokalemia 5
• Suppressed renin levels 5

Monitoring Parameters

• Blood pressure in both supine AND standing positions 1, 4
• Serum sodium and potassium 1, 4, 5
• Plasma renin activity (shows dose-dependent inverse correlation with fludrocortisone dose) 5
• Clinical symptoms: salt cravings, lightheadedness, peripheral edema 1, 4
• Annual review minimum, with assessment of weight, blood pressure, and electrolytes 1, 4

Special Populations and Situations

Pregnancy

• Fludrocortisone dose often needs to be increased during late pregnancy, particularly the third trimester 1, 4
• Progesterone has anti-mineralocorticoid effects, necessitating dose increases 1
• Plasma renin activity is not reliable for dose adjustment during pregnancy; use salt cravings, blood pressure, and electrolytes instead 1

Long-term Follow-up

• Fludrocortisone dose may be reduced in long-term follow-up (>60 months) 5
• Approximately half of patients maintain stable doses of 50-75 μg daily over time 5

Critical Drug Interactions and Contraindications

AVOID These Medications

• Diuretics 1, 4
• Acetazolamide 1
• NSAIDs 1
• Carbenoxolone 1
• Liquorice (potentiates mineralocorticoid effect) 1
• Grapefruit juice (potentiates mineralocorticoid effect) 1

May Require Dose Adjustment

• Drospirenone-containing contraceptives may require HIGHER fludrocortisone doses 1, 4

Dietary Recommendations

• Patients should take salt and salty foods ad libitum (without restriction) 1, 4
• AVOID potassium-containing salt substitutes marketed as "healthy" 1
• Unrestricted sodium intake is an important third component of substitution therapy 1

Critical Safety Considerations

Under-replacement Risks

• Under-replacement with fludrocortisone is common and may predispose patients to recurrent adrenal crises 1, 4
• Under-replacement is sometimes compensated for by over-replacement of glucocorticoids 1

Hypertension Management

• If essential hypertension develops, add a vasodilator rather than stopping mineralocorticoid replacement 1, 4
• Reduce fludrocortisone dose but do NOT discontinue completely 1, 4

Abrupt Discontinuation

• Abrupt discontinuation can trigger adrenal crisis with hypotension, hyponatremia, hyperkalemia, and potentially life-threatening cardiovascular collapse 4
• Fludrocortisone should be tapered over at least 1-3 days rather than abruptly discontinued 4
• Patients with primary adrenal insufficiency are at higher risk for severe consequences from abrupt discontinuation 4

Common Pitfalls to Avoid

• Do NOT stop fludrocortisone completely when hypertension develops—reduce the dose instead 1, 4
• Do NOT rely solely on plasma renin activity during pregnancy for dose adjustment 1
• Do NOT forget to adjust fludrocortisone during pregnancy or periods of increased physical stress 4
• Do NOT allow patients to use potassium-containing salt substitutes 1
• Do NOT overlook drug interactions, particularly with diuretics and NSAIDs 1, 4