Fludrocortisone - Drug Monograph

Introduction

Fludrocortisone acetate is a synthetic fluorinated corticosteroid with potent mineralocorticoid activity and moderate glucocorticoid effects. It is primarily used for its mineralocorticoid properties to manage conditions involving aldosterone deficiency. First approved by the FDA in the 1950s, fludrocortisone remains an essential medication in endocrine disorders and represents a cornerstone therapy for adrenal insufficiency.

Mechanism of Action

Fludrocortisone acts primarily as a mineralocorticoid receptor agonist, promoting sodium reabsorption and potassium excretion in the distal renal tubules. It enhances water retention through osmotic effects secondary to sodium retention. The drug also exhibits glucocorticoid activity approximately 10-15 times that of hydrocortisone, contributing to anti-inflammatory and immunosuppressive effects. Fludrocortisone binds to intracellular corticosteroid receptors, modifying transcription and protein synthesis.

Indications

• Primary adrenal insufficiency (Addison's disease) as partial replacement therapy
• Salt-losing forms of congenital adrenal hyperplasia
• Treatment of orthostatic hypotension (particularly in autonomic dysfunction)

• Secondary adrenal insufficiency
• Prevention of hypotension in dialysis patients
• Management of cerebral salt wasting syndrome

Dosage and Administration

• Addison's disease: 0.1 mg orally daily (range 0.1 mg 3 times weekly to 0.2 mg daily)
• Salt-losing adrenal hyperplasia: 0.1-0.2 mg daily
• Orthostatic hypotension: 0.1 mg daily, titrated upward to maximum 1 mg daily

• 0.05-0.1 mg daily orally; titrate based on clinical response and electrolyte monitoring

• Administer with food to minimize gastrointestinal upset
• Morning administration is preferred to mimic circadian rhythm
• Dose adjustments based on blood pressure, electrolyte levels, and clinical symptoms

• Hepatic impairment: Use with caution; monitor closely
• Renal impairment: Contraindicated in severe renal impairment
• Elderly: Start with lower doses due to increased cardiovascular risk

Pharmacokinetics

Contraindications

• Systemic fungal infections
• Known hypersensitivity to fludrocortisone or components
• Uncontrolled hypertension
• Congestive heart failure (unless in adrenal crisis)
• Severe renal impairment

Warnings and Precautions

• May cause hypertension, hypokalemia, and fluid retention
• Increased risk of infections due to immunosuppression
• Monitor for signs of adrenal suppression with long-term use
• Use with caution in patients with diabetes mellitus
• May exacerbate psychiatric disorders
• Osteoporosis risk with prolonged therapy
• Peptic ulcer disease may be exacerbated

Drug Interactions

• Diuretics: Potassium-wasting diuretics (furosemide, hydrochlorothiazide) increase hypokalemia risk
• Anticoagulants: Altered response to warfarin
• Antidiabetic agents: May increase blood glucose levels
• CYP3A4 inducers (rifampin, phenytoin): Decreased fludrocortisone levels
• CYP3A4 inhibitors (ketoconazole, erythromycin): Increased fludrocortisone levels
• Digoxin: Hypokalemia may increase digoxin toxicity
• NSAIDs: Increased risk of gastrointestinal bleeding and fluid retention

Adverse Effects

• Hypertension (15-20%)
• Fluid retention/edema (12-18%)
• Hypokalemia (10-15%)
• Headache (10-12%)

• Insomnia, mood changes
• Increased sweating
• Glucose intolerance
• Muscle weakness

• Congestive heart failure
• Severe hypokalemia
• Peptic ulcer disease
• Osteoporosis with long-term use
• Adrenal suppression
• Anaphylactic reactions

Monitoring Parameters

• Complete blood count, electrolytes, renal function
• Blood pressure, weight
• ECG if cardiac risk factors present

• Blood pressure weekly until stable, then monthly
• Serum electrolytes (sodium, potassium) every 1-2 weeks initially, then every 3-6 months
• Weight regularly
• Blood glucose monitoring in diabetic patients
• Bone density assessment with long-term therapy
• Clinical assessment for edema, hypertension symptoms

Patient Education

• Take medication exactly as prescribed; do not stop abruptly
• Regular monitoring of blood pressure and weight at home if recommended
• Report signs of fluid retention (swelling, rapid weight gain)
• Watch for symptoms of hypokalemia (muscle weakness, cramps)
• Maintain consistent sodium intake unless otherwise directed
• Carry medical identification indicating steroid dependence
• Inform all healthcare providers about fludrocortisone use
• Report signs of infection promptly
• Rise slowly from sitting/lying position to prevent dizziness
• Do not receive live vaccines while on therapy

References

1. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-389.

2. National Institutes of Health. Fludrocortisone acetate monograph. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2020.

3. Grossman A, Johannsson G, Quinkler M, et al. Therapy of endocrine disease: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe. Eur J Endocrinol. 2013;169(2):R165-R175.

4. FDA Prescribing Information: Fludrocortisone acetate tablets. Revised 2022.

5. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.

6. Raff H, Sharma ST, Nieman LK. Physiological basis for the etiology, diagnosis, and treatment of adrenal disorders: Cushing's syndrome, adrenal insufficiency, and congenital adrenal hyperplasia. Compr Physiol. 2014;4(2):739-769.