Fludrocortisone Acetate

Approved Indications:

• Primary adrenal insufficiency (Addison’s disease): Replacement therapy to correct mineralocorticoid deficiency.
• Salt-losing adrenogenital syndrome (congenital adrenal hyperplasia): To maintain electrolyte balance and blood pressure.
• Orthostatic hypotension: To increase blood volume and vascular tone in refractory cases.
• Postural tachycardia syndrome (POTS): Off-label use to increase plasma volume and reduce symptoms.
• Hypotension due to mineralocorticoid deficiency: In various clinical settings.

• Adults:
• Typical dose: 0.1 mg orally once daily.
• Dose adjustments based on clinical response, electrolyte levels, and blood pressure.
• Pediatrics:
• Initial dose: 0.05 to 0.2 mg/day orally, divided doses depending on clinical condition.
• Elderly:
• Use with caution; start at lower doses and titrate carefully due to increased sensitivity.
• Renal/Hepatic Impairment:
• No specific dose adjustment, but monitor for fluid retention and electrolyte imbalance.
• Administration:
• Oral tablets, taken once daily in the morning to mimic natural hormone rhythm.
• Duration:
• Usually long-term or lifelong in adrenal insufficiency.

Fludrocortisone acetate is a synthetic corticosteroid with potent mineralocorticoid activity and moderate glucocorticoid effects. It acts by binding to mineralocorticoid receptors in the distal renal tubules, increasing sodium reabsorption and potassium and hydrogen ion excretion. This action promotes water retention, expands extracellular fluid volume, and increases blood pressure. The glucocorticoid activity contributes to anti-inflammatory and immunosuppressive effects but is minimal at replacement doses.

• Absorption:
  Rapid and complete oral absorption.
• Distribution:
  Widely distributed; crosses cell membranes to bind intracellular receptors.
• Metabolism:
  Hepatic metabolism primarily via reduction and conjugation.
• Elimination:
  Excreted mainly in urine as metabolites.
• Half-life:
  Biological half-life approximately 18 to 36 hours, allowing once-daily dosing.

• Pregnancy:
  FDA Category C. Use only if potential benefits justify risks. Limited human data; animal studies suggest possible fetal harm at high doses.
• Lactation:
  Fludrocortisone is excreted in breast milk in small amounts; caution advised. Use only if clearly needed and monitor the infant.

• Primary class: Corticosteroid
• Subclass: Mineralocorticoid receptor agonist

• Known hypersensitivity to fludrocortisone or any excipients.
• Systemic fungal infections.
• Uncontrolled hypertension or congestive heart failure.
• Severe renal impairment with fluid overload.
• Hypokalemia or hypernatremia without correction.

• Hypertension and fluid retention: Monitor blood pressure and signs of edema closely.
• Electrolyte imbalance: Regularly check serum potassium and sodium.
• Heart failure: Use with caution due to risk of exacerbation.
• Infections: Immunosuppressive effects may increase susceptibility.
• Adrenal suppression: Avoid abrupt withdrawal to prevent adrenal crisis.
• Diabetes mellitus: May worsen glycemic control.
• Osteoporosis: Long-term use may reduce bone density; monitor bone health.

Common Adverse Effects:

• Fluid retention and edema
• Hypertension
• Hypokalemia
• Headache
• Increased sweating

Serious/Rare Side Effects:

• Congestive heart failure exacerbation
• Cardiac arrhythmias secondary to electrolyte disturbances
• Muscle weakness
• Psychiatric effects (e.g., mood swings, depression)
• Allergic reactions (rare)

• Potassium-depleting agents: Increased risk of hypokalemia (e.g., diuretics, laxatives).
• Digitalis glycosides: Increased risk of arrhythmias with hypokalemia.
• Antidiabetic agents: May decrease effectiveness; monitor blood glucose.
• Nonsteroidal anti-inflammatory drugs (NSAIDs): Increased risk of fluid retention and hypertension.
• CYP3A4 inducers/inhibitors: May affect fludrocortisone metabolism and efficacy.

• Emphasis on individualized dosing to minimize side effects while maintaining efficacy.
• Updated monitoring recommendations for electrolyte and blood pressure control.
• Recognition of off-label uses such as POTS with clinical evidence supporting efficacy.
• No major changes in approved indications; ongoing research into mineralocorticoid receptor modulators continues.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in tightly closed containers.
• Do not freeze.
• Keep out of reach of children.