FLUDROCORTISONE ACETATE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Mineralocorticoid receptor agonist; promotes sodium reabsorption and potassium excretion in renal distal tubules, increasing extracellular fluid volume. Also has glucocorticoid activity.
| Metabolism | Hepatic via CYP3A4; also reduced by 5α-reductase and 5β-reductase. |
| Excretion | Renal (80%) as inactive metabolites; less than 5% unchanged; minor biliary/fecal elimination. |
| Half-life | Terminal elimination half-life is 3.5 hours (range 2–5 h); clinical effect duration exceeds half-life due to mineralocorticoid receptor binding. |
| Protein binding | Approximately 90% bound primarily to corticosteroid-binding globulin (CBG, transcortin) and albumin. |
| Volume of Distribution | 0.3–0.4 L/kg; reflects primarily extracellular distribution and low tissue binding. |
| Bioavailability | Oral: approximately 100% (well absorbed); IM: 100%. |
| Onset of Action | Oral: 1–2 hours; peak effect at 6–8 hours; intramuscular: 1–2 hours. |
| Duration of Action | Oral: Approximately 12–24 hours; IM: Up to 24 hours; sustained effect due to salt-retaining activity. |
0.1 mg orally once daily, range 0.05-0.2 mg/day
| Dosage form | TABLET |
| Renal impairment | No adjustment required |
| Liver impairment | No adjustment required |
| Pediatric use | 0.1 mg/m² orally once daily |
| Geriatric use | Use lowest effective dose; monitor for electrolyte disturbances and edema |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other drugs that lower potassium may have additive effects Can cause hypertension and hypokalemia.
| Breastfeeding | Fludrocortisone acetate is excreted into human breast milk in small amounts; the milk-to-plasma ratio is unknown but expected to be low due to high protein binding. Limited data suggest no adverse effects in breastfed infants at maternal replacement doses (0.1-0.2 mg/day). Caution is advised, but generally considered compatible with breastfeeding. |
| Teratogenic Risk | Corticosteroids including fludrocortisone are associated with an increased risk of orofacial clefts (odds ratio ~1.3-3.3) following first-trimester exposure, based on observational studies. Second and third trimester exposure may increase risk of fetal growth restriction, preterm birth, and adrenal suppression. Animal studies show dose-dependent teratogenicity including cleft palate and fetal loss. Overall risk is low at typical replacement doses in adrenal insufficiency. |
■ FDA Black Box Warning
No FDA boxed warning.
| Common Effects | Hyperglycemia |
| Serious Effects |
["Systemic fungal infections","Hypersensitivity to fludrocortisone or components","Live or attenuated virus vaccines (relative)"]
| Precautions | ["May cause hypertension, fluid retention, hypokalemia, and cardiac hypertrophy.","Monitor blood pressure, electrolytes, and signs of infection; suppress hypothalamic-pituitary-adrenal axis.","May mask signs of infection and decrease immune response."] |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium and sodium), and clinical signs of fluid overload, hypertension, or hypokalemia. In pregnancy, fetal growth assessed by serial ultrasound for growth restriction; fetal adrenal suppression may be suspected if maternal dose exceeds physiologic replacement (e.g., >0.2 mg/day). Neonatal monitoring for adrenal insufficiency if prolonged high-dose exposure near delivery. |
| Fertility Effects | No known direct effect on fertility in humans. In men with congenital adrenal hyperplasia, fludrocortisone replacement therapy may improve spermatogenesis by normalizing adrenal androgen excess. In women, correction of menstrual irregularities may occur with appropriate glucocorticoid and mineralocorticoid replacement, potentially improving fertility. |