Fludrocortisone
Fludrocortisone
Generic Name
Fludrocortisone
Mechanism
Fludrocortisone acts as a high‑affinity agonist of the mineralocorticoid receptor (MR) in renal cortical cells, vascular smooth muscle, and intestinal epithelium.
• ↑ Na⁺/Cl⁻ absorption in the distal nephron → ↑ plasma volume, ↑ systolic BP
• ↑ K⁺ and H⁺ excretion → ↓ serum potassium, ↓ acidemia
• Relatively weak glucocorticoid activity (≈ 5‑10 % of cortisol potency) – the drug’s therapeutic effects rely mainly on its mineralocorticoid properties.
In contrast to aldosterone, fludrocortisone has a longer duration of action (~30 h) and oral bioavailability of ~90 %.
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Oral bioavailability ~90 % | Rapid absorption; peak plasma 1–2 h |
| Distribution | Volume of distribution ≈ 12 L | Protein‑binding ~80 % (α‑1‑acid glycoprotein) |
| Metabolism | Hepatic CYP3A4 mainly → 4‑hydroxy metabolite | Minimal renal excretion; metabolite inactive |
| Elimination half‑life | 11–18 h (clinical) | Clinical effect may last 20–30 h |
| Excretion | 70–80 % biliary, 10–20 % renal | No dose adjustment for mild‑moderate renal disease |
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Indications
- Addison’s disease (primary adrenal insufficiency) – maintenance and adrenal crisis rescue.
- Secondary adrenal insufficiency when mineralocorticoid replacement is needed (e.g., post‑adrenalectomy).
- Orthostatic hypotension secondary to low plasma volume (post‑tropic).
- Hypovolemia and sodium‑loss disorders (e.g., Bartter syndrome, loop‑diuretic side effects).
- Low‑dose “Addisonian challenge” in endocrinology work‑ups to evaluate endogenous cortisol production.
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Contraindications
- Absolute Contraindications
- Known hypersensitivity to fludrocortisone or excipients.
- Untreated or severe hypertension—risk of exacerbation.
- Cushing syndrome or any condition of hypercortisolism.
- SIADH (syndrome of inappropriate ADH secretion).
- Fluid‑overload states (CHF, cirrhosis); risk of edema, pulmonary congestion.
- Warnings
- Hypernatremia and hyponatremia – monitor sodium; adjust dose.
- Hypokalemia – risk of arrhythmia, especially with concomitant diuretics.
- Glucose intolerance/diabetes mellitus – may worsen glycemic control.
- Osteoporosis & bone fractures with prolonged use.
- Pregnancy – category C; use only if benefits outweigh risks.
- Concomitant CYP3A4 inhibitors (ketoconazole, clarithromycin) ↑ exposure → monitor signs of hypertension, electrolyte imbalance.
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Dosing
- Addison’s disease
- Oral tablets (0.1 mg) once daily (preferably in the evening).
- Rescue (adrenal crisis): 0.2 mg IV or IM, repeat every 6 h until stabilization, then bridge to oral.
- Orthostatic hypotension / other indications
- 0.05 – 0.1 mg daily; titrate to BP/weight changes.
- Administration tips
- Swallow whole; do not chew or crush to avoid dose variability.
- Consistently take at the same time of day to reduce circadian fluctuations.
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Adverse Effects
| Adverse Effect | Frequency | Notes |
| Hypertension | ↑ 7–12 % | Dose‑dependent; monitor BP. |
| Hypokalemia | ↑ 5–10 % | Can precipitate arrhythmias; monitor K⁺. |
| Edema / weight gain | ≤ 5 % | Fluid retention, especially in elderly. |
| Mood changes, insomnia, anxiety | ≤ 3 % | Corticosteroid spectrum. |
| Hyperglycemia | ≤ 3 % | Worsens pre‑existing diabetes. |
| Mastitis / milk engorgement | Rare | In lactating patients. |
| Serious: Severe electrolyte disturbances, congestive heart failure exacerbation, adrenal crisis if discontinued acutely. |
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Monitoring
| Parameter | Frequency | Rationale |
| Serum sodium & potassium | Baseline, then 1–2 wk after dose change, then monthly | Detect hypo/hypernatremia, hypokalemia. |
| Serum creatinine & eGFR | Baseline, then every 3 mo | Renal function influences clearance. |
| Blood pressure | Each clinic visit; home BP as needed | Hypertension risk. |
| Weight | Each visit | Fluid retention. |
| Morning serum cortisol levels | Before titration; every 6–8 wk if clinical suspicion | Verify adequate adrenal replacement. |
| Bone density (DEXA) | After ≥ 1 yr of therapy, especially > 50 y | Evaluate osteoporosis risk. |
| Pregnancy screening | For women of childbearing age | Avoid teratogenic exposure if possible. |
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Clinical Pearls
- Low‑dose Challenge Test – A single 15 mg dose of hydrocortisone or 0.1 mg fludrocortisone can unmask adrenal insufficiency; useful when ACTH is unreliable.
- Fluid‑balanced Regimen – Combine fludrocortisone with a low‑dosage β‑blocker if hypertension is problematic; this preserves electrolyte balance while controlling BP.
- Avoid Abrupt Discontinuation – Sudden withdrawal may precipitate adrenal crisis; consider tapering over 3–5 days if dose reduction is needed.
- Kidney Function Doesn’t Necessarily Require Dose Adjustment – Most patients with mild–moderate CKD tolerate same dosing; however, monitor electrolytes closely.
- CYP3A4 Inhibitors – Double‑check drug interactions; when co‑administered with potent inhibitors, reduce dose and monitor serum electrolytes/ BP.
- High‑altitude Use – In climbers with impaired adrenal function, fludrocortisone at 0.05–0.1 mg/day can prevent orthostatic hypotension and maintain plasma volume.
- Pregnancy – If pregnancy is confirmed, switch to hydrocortisone 15 mg/day + chlorothiazide 12.5 mg (to mimic mineralocorticoid effect safely) until delivery.
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• Key Takeaway:
Fludrocortisone is a reliable mineralocorticoid replacement for adrenal insufficiency and fluid‑balance disorders. Careful dose titration, vigilant monitoring of electrolytes & BP, and attention to drug interactions are essential for safe, effective therapy.