Is Mifepristone safe to use with impaired renal function?

Mifepristone Use with Creatinine 2.4 mg/dL

Mifepristone can be used in patients with renal impairment including a creatinine of 2.4 mg/dL, but the maximum dose must be limited to 600 mg daily rather than the standard maximum of 1200 mg. 1

Dosing Recommendations for Renal Impairment

• No change in the initial starting dose of 300 mg once daily is required for patients with renal impairment 1
• The maximum dose should be capped at 600 mg daily (rather than the standard 1200 mg maximum) in patients with any degree of renal impairment 1
• Dose increases should still occur no more frequently than every 2-4 weeks, with increments of 300 mg as tolerated 1

Pharmacokinetic Rationale

• Mifepristone is primarily metabolized hepatically via CYP3A4 through demethylation and hydroxylation pathways, not renally cleared 2
• The drug has a long half-life of 25-30 hours and is extensively bound to alpha-1-acid glycoprotein (AAG), which limits tissue availability and results in low metabolic clearance 2
• Active metabolites (monodemethylated, didemethylated, and hydroxylated forms) retain considerable receptor affinity and contribute to clinical effects 2

Clinical Monitoring Considerations

• Calculate creatinine clearance or eGFR before initiating therapy rather than relying solely on serum creatinine, as creatinine can be misleading in elderly patients with low muscle mass 3
• A creatinine of 2.4 mg/dL typically corresponds to a creatinine clearance well below 50 mL/min, placing the patient in the category requiring dose limitation 1
• Monitor for adrenal insufficiency clinically rather than by serum cortisol levels, as mifepristone blocks cortisol receptors while cortisol levels remain elevated or increase 1
• Ensure adequate hydration when initiating therapy to minimize potential nephrotoxic effects 3

Important Caveats

• If the patient has severe hepatic impairment in addition to renal dysfunction, mifepristone should not be used 1
• Avoid concomitant nephrotoxic medications (NSAIDs, aminoglycosides) as this compounds toxicity risk in patients with existing renal impairment 3
• If using strong CYP3A inhibitors concurrently (ketoconazole, ritonavir, clarithromycin), further dose adjustments are required with a maximum of 900 mg when starting at 300 mg 1