Does mifepristone (Korlym) interact with the patient's current medications: eszopiclone (Lunesta), bupropion (Wellbutrin XL), trazodone, atorvastatin, tirzepatide (Zepbound), metoprolol succinate extended‑release, and losartan‑hydrochlorothiazide?

Korlym Has Critical Drug Interactions with This Patient's Medications

Yes, Korlym (mifepristone) has clinically significant interactions with multiple medications on this patient's list, most critically with atorvastatin and bupropion, requiring immediate intervention before starting Korlym. 1

Critical Contraindicated Interactions

Atorvastatin - HIGH RISK

• Korlym is a potent CYP3A inhibitor and will significantly increase atorvastatin exposure, creating substantial risk for myopathy and rhabdomyolysis 1
• The FDA label explicitly contraindicates simvastatin and lovastatin with Korlym due to this mechanism 1
• While atorvastatin is not explicitly contraindicated in the label, it is metabolized by CYP3A4 and will have significantly increased exposure 2
• Action required: Switch to a non-CYP3A4 metabolized statin (pravastatin, rosuvastatin, or pitavastatin) before initiating Korlym 2

Major Interactions Requiring Dose Adjustment

Bupropion (Wellbutrin XL 450mg total daily) - MODERATE RISK

• Korlym inhibits CYP2B6, which metabolizes bupropion 1
• The FDA label specifically warns to "use caution" with bupropion when combined with Korlym 1
• At 450mg daily (300mg + 150mg), this patient is on a high dose that increases seizure risk
• Bupropion also inhibits CYP2D6, which can interact with metoprolol (see below) 3, 4
• Action required: Consider dose reduction of bupropion or close monitoring for increased bupropion effects (agitation, tremor, seizure risk)

Metoprolol Succinate ER 100mg - MODERATE RISK

• Metoprolol is metabolized by CYP2D6, not CYP3A4, so no direct interaction with Korlym expected
• However, the concurrent bupropion is a potent CYP2D6 inhibitor that increases metoprolol exposure 4-6 fold 3, 4
• This combination (bupropion + metoprolol) has caused severe bradycardia and AV block 3
• Action required: Monitor heart rate and blood pressure closely; consider switching to a beta-blocker not metabolized by CYP2D6 (bisoprolol, atenolol) or reducing metoprolol dose

Minor/Manageable Interactions

Eszopiclone (Lunesta) - LOW RISK

• Eszopiclone is metabolized by multiple CYP enzymes including CYP3A4, but less dependent than older benzodiazepines 5
• Korlym may increase eszopiclone levels modestly
• Action: Use lowest effective dose (patient already on 1-2mg, which is appropriate); monitor for increased sedation

Trazodone (tapering off) - LOW RISK

• Trazodone is partially metabolized by CYP3A4
• Since patient is tapering off, this interaction becomes less relevant over time
• Action: Continue taper as planned; monitor for increased sedation if still on trazodone when Korlym starts

Losartan-HCTZ - MINIMAL RISK

• Losartan is metabolized by CYP2C9 (which Korlym also inhibits) 1
• However, Korlym's effect on CYP2C9 substrates is less pronounced than on CYP3A4 substrates
• Action: Monitor blood pressure; may see modest increase in losartan effect

Tirzepatide (Zepbound) - NO INTERACTION

• GLP-1 receptor agonists are peptides metabolized by proteolytic degradation, not CYP enzymes 6
• No interaction expected

Critical Timing Consideration

Due to mifepristone's extremely long half-life (85 hours at steady state), allow at least 2 weeks after stopping Korlym before increasing doses of any interacting medications 1

Recommended Action Plan

1. Before starting Korlym:

   • Switch atorvastatin 10mg to pravastatin 40mg, rosuvastatin 10mg, or pitavastatin 2mg
   • Consider reducing bupropion dose from 450mg to 300mg daily OR increase monitoring
   • Consider switching metoprolol to bisoprolol or atenolol, OR reduce metoprolol dose by 50%

2. When starting Korlym:

   • Limit Korlym dose to 900mg daily maximum (standard dosing) 1
   • Monitor for signs of excessive beta-blockade (bradycardia <50 bpm, hypotension, dizziness)
   • Monitor for bupropion toxicity (tremor, agitation, insomnia)

3. Ongoing monitoring:

   • Check CK levels if muscle symptoms develop
   • Monitor heart rate and blood pressure at each visit
   • Assess for CNS effects from increased eszopiclone/trazodone exposure

Common pitfall: Failing to recognize that Korlym's CYP3A4 inhibition persists for weeks after discontinuation due to its long half-life, requiring extended caution periods when adjusting other medications.