Relacorilant and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Relacorilant
Simvastatin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Here's what's going on. Simvastatin (Zocor) is a cholesterol medicine that your body breaks down using a liver enzyme called CYP3A4. Relacorilant (Lifyorli) can slow that enzyme down. When the enzyme is slowed, simvastatin can build up in your body to higher levels than intended.
With statins, higher levels can mean a bigger chance of muscle aches or, rarely, more serious muscle problems. The good news is that this is very manageable. Your care team knows about this combination and can watch you closely, adjust things, or choose a different option if needed. Please don't stop either medicine on your own, just check in with your pharmacist or doctor.
Mechanism: Relacorilant inhibits CYP3A4, the primary enzyme metabolizing simvastatin (a CYP3A4 substrate). Neither drug is a prodrug here, so inhibition raises simvastatin exposure.
- Direction: Increased simvastatin AUC/Cmax and increased risk of statin-related adverse effects (myopathy, rhabdomyolysis).
- Severity/evidence: Major; substantiation probable.
- Onset: Unspecified.
- Management: Manufacturer guidance is to avoid concomitant use unless otherwise recommended. If co-administered, individualize dosing and monitor for muscle pain, weakness, and CK; consider a statin less dependent on CYP3A4 as an alternative per the care team.
What happens
Increased CYP3A4 substrate exposure and an increased risk of CYP3A4-substrate-related adverse reactions
Interaction Deep Dive
Unless there is a specific recommendation to do otherwise, the combined use of relacorilant with CYP3A4 substrates should be avoided. Using them together may raise the exposure to these substrates and heighten the likelihood of adverse reactions associated with them1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of relacorilant
How to manage this interaction
What your care team may do:
- Because relacorilant can raise simvastatin levels, the labeling recommends avoiding this combination unless your team decides it's needed.
- If both are used, your team may adjust the simvastatin dose, monitor you more closely for muscle symptoms, or consider a different cholesterol medicine.
What you should do:
- Keep taking both exactly as prescribed until your care team tells you otherwise.
- Report any muscle pain, tenderness, weakness, or dark urine promptly.
- Ask your pharmacist or prescriber whether this combination is right for you or if an alternative fits better.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In studies evaluating drug interactions, giving relacorilant 350 mg in the fasted state (equivalent to 1.8 times the relacorilant exposure achieved at the recommended dose) once daily over 10 days together with midazolam (a CYP3A4 substrate) raised the Cmax by 3.1-fold and the AUC by 8.9-fold 1.
Common questions
Can I take Relacorilant and Simvastatin together?
Relacorilant can raise simvastatin levels and the risk of muscle side effects, so this combination is generally avoided unless your care team specifically recommends it. Keep taking both as prescribed and check with your pharmacist or doctor about the safest plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relacorilant and Simvastatin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Relacorilant and Simvastatin interaction managed?
What your care team may do: Because relacorilant can raise simvastatin levels, the labeling recommends avoiding this combination unless your team decides it's needed. If both are used, your team may adjust the simvastatin dose, monitor you more closely for muscle symptoms, or consider a different cholesterol medicine. What you should do: Keep taking both exactly as prescribed until your care team… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Relacorilant or Simvastatin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: LIFYORLI™ oral capsules, relacorilant oral capsules. Corcept Therapeutics Incorporated (Per Manufacturer), Redwood City, CA, 2026. DailyMed
Keep reading about Relacorilant
Keep reading about Simvastatin
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