Relacorilant and Acetaminophen And Codeine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Relacorilant
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 is what is going on. Relacorilant can slow down a liver enzyme called CYP3A4. That same enzyme helps clear the codeine in your pain medicine out of your body. When the enzyme is slowed, more of the medicine can build up.
For codeine, that can mean stronger opioid effects, like extra drowsiness, dizziness, constipation, or slowed breathing. The acetaminophen part is not the main worry here. The good news is your care team can manage this by keeping a close eye on you or choosing a different pain option if needed. Please do not stop or change either medicine on your own. Just check in with your pharmacist or doctor first.
Mechanism: Relacorilant inhibits CYP3A4, reducing metabolism of CYP3A4 substrates and increasing their exposure (AUC/Cmax).
- Direction: Codeine is partly metabolized by CYP3A4 (to norcodeine) with CYP2D6 producing the active morphine. Reduced CYP3A4 clearance can raise codeine exposure and enhance opioid effects (sedation, respiratory depression, constipation).
- Evidence: Probable. Severity major. Onset unspecified.
- Management: Avoid concomitant use unless otherwise recommended. If unavoidable, individualize opioid dosing and monitor closely for opioid toxicity. Acetaminophen is not the primary concern.
What happens
Increased CYP3A4 substrate exposure and an increased risk of CYP3A4-substrate-related adverse reactions
Interaction Deep Dive
Unless specifically advised otherwise, do not use relacorilant together with CYP3A4 substrates. Taking them concurrently can raise exposure to those substrates, thereby heightening the potential for 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:
- The label advises avoiding this combination unless your prescriber specifically recommends it, so they may choose a different pain medicine.
- If both are needed, your opioid dose may be adjusted and individualized, and your team may monitor you more closely for opioid side effects.
What you should do:
- Keep taking both as prescribed until you speak with your care team.
- Tell your pharmacist or doctor right away about unusual drowsiness, confusion, slow or shallow breathing, or severe constipation.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In studies examining drug interactions, giving relacorilant 350 mg once daily under fasted conditions (equivalent to 1.8 times the relacorilant exposure achieved at the recommended dose) for 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 Acetaminophen And Codeine together?
Relacorilant can slow the breakdown of codeine, raising the risk of opioid side effects, so this combination is generally avoided unless your prescriber says otherwise. Talk with your pharmacist or doctor before making any changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relacorilant and Acetaminophen And Codeine 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 Acetaminophen And Codeine interaction managed?
What your care team may do: The label advises avoiding this combination unless your prescriber specifically recommends it, so they may choose a different pain medicine. If both are needed, your opioid dose may be adjusted and individualized, and your team may monitor you more closely for opioid side effects. What you should do: Keep taking both as prescribed until you speak with your care team. Te… 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.
Questions for your pharmacist
- Does my dose of Relacorilant or Acetaminophen And Codeine 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
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