Acetaminophen And Codeine and Telotristat Ethyl: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Telotristat Ethyl
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.
Your pain medicine here is codeine (combined with acetaminophen/Tylenol). Codeine is a prodrug, meaning your body has to convert it into morphine to actually relieve pain. The other medicine, telotristat ethyl (Xermelo), can speed up the liver enzyme that handles codeine.
When codeine is broken down too fast, less of it turns into morphine. That can mean less pain relief, and if your body is used to the opioid, you might feel withdrawal-like symptoms such as chills, aches, or a runny nose. This is based on theory rather than strong studies, so please don't change anything on your own. Your care team can watch how you feel and adjust your dose so you stay comfortable.
Effect: Telotristat ethyl may induce CYP3A4, increasing codeine's metabolism to inactive norcodeine and shunting away from CYP2D6-mediated conversion to morphine (the active analgesic). Net result: reduced morphine exposure, decreased opioid efficacy, and possible withdrawal in physically dependent patients.
- Direction: Reduced opioid effect (codeine is a prodrug).
- Onset: Unspecified.
- Evidence: Theoretical.
- Management: If co-administered, monitor for reduced analgesia and withdrawal signs; codeine dose may be increased and individualized. If telotristat is later discontinued, anticipate rising morphine levels, consider dose reduction, and monitor for sedation/respiratory depression.
What happens
Reduced codeine and morphine exposure, reduced opioid efficacy and precipitation of opioid withdrawal
Interaction Deep Dive
When codeine is taken together with CYP3A4 inducers, codeine concentrations may fall while norcodeine concentrations rise, and CYP2D6-mediated metabolism may decrease, producing lower morphine levels. This can diminish efficacy or trigger a withdrawal syndrome in patients who have become physically dependent. Should concurrent use be required, monitor patients carefully for reduced efficacy or indications of opioid withdrawal syndrome, and consider raising the codeine dose when needed. When a CYP3A4 inducer is being stopped, consider lowering the codeine dose and watch patients closely for evidence of respiratory depression or sedation12.
Why it happens (mechanism)
Induction of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. This interaction can be managed with attention and follow-up.
- Watch for less pain relief than usual, or withdrawal signs (chills, sweating, body aches, runny nose, stomach upset).
- If your pain isn't controlled, tell your care team. Your codeine dose may need to be adjusted and individualized by them.
- If telotristat is ever stopped, let your team know, since codeine's effect may increase and your dose may need lowering with closer monitoring.
Report any excessive drowsiness or slowed breathing right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Telotristat Ethyl together?
Telotristat ethyl may speed up codeine's breakdown so you get less pain relief and could feel opioid withdrawal; don't change anything yourself, but tell your care team if pain returns or you feel withdrawal, and they can adjust your dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Telotristat Ethyl 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 Acetaminophen And Codeine and Telotristat Ethyl interaction managed?
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. This interaction can be managed with attention and follow-up. Watch for less pain relief than usual, or withdrawal signs (chills, sweating, body aches, runny nose, stomach upset). If your pain isn't controlled, tell your care team. Your codeine dose may need to be adjusted and individualized by them. If te… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Telotristat Ethyl 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 (2)
- Product Information: Codeine sulfate oral solution, codeine sulfate oral solution. Hikma Pharmaceuticals USA Inc(per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. Hikma Pharmaceuticals USA Inc. (per FDA), Berkeley Heights, NJ, 2023. DailyMed
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