Exenatide and Acetaminophen And Codeine: 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
Exenatide
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.
What's going on: Exenatide (Byetta or Bydureon) is a diabetes medicine that slows down how fast your stomach empties into your intestines. Because your body absorbs the acetaminophen part of your pain pill mostly from the intestine, that acetaminophen can be absorbed more slowly and reach a lower peak level. In plain terms, your pain relief from the acetaminophen may kick in slower or feel weaker.
The good news is this is easy to work around. One simple approach your care team may suggest is taking the acetaminophen and codeine at least an hour before your exenatide shot. Please talk with your pharmacist or doctor before changing anything, and they can help you find the best timing.
Mechanism: Exenatide delays gastric emptying, slowing and reducing absorption of oral acetaminophen (a PK, not PD, interaction). The codeine component is not the focus here; concern is the acetaminophen analgesic/antipyretic.
- Direction: Reduced acetaminophen rate and extent of absorption (reduced efficacy, especially where a threshold concentration is needed).
- Magnitude: AUC decreased ~14 to 24%, Cmax decreased ~37 to 56%, Tmax delayed (up to ~4 h) when given after exenatide.
- Onset: Rapid. Evidence: Probable (dedicated PK study).
- Management: Give oral acetaminophen at least 1 h before exenatide injection; timing separation normalized AUC/Cmax/Tmax. Individualize and monitor analgesic response.
What happens
Reduced oral acetaminophen absorption and reduced efficacy of oral acetaminophen
Interaction Deep Dive
Exenatide slows gastric emptying. Therefore, exenatide has the potential to reduce the rate of absorption of orally administered acetaminophen. Exert caution when exenatide is coadministered with oral acetaminophen, where a slower rate of oral absorption may be clinically meaningful. For oral acetaminophen that are dependent on threshold concentrations for efficacy, advise patients to take those drugs at least 1 hour before exenatide injection. If such drugs are to be administered with food, advise patients to take them with a meal or snack when exenatide is not administered. In a drug interaction study, when 1000 mg acetaminophen elixir was given with 10 mcg exenatide (0 hour) and 1 hour, 2 hours, and 4 hours after exenatide injection, acetaminophen AUCs were decreased by 21%, 23%, 24%, and 14%, respectively; Cmax was decreased by 37%, 56%, 54%, and 41%, respectively; Tmax was increased from 0.6 hour in the control period to 0.9 hour, 4.2 hours, 3.3 hours, and 1.6 hours, respectively. Acetaminophen AUC, Cmax and Tmax were not significantly changed when acetaminophen was given 1 hour before exenatide injection1.
Why it happens (mechanism)
Slowed gastric emptying by exenatide
How to manage this interaction
Keep taking both medicines as prescribed. This interaction is usually about timing, not danger.
- Your care team may suggest taking the oral acetaminophen and codeine at least 1 hour before your exenatide injection, which in studies restored normal absorption.
- If your pain pill needs to be taken with food, your team may have you take it with a meal or snack at a time when you are not injecting exenatide.
- Let your pharmacist or prescriber know if your pain relief seems slower or weaker than usual, so they can adjust your timing or plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a study evaluating drug interactions, 1000 mg of acetaminophen elixir was administered together with 10 mcg exenatide (at 0 hour) and at 1 hour, 2 hours, and 4 hours following the exenatide injection. Under these conditions, acetaminophen AUCs fell by 21%, 23%, 24%, and 14%, respectively; Cmax fell by 37%, 56%, 54%, and 41%, respectively; and Tmax rose from 0.6 hour during the control period to 0.9 hour, 4.2 hours, 3.3 hours, and 1.6 hours, respectively. When acetaminophen was administered 1 hour prior to the exenatide injection, its AUC, Cmax, and Tmax showed no significant changes 1.
Common questions
Can I take Exenatide and Acetaminophen And Codeine together?
Exenatide can slow and weaken absorption of the acetaminophen in your pill, so pain relief may be delayed or reduced; taking the acetaminophen and codeine at least an hour before your exenatide shot usually fixes this. Check timing with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Exenatide 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 "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Exenatide and Acetaminophen And Codeine interaction managed?
Keep taking both medicines as prescribed. This interaction is usually about timing, not danger. Your care team may suggest taking the oral acetaminophen and codeine at least 1 hour before your exenatide injection, which in studies restored normal absorption. If your pain pill needs to be taken with food, your team may have you take it with a meal or snack at a time when you are not injecting exena… 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 Exenatide 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: BYETTA(R) subcutaneous injection, exenatide subcutaneous injection. AstraZeneca Pharmaceuticals LP (per FDA), Wilmington, DE, 2025. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Exenatide
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