Celecoxib 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
Celecoxib
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 with these two medicines. Your pain pill contains codeine, which your body turns into morphine using a liver enzyme called CYP2D6. Celecoxib (Celebrex) can slow that same enzyme down a bit.
Because codeine has to be activated to work, slowing this enzyme could mean less pain relief from the codeine, and it could also change how much of the acetaminophen-codeine builds up in your system. Honestly, this concern is theoretical, meaning it's based on how the drugs work rather than strong real-world proof. Please don't stop either medicine on your own. Just let your pharmacist or doctor know you take both, and they can watch how you're doing and adjust things if needed.
Mechanism: Celecoxib is a weak CYP2D6 inhibitor. Codeine is a prodrug requiring CYP2D6-mediated O-demethylation to morphine, its active metabolite. The database entry frames this as increased CYP2D6-substrate exposure; note the prodrug caveat.
- Direction: For codeine specifically, CYP2D6 inhibition tends to reduce morphine formation and may blunt analgesia. The generic on-file concern (raised parent-drug levels, greater adverse effects) applies to non-prodrug CYP2D6 substrates.
- Evidence: Theoretical only.
- Onset: Unspecified.
- Management: If used together, assess analgesic efficacy and monitor for adverse effects at frequent intervals; individualize dosing.
What happens
Increased CYP2D6 substrate exposure and an increased risk of CYP2D6 substrate-related adverse effects
Interaction Deep Dive
Coadministration of celecoxib (a CYP2D6 inhibitor) with CYP2D6 substrates increases the concentration of CYP2D6 substrates, which may increase the risk of adverse reactions related to these substrates. If concomitant use of a CYP2D6 substrate drug is necessary, evaluate patients at frequent intervals for adverse events of CYP2D6 substrate drug1.
Why it happens (mechanism)
Inhibition of CYP2D6-substrate metabolism by celecoxib
How to manage this interaction
You can usually take both as prescribed, but keep your care team in the loop.
- Keep taking both unless your prescriber tells you otherwise.
- Watch how well your pain is controlled. Because codeine must be activated by the enzyme celecoxib can slow, you may notice less pain relief. Report this rather than taking extra doses.
- Watch for side effects like drowsiness, nausea, or constipation, and mention them.
- Your team may monitor you more closely and can adjust or individualize your pain medicine if needed.
Tell your pharmacist or doctor you take both so they can tailor your plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a retrospective analysis of premenopausal women with stage I to III breast cancer drawn from the Predictors of Breast Cancer Recurrence (ProBe CaRe) cohort (N=4493), employing Bayesian joint modeling, women who took tamoxifen together with a CYP2D6 inhibitor, such as celecoxib, for more than half of the planned tamoxifen-treatment duration experienced a greater rate of breast cancer recurrence than women who did not receive a CYP2D6 inhibitor alongside tamoxifen (HR, 1.24; 95% CI, 0.96 to 1.58). This relationship was more pronounced with strong CYP2D6 inhibitors (HR, 1.25; 95% CI, 0.88 to 1.73) than with weak CYP2D6 inhibitors (HR, 1.15; 95% CI, 0.57 to 1.53) 2. Plasma levels of 4-hydroxy-N-desmethyl tamoxifen (endoxifen), the active metabolite of tamoxifen, rely heavily on the CYP2D6 metabolic route. Research has demonstrated that using tamoxifen concurrently with paroxetine, another potent CYP2D6 inhibitor, produced lowered plasma concentrations of endoxifen 3.
Common questions
Can I take Celecoxib and Acetaminophen And Codeine together?
Taking Celebrex with acetaminophen-codeine may change how well the codeine works, since celecoxib can slow the enzyme that activates it. This is theoretical, so keep taking both as prescribed and tell your pharmacist or doctor so they can monitor and adjust if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Celecoxib 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 Celecoxib and Acetaminophen And Codeine interaction managed?
You can usually take both as prescribed, but keep your care team in the loop. Keep taking both unless your prescriber tells you otherwise. Watch how well your pain is controlled. Because codeine must be activated by the enzyme celecoxib can slow, you may notice less pain relief. Report this rather than taking extra doses. Watch for side effects like drowsiness, nausea, or constipation, and mention… 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 Celecoxib 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 (3)
- Product Information: SEGLENTIS(R) oral tablets, celecoxib tramadol HCl oral tablets. Kowa Pharmaceuticals America Inc (per FDA), Montgomery, AL, 2023.
- Woolpert KM, Cronin-Fenton DP, Damkier P, et al: Drug interactions with tamoxifen and treatment effectiveness in premenopausal breast cancer patients: a Bayesian joint modeling approach. Pharmacoepidemiol Drug Saf 2025; 34(5):e70157-. PubMed
- Johnson MD, Zuo H, Lee KH, et al: Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat 2004; 85(2):151-159. PubMed
Keep reading about Acetaminophen And Codeine
Keep reading about Celecoxib
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major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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