Dicloxacillin 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
Dicloxacillin
No brand names on record
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. Codeine is a "prodrug," which means your body has to change it into the active pain reliever (morphine) before it works. Dicloxacillin, an antibiotic, may speed up one of the liver enzymes that handles codeine. When that happens, less of your codeine may turn into morphine, so it might not control your pain as well.
If you have been taking codeine regularly, weaker levels could even bring on mild withdrawal-type feelings, like aches, restlessness, or a runny nose. The good news is this is easy for your care team to manage. Don't change anything on your own, just let your pharmacist or doctor know how your pain relief is going.
Mechanism: Dicloxacillin is a CYP3A4 inducer. Codeine is a prodrug; CYP3A4 induction shunts more codeine to inactive norcodeine, leaving less available for CYP2D6-mediated conversion to morphine (the active analgesic).
Direction/effect: Reduced codeine and morphine exposure, decreased analgesic efficacy, and possible opioid withdrawal in physically dependent patients.
- Evidence: theoretical; magnitude not quantified.
- Onset: unspecified.
- Management: Monitor for reduced efficacy and withdrawal; codeine dose may need individualized upward adjustment. On discontinuing dicloxacillin, anticipate rising morphine levels and monitor for sedation/respiratory depression, with possible codeine dose reduction.
What happens
Reduced codeine and morphine exposure, reduced opioid efficacy and precipitation of opioid withdrawal
Interaction Deep Dive
Concomitant use of codeine with CYP3A4 inducers may result in reduced codeine levels, greater norcodeine levels, and less metabolism via CYP2D6 with resultant lower morphine levels, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If concomitant use is needed, closely monitor patients for decreased efficacy or signs of opioid withdrawal syndrome, and consider increasing the dose of codeine as necessary. If a CYP3A4 inducer is being discontinued, consider codeine dose reduction and closely monitor patients for signs of respiratory depression or sedation12.
Why it happens (mechanism)
Induction of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This interaction is manageable.
- Watch for signs your pain relief is weaker than usual, or withdrawal-type symptoms (aches, sweating, restlessness, runny nose, upset stomach).
- Report these to your pharmacist or doctor. Your codeine dose may need to be adjusted and individualized by your care team, and they may monitor you more closely.
- When the antibiotic course ends, tell your care team, since your codeine dose may need to be brought back down and you should watch for extra drowsiness or slowed breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Dicloxacillin and Acetaminophen And Codeine together?
Dicloxacillin may speed up how your body handles codeine, which can make codeine work less well or trigger mild withdrawal. Keep taking both as prescribed and tell your care team if pain relief drops off, since they can adjust your dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Dicloxacillin 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 Dicloxacillin and Acetaminophen And Codeine interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This interaction is manageable. Watch for signs your pain relief is weaker than usual, or withdrawal-type symptoms (aches, sweating, restlessness, runny nose, upset stomach). Report these to your pharmacist or doctor. Your codeine dose may need to be adjusted and individualized by your care team, and they may moni… 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 Dicloxacillin 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 (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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