Acetaminophen And Codeine and Ketobemidone: 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
Ketobemidone
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.
Your medicine has codeine (an opioid pain reliever) plus acetaminophen. Ketobemidone is also an opioid painkiller. Both slow down the brain and breathing, so taking them together can add up. This can make you very drowsy, slow your breathing, lower your blood pressure, or in rare cases trigger a reaction called serotonin syndrome (agitation, fast heartbeat, sweating, shaking).
This is a serious combination, so it's usually avoided. The good news is your care team can manage it by using the lowest dose needed and watching you closely. Don't start or stop anything on your own, just talk with your doctor or pharmacist first.
Effect: Additive CNS and respiratory depression from two opioid agonists (codeine plus ketobemidone), with additive serotonergic risk (serotonin syndrome).
- Mechanism: Pharmacodynamic additive CNS depression and additive serotonergic effects. Note codeine is a prodrug activated via CYP2D6 to morphine, but this interaction is PD, not PK.
- Direction/magnitude: Increased sedation, hypoventilation, hypotension; magnitude not quantified.
- Onset: Unspecified. Evidence: Theoretical.
- Management: Avoid where possible; if required, use lowest effective dose and shortest duration, reduce one agent, monitor for sedation, respiratory depression, and serotonin syndrome, especially at initiation/titration. Consider naloxone. Discontinue codeine if serotonin syndrome suspected.
What happens
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome
Interaction Deep Dive
Do not combine opioid cough medication formulations with CNS depressants2. The joint use of non-cough codeine products together with CNS depressants should be limited to patients for whom other options are insufficient. When such combined use cannot be avoided, apply the lowest dose and the shortest duration required to meet treatment objectives. A reduced dose of either codeine or the CNS depressant should be considered, along with close monitoring for sedation, respiratory depression, and the signs and symptoms of serotonin syndrome. Serotonin syndrome has also been reported when opioids are used together with serotonergic drugs. Where concurrent use is required, observe the patient carefully, especially when starting therapy and when adjusting doses. Prescribing naloxone for the emergency management of opioid overdose should be considered. Stop codeine if serotonin syndrome is suspected 134.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
Because both drugs are opioids that depress breathing and the brain, this combination is generally avoided. Keep taking both exactly as prescribed and do not change doses on your own.
Here's what a care team typically does:
- Uses the lowest dose and shortest duration that works, and may lower the dose of one medicine.
- Monitors closely for heavy drowsiness, slow or shallow breathing, and signs of serotonin syndrome.
- May prescribe naloxone as a rescue medicine for opioid overdose.
Call your doctor or pharmacist right away if you feel very sleepy, confused, shaky, sweaty, or have trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) One study found that emergency department visits related to nonmedical use occurring between 2004 and 2011 and involving both opioid analgesics and benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed and above-prescribed doses of both drug classes likewise rose significantly from 0.6 to 1.7 per 100,000, and overdose deaths attributable to benzodiazepines rose significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose deaths linked to the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than that associated with dispensing opioid analgesics alone (7 versus 0.7 per 10,000 person years) 2.
c) In a cohort study drawing on data from 2004 to 2009, the risk of fatal overdose rose significantly by 2.33 fold among patients receiving opioid analgesics who had a history of a benzodiazepine prescription, and rose by 3.86 fold among those with a current benzodiazepine prescription, when compared with patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of death from drug overdose increased as daily benzodiazepine doses increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related mortality relative to using opioid analgesics alone. Given the comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used together with opioid analgesics 34.
e) Instances of serotonin syndrome, a condition that can be life-threatening, have been reported when opioids are used together with serotonergic drugs 34.
Common questions
Can I take Acetaminophen And Codeine and Ketobemidone together?
Combining codeine with ketobemidone stacks two opioids, raising the risk of dangerous sedation, slowed breathing, and serotonin syndrome. This pairing is usually avoided, so check with your doctor or pharmacist before using both. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Ketobemidone 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 Ketobemidone interaction managed?
Because both drugs are opioids that depress breathing and the brain, this combination is generally avoided. Keep taking both exactly as prescribed and do not change doses on your own. Here's what a care team typically does: Uses the lowest dose and shortest duration that works, and may lower the dose of one medicine. Monitors closely for heavy drowsiness, slow or shallow breathing, and signs of se… 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 Ketobemidone 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 (4)
- Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. US Food and Drug Administration (FDA). Silver Spring, MD. 2016.
- 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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