Clobazam 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
Clobazam
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 contains codeine, which your body has to turn into morphine (its active pain-relieving form) using a liver enzyme called CYP2D6. Clobazam can slow that enzyme down, so you may get less pain relief from your codeine even though the codeine itself builds up.
There is also a second concern: both codeine and clobazam calm the brain and slow breathing. Together they can cause heavy drowsiness, very slow breathing, or dangerously low blood pressure. This is based mostly on how these drugs work in theory, not on strong studies, but it is taken seriously. The good news is your care team can manage this by fine-tuning your dose and watching you closely. Please talk with your pharmacist or doctor before changing anything.
Codeine is a prodrug requiring CYP2D6 conversion to morphine for analgesia. Clobazam is a weak CYP2D6 inhibitor, so co-use may lower morphine (active metabolite) exposure, reducing efficacy and potentially precipitating opioid withdrawal, while parent codeine exposure rises.
Separately, additive CNS depression raises risk of hypotension, respiratory depression, profound sedation, coma, and death.
- Direction: reduced analgesic effect (PD) plus additive sedation/respiratory depression
- Evidence: theoretical; onset unspecified; severity major
- Management: reserve for when alternatives inadequate; use lowest effective dose/duration; monitor for withdrawal and for sedation/respiratory depression; on inhibitor discontinuation, anticipate rising morphine and monitor for respiratory depression; consider naloxone.
What happens
Increased codeine exposure, reduced active metabolite (morphine) exposure and an increased risk of CNS depression
Interaction Deep Dive
Concomitant use of codeine and a CYP2D6 inhibitor may reduce plasma concentrations of morphine, the active metabolite of codeine, thus potentially leading to reduced efficacy and withdrawal symptoms. If concomitant use is necessary, monitor patients for withdrawal symptoms and consider increasing the codeine dose. Once the CYP2D6 inhibitor is discontinued, consider reducing the codeine dose and monitor for respiratory depression2. Concomitant use of codeine with CNS depressants can increase the risk of hypotension, respiratory depression, profound sedation, coma and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose 1.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated codeine metabolism; additive CNS depression
How to manage this interaction
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination is best reserved for when other options are not enough, at the lowest dose for the shortest time needed.
- Your team may monitor you more closely for reduced pain control or signs of opioid withdrawal, and your codeine dose may need to be adjusted and individualized.
- Watch for excessive drowsiness, slow or shallow breathing, confusion, or lightheadedness, and get help right away if these occur.
- Your prescriber may consider providing naloxone for emergencies.
- Tell your care team before stopping either drug, since dose changes may be needed.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Clobazam and Acetaminophen And Codeine together?
Clobazam can lower codeine's pain-relieving effect while adding heavy sedation and slowed breathing risk, so use only if needed, at the lowest dose, with close monitoring and a plan discussed with your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clobazam 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 Clobazam and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination is best reserved for when other options are not enough, at the lowest dose for the shortest time needed. Your team may monitor you more closely for reduced pain control or signs of opioid withdrawal, and your codeine dose may need to be adjusted and individualized. Watch for excessive drowsiness, sl… 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 Clobazam 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: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
- Product Information: codeine sulfate oral tablets, codeine sulfate oral tablets. West-Ward Pharmaceuticals Corp. (per FDA), Eatontown, NJ, 2017. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Clobazam
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major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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