Buspirone 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
Buspirone
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 two medicines can add up in ways worth knowing about. Codeine (in your acetaminophen with codeine) is an opioid that can make you sleepy and slow your breathing. Buspirone is a medicine for anxiety that affects serotonin, a brain chemical. When taken together, they may cause more drowsiness and, rarely, a reaction called serotonin syndrome (things like restlessness, shivering, fast heartbeat, or muscle twitching).
The good news is that this is a theoretical concern, and your care team can manage it. Please don't stop either medicine on your own. Talk with your pharmacist or doctor so they can use the right dose and keep an eye on how you're doing.
Effect: Additive CNS/respiratory depression plus additive serotonergic effect, raising the theoretical risk of oversedation and serotonin syndrome.
Mechanism/direction: Codeine (an opioid, and a serotonergic agent) combined with buspirone (a serotonergic 5-HT1A partial agonist) produces additive PD effects, not a PK interaction. No dose-conversion figure applies.
- Evidence: theoretical; severity: major; onset: unspecified.
- Management: Reserve concurrent use for when alternatives are inadequate; use lowest effective dose and shortest duration. Monitor for sedation, respiratory depression, and serotonin syndrome, especially at initiation and dose changes. Consider prescribing naloxone. Discontinue codeine if serotonin syndrome is suspected.
What happens
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome
Interaction Deep Dive
Avoid concomitant use of opioid cough medication formulations and CNS depressants2. Reserve the concomitant use of non-cough codeine products and CNS depressants to patients for whom alternatives are inadequate. If concomitant use is necessary, use the lowest dose and shortest duration necessary to achieve treatment goals. Consider using a lower dose of codeine or the CNS depressant and closely monitor for sedation, respiratory depression, and signs and symptoms of serotonin syndrome. Additionally, concomitant use of opioids with serotonergic drugs has resulted in serotonin syndrome. If concomitant use is needed, carefully observe the patient, particularly during treatment initiation and dose adjustments. Consider prescribing naloxone for the emergency treatment of opioid overdose. Discontinue codeine if serotonin syndrome is suspected 134.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
Both medicines can usually be used together safely when your care team plans for it. Here is what typically happens:
- Your prescriber may reserve this combination for when other options aren't enough, and may use the lowest dose for the shortest time.
- The dose of codeine or buspirone may be adjusted and individualized by your care team.
- They may monitor you more closely for heavy drowsiness, slowed breathing, or serotonin syndrome (agitation, shivering, sweating, fast heartbeat, muscle stiffness), especially when starting or changing doses.
- Your doctor may also prescribe naloxone as a safety measure.
Keep taking both as prescribed, and ask your pharmacist or doctor before making any changes.
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 linked to nonmedical use and involving both opioid analgesics and benzodiazepines rose significantly between 2004 and 2011, from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed and greater than prescribed doses of both drug classes likewise increased significantly, from 0.6 to 1.7 per 100,000, and overdose deaths caused by benzodiazepines rose significantly from 18% to 31% 2.
b) A prospective cohort study showed that the rate of overdose deaths associated with the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than with the dispensing of opioid analgesics alone (7 vs 0.7 per 10,000 person years) 2.
c) In a cohort study using data from 2004 to 2009, the risk of fatal overdose rose significantly by 2.33 fold in patients taking opioid analgesics who had a history of a benzodiazepine prescription, and rose by 3.86 fold in those with a current benzodiazepine prescription, when compared with patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew 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 characteristics, 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 Buspirone and Acetaminophen And Codeine together?
Taking acetaminophen with codeine alongside buspirone can add up to more drowsiness, slowed breathing, and a small risk of serotonin syndrome, so use the lowest dose needed and let your care team monitor you. Do not stop either medicine on your own; check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buspirone 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 Buspirone and Acetaminophen And Codeine interaction managed?
Both medicines can usually be used together safely when your care team plans for it. Here is what typically happens: Your prescriber may reserve this combination for when other options aren't enough, and may use the lowest dose for the shortest time. The dose of codeine or buspirone may be adjusted and individualized by your care team. They may monitor you more closely for heavy drowsiness, slowed… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Buspirone 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 (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
Keep reading about Acetaminophen And Codeine
Keep reading about Buspirone
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