Tilidine 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
Tilidine
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.
Both of your medicines are opioids. The acetaminophen-and-codeine product contains codeine, and tilidine is another opioid pain reliever. When you take two opioids together, their effects add up. That can make you very drowsy and, more importantly, slow your breathing. There is also a smaller, theoretical chance of something called serotonin syndrome, which can cause agitation, shaking, sweating, or a fast heartbeat.
Please don't stop or change either medicine on your own. This is very manageable. Talk with your pharmacist or doctor so they can pick the safest plan for you, adjust doses if needed, and keep a closer eye on how you're doing.
Effect: Additive CNS and respiratory depression from two opioid agonists (codeine plus tilidine), with a theoretical additive serotonergic risk (serotonin syndrome).
- Mechanism: Additive mu-opioid CNS/respiratory depression; additive serotonergic effects.
- Direction: Enhanced pharmacodynamic depressant effect (codeine is a prodrug activated via CYP2D6, but the concern here is PD additivity, not a metabolic interaction).
- Evidence: Theoretical; severity rated major. Onset unspecified.
- Management: Avoid combined use where possible; reserve for inadequate alternatives. Use lowest effective dose and shortest duration; consider reducing codeine or the other agent. 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
Do not combine opioid formulations intended for cough with CNS depressants2. When it comes to codeine products not used for cough, limit concurrent administration with CNS depressants to those patients in whom other options are insufficient. Should combined use be required, employ the smallest dose and briefest duration needed to reach therapeutic objectives. It is advisable to reduce the dose of either codeine or the CNS depressant while carefully watching for sedation, respiratory depression, and any indications of serotonin syndrome. Furthermore, giving opioids together with serotonergic agents has produced serotonin syndrome. When such combined use is necessary, monitor the patient closely, especially when starting therapy and when doses are being changed. Prescribing naloxone for 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
Both medicines are opioids, so care teams generally try to avoid using them together unless there is a strong reason. If both are truly needed, here is what typically happens:
- Your team may use the lowest effective dose for the shortest time, and doses may need to be adjusted and individualized.
- They may monitor you more closely for heavy drowsiness, slowed or shallow breathing, and signs of serotonin syndrome (agitation, shaking, sweating, fast heartbeat), especially when starting or changing a dose.
- Your prescriber may consider naloxone for emergency use.
Keep taking both exactly as prescribed, and ask your pharmacist or doctor before making any change. Get urgent help if breathing slows or you feel very confused.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) One study found that the rate of 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. Drug overdose deaths attributable to prescribed and greater than 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 involving the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than that associated 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 among patients taking opioid analgesics who had a history of a benzodiazepine prescription, and rose by 3.86 fold among those with a current benzodiazepine prescription, compared with patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew as the daily doses of benzodiazepines increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related mortality relative to use of opioid analgesics alone. Given their comparable pharmacological properties, it is reasonable to anticipate a comparable risk when other CNS depressant drugs are used concurrently 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 Tilidine and Acetaminophen And Codeine together?
Taking codeine and tilidine together stacks two opioids, raising the risk of dangerous drowsiness and slowed breathing (plus a theoretical serotonin syndrome risk). Don't combine them without your prescriber's guidance, use the lowest dose possible, and seek urgent help for very slow breathing or severe confusion. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tilidine 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 Tilidine and Acetaminophen And Codeine interaction managed?
Both medicines are opioids, so care teams generally try to avoid using them together unless there is a strong reason. If both are truly needed, here is what typically happens: Your team may use the lowest effective dose for the shortest time, and doses may need to be adjusted and individualized. They may monitor you more closely for heavy drowsiness, slowed or shallow breathing, and signs of serot… 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 Tilidine 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
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