Acetaminophen And Codeine and Tolonium Chloride: 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
Tolonium Chloride
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 two medicines are acetaminophen with codeine (a pain reliever that contains an opioid) and tolonium chloride. Both can slow down your brain and breathing a bit. When taken together, that calming effect can add up. This may make you feel more sleepy or lightheaded than usual, and in more serious cases it could slow your breathing.
The good news is this is a theoretical concern, meaning it is based on how these drug types work rather than lots of reports. Your care team can manage it by using the lowest dose needed and watching you closely. Please talk with your pharmacist or doctor before changing anything, and let them know right away if you feel very drowsy or short of breath.
Mechanism: additive CNS and respiratory depression. Codeine is an opioid (a CYP2D6-activated prodrug for its analgesic effect, but the concern here is pharmacodynamic, not metabolic); combined with another agent carrying sedative potential, depressant effects summate.
Direction/effect: increased risk of hypotension, profound sedation, respiratory depression, coma, death.
- Severity: major; Evidence: theoretical; Onset: unspecified.
- Management: reserve concomitant use for when alternatives are inadequate; use lowest effective dose and shortest duration; consider dose reduction of either agent.
- Monitor: sedation, respiratory rate, blood pressure. Consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid cough medication products with CNS depressants. Taking opioid analgesics alongside benzodiazepines has been linked to a higher frequency of emergency department visits and fatal overdose2. When codeine is used together with CNS depressants, the likelihood of hypotension, respiratory depression, profound sedation, coma, and death rises. Prescribing these agents together should be limited to patients in whom other treatment options prove inadequate. Keep doses and treatment durations to the lowest amount necessary. Monitor patients closely for indications of sedation and respiratory depression. Where concurrent use is justified, consider prescribing naloxone to enable emergency management of opioid overdose 341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. Here is how teams typically handle this combination:
- They may reserve using both together for when other options are not enough.
- Doses may be adjusted and individualized, often to the lowest amount for the shortest time needed.
- They may monitor you more closely for heavy drowsiness, slow or shallow breathing, and low blood pressure.
- In some cases they may prescribe naloxone as an emergency backup.
Ask your pharmacist or doctor whether this combination is right for you, and get help right away if you feel unusually sleepy, confused, or short of breath.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, the rate of emergency department visits related to nonmedical use that took place between 2004 and 2011 and involved opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths 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 involving the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than the rate with dispensing of opioid analgesics alone (7 versus 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, compared with those taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew as daily doses of benzodiazepines increased 2.
d) Observational studies have shown that concurrent use of opioid analgesics and benzodiazepines raises the risk of drug-related mortality relative to use of opioid analgesics alone. Given similar pharmacological properties, it is reasonable to anticipate comparable risk when other CNS depressant drugs are used together with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Tolonium Chloride together?
Taking acetaminophen with codeine alongside tolonium chloride can add up to more sedation and slowed breathing, so use it only when needed at the lowest dose and let your care team monitor you closely. Get help right away for severe drowsiness or trouble breathing. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Tolonium Chloride 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 Tolonium Chloride interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Here is how teams typically handle this combination: They may reserve using both together for when other options are not enough. Doses may be adjusted and individualized, often to the lowest amount for the shortest time needed. They may monitor you more closely for heavy drowsiness, slow or shallow breathing, and low… 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 Tolonium Chloride 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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