Acetaminophen And Codeine and Dichloralphenazone: 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
Dichloralphenazone
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 can both slow down your brain and body. Codeine is an opioid pain reliever (combined here with acetaminophen), and dichloralphenazone is a sedating medicine (often used in some headache products). When taken together, their calming effects can add up.
This can make you very sleepy and, more seriously, can slow your breathing. Signs to watch for include heavy drowsiness, confusion, feeling dizzy or faint, or slow and shallow breathing. The good news is your care team can manage this. Please don't stop or change either medicine on your own, but do talk with your pharmacist or doctor about the best and safest plan for you.
Mechanism: additive CNS depression from an opioid (codeine) plus a sedative (dichloralphenazone). Effect is pharmacodynamic, not a metabolic (enzyme/transporter) interaction. Neither drug's activation status changes the direction here; the combined depressant effect is what matters.
Direction/magnitude: increased risk of hypotension, profound sedation, respiratory depression, coma, and death. Onset unspecified; evidence theoretical but severity is rated major given documented opioid + CNS-depressant overdose outcomes.
- Reserve combined use for when alternatives are inadequate.
- Use lowest effective dose and shortest duration; consider reducing codeine or the depressant.
- Monitor closely for sedation and respiratory depression.
- Consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Avoid concomitant use of opioid cough medication formulations and CNS depressants. Concomitant use of opioid analgesics with benzodiazepines has been associated with increased rates of emergency department visits and fatal overdose2. 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 341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
The main concern is that both medicines calm the nervous system, so together they can cause too much sedation and slowed breathing.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop or change doses on your own.
- Your care team may reserve this combination for when other options aren't enough, and may use the lowest dose for the shortest time.
- The dose of one or both may be individualized, and your team may monitor you more closely for sedation and breathing.
- Your prescriber may also consider naloxone as a safety backup.
Tell your pharmacist or doctor right away about unusual sleepiness, confusion, or slow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, emergency department visits linked to nonmedical use that occurred between 2004 and 2011 and involved both opioid analgesics and benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributed to prescribed and to greater than prescribed doses of both drug classes likewise rose significantly from 0.6 to 1.7 per 100,000, and overdose deaths attributed to benzodiazepines rose significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose deaths associated with dispensing both opioid analgesics and benzodiazepines was 10 times greater than that with dispensing 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 receiving 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 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 using opioid analgesics on their own. Given their comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used concurrently with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Dichloralphenazone together?
Taking codeine (with acetaminophen) together with dichloralphenazone can add up to dangerous sedation and slowed breathing, so use it only if your care team decides it's needed and monitors you. Watch for heavy drowsiness or slow breathing and report them right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Dichloralphenazone 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 Dichloralphenazone interaction managed?
The main concern is that both medicines calm the nervous system, so together they can cause too much sedation and slowed breathing. Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop or change doses on your own. Your care team may reserve this combination for when other options aren't enough, and may use the lowest dose for the shortest time. The dose of one or… 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 Dichloralphenazone 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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