Paregoric 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
Paregoric
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 these medicines are opioids. Your acetaminophen and codeine also contains codeine, and paregoric is a liquid opioid too. Taking them together stacks up the same effects, so they can make you very sleepy and, more seriously, slow down your breathing. There is also a smaller, more theoretical concern about too much serotonin activity, which can cause things like shakiness, sweating, or a fast heartbeat.
The good news is that your care team can manage this. They may use the lowest dose for the shortest time and watch you closely. Please talk with your pharmacist or doctor before combining them, and never change your doses on your own.
Mechanism: additive CNS and respiratory depression from two opioids (codeine plus paregoric/opium tincture), plus additive serotonergic effects raising theoretical risk of serotonin syndrome. Neither the additive depressant effect nor serotonergic risk depends on CYP2D6 activation of codeine here; the concern is pharmacodynamic summation.
- Direction: increased opioid effect, increased sedation and respiratory depression risk.
- Evidence: theoretical; severity major.
- Management: avoid or reserve for inadequate alternatives; use lowest effective dose and shortest duration; consider reducing codeine or the CNS depressant. Monitor for sedation, hypoventilation, 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 cough medication formulations with CNS depressants2. For non-cough codeine products, restrict concurrent administration with CNS depressants to those patients in whom alternative options prove insufficient. When such combined use cannot be avoided, employ the lowest dose and the shortest duration required to reach the therapeutic objectives. It is advisable to reduce the dose of either codeine or the CNS depressant and to monitor carefully for sedation, respiratory depression, and any signs and symptoms indicative of serotonin syndrome. In addition, using opioids together with serotonergic agents has led to serotonin syndrome. Should concurrent use be required, observe the patient closely, especially when starting therapy and when altering the dose. Prescribing naloxone for emergency management of opioid overdose should be considered. Codeine should be stopped if serotonin syndrome is suspected 134.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
Keep taking both only as your prescriber directed, and do not stop or adjust either one on your own.
- Because both are opioids, your care team will usually avoid pairing them unless there is no good alternative.
- If both are needed, they will use the lowest dose for the shortest time and may lower the dose of one medicine.
- They may monitor you more closely for heavy drowsiness, slow or shallow breathing, and signs of serotonin excess (agitation, sweating, tremor, fast heartbeat).
- Your team may prescribe naloxone as a safety backup.
Call your pharmacist or doctor with questions, and seek emergency help for very slow breathing or extreme sleepiness.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) One study found that between 2004 and 2011, the rate of nonmedical use-related emergency department visits involving both opioid analgesics and benzodiazepines rose significantly, from 11 to 34.2 per 100,000. Overdose deaths attributed to prescribed and higher-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 the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than 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 on 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 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 using opioid analgesics alone. Given the comparable pharmacological properties, 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 Paregoric and Acetaminophen And Codeine together?
These are two opioids taken together, which can dangerously add up to heavy sedation and slowed breathing, so use them together only under close medical supervision at the lowest doses. Talk with your pharmacist or doctor before combining them. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Paregoric 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 Paregoric and Acetaminophen And Codeine interaction managed?
Keep taking both only as your prescriber directed, and do not stop or adjust either one on your own. Because both are opioids, your care team will usually avoid pairing them unless there is no good alternative. If both are needed, they will use the lowest dose for the shortest time and may lower the dose of one medicine. They may monitor you more closely for heavy drowsiness, slow or shallow breat… 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 Paregoric 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 Paregoric
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist