Molindone 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
Molindone
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.
These two medicines can add up in a way that slows you down too much. Codeine is an opioid pain reliever, and molindone is a medicine that calms the mind. Both can make you sleepy and both can slow your breathing. Taken together, that effect can stack up, and in serious cases it can lead to very deep sleepiness, low blood pressure, or dangerously slow breathing.
The good news is that your care team can manage this. If you truly need both, they can use the lowest doses for the shortest time and watch you closely. Never start, stop, or change either medicine on your own. Please talk with your pharmacist or doctor about the safest plan for you.
Mechanism: additive CNS depression. Codeine (an opioid; note it is a prodrug activated via CYP2D6 to morphine for analgesia, but that does not change this PD interaction) plus molindone, a dopamine-antagonist antipsychotic with sedative properties, produce overlapping CNS and respiratory depressant effects.
- Direction: additive/synergistic increase in sedation and respiratory depression.
- Severity: major; evidence: theoretical; onset: unspecified.
- Management: avoid where possible. If required, use lowest effective doses and shortest duration; consider reducing dose of codeine or molindone. Monitor for hypotension, profound sedation, respiratory depression. Consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid-based cough preparations with agents that depress the CNS. Taking opioid analgesics together with benzodiazepines has shown links to higher rates of both emergency department presentations and lethal overdose2. When codeine is used alongside CNS depressants, patients face a greater likelihood of hypotension, respiratory depression, profound sedation, coma and death. Prescribing these medications together should be limited to patients for whom other treatment options prove inadequate. Keep both the doses and the length of treatment at the lowest level necessary. Watch patients carefully for indications of sedation and respiratory depression. Where combined use is justified, consider providing naloxone so opioid overdose can be treated as an emergency 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 usually handle this:
- They may avoid using both together when another option works.
- If you need both, they use the lowest dose and shortest duration possible.
- They may lower the dose of the codeine product or the molindone, and monitor you more closely for heavy sedation or slowed breathing.
- They may prescribe naloxone as a safety backup.
Call your doctor or pharmacist if you notice unusual drowsiness, confusion, slow or shallow breathing, or dizziness.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that emergency department visits related 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. Deaths from drug overdose attributable 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 involving benzodiazepines rose significantly from 18% to 31% 2.
b) A prospective cohort study reported that the rate of overdose deaths associated with dispensing of both opioid analgesics and benzodiazepines was 10 times greater than 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 receiving opioid analgesics who had a prior benzodiazepine prescription and rose by 3.86 fold among those with a current benzodiazepine prescription, relative to patients taking opioid analgesics with 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 and benzodiazepines together raises the risk of drug-related death compared with using opioid analgesics on their own. Given their comparable pharmacological characteristics, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used together with opioid analgesics 34.
Common questions
Can I take Molindone and Acetaminophen And Codeine together?
Combining acetaminophen with codeine and molindone can add up to dangerous sedation and slowed breathing, so use both only if truly needed, at the lowest dose, with close monitoring. Talk to your pharmacist or doctor before changing anything. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Molindone 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 Molindone and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Here is how teams usually handle this: They may avoid using both together when another option works. If you need both, they use the lowest dose and shortest duration possible. They may lower the dose of the codeine product or the molindone, and monitor you more closely for heavy sedation or slowed breathing. They may… 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 Molindone 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 Molindone
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