Acetaminophen And Codeine and Remimazolam: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Remimazolam
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 calm down your brain and nervous system. The codeine in your acetaminophen with codeine is an opioid pain reliever, and remimazolam (Byfavo) is a sedative used to relax you for medical procedures. When they are given together, their sleepy effects can add up.
That combined effect can make you very drowsy and, more importantly, can slow your breathing too much. In serious cases this can lead to deep sedation or trouble breathing. The good news is that this usually happens in a monitored setting, and your care team can manage it by adjusting the dose and watching you closely. Always tell your providers about every medicine you take.
Mechanism: Additive CNS depression. Codeine (opioid) and remimazolam (short-acting IV benzodiazepine) both depress central respiratory drive and consciousness; effects are pharmacodynamically additive. Neither drug's activation is relevant here, so the interaction goes toward enhanced sedation.
- Effect: Profound sedation, respiratory depression, hypotension, airway obstruction, apnea, oxygen desaturation; rarely coma/death.
- Evidence: Theoretical, but severity is major given the outcomes.
- Management: Continuously monitor depth of sedation and respiratory status. Titrate remimazolam to desired clinical response. Heightened risk in OSA, elderly, and ASA Physical Status 3-4. Have reversal/airway support available.
What happens
Increased risk of profound sedation, respiratory depression, coma, and death
Interaction Deep Dive
Taking remimazolam together with opioid analgesics can lead to deep sedation, respiratory depression, coma, and death. Other CNS depressants given at the same time, such as additional benzodiazepines and propofol, can heighten the sedative action of intravenous remimazolam. Maintain continuous monitoring of patients for both the degree of sedation and any respiratory depression. When remimazolam is combined with opioid analgesics and sedative-hypnotics, adjust its dose to reach the intended clinical response. Sedated patients should be watched continuously for hypotension, obstruction of the airway, hypoventilation, apnea, and oxygen desaturation. Such cardiorespiratory effects may occur more readily in elderly individuals, those with obstructive sleep apnea, and patients classified as American Society of Anesthesiologists Physical Status 3 or 41.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This is managed, not avoided, in a clinical setting. Remimazolam is given by professionals during procedures, so the main step is that your care team accounts for any opioids like codeine that you take.
- The remimazolam dose may need to be adjusted and individualized and titrated to the desired effect.
- Your team will continuously monitor your breathing, oxygen level, blood pressure, and sedation depth.
- Tell your providers if you have sleep apnea, are older, or have other health issues, since these raise the risk.
Keep taking your prescribed medicines, and always share your full medication list before any procedure.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Remimazolam together?
Codeine and remimazolam both depress the brain and breathing, so together they can cause dangerous oversedation; your care team manages this by adjusting the remimazolam dose and monitoring you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Remimazolam 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 Remimazolam interaction managed?
This is managed, not avoided, in a clinical setting. Remimazolam is given by professionals during procedures, so the main step is that your care team accounts for any opioids like codeine that you take. The remimazolam dose may need to be adjusted and individualized and titrated to the desired effect. Your team will continuously monitor your breathing, oxygen level, blood pressure, and sedation de… 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 Remimazolam 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 (1)
- Product Information: BYFAVO(TM) intravenous injection, remimazolam intravenous injection. Acacia Pharma Inc (per FDA), Indianapolis, IN, 2020. DailyMed
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