Flibanserin 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
Flibanserin
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 pain medicine contains codeine, an opioid, and it's paired here with flibanserin (Addyi). Both can slow down your brain and calm your body. Taken together, they can add up and make you very sleepy, slow your breathing, and lower your blood pressure. In serious cases this can be dangerous.
The good news is this is very manageable. Your care team can decide if both are truly needed, use the lowest dose for the shortest time, and keep a close eye on you. Please don't stop or change either medicine on your own. Just talk with your pharmacist or doctor, and tell them right away if you feel unusually drowsy or short of breath.
Mechanism: additive CNS depression. Codeine (an opioid; note it is a prodrug activated via CYP2D6 to morphine, but the concern here is pharmacodynamic, not metabolic) combined with flibanserin produces additive sedation and respiratory depression. Direction is PD-additive, not a PK shift.
- Effect: increased risk of sedation, respiratory depression, hypotension, coma, death
- Severity: major; evidence: theoretical; onset: unspecified
- Management: avoid if possible; reserve for inadequate alternatives; use lowest effective dose and shortest duration; consider dose reduction of either agent; monitor for sedation/respiratory depression; consider prescribing naloxone if co-use is warranted
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
Your care team can manage this by tailoring your therapy:
- They may check whether both drugs are truly needed or whether an alternative would work.
- If both are used, they typically prescribe the lowest dose for the shortest time and may lower the dose of the codeine product or the flibanserin.
- 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.
Keep taking both as prescribed unless told otherwise, and raise any excess sleepiness or breathing changes with your pharmacist or prescriber promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, the frequency of emergency department visits related to nonmedical use that took place between 2004 and 2011 and involved opioid analgesics along with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed and above-prescribed doses of both classes of drugs 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 frequency of overdose deaths associated with the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than the dispensing of opioid analgesics on their own (7 vs 0.7 per 10,000 person years) 2.
c) In a cohort study using data from 2004 to 2009, the likelihood of fatal overdose rose significantly by 2.33 fold among patients using opioid analgesics who had a prior benzodiazepine prescription and rose by 3.86 fold among those with a current benzodiazepine prescription, compared with patients using opioid analgesics who had no history of a benzodiazepine prescription. The likelihood of drug overdose deaths grew as daily benzodiazepine doses increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related death compared with using opioid analgesics on their own. Given 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 Flibanserin and Acetaminophen And Codeine together?
Combining codeine (in your acetaminophen/codeine pain medicine) with flibanserin can add up to cause dangerous sleepiness, slowed breathing, and low blood pressure, so use them together only if your care team decides it's needed, at the lowest dose, with close monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Flibanserin 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 Flibanserin and Acetaminophen And Codeine interaction managed?
Your care team can manage this by tailoring your therapy: They may check whether both drugs are truly needed or whether an alternative would work. If both are used, they typically prescribe the lowest dose for the shortest time and may lower the dose of the codeine product or the flibanserin. They may monitor you more closely for heavy drowsiness, slow or shallow breathing, and low blood pressure.… 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 Flibanserin 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 Flibanserin
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