Zuranolone and Acetaminophen And Codeine: 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
Zuranolone
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 to make you very sleepy. Your acetaminophen with codeine contains an opioid painkiller (codeine), which slows down the brain and can cause drowsiness. Zuranolone (Zurzuvae) is a medicine for postpartum depression that also has a calming, sedating effect. Taken together, they can make you much more drowsy, slow your thinking and reactions, and in a strong case slow your breathing.
The good news is your care team can manage this. They may lower one of the doses and watch you a bit more closely. Don't stop either medicine on your own, but do check in with your pharmacist or doctor, and avoid driving until you know how the combination affects you.
Additive CNS depression between codeine (an opioid, in the acetaminophen/codeine product) and zuranolone (a neuroactive steroid GABA-A positive allosteric modulator). This is a pharmacodynamic, not pharmacokinetic, interaction, so no enzyme induction/inhibition drives it.
- Direction: additive sedation, psychomotor impairment, and potential respiratory depression
- Severity: major; evidence: probable; onset: unspecified
- Management: avoid combination if possible; if unavoidable, consider zuranolone dose reduction and use caution. Counsel against driving/operating machinery. Monitor sedation, respiratory status, and mental status.
What happens
An increased risk of CNS depression
Interaction Deep Dive
Taking zuranolone together with CNS depressants can heighten the likelihood of psychomotor performance impairment or CNS depressant effects, which stems from additive pharmacological effects. When such combined use cannot be avoided, caution should be exercised and a reduction in dosage should be considered1.
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. This combination adds up two sedating effects, so here is what typically happens and what you can do:
- Your team may reduce the dose of one medicine (often zuranolone) and monitor you more closely for excess drowsiness.
- Avoid driving or operating machinery until you know how you react.
- Do not add alcohol or other sedatives.
- Tell your pharmacist or prescriber right away if you feel very sleepy, confused, or notice slowed or shallow breathing.
Ask your pharmacist to review your full medication list so the dose can be tailored safely to you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
6 reports — tap to read
a) Giving repeated daily doses of 50 mg zuranolone together with alprazolam produced impairment of psychomotor performance 1.
b) In a study of drug interactions, the geometric mean ratios for zuranolone with versus without alprazolam were 0.92 for Cmax and 0.95 for AUC 1.
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Ethanol
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Grapefruit Juice
Common questions
Can I take Zuranolone and Acetaminophen And Codeine together?
Combining acetaminophen/codeine with zuranolone can cause added drowsiness and slowed breathing, so keep taking both as prescribed but tell your pharmacist or doctor, who may lower a dose and monitor you, and avoid driving until you know how you feel. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Zuranolone 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 Zuranolone and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination adds up two sedating effects, so here is what typically happens and what you can do: Your team may reduce the dose of one medicine (often zuranolone) and monitor you more closely for excess drowsiness. Avoid driving or operating machinery until you know how you react. Do not add alcohol or other seda… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Zuranolone 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 (1)
- Product Information: ZURZUVAE(TM) oral capsules, zuranolone oral capsules. Biogen Inc (per FDA), Cambridge, MA, 2023. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Zuranolone
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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