Perampanel 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
Perampanel
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 your breathing and makes you very sleepy. Codeine is an opioid pain reliever, and perampanel (Fycompa) is a seizure medicine. Both can calm down the brain and nervous system. Taken together, they can cause too much drowsiness, slowed breathing, very low blood pressure, and in serious cases can be dangerous.
This warning is based mostly on how the drugs work rather than lots of reported cases, but it's still taken seriously. Please don't stop either medicine on your own. Talk with your pharmacist or doctor. Your care team can manage this by keeping doses low and watching you closely.
Effect: Additive CNS and respiratory depression when acetaminophen/codeine is combined with perampanel.
Mechanism: Pharmacodynamic (additive CNS depression); codeine is a mu-opioid agonist (and CYP2D6-activated prodrug for morphine), while perampanel is a CNS-active AMPA antagonist with known sedating effects. This is a PD, not PK, interaction.
- Direction/magnitude: Increased risk of hypotension, sedation, respiratory depression, coma, death.
- Onset: Unspecified.
- Evidence: Theoretical.
- Management: Reserve for when alternatives are inadequate; use lowest effective dose and shortest duration; consider reducing dose of either agent; monitor sedation and respiratory status; consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid cough medication products with CNS depressants. Taking opioid analgesics together with benzodiazepines has been linked to a higher incidence of emergency department visits and deaths from overdose2. When codeine is used alongside CNS depressants, there is a heightened risk of hypotension, respiratory depression, profound sedation, coma, and death. Prescribing these medications together should be limited to patients whose alternative treatment choices prove insufficient. Keep both the doses and the treatment periods to the lowest amount necessary. Monitor patients carefully for indications of sedation and respiratory depression. Should combined use be justified, consider prescribing naloxone to manage opioid overdose in an emergency 341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
The good news: your care team can manage this by tailoring doses and monitoring you.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your team may use the lowest dose and shortest duration of each medicine, and may lower one of the doses.
- They will watch closely for heavy sedation, slowed or shallow breathing, confusion, or very low blood pressure.
- In some cases they may prescribe naloxone as an emergency rescue medicine.
Get help right away if you notice extreme drowsiness, trouble breathing, or you can't wake someone. Ask your pharmacist or doctor before adding any other sedating medicine, including alcohol.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) A study found that the rate of emergency department visits related to nonmedical use between 2004 and 2011 involving opioid analgesics together 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 drug classes also 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 rate of overdose deaths involving the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than the rate 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 taking 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 daily benzodiazepine doses increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related mortality compared with using opioid analgesics alone. Given comparable pharmacological properties, 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 Perampanel and Acetaminophen And Codeine together?
Combining acetaminophen/codeine with perampanel can add up to dangerous drowsiness and slowed breathing, so use it only when needed, at the lowest dose, with close monitoring, and never stop either drug on your own without talking to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Perampanel 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 Perampanel and Acetaminophen And Codeine interaction managed?
The good news: your care team can manage this by tailoring doses and monitoring you. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team may use the lowest dose and shortest duration of each medicine, and may lower one of the doses. They will watch closely for heavy sedation, slowed or shallow breathing, confusion, or very low blood pressure. In some cases… 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 Perampanel 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 Perampanel
These medications also interact with supplements
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.
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