Acetaminophen And Codeine and Paliperidone: 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
Paliperidone
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 that can make you sleepy and slow your breathing. Paliperidone (Invega) is a medicine for mental health that can also cause drowsiness. When you take both, these calming effects can add up. You might feel more tired, dizzy, or foggy than usual, and in stronger cases your breathing could slow down.
This is based mostly on how these drugs are known to work together, not on a specific study, but it is worth taking seriously. The good news is your care team can manage this. Please talk with your pharmacist or doctor before making any changes, and let them know if you feel unusually drowsy.
Effect: Additive CNS depression when acetaminophen/codeine is combined with paliperidone.
- Mechanism: Pharmacodynamic additive sedation. Codeine (opioid) and paliperidone (atypical antipsychotic) both depress the CNS. This is a PD interaction, not a CYP-mediated PK one.
- Direction/magnitude: Increased sedation, dizziness, and potential respiratory depression; magnitude not quantified.
- Onset: Unspecified.
- Evidence: Theoretical; rated major.
- Management: Use caution; monitor for excess sedation and respiratory compromise. Dose may be individualized by the care team; avoid other CNS depressants and alcohol.
What happens
An increased risk of CNS depression
Interaction Deep Dive
Caution is advised if paliperidone is given alongside other agents that act centrally1.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. The main concern is added drowsiness.
- Your team may monitor you more closely for sleepiness, dizziness, or slowed breathing, especially when either dose changes.
- Doses may need to be adjusted and individualized by your prescriber.
- Avoid alcohol and other sedating medicines unless cleared by your care team.
- Be careful driving or operating machinery until you know how you feel.
Call your pharmacist or doctor if you feel very drowsy, confused, or hard to wake, or if your breathing feels slow.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Paliperidone together?
Taking codeine (in your acetaminophen/codeine) with paliperidone can add up to extra drowsiness and, rarely, slowed breathing. Keep taking both as prescribed, watch for heavy sleepiness, avoid alcohol, and check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Paliperidone 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 Paliperidone interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. The main concern is added drowsiness. Your team may monitor you more closely for sleepiness, dizziness, or slowed breathing, especially when either dose changes. Doses may need to be adjusted and individualized by your prescriber. Avoid alcohol and other sedating medicines unless cleared by your care team. Be caref… 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 Paliperidone 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: ERZOFRI(R) intramuscular extended-release injectable suspension, paliperidone palmitate intramuscular extended-release injectable suspension. Luye Pharma (USA) Ltd (per FDA), Princeton, NJ, 2024.
Keep reading about Acetaminophen And Codeine
Keep reading about Paliperidone
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.
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