Acetaminophen And Codeine and Verapamil: 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
Verapamil
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, and verapamil (a heart and blood pressure medicine) can slow down one of the enzymes your body uses to process codeine. That can let codeine and its active form, morphine, build up higher than expected. When that happens, you may feel more drowsy or sedated, and in serious cases your breathing can slow down too much.
The good news is your care team can manage this. They may watch you a bit more closely or adjust your codeine dose so you stay comfortable and safe. Please don't stop either medicine on your own. Just call your pharmacist or doctor if you feel unusually sleepy, foggy, or short of breath.
Effect: Increased codeine and morphine exposure via verapamil inhibition of CYP3A4. Codeine is metabolized by CYP3A4 (to norcodeine) and CYP2D6 (to morphine, its active opioid metabolite). CYP3A4 inhibition shunts more codeine toward CYP2D6, raising active morphine concentrations.
- Direction: Increased opioid effect (sedation, respiratory depression).
- Evidence: Theoretical; magnitude not quantified.
- Onset: Unspecified; higher risk when inhibitor added to a stable codeine dose.
- Management: Monitor for respiratory depression and sedation; consider codeine dose reduction until stable effects seen. If verapamil is stopped, monitor for opioid withdrawal and consider increasing codeine.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Taking codeine together with CYP3A4 inhibitors has been shown to raise the concentrations of both codeine and morphine, an effect that may intensify or extend adverse reactions and can produce respiratory depression that is potentially fatal, especially when the inhibitor is introduced after codeine has already been titrated to a stable dose. When these agents must be given together, watch patients carefully for sedation and respiratory depression, and consider lowering the codeine dose until stable drug effects are seen. Should a CYP3A4 inhibitor be stopped, observe patients for indications of opioid withdrawal and consider raising the codeine dose until stable drug effects are seen12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because this combination can raise opioid levels, here is what typically happens:
- Your team may monitor you more closely for excess drowsiness, confusion, or slowed breathing, especially soon after starting verapamil.
- Your codeine dose may need to be adjusted and individualized until your response is stable.
- If verapamil is later stopped, watch for signs of opioid withdrawal, and your dose may be revisited.
Call your pharmacist or doctor right away if you feel very sleepy, hard to wake, or short of breath.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Verapamil together?
Verapamil can raise codeine and morphine levels, increasing sedation and, rarely, dangerous slowed breathing; keep taking both as prescribed but tell your care team so they can monitor you and adjust the codeine dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Verapamil 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 Verapamil interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because this combination can raise opioid levels, here is what typically happens: Your team may monitor you more closely for excess drowsiness, confusion, or slowed breathing, especially soon after starting verapamil. Your codeine dose may need to be adjusted and individualized until your response is stable. If ver… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Verapamil 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 (2)
- 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 Verapamil
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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