Cyclosporine 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
Cyclosporine
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.
Here's what's going on. Your pain medicine contains codeine, and cyclosporine can slow down one of the liver enzymes (called CYP3A4) that helps break codeine down. When that enzyme is slowed, more codeine (and the morphine your body makes from it) can build up in your system.
That means the opioid effects can be stronger than expected, causing extra drowsiness, or in serious cases, slow or shallow breathing. This is more of a theoretical concern, but it's worth taking seriously. Please don't change anything on your own. Your care team can manage this well by watching how you feel and adjusting your codeine dose if needed. Let them know if you feel unusually sleepy or short of breath.
Mechanism: Cyclosporine inhibits CYP3A4, a pathway involved in codeine metabolism. Reduced CYP3A4 activity can shift codeine toward CYP2D6-mediated conversion, raising codeine and morphine exposure (increased opioid effect).
- Direction: Increased codeine/morphine concentrations and opioid effect.
- Risk: Enhanced or prolonged adverse reactions, including sedation and potentially fatal respiratory depression, especially when the inhibitor is added to a stable codeine dose.
- Evidence: Theoretical; magnitude and onset not well characterized.
- Management: Monitor for respiratory depression and sedation; consider codeine dose reduction until stable effects seen. If cyclosporine is discontinued, monitor for opioid withdrawal and consider increasing codeine dose.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Concomitant use of codeine with CYP3A4 inhibitors has resulted in increased codeine and morphine concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of codeine is achieved. If concomitant use is needed, closely monitor patients for respiratory depression and sedation, and consider dose reduction of codeine until stable drug effects have been observed. If a CYP3A4 inhibitor is being discontinued, monitor patients for signs of opioid withdrawal, and consider increasing dose of codeine until stable drug effects have been observed12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
The good news: your care team can manage this by tailoring your dose and watching you more closely.
- Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team may reduce your codeine dose and watch how you respond, especially soon after starting cyclosporine.
- Watch for and report unusual drowsiness, confusion, or slow/shallow breathing right away.
- If cyclosporine is ever stopped, tell your team, since your codeine dose may need to be adjusted back up and you may be watched for withdrawal.
Bring any new or refilled medicines to your pharmacist so they can double-check everything for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Cyclosporine and Acetaminophen And Codeine together?
Cyclosporine may raise codeine and morphine levels, increasing sedation and breathing risks, so keep taking both as prescribed but tell your care team, who can adjust your codeine dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cyclosporine 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 Cyclosporine and Acetaminophen And Codeine interaction managed?
The good news: your care team can manage this by tailoring your dose and watching you more closely. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may reduce your codeine dose and watch how you respond, especially soon after starting cyclosporine. Watch for and report unusual drowsiness, confusion, or slow/shallow breathing right away. If cyc… 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 Cyclosporine 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 (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 Cyclosporine
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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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