Clofazimine 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
Clofazimine
No brand names on record
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, which your body turns into other substances, including morphine, to relieve pain. Clofazimine can slow down one of the liver enzymes (called CYP3A4) that helps clear codeine. That means more codeine and morphine can build up in your system.
When that happens, you could feel extra sleepy, or your breathing could slow down too much, which can be serious. This is based on how these drugs work rather than lots of real-world reports, but it is worth taking seriously. The good news: your care team can manage this by watching you closely and adjusting your dose if needed. Please talk with your pharmacist or doctor before making any changes.
Effect: Clofazimine (a CYP3A4 inhibitor) may reduce codeine clearance, increasing codeine and its active metabolite morphine exposure. Codeine is a prodrug; however, the primary safety concern here is accumulation of the parent and active opioid metabolites, raising the risk of sedation and respiratory depression.
- Mechanism: inhibition of CYP3A4-mediated codeine metabolism.
- Direction: increased opioid exposure/effect.
- Evidence: theoretical; magnitude unquantified; onset unspecified.
- Management: monitor for respiratory depression and sedation; consider codeine dose reduction until stable effects seen. If clofazimine 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
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This interaction can usually be managed safely.
- Your team may monitor you more closely for excessive drowsiness or slowed, shallow breathing, especially when clofazimine is first added.
- Your codeine dose may need to be adjusted and individualized by your care team until your response is stable.
- If clofazimine is later stopped, watch for signs of opioid withdrawal, and your team may adjust codeine again.
- Call your pharmacist or doctor right away if you feel very sleepy, confused, or have trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Clofazimine and Acetaminophen And Codeine together?
Clofazimine may raise codeine and morphine levels, increasing the risk of heavy sedation or slowed breathing, so your care team may adjust your codeine dose and watch you closely. Don't change either medicine on your own; check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clofazimine 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 Clofazimine and Acetaminophen And Codeine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This interaction can usually be managed safely. Your team may monitor you more closely for excessive drowsiness or slowed, shallow breathing, especially when clofazimine is first added. Your codeine dose may need to be adjusted and individualized by your care team until your response is stable. If clofazimi… 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 Clofazimine 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 Clofazimine
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