Acetaminophen And Codeine and Lumefantrine: 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
Lumefantrine
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 morphine using a liver enzyme called CYP2D6. Lumefantrine (a malaria medicine) can slow that same enzyme. This is a bit unusual: because codeine is a prodrug that needs CYP2D6 to become active, blocking the enzyme could mean less pain relief from the codeine, while the codeine itself can pile up. On top of that, both medicines can affect your heart's rhythm (the QT interval), so using them together may add up.
The good news is your care team can manage this by checking your heart and adjusting things as needed. Don't change either medicine on your own, but do talk with your pharmacist or doctor.
Effect: Concurrent lumefantrine (with artemether) may inhibit CYP2D6, altering exposure of CYP2D6 substrates and adding to QT-interval prolongation risk.
- Direction: Codeine is a CYP2D6 prodrug activated to morphine; CYP2D6 inhibition can reduce analgesic efficacy while increasing parent codeine levels. Regardless, additive QT risk is the primary concern.
- Evidence: Theoretical; onset unspecified; severity major.
- Management: Manufacturer advises avoiding coadministration. If unavoidable, monitor ECG/QTc, electrolytes (K+, Mg2+), and for opioid-related adverse effects. Individualize therapy.
What happens
Increased CYP2D6 substrate exposure and an increased risk of CYP2D6 substrate-related adverse reactions
Interaction Deep Dive
Avoid giving artemether/lumefantrine together with CYP2D6 substrates, because doing so can produce an additive effect on the QT interval, substantially raise exposure to the CYP2D6 substrates, and heighten the likelihood of adverse effects. For this reason, watch for prolongation of the QT interval1.
Why it happens (mechanism)
Inhibition of CYP2D6-substrate metabolism by artemether/lumefantrine
How to manage this interaction
Both of these medicines can affect your heart rhythm, and lumefantrine can change how your body handles codeine. Your care team's usual approach is to avoid using them together when possible.
- Keep taking both exactly as prescribed until you speak with your prescriber or pharmacist.
- Your team may check your heart rhythm (an ECG) and blood minerals, and watch you more closely for side effects.
- They may choose a different pain option or malaria treatment, and doses can be adjusted and individualized by your care team.
- Report any fainting, dizziness, palpitations, or unusual drowsiness right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Lumefantrine together?
Combining lumefantrine with acetaminophen-codeine is usually avoided because both can prolong the QT interval and lumefantrine can alter codeine handling; let your pharmacist or doctor coordinate this and watch your heart rhythm. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Lumefantrine 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 Lumefantrine interaction managed?
Both of these medicines can affect your heart rhythm, and lumefantrine can change how your body handles codeine. Your care team's usual approach is to avoid using them together when possible. Keep taking both exactly as prescribed until you speak with your prescriber or pharmacist. Your team may check your heart rhythm (an ECG) and blood minerals, and watch you more closely for side effects. They… 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 Lumefantrine 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: COARTEM® oral tablets, artemether lumefantrine oral tablets. Novartis Pharmaceuticals Corporation (per DailyMed), East Hanover, NJ, 2025. DailyMed
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