Acetaminophen And Codeine and Indinavir: 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
Indinavir
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.
What's going on: Your pain medicine contains codeine. Codeine is broken down in your body by an enzyme, and indinavir slows part of that process. This can let more codeine and its active form, morphine, build up in your body.
Because of this, the codeine could hit harder or last longer than usual. The main worry is too much sedation or slowed, shallow breathing, especially if indinavir is started after you're already settled on your codeine dose. The good news is your care team can manage this by adjusting your dose and watching you more closely. Please talk with your pharmacist or doctor before changing anything, and get help right away if you feel very drowsy or hard to wake.
Mechanism: Indinavir inhibits CYP3A4, reducing an oxidative metabolic pathway of codeine and increasing codeine and morphine exposure (Cmax/AUC). Codeine is a prodrug, but its analgesic/CNS activity here is driven by increased overall parent and morphine concentrations, so net effect is enhanced opioid effect.
- Direction: Increased opioid exposure and toxicity risk
- Severity: Major; evidence: theoretical
- Onset: Unspecified; highest risk when inhibitor added to a stable codeine regimen
Management: Monitor for respiratory depression and excessive sedation; consider codeine dose reduction until stable effects observed. On indinavir discontinuation, watch for opioid withdrawal and consider a codeine dose increase.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Taking codeine together with CYP3A4 inhibitors has led to elevated levels of both codeine and morphine, an effect that may intensify or extend adverse reactions and can produce respiratory depression that is potentially fatal, especially in cases where the inhibitor is introduced once a stable codeine dose has already been reached. When these agents must be used together, watch patients carefully for sedation and respiratory depression, and think about lowering the codeine dose until the drug effects have become stable. In situations where a CYP3A4 inhibitor is being stopped, observe patients for indications of opioid withdrawal, and consider raising the codeine dose until stable drug effects have been seen12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both as prescribed unless your prescriber tells you otherwise. This interaction is manageable with the right monitoring.
- Your care team may reduce your codeine dose and individualize it until they see how you respond.
- They may monitor you more closely for excessive drowsiness or slowed, shallow breathing, especially if indinavir is added after you're stable on codeine.
- If indinavir is later stopped, your team may watch for withdrawal and adjust your codeine dose back up as needed.
Ask your pharmacist or doctor before making any changes, and seek urgent care for hard-to-wake sleepiness or trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Indinavir together?
Indinavir can raise codeine and morphine levels, increasing the risk of over-sedation and dangerously slowed breathing. Keep taking both as prescribed, but talk with your care team so they can adjust the codeine dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Indinavir 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 Indinavir interaction managed?
Keep taking both as prescribed unless your prescriber tells you otherwise. This interaction is manageable with the right monitoring. Your care team may reduce your codeine dose and individualize it until they see how you respond. They may monitor you more closely for excessive drowsiness or slowed, shallow breathing, especially if indinavir is added after you're stable on codeine. If indinavir is… 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 Indinavir 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 Indinavir
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