Acetaminophen And Codeine and Chloramphenicol: 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
Chloramphenicol
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.
You've been given a medicine that combines acetaminophen (Tylenol) with codeine for pain, along with an antibiotic called chloramphenicol. When these are taken together at higher doses, there have been reports that the amount of chloramphenicol in your body can change. If it builds up too much, it may cause things like vomiting, low blood pressure, or feeling cold.
The good news is that this is considered a minor interaction, and the reports have been mixed. Please keep taking both medicines exactly as prescribed. Your care team can easily manage this by checking your chloramphenicol levels and fine-tuning the dose if needed.
Effect: Reported alteration in chloramphenicol pharmacokinetics with possible chloramphenicol toxicity (emesis, hypotension, hypothermia).
- Direction/magnitude: Inconsistent. High-dose acetaminophen (>=1 g QID) with chloramphenicol (>=500 mg q6h) has been reported to increase, decrease, or not change chloramphenicol half-life.
- Mechanism: Unknown.
- Onset: Delayed. Evidence: Probable. Severity: Minor.
- Note: Neither the direction nor magnitude is consistent, so clinical significance is variable.
Management: Monitor serum chloramphenicol concentrations and adjust chloramphenicol dosing as needed to maintain the therapeutic range.
What happens
Chloramphenicol toxicity (vomiting, hypotension, hypothermia)
Interaction Deep Dive
Concomitant use of acetaminophen (greater than or equal to 1 g four times daily) and chloramphenicol (greater than or equal to 500 mg every six hours) has been reported to increase, decrease, and have no change on the chloramphenicol half-life4.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise.
- Your team may monitor your chloramphenicol blood levels more closely while you are on both.
- The chloramphenicol dose may need to be adjusted and individualized based on those levels.
- Let your pharmacist or doctor know if you notice vomiting, dizziness or lightheadedness (possible low blood pressure), or feeling unusually cold.
This is generally a minor, manageable interaction, so there is no need to stop anything on your own. Just check in with your prescriber or pharmacist.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) One study found that the half-life of chloramphenicol rose from 2 to 3 hours up to 18 to 24 hours in children given concurrent acetaminophen therapy, and from 3.25 hours to 15 hours in 6 adults tested in the same way. The suggested mechanism was competitive metabolism, and a reduction in the chloramphenicol dose was recommended 1.
b) No pharmacokinetic interaction was observed between intravenous chloramphenicol succinate and oral acetaminophen in acutely febrile children receiving both agents together. This suggests that acetaminophen and chloramphenicol (succinate) may be administered together in children at the currently recommended doses without changes in chloramphenicol disposition. Nevertheless, concurrent use of intravenous chloramphenicol and oral acetaminophen was reported to produce significant increases in chloramphenicol clearance, along with reductions in peak chloramphenicol serum concentrations and elimination half-life. These effects are thought to be linked to enhanced glucuronidation of chloramphenicol. Until additional data become available, serum level monitoring is warranted during combined therapy 23.
Common questions
Can I take Acetaminophen And Codeine and Chloramphenicol together?
Taking high-dose acetaminophen/codeine with chloramphenicol may change chloramphenicol levels, so your team may check its blood levels and adjust the dose. Keep taking both as prescribed and report vomiting, dizziness, or feeling cold. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Chloramphenicol interaction?
It is rated minor. Usually limited clinical impact.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Acetaminophen And Codeine and Chloramphenicol interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Your team may monitor your chloramphenicol blood levels more closely while you are on both. The chloramphenicol dose may need to be adjusted and individualized based on those levels. Let your pharmacist or doctor know if you notice vomiting, dizziness or lightheadedness (possible low blood pressure), or feeling unu… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Chloramphenicol 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 anything you'd monitor while I'm on both?
References (4)
- Buchanan N & Moodley BP: Interaction between chloramphenicol and paracetamol. Br Med J 1979; 2:307-308. PubMed
- Spika JS, Davis DJ, Martin SR, et al: Interaction between chloramphenicol and acetaminophen. Arch Dis Child 1986; 61:1121-1124. PubMed
- Kearns GL, Bocchini JA Jr, Brown RD, et al: Absence of a pharmacokinetic interaction between chloramphenicol and acetaminophen in children. J Pediatr 1985; 107:134-139. PubMed
- Stein CM, Thornhill DP, Neill P, et al: Lack of effect of paracetamol on the pharmacokinetics of chloramphenicol. Br J Clin Pharmacol 1989; 2:262-264. PubMed
Keep reading about Acetaminophen And Codeine
Keep reading about Chloramphenicol
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