Acetaminophen Rectal and Metyrapone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 10, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Metyrapone
Acetaminophen Rectal
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 happens
An increased risk of acetaminophen toxicity
Interaction Deep Dive
The elimination of a single dose of acetaminophen in patients receiving metyrapone has been studied1. The overall elimination of acetaminophen was decreased when administered with metyrapone, possibly due to inhibition of acetaminophen glucuronide formation. These results suggest that metyrapone could enhance acetaminophen toxicity.
Why it happens (mechanism)
Inhibition of acetaminophen glucuronide formation
Literature reports
1 report — tap to read
a) Eight healthy male volunteers participated in a study to determine the effect of metyrapone on the elimination rate of acetaminophen and on the apparent formation rate of acetaminophen metabolites. Major routes of elimination for acetaminophen include two capacity-limited processes for the formation of acetaminophen sulfate and acetaminophen glucuronide. Metyrapone is an inhibitor of cytochrome P-450-mediated oxidation, a minor route of elimination for acetaminophen. During an overdose of acetaminophen, the two capacity-limited pathways become saturated and a larger percentage of the drug is available for cytochrome P-450 oxidation. This randomized, crossover study involved subjects receiving a single oral dose of acetaminophen 1 gram on two separate occasions. On one occasion, subjects also received metyrapone 750 mg one hour before and three hours after the acetaminophen dose. Metyrapone increased the half-life of acetaminophen by 46% (from 2.4 hours to 3.5 hours). The fraction of the acetaminophen dose recovered as the glucuronide metabolite was decreased by 31% in the presence of metyrapone, while the fraction recovered as the sulfate and mercapturic acid conjugates were increased by 53% and 127%, respectively. These results suggest that metyrapone could potentiate acetaminophen toxicity by being a more potent inhibitor of glucuronide conjugation than of oxidation 1.
Common questions
Can I take Acetaminophen Rectal and Metyrapone together?
An increased risk of acetaminophen toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen Rectal and Metyrapone 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 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 Rectal or Metyrapone 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 (1)
- Galinsky RE, Nelson EB, & Rollins DE: Pharmacokinetic consequences and toxicologic implications of metyrapone-induced alterations of acetaminophen elimination in man. Eur J Clin Pharmacol 1987; 33:391-396. PubMed
Keep reading about Acetaminophen Rectal
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