Acetaminophen with Metyrapone Interaction Details
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 25, 2024
Interaction Effect
An increased risk of acetaminophen toxicity
Interaction Summary
The elimination of a single dose of acetaminophen in patients receiving metyrapone has been studied[1]. 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.
Severity
Minor
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Use caution when administering acetaminophen to a patient on metyrapone therapy. Lower doses of acetaminophen may be warranted. Alternatively, an analgesic that does not contain acetaminophen could be administered.
Mechanism Of Interaction
Inhibition of acetaminophen glucuronide formation
Literature Reports
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].
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.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
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Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.