Mercaptopurine with Allopurinol Interaction Details

Brand Names Associated with Mercaptopurine

Brand Names Associated with Allopurinol

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 27, 2024

Interaction Effect

Increased mercaptopurine toxicity (bone marrow suppression, nausea, vomiting)

Interaction Summary

Avoid the concomitant use of allopurinol and oral mercaptopurine. Allopurinol inhibits the first pass oxidative metabolism of mercaptopurine by xanthine oxidase, resulting in increased toxicity (myelosuppression, nausea, vomiting)[1] due to prolongation of the activity of mercaptopurine. However, if coadministration is required, reduce the dose of mercaptopurine to one-third to one-fourth of the usual dose. Monitor closely and make subsequent dose adjustments on the basis of response to therapy and presence of toxicities [2]. The kinetics of IV mercaptopurine are not altered by the concomitant administration of allopurinol [3].

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Avoid the concomitant use of allopurinol and oral mercaptopurine. Allopurinol inhibits the first pass oxidative metabolism of mercaptopurine by xanthine oxidase, resulting in increased toxicity (myelosuppression, nausea, vomiting)[1]. However, if coadministration is required, reduce the dose of mercaptopurine to one-third to one-fourth of the usual dose. Monitor closely and make subsequent dose adjustments on the basis of response to therapy and presence of toxicities [2]. The kinetics of IV mercaptopurine are not altered by the concomitant administration of allopurinol [3].

Mechanism Of Interaction

Inhibition of first-pass metabolism of oral mercaptopurine by allopurinol

References

1 ) Product Information: PURIXAN(R) oral suspension, mercaptopurine oral suspension. Rare Disease Therapeutics, Inc. (per FDA), Franklin, TN, 2017.

2 ) Product Information: DUZALLO(R) oral tablets, lesinurad, allopurinol oral tablets. Ironwood Pharmaceuticals, Inc (per manufacturer), Cambridge, MA, 2017.

3 ) Zimm S, Collins JM, O'Neill D, et al: Inhibition of first-pass metabolism in cancer chemotherapy: interaction of 6-mercaptopurine and allopurinol. Clin Pharmacol Ther 1983; 34:810-817.

Mercaptopurine Overview

• Mercaptopurine is used alone or with other chemotherapy drugs to treat acute lymphocytic leukemia (ALL; also called acute lymphoblastic leukemia and acute lymphatic leukemia; a type of cancer that begins in the white blood cells). Mercaptopurine is in a class of medications called purine antagonists. It works by stopping the growth of cancer cells.

Allopurinol Overview

• Allopurinol is used to treat gout (a type of arthritis in which uric acid, a naturally occurring substance in the body, builds up in the joints and causes sudden attacks of redness, swelling, pain, and heat in one or more joints). Allopurinol is also used to treat high levels of uric acid that builds up in the blood as tumors break down in people with certain types of cancer who are being treated with chemotherapy medications. It is also used to treat kidney stones that have come back in people who have high levels of uric acid in their urine. Allopurinol is in a class of medications called xanthine oxidase inhibitors. It works by reducing the production of uric acid in the body. High levels of uric acid may cause gout attacks or kidney stones. Allopurinol is used to prevent gout attacks, not to treat them once they occur.

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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.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.