Allopurinol and Mercaptopurine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Mercaptopurine
Allopurinol
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 myelosuppression, an increased risk of hepatotoxicity and an azaTHIOprine toxicity (nausea, vomiting, leukopenia, anemia)
Interaction Deep Dive
Allopurinol may prolong the activity of azaTHIOprine via inhibition of xanthine oxidase2. If coadministered, reduce the azaTHIOprine dose to one-third to one-fourth of the usual dose. Monitor closely and adjust subsequent doses based on response to therapy and presence of toxicities 23. Further dose reduction or alternative therapy may be required for patients with low or absent thiopurine S-methyltransferase (TPMT) activity 3. Allopurinol inhibits the first pass oxidative metabolism of mercaptopurine by xanthine oxidase, which can lead to an increased risk of mercaptopurine adverse reactions. Mercaptopurine is hepatotoxic. Hepatotoxicity may be increased when mercaptopurine is coadministered with other products that can cause hepatoxicity, such as allopurinol. Monitor serum transaminase levels, alkaline phosphatase, and bilirubin levels at weekly intervals when first beginning therapy and at monthly intervals thereafter. Withhold mercaptopurine at onset of hepatotoxicity 1.
Why it happens (mechanism)
Inhibition of xanthine oxidase; additive myelosuppression; additive hepatotoxic effects; inhibition of first-pass metabolism of oral mercaptopurine by allopurinol
Literature reports
6 reports — tap to read
a) Concomitant allopurinol and azaTHIOprine therapy has been reported to impair the conversion of 6-mercaptopurine (the first metabolite of azaTHIOprine) to inactive products by inhibiting xanthine oxidase, resulting in higher blood levels of 6-mercaptopurine. Increased blood levels of 6-mercaptopurine may exert serious toxic effects on bone marrow and other tissues 56.
b) Several patients receiving azaTHIOprine developed reversible anemia, leukopenia, and thrombocytopenia after allopurinol therapy was added. After discontinuation of concomitant therapy, the hematocrit, hemoglobin, red blood cells, white blood cells and platelets increased 78.
c) A 63-year-old heart transplant patient was hospitalized for pancytopenia six weeks after his local physician prescribed allopurinol for wrist pain thought to be gout related. The patient had been maintained on azaTHIOprine 200 mg daily, along with other medications. After the allopurinol was started, the patient developed progressive dizziness and weakness. Six days before admission to the hospital, the patient had a syncopal episode which resulted in a fall. Upon admission to the hospital, the allopurinol and azaTHIOprine were held, and the patient required packed red blood cells and regramostim (GM-CSF). The therapy was successful and the patient left the hospital eight days after admission. azaTHIOprine was titrated back to the patient's previous dose 9.
d) Twenty-four transplant patients receiving azaTHIOprine and allopurinol were retrospectively studied. At the initiation of allopurinol therapy, the mean reduction of azaTHIOprine was 73.3%, but ranged from 0% to 90%. Within three months of concurrent therapy, 46% of the patients became leukopenic, 30% became moderately anemic, and 22% became thrombocytopenic. The risk of myelotoxicity was not eliminated in patients who had their dose of azaTHIOprine reduced by two-thirds or more at the start of allopurinol therapy. This study highlighted the need for careful and continuous monitoring of patients on concurrent azaTHIOprine and allopurinol regimens, since some patients did not develop myelotoxicity until the second or third month of combined therapy 4.
e) Five cases of allopurinol and azaTHIOprine interactions causing bone marrow suppression are reported. In all of the cases, bone marrow suppression occurred within one to three months after starting combination therapy with allopurinol and azaTHIOprine. These observations again reiterate the dangers of this drug interaction. Frequent monitoring of blood parameters and initial reduction of the azaTHIOprine dose by 75% in the presence of allopurinol is reinforced 10.
f) A case report described a 68-year-old male who had persistent thrombocytopenia and leukopenia that responded to steroid treatment. A trial of azaTHIOprine was started at 150 mg daily. Two weeks later, the patient presented with new petechiae on the lower extremities and large purpura on the arms. At that time, it became known that allopurinol 300 mg daily had been prescribed by a different physician. Both azaTHIOprine and allopurinol were discontinued and the patient required red cell and platelet transfusions. The platelet count began to recover by the 15th day after the discontinuation of the offending agents 11.
Common questions
Can I take Allopurinol and Mercaptopurine together?
An increased risk of myelosuppression, an increased risk of hepatotoxicity and an azaTHIOprine toxicity (nausea, vomiting, leukopenia, anemia) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Allopurinol and Mercaptopurine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Allopurinol or Mercaptopurine 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 (11)
- Product Information: PURIXAN(R) oral suspension, mercaptopurine oral suspension. Rare Disease Therapeutics Inc (per FDA), Franklin, TN, 2024. DailyMed
- Product Information: DUZALLO(R) oral tablets, lesinurad, allopurinol oral tablets. Ironwood Pharmaceuticals, Inc (per manufacturer), Cambridge, MA, 2017.
- Product Information: IMURAN(R) oral tablets, azathioprine oral tablets. Prometheus Laboratories Inc. (per FDA), San Diego, CA, 2014. DailyMed
- Cummins D, Muthasamy S, Halil O, et al: Myelosuppression associated with azathioprine-allopurinol interaction after heart and lung transplantation. Transplantation 1996; 61:1661-1662. PubMed
- Rundles RW, Wyngaarden JB, & Hitchings GH: Effects of a xanthine oxidase inhibitor on thiopurine metabolism, hyperuricemia and gout. Trans Assoc Am Physicians 1963; 76:126.
- 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. PubMed
- Zazgornik J, Kopsa H, Schmidt P, et al: Increased danger of bone marrow damage in simultaneous azathioprine-allopurinol therapy. Int J Clin Pharmacol Ther Toxicol 1981; 19:96-97.
- Boyd IW: Allopurinol-azathioprine interaction (letter). J Intern Med 1991; 229:386.
- Kennedy DT, Hayney MS, & Lake KD: Azathioprine and allopurinol: the price of an avoidable drug interaction. Ann Pharmacother 1996; 30:951-954. PubMed
- Venkat Raman G, Sharman VL, & Lee HA: Azathioprine and allopurinol: a potentially dangerous combination. J Intern Med 1990; 228:69-71. DOI
- Brooks RJ, Dorr RT, & Durie BGM: Interaction of allopurinol with 6-mercaptopurine and azathioprine. Biomed Pharmacother 1982; 36:217-222.
Keep reading about Mercaptopurine
Keep reading about Allopurinol
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