Rheumatology: azathioprine and allopurinol interaction: practice question

A General Medicine question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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General Medicine · Rheumatology: azathioprine and allopurinol interaction

Sample item

A 40-year-old woman with lupus nephritis is on stable azathioprine. After a gout-like attack she is started on allopurinol, and two weeks later she has pancytopenia. What is the mechanism?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

B. Reduced breakdown of 6-mercaptopurine by xanthine oxidase

Azathioprine is converted to 6-mercaptopurine, which is inactivated mainly by xanthine oxidase. Allopurinol blocks this enzyme, so active thiopurine levels rise and cause severe myelosuppression. The azathioprine dose must be sharply reduced when both are used.

Option by option

  • A. Direct marrow suppression by allopurinol alone

    Allopurinol rarely suppresses marrow on its own at this timescale.

  • B. Reduced breakdown of 6-mercaptopurine by xanthine oxidase (correct)

    Correct. Xanthine oxidase inhibition leaves excess active thiopurine.

  • C. Induction of thiopurine methyltransferase

    Induction of the methyltransferase would lower drug toxicity, not raise it.

  • D. Competition for renal tubular secretion

    Renal tubular competition explains the probenecid-type interactions, not this one.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this General Medicine question

What is the answer to this General Medicine question?

The best answer is B, Reduced breakdown of 6-mercaptopurine by xanthine oxidase. Azathioprine is converted to 6-mercaptopurine, which is inactivated mainly by xanthine oxidase.

Why is "Direct marrow suppression by allopurinol alone" not the answer?

Allopurinol rarely suppresses marrow on its own at this timescale.

Why is "Induction of thiopurine methyltransferase" not the answer?

Induction of the methyltransferase would lower drug toxicity, not raise it.

Why is "Competition for renal tubular secretion" not the answer?

Renal tubular competition explains the probenecid-type interactions, not this one.

What concept does this question test?

It tests Rheumatology: azathioprine and allopurinol interaction in General Medicine. Allopurinol blocks this enzyme, so active thiopurine levels rise and cause severe myelosuppression. The azathioprine dose must be sharply reduced when both are used.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Rheumatology: azathioprine and allopurinol interaction?

For each disease know the classic presentation, the best test, and the first-line treatment. Then use the flashcards and the other General Medicine questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.