Published: 3 September 2020

Publications

Allopurinol – Life-threatening interaction with azathioprine or mercaptopurine

Published: 3 September 2020
Prescriber Update 41(3): 47
September 2020

Background

Allopurinol is a xanthine oxidase inhibitor used to reduce hyperuricaemia of patients with gout.¹

Azathioprine is an immunosuppressive agent. It is metabolised in the liver, initially to mercaptopurine, which in turn is converted into inactive products by xanthine oxidase.²

Mercaptopurine is a cytotoxic drug used in the treatment of leukaemia. It is converted to inactive products by xanthine oxidase.³

The interaction and what to do about it

Inhibition of xanthine oxidase by allopurinol decreases the rate of conversion of azathioprine and mercaptopurine to inactive metabolites. The subsequent increased plasma concentrations of the active metabolites may lead to life-threatening leukopenia, thrombocytopenia or pancytopenia.²

Concomitant use of allopurinol and azathioprine or mercaptopurine is not recommended. However, if co-administration is necessary, reduce the dose of azathioprine or mercaptopurine to 25 percent of the recommended dose and closely monitor the patient’s blood count.^2,4 For example, if a transplant patient taking a maintenance dose of azathioprine of 1–4 mg/kg bodyweight per day requires concomitant allopurinol, the azathioprine dose should be reduced to 0.25–1 mg/kg bodyweight per day.

New Zealand case reports

Up to 30 June 2020, the Centre for Adverse Reactions Monitoring (CARM) had received 14 cases describing an interaction between allopurinol and azathioprine. In 13 of these cases, the patient experienced bone marrow suppression. Two recent cases reported pancytopenia (CARM IDs: 136060 and 136652). The majority of the 14 cases did not report that a dose reduction had occurred.

References

1. New Zealand Formulary. 2020. New Zealand Formulary v97: Allopurinol 1 July 2020. URL: nzf.org.nz/nzf_5681 (accessed 10 July 2020).
2. Medsafe. 1998. Azathioprine-allopurinol interaction: Danger! Prescriber Update 17: 16-17. URL: medsafe.govt.nz/profs/puarticles/azathioprine.htm (accessed 7 July 2020).
3. Pharmacy Retailing Pty Ltd. 2004. Puri-nethol New Zealand Data Sheet 2 September 2019. URL: medsafe.govt.nz/profs/Datasheet/p/Puri-netholtab.pdf (accessed 16 July 2020).
4. Douglas Pharmaceuticals Ltd. 2019. Azamun New Zealand Data Sheet 25 October 2019. URL: medsafe.govt.nz/profs/Datasheet/a/Azamuntab.pdf (accessed 3 July 2020).