Published: 6 September 2018

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Febuxostat – Interaction with Azathioprine or Mercaptopurine

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Prescriber Update 39(3): 46–47
September 2018

Indications and use in New Zealand

Febuxostat (Adenuric) is a potent, non-purine, selective inhibitor of xanthine oxidase that reduces the formation of uric acid¹.

Febuxostat is approved in New Zealand for the treatment of chronic hyperuricaemia in patients with gout. It is also approved for the prevention and treatment of hyperuricaemia in patients undergoing chemotherapy for haematological malignancy at intermediate- to high-risk of Tumour Lysis Syndrome¹.

The use of febuxostat has increased significantly² in New Zealand since it was funded by PHARMAC on 1 June 2014, subject to Special Authority criteria³.

Interactions with azathioprine and its metabolite – 6-mercaptopurine

Azathioprine is an immunosuppressive agent. It is first metabolised to 6-mercaptopurine, which in turn is converted to inactive products by xanthine oxidase⁴. Inhibition of xanthine oxidase by febuxostat may cause increased plasma concentrations of azathioprine or mercaptopurine, leading to toxicity¹.

There are no drug interaction studies for febuxostat co-administered with medicines metabolised by xanthine oxidase. A number of post-marketing and literature cases of interaction with azathioprine have been reported globally^1,5. As at 30 June 2018 there had been no reports from New Zealand.

Febuxostat is not recommended in patients concomitantly treated with azathioprine or mercaptopurine¹. Where the combination cannot be avoided, closely monitor patients and reduce the dose of azathioprine or mercaptopurine to avoid possible haematological effects¹.

Please report any adverse reactions to CARM (https://nzphvc.otago.ac.nz/report/).

References

1. A.Menarini New Zealand Pty Ltd. 2016. Adenuric New Zealand Data Sheet 18 May 2016. URL: www.medsafe.govt.nz/profs/Datasheet/a/adenurictab.pdf (accessed 23 July 2018).
2. Ministry of Health. 2018. DataPharm (beta) version 15 March 2018 (data extracted from Pharmaceutical Collection on 18 December 2017). URL: https://minhealthnz.shinyapps.io/datapharm-beta/ (accessed 23 July 2018).
3. Medsafe. 2014. Febuxostat - an additional xanthine oxidase inhibitor. Prescriber Update 35(3): 39. URL: www.medsafe.govt.nz/profs/PUArticles/September2014Febuxostat.htm (accessed 23 July 2018).
4. Medsafe. 1998. Azathioprine-allopurinol interaction: Danger! Prescriber Update 17: 16–17. URL: www.medsafe.govt.nz/profs/puarticles/azathioprine.htm (accessed 23 July 2018).
5. Jordan A and Gresser U. 2018. Side effects and interactions of the xanthine oxidase inhibitor febuxostat. Pharmaceuticals 11(2): 51. DOI: 10.3390/ph11020051 (accessed 23 July 2018).