Background Thiopurines play an important role in maintaining remission in inflammatory bowel disease (IBD). Optimising therapeutic strategies is of paramount importance in preventing treatment failure. Co-administration of Allopurinol, a Xanthine Oxidase inhibitor, with thiopurines has become established practice in achieving target thioguanine concentrations. The recommended dose of Allopurinol is 100 mg combined with modified thiopurine dosing (<25% of standard dose).
Purpose The aim of the study was to explore whether Allopurinol 50 mg could achieve the correct thioguanine nucleotide to methylmercaptopurine (TGN:MeMP) ratio while observing the side effects and safety profile of combined therapy.
Material and methods Combined Allopurinol and thiopurines therapy were started in a virtual pharmacist clinic in a cohort of patients who had failed thiopurines monotherapy. Patients were contacted by telephone, text or e-mail according to patients’ preference. Thioguanine results were requested from our laboratory and obtained from Guy’s NHS Hospital, which recommended the addition of Allopurinol if the ratio TGN:MeMP >11.
The total number of patients recruited was 44, of which 20 were female, 17 had Crohn’s disease, 27 had ulcerative colitis. The average weight was 86 kg. Two patients were TPMT carriers ((10–25) pmol/h/mgHb), the rest were normal (26–51). The Azathioprine dosing range was (0.12–0.64) mg/kg (23 patients): the 6-Mercaptopurine dosing range was (0.11–0.54) mg/kg (21 patients).
Results Of the 44 patients entered into the study, 14 patients discontinued treatment during the first week, 11 patients due to intolerance and three patients (with normal TPMT levels) due to recurrent hepatotoxicity. 30/44 patients tolerated combined therapy. 27/30 patients achieved an optimised TGN:MeMP ratio (<11). Specific ratios included 0 (n=13), 1 (n=9), 2 (n=4), 3 (n=1). 3/30 patients required Allopurinol 100 mg to obtain a ratio <11.
Conclusion The majority of patients (90%) obtained an effective TGN:MeMP ratio with reduced Allopurinol dosing at 50 mg. Those that did not achieve this ratio (10%) responded to dose escalation to 100 mg. TPMT status did not appear to influence the effect of low-dose Allopurinol. Hepatotoxicity may still occur with combined Allopurinol and thiopurines therapy. Low-dose Allopurinol may be considered a viable therapeutic strategy providing that appropriate clinical and biochemical surveillance is maintained.
References and/or acknowledgements Thanks to gastroenterologists and the chief pharmacist.
No conflict of interest.