IMPORTANCE OF THE FIELD: traditional immunosuppressants, including azathioprine, 
remain the mainstay of therapy in steroid dependent/refractory patients with 
inflammatory bowel diseases (IBD). The main limitations of its use are its side 
effects appearing in about a fifth of the patients, including myelosuppression 
and liver toxicity. Major complications occur in patients with low 
thiopurine-S-methyltransferase (TPMT) enzyme activity; however, the clinical 
relevance of these tests remains conflictive.
AREAS COVERED IN THIS REVIEW: in this review, the authors aim to summarize the 
new data regarding the relationship between the pharmacology of thiopurines and 
pathogenesis of adverse events.
WHAT THE READER WILL GAIN: readers will gain an understanding of the metabolism 
of thiopurines, side effect profile, pharmacological background of side effects, 
importance of metabolite monitoring, clinical relevance of inherited differences 
in drug metabolism and other conditions (e.g., concomitant use of allopurinol) 
which can modify enzyme activity. By gaining an understanding of the 
pharmacology and metabolism of thiopurines, clinicians will be able to optimize 
thiopurine therapy in IBD.
TAKE HOME MESSAGE: TPMT testing and metabolite monitoring are still not 
considered the standard of care, and clinicians will continue to choose the 
approach that best suits their clinical practice and patient needs. Regardless 
of what strategy is chosen, patients need to be carefully monitored and well 
informed about the potential risks.