Monitoring of Azathioprine

Monitoring of Azathioprine

Baseline full blood examination, serum creatinine, and liver function tests should be performed. Full blood count should be monitored every 1 to 2 weeks during dosage titration, then every 1 to 3 months. Regular liver function testing should also be performed.

Both azathioprine and mercaptopurine are metabolised to a number of inactive products and to 6-thioguanine nucleotides (6-TGNs). Remission rates are proportional to red blood cell (RBC) levels of 6-TGNs (therapeutic range 235–450 pmol/108 RBCs). The major enzyme catalysing the conversion of mercaptopurine to inactive metabolites is thiopurine methyltransferase (TPMT). There is trimodal distribution of this enzyme in the population controlled by a genetic polymorphism. One in 300 individuals have low or undetectable TPMT activity, 8% to 11% have intermediate, and the remainder normal to high activity. Those with low levels of enzyme produce fewer inactive metabolites but higher concentrations of 6-TGNs resulting in a greater risk of myelotoxicity. Those with very high enzyme content may produce inadequate red blood cell concentrations of 6-TGNs and hence therapeutic inefficacy. Red blood cell 6-TGN concentration or metabolism profiling may be available in specialist centres and could provide a means of predicting patients likely to respond to azathioprine and mercaptopurine. Individuals deficient in this enzyme are particularly susceptible to myelosuppression with azathioprine, especially if they are also taking other drugs that inhibit TPMT, such as sulfasalazine, olsalazine, or mesalazine. TPMT testing does not identify all patients at risk of severe toxicity, and close monitoring of blood counts is still recommended.