Frequency of use and standards of care for the use of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease: a systematic review of the literature and a survey of Canadian gastroenterologists.
OBJECTIVE
To identify the frequency of use and appropriate monitoring guidelines for the adverse effects of azathioprine and 6-mercaptopurine (6-MP) in the therapy of patients with inflammatory bowel disease (IBD).


METHODS
Surveys were sent to all physician members of the Canadian Association of Gastroenterology. Physicians were asked to describe their monitoring practices for IBD patients receiving azathioprine or 6-MP. A systematic literature search was also performed using MEDLINE for articles published in English between 1966 and 1999 using the MeSH terms 'azathioprine', '6-mercaptopurine', 'inflammatory bowel disease' and 'drug monitoring'.


RESULTS
Azathioprine and 6-MP were used to treat an average of 7% of patients - a surprisingly low number given the proven efficacy of these agents. All respondents reported monitoring complete blood counts (CBC), while liver enzyme and pancreatic enzyme levels were monitored by 62% and 29% of respondents, respectively. The most commonly reported initial CBC testing frequencies were weekly (42%), monthly (26%) and biweekly (23%). From the literature, it was determined that severe leukopenia (less than 2.10 g/L) occurs in less than 2% of cases and is sometimes associated with serious outcomes, including death. Most cases of severe leukopenia occurred abruptly, early in treatment. Other reported adverse effects and incidences were pancreatitis (3% to 5%), hepatotoxicity (less than 1%) and hypersensitivity (2% to 3%). Data concerning an increased risk of non-Hodgkin's lymphoma were equivocal.


CONCLUSIONS
Use of azathioprine or 6-MP is low in patients with IBD. A CBC should be performed at weeks 1, 2, 4, 6, 8 and 12, with subsequent testing every eight weeks for the duration of azathioprine or 6-MP treatment. The evidence in support of pancreatic and hepatic monitoring is weak. The risk of non-Hodgkin's lymphoma is likely low.
Wallace
T M
TM
Department of Medicine, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, Canada.
Veldhuyzen van Zanten
S J
SJ
D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D002170:Canada; D004363:Drug Utilization; D005762:Gastroenterology; D019538:Health Care Surveys; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007970:Leukopenia / Q000139:chemically induced; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use*; D010818:Practice Patterns, Physicians'
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine