Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease.
OBJECTIVE
The thiopurine drugs, azathioprine and 6-mercaptopurine are effective in the treatment of inflammatory bowel disease (IBD). However, their use is limited by serious adverse effects that can lead to cessation of therapy. The incidence of these adverse effects has been reported to be approximately 9% but in Christchurch it was felt that the incidence was higher.


METHODS
We searched our letter database to identify all patients with IBD who had received a thiopurine drug between 1996 and 2002. The case notes were then reviewed to identify those patients who had suffered an adverse effect that required cessation of the drug.


RESULTS
From a total of 216 patients with IBD taking a thiopurine drug, 56 (25.9%) had an adverse reaction requiring cessation of the drug. Adverse effects included allergic-type (25%), liver test abnormalities (34%), nausea/vomiting (6%), bone marrow suppression (7%), pancreatitis (7%) and other (9%). Males were significantly more likely than females to have an allergic-type reaction (p = 0.003). All adverse effects resolved with cessation of the drug, with a median of 7 days to resolution. Of the patients with liver test abnormalities on azathioprine, most were able to tolerate 6-mercaptopurine, however challenge with 6-mercaptopurine was not successful for most other patients.


CONCLUSIONS
In Canterbury, New Zealand, patients with IBD have a high rate of therapy-limiting adverse effects to thiopurine drugs. There is a significant gender bias for allergic-type adverse effects. Mechanisms for both these observations are not clear.
Gearry
Richard B
RB
Department of Gastroenterology, Christchurch Hospital, New Zealand. richard.gearry@cdhb.govt.nz
Barclay
Murray L
ML
Burt
Michael J
MJ
Collett
Judith A
JA
Chapman
Bruce A
BA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects*; D008875:Middle Aged; D009520:New Zealand / Q000453:epidemiology; D017891:Pharmacoepidemiology; D017678:Sex Distribution
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine