Korean J Gastroenterol.  2013 Aug;62(2):111-116. 10.4166/kjg.2013.62.2.111.

How Should Azathioprine Be Dosed in Crohn's Disease? A Novel Strategy of Maximum Dose-titration Based on the Lower Limit of Leukocyte Count and Tolerability

• Lim CS
• Moon W
• Park SJ
• Park MI
• Choi JM
• Yoo JH
• Kim JB
• Lee JS

• KMID: 1775748
• DOI: http://doi.org/10.4166/kjg.2013.62.2.111

Abstract

BACKGROUND/AIMS
Although general guidelines have suggested weight-based dosing of azathioprine (AZA, 2.5 mg/kg/day) for Crohn's disease (CD), a substantial number of patients develop bone marrow suppression. The aim of this study was to evaluate the maximum dose of AZA not based on weight but titrated according to the lower limit of leukocyte count for maintaining remission in patients with CD.
METHODS
Among a total of seventy-eight patients with CD, who had been followed-up at Kosin University Gospel Hospital (Busan, Korea) from 2010 to 2011, those treated with the maximum dose of AZA meeting both drug-tolerability and leukocytes count of more than 4,000/mm3 for steroid-free maintaining remission were enrolled. The titrated maximum AZA dose and its relationship with weight were evaluated.
RESULTS
A total of 42 patients (male, 32 patients; mean age, 31 years) were enrolled. The maximum dose of AZA was 49.1 mg/day. The dose per weight was 0.87 mg/kg/day and negatively correlated with body weight (gamma=-0.51, p=0.01) and BMI (gamma=-0.33, p=0.034). AZA dose per weight in the below 40 years old group was significantly higher than that in the above 40 years old group (p=0.039).
CONCLUSIONS
Dose decision of AZA based only on weight could put the patients to inappropriately low or high dose resulting in need of additional therapy or serious side effect, respectively. Therefore, the maximum dose-titration based on the lower limit of leukocyte count and tolerability is a novel and a valuable strategy in deciding the dose of thiopurines.

Keyword

Azathioprine; Crohn disease; Bone marrow; Leukocyte count

MeSH Terms

Adolescent
Adult
Aged
Azathioprine/*therapeutic use
Crohn Disease/*drug therapy
Dose-Response Relationship, Drug
Drug Dosage Calculations
Drug Tolerance
Female
Follow-Up Studies
Humans
Immunosuppressive Agents/*therapeutic use
Leukocyte Count
Leukocytes/*cytology
Male
Middle Aged
Young Adult
Azathioprine
Immunosuppressive Agents

Figure

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  Fig. 1. Distribution of maximal dose of azathioprine. The number of patients according to the azathioprine dose/body weight/day were 10 (23.8%) in 0.1–0.5 mg/kg/day group, 23 (54.8%) in 0.6–1.0 mg/kg/day group, 6 (14.3%) in 1.1–1.5 mg/kg/day group, and 3 (7.2%) in 1.6–3.0 mg/kg/day group.

Reference

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