Safety of thiopurines in the treatment of inflammatory bowel disease
| Autor: | P M Hooymans, Anton H. Naber, Dirk J de Jong, Cjj Mulder, L J J Derijks |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Drug-Related Side Effects and Adverse Reactions Azathioprine Inflammatory bowel disease law.invention Randomized controlled trial law medicine Humans Adverse effect Intensive care medicine medicine.diagnostic_test Thiopurine methyltransferase biology Mercaptopurine business.industry Gastroenterology Inflammatory Bowel Diseases medicine.disease Rash Clinical trial Treatment Outcome Therapeutic drug monitoring biology.protein Drug Monitoring medicine.symptom business Immunosuppressive Agents medicine.drug |
| Zdroj: | Scandinavian Journal of Gastroenterology. 38:69-72 |
| ISSN: | 0036-5521 |
| DOI: | 10.1080/00855920310002726 |
| Popis: | Background Thiopurines have proven efficacy in inflammatory bowel disease. However, concerns regarding toxicity have limited the use of these agents as first line of medical therapy. Methods Review of the literature regarding metabolism, efficacy and side effects. Results In clinical trials, up to 15% of patients discontinued 6-mercaptopurine or its pro-drug azathioprine prematurely due to adverse events. These events may be divided into dose-independent idiosyncratic reactions and dose-related, pharmacologically explainable toxicity. Dose-independent reactions include skin rash, fever, diarrhoea and pancreatitis. Most frequently observed dose-dependent adverse events are nausea, malaise and myelotoxicity. Furthermore, dose-dependent and dose-independent hepatotoxicity may occur. Recent insights obtained by therapeutic drug monitoring in patients on azathioprine or 6-mercaptopurine have led to strategies to reduce toxicity. One strategy is to detect poor metabolisers of thiopurines by establishing the activity of the key enzyme thiopurine methyltransferase. However, the clinical relevance of this strategy is still a point of debate. Another strategy is to administer 6-thioguanine, which is an agent close to the effective 6-thioguanine nucleotides. Conclusion Therapeutic drug monitoring of thiopurines resulted in strategies to reduce toxicity. The value of these strategies has yet to be proven in prospective randomized trials. |
| Databáze: | OpenAIRE |
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