| Summary: | 碩士 === 國立臺灣大學 === 臨床藥學研究所 === 91 === During the past 4-5 years, there were 44 cases of carbamazepine-related adverse reaction applied for drug relief fund and 160 cases reported to National Reporting Center of Adverse Drug Reactions in Taiwan. According to literature, the incidence of severe adverse reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and agranulocytosis after the administration of carbamazepine (CBZ) were rare. However, the incidence in Taiwan may be higher according to the data in the reporting system and underreporting situation. In addition, many claimants of severe adverse drug reactions related to off-label use of CBZ were not able to get reimbursement according to the Drug Relief Law. Therefore, it is important to understand the present prescribing pattern of CBZ.
There were four parts in this study. The first and second parts were to review the CBZ-related cases applied for drug relief fund and those reported to National Reporting Center of Adverse Drug Reactions in Taiwan, in order to understand the types of the CBZ-related adverse reactions. The third part was to review the prescribing pattern of CBZ in National Taiwan University Hospital (NTUH), based on the data collecting from the computer systems of NTUH. The forth part was to conduct a case-control study to quantify the risk factors associated with the CBZ-related severe skin reactions.
From the retrospective analysis of the 44 CBZ-related adverse reaction cases applied for drug relief fund, there were 43 cases suffered from severe cutaneous adverse reactions and one case suffered from agranulocytosis. Fourteen claimants (31.8%) of severe adverse drug reactions related to off-label use of carbamazepine were unable to receive benefit according to the Drug Relief Law. However, it was found that there were some inconsistencies among the cases for the benefit decision-making process. The majority (n=123, 76.9%) of the reported reactions of the 160 cases reported to National Reporting Center of Adverse Drug Reactions were also on skin reactions. Among them, 68.3% were EM/SJS/TEN. From the data of the present clinical utilization pattern of CBZ in NTUH, most of cases in outpatients were described for epilepsy (>50%); however, most in hospitalized patients were described for neuropathies except trigeminal neuralgia (around 30-50%). The off-label use of CBZ in outpatients and hospitalized patients were around 60% and 80%, respectively.
The analysis of the risk factors associated with CBZ-related EM/SJS/TEN was based on 43 cases and 129 controls. Trigeminal neuralgia showed a strong correlation than epilepsy. Cardiovascular diseases (CVD) also had a significant correlation. From the concurrent drugs analysis, phenothiazines, vitamins, oxethazaine, dihydropyridines and dextromethorphan were significantly correlated with CBZ-related EM/SJS/TEN in multivariate analysis. Alcohol consumption as well as CVD showed a significant correlation with the severe adverse reactions.
Despite many limitations in this study, the results may provide clinicians information of occurrence of severe skin reactions to improve drug safety.
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