Carbamazepine相關不良反應之回溯性研究

A Retrospective Study of Adverse Drug Reactions Associated with Carbamazepine

王增蕙(Tseng-Hui Wang)

指導教授 ： 高純琇

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.01863

摘要

Carbamazepine（CBZ）廣泛使用於抗癲癇及各種神經性疼痛、精神疾病之治療，自民國88年至92年12月底在全國藥品不良反應通報中心之通報案例中，疑似因服用CBZ引起不良反應者，共有212件，且五年來CBZ一直列在不良反應通報案例之可疑藥品前10名之列。另，自民國89年5月31日「藥害救濟法」經總統公佈實施以來，至民國90年底完成審議的藥害救濟申請案中，因服用CBZ引起嚴重不良反應而申請藥害救濟者有38件，因而獲得給付者有19人，為獲救濟給付案例之藥品的第一位。
由上述的資料可知，國人因服用CBZ發生嚴重不良反應並非不常見，因此有必要對於包括溫和及嚴重的不良反應發生情形做一分析研究，本研究主要目的在於探討因使用CBZ引起之不良反應的發生率、發生種類、危險因子等。
本研究所收入之病患為民國91年5月1日至7月31日止，首次於臺大醫院門診開方領用CBZ的病患。由臺大醫院之電腦資料庫提供民國90年及91年門診使用過CBZ的病患資料，經篩選及以查閱病歷方式，共收入277位病患。在資料收集方面，則以記錄病人基本資料、併存疾病以及各項實驗室檢驗值，不良反應發生的種類及臨床處理方式等為主。
在所收入277位病患中，有84位病患發生了115件不良反應，不良反應發生率為30.3%。在此115件不良反應中，35件（30.4%）是屬於型態A反應，76件（66.1%）是屬於型態B反應，另外有4件因病歷未記載不良反應的症狀，所以無法判別其型態。依本研究的定義，嚴重度屬重度的個案數有6件（5.2%），屬中度的不良反應有41件（35.6%），而屬輕度的案件則有68件（59.1%）。在藥物相關性的評估方面，極有可能者有10件（8.7%），可能者有104件（90.4%），存疑者則有1件（0.9%）。服藥後到發生不良反應之時間為服藥當天到服藥後第203天不等，平均為26.2天。不良反應發生種類以神經學及皮膚學方面的不良反應最多，分別為25.2%及14.8%。臨床上對不良反應的處理則以停藥處理佔最多（55.7%）。
在導致不良反應發生的因素分析方面，可觀察到成人服用較高的平均每日劑量、有皰疹感染史者、60歲以上老年人及兒童，在發生不良反應病人組及未發生不良反應病人組之間，具統計上有意義的差異。開方注意事項方面，發現有房室阻斷性心律不整相關診斷的病患服用CBZ後，發生不良反應（8.3%）與未發生不良反應（2.1%）病患之比例具有統計上顯著之不同（p= 0.01）；在骨髓功能不良之開方禁忌症方面，雖然發生不良反應（7.1%）比未發生不良反應（3.6%）的病患比例高，但未具有統計上顯著之不同。研究顯示，具CBZ開方禁忌症之患者，不宜服用CBZ。
另外，本研究發現有房室阻斷性心律不整相關診斷暨年紀大者，在首次服用CBZ後易發生心血管不良反應，例如：心悸、血壓下降、心律不整發作、病竇症候群（Sick Sinus Syndrome, SSS）等。服用CBZ發生心血管方面不良反應的發生率為1.4%（4/277），這是以往在國內較少被注意到的不良反應，在此藉本研究結果提醒並建議對於有房室阻斷性之心律不整相關診斷且年紀大者，應審慎評估其CBZ的使用。同時，建議加強臨床人員對CBZ的知識及做好病患用藥教育，方能正確安全使用CBZ。

關鍵字

不良反應

並列摘要

There were 212 cases of carbamazepine (CBZ) related adverse reactions reported to National Reporting Center of Adverse Drug Reactions in Taiwan from 1999 to 2003. There were 38 patients of CBZ-related severe adverse reactions applied for drug relief fund from 1999-2002, in which 19 of them obtained compensation. The number received reimbursement with CBZ-related severe adverse reactions is the highest one among the applications. However, the incidence of CBZ-related severe adverse reactions in Taiwan is still not known yet. It is important to evaluate CBZ-related adverse drug reactions (ADRs). The purpose of this study is to analyze the incidence rate, types and risk factors of CBZ-related adverse drug reactions (ADRs) based on a retrospective study of a medical center.
In the study, 277 patients who were prescribed for CBZ for the first time in outpatient setting of National Taiwan University Hospital during May 2002 to July 2002 were included. There were 84 patients developed 115 ADRs after administration of CBZ. Among the 115 ADRs, 35 ADRs (30.4%) were type A reactions, 76 ADRs (66.1%) were type B reactions, and the other 4 ADRs were unknown. In terms of severity of ADRs, 6 cases (5.2%) were severe, 41 cases (35.6%) were moderate and 68 cases (59.1%) were mild. The causality analysis of CBZ-related events: ten cases (8.7%) were probable, 104 cases (90.4%) were possible, and one case (0.9%) was doubtful. The onset day of ADR occurred was from the day of administration to the 203th day after administration, and the mean of onset day was 26.2 days after administration. Base on ADR classification, the incidence of neurological ADR and dermatological ADR are 25.2% and 14.8%, respectively. Discontinuing the usage of CBZ was the most common (55.7%) management when an ADR occurred.
It is found that high mean daily dose in adults, history of herpes zoster infection, older than 60 years old and children under age of 10 were the risk factors in developing ADR. There was significant difference (p= 0.01) between patients with ADR and patients without ADR in patients with a history of AV-block related arrhythmia. But there was not significant difference between patients with ADR and without ADR in the history of bone marrow suppression. It should be warned that it is not suitable to take CBZ with precautions or contraindications. It should be careful as prescribing CBZ to patients with underlying AV-block related arrhythmia and to elderly patients.
The results of the incidence of ADR are comparatable with the data reported in literatures. It was observed that one patient developed the Stevens- Johnson syndrome and some developed the cardiovascular ADRs in this study. None of were fatal, indicated ADRs observed a good management as ADRs developed. Medical health providers should be aware of the safety profile of CBZ and provide proper informations to patients using of CBZ.

並列關鍵字

carbamazepine

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