Martín-Merino Elisa, de Abajo Francisco J, Gil Miguel
BIFAP Research Unit, Spanish Agency on Medicines and Medical Devices (AEMPS), C/ Campezo n° 1, Edificio 8, 28022, Madrid, Spain.
Department of Biomedical Sciences, School of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Eur J Clin Pharmacol. 2015 Jun;71(6):759-766. doi: 10.1007/s00228-015-1850-y. Epub 2015 May 5.
We aim to estimate the incidence of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) among tetrazepam users and compare it with benzodiazepine users in a Spanish primary care database (BIFAP). The incidence in the general population (GenPop) and among phenytoin new users (as a positive control) was also estimated.
We identified a cohort of GenPop free of SJS/TEN (N = 3,155,364). Cohort entry was the date after 1 year of register with the physician during 2001-2011. No age restrictions were applied. Patients were followed from entry up to the first of the following: a record of SJS/TEN (potential cases), death, end of information, or December 2011. History of potential cases were manually reviewed blinded to exposure and considered "probable" when diagnosed in referral reports. Three cohorts of patients newly prescribed with benzodiazepines (N = 531,813), tetrazepam (N = 343,568), or phenytoin (N = 4993) were extracted from the GenPop cohort. Incidence rate (cases per million person-years (py)) for the GenPop and cumulative incidence (per million new users) during the first 9 weeks after each drug prescription were computed.
In the GenPop, 48 probable cases (38 SJS and 10 TEN) were identified (3.21/million py; 3.37 in men and 2.94 in women). In the benzodiazepines cohort, 2 probable TEN cases was identified (3.76/mill.). In the tetrazepam cohort, 1 probable SJS/TEN case was identified (2.91/mill.). In the phenytoin cohort, 4 probable cases (2 SJS and 2 TEN) were identified (801.12/mill.).
The incidence of SJS/TEN in tetrazepam users was very rare and similar to benzodiazepines users. The incidence in the GenPop and among users of phenytoin agreed with the literature.
我们旨在评估西班牙初级医疗数据库（BIFAP）中使用替马西泮的患者发生史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）的发生率，并将其与使用苯二氮䓬类药物的患者进行比较。同时还评估了普通人群（GenPop）和苯妥英新使用者（作为阳性对照）中的发生率。
我们确定了一个无SJS/TEN的GenPop队列（N = 3,155,364）。队列进入时间为2001年至2011年期间与医生登记满1年后的日期。无年龄限制。对患者从进入队列开始进行随访，直至出现以下情况之一：SJS/TEN记录（潜在病例）、死亡、信息结束或2011年12月。对潜在病例的病史进行人工审查，审查时对暴露情况不知情，在转诊报告中诊断为“可能”的视为“可能病例”。从GenPop队列中提取了三个新开具苯二氮䓬类药物（N = 531,813）、替马西泮（N = 343,568）或苯妥英（N = 4993）的患者队列。计算了GenPop的发病率（每百万人口年（py）的病例数）以及每种药物处方后前9周的累积发病率（每百万新使用者）。
在GenPop中，确定了48例可能病例（38例SJS和10例TEN）（3.21/百万py；男性为3.37，女性为2.94）。在苯二氮䓬类药物队列中，确定了2例可能的TEN病例（3.76/百万）。在替马西泮队列中，确定了1例可能的SJS/TEN病例（2.91/百万）。在苯妥英队列中，确定了4例可能病例（2例SJS和2例TEN）（801.12/百万）。
替马西泮使用者中SJS/TEN的发生率非常低，与苯二氮䓬类药物使用者相似。GenPop和苯妥英使用者中的发生率与文献一致。
