Service des maladies infectieuses et tropicales, Hôpital Avicenne AP-HP et Université Paris 13, 125 rue de Stalingrad, 93009 Bobigny, France.
Malar J. 2009 Dec 10;8:289. doi: 10.1186/1475-2875-8-289.
Halofantrine (HF) was considered an effective and safe treatment for multi-drug resistant falciparum malaria until 1993, when the first case of drug-associated death was reported. Since then, numerous studies have confirmed cardiac arrythmias, possibly fatal, in both adults and children. The aim of the study was to review fatal HF related cardiotoxicity.
In addition, to a systematic review of the literature, the authors have had access to the global safety database on possible HF related cardiotoxicity provided by GlaxoSmithKline.
Thirty-five cases of fatal cardiotoxicity related to HF, including five children, were identified. Females (70%) and patients from developing countries (71%) were over-represented in this series. Seventy-four percent of the fatal events occurred within 24 hours of initial exposure to HF. Twenty six patients (74%) had at least one predisposing factor for severe cardiotoxicity, e.g., underlying cardiac disease, higher than recommended doses, or presence of a concomitant QT-lengthening drug. All (100%) of the paediatric cases had either a contraindication to HF or an improper dose was given. In six cases there was no malaria.
A distinction should be made between common but asymptomatic QT-interval prolongation and the much less common ventricular arrhythmias, such as torsades de pointes, which can be fatal and seem to occur in a very limited number of patients. The majority of reported cardiac events occurred either in patients with predisposing factors or with an improper dose.Therefore, in the rare situations in which HF is the only therapeutic option, it can still be given after carefully checking for contraindications, such as underlying cardiac disease, bradycardia, metabolic disorders, personal or family history of long QT-interval or concomitant use of another QT-prolonging drug (e.g., mefloquine), especially in females.
直到 1993 年，卤泛群（HF）被认为是一种有效且安全的治疗多药耐药性恶性疟原虫疟疾的药物，但同年首例与药物相关的死亡病例报告后，其安全性受到质疑。此后，许多研究证实了 HF 可导致成人和儿童出现心律失常，甚至可能致命。本研究旨在综述与 HF 相关的致死性心脏毒性。
除了对文献进行系统回顾，作者还查阅了葛兰素史克公司提供的关于 HF 相关心脏毒性的全球安全数据库。
共确定了 35 例与 HF 相关的致死性心脏毒性病例，其中包括 5 例儿童。该系列病例中女性（70%）和发展中国家患者（71%）的比例过高。74%的致死性事件发生在首次接触 HF 后 24 小时内。26 例（74%）患者至少存在一种严重心脏毒性的易感因素，如潜在的心脏疾病、高于推荐剂量或同时使用延长 QT 间期的药物。所有（100%）儿科病例均存在 HF 用药禁忌或剂量不当。6 例病例无疟疾。
应区分常见但无症状的 QT 间期延长与较少见的尖端扭转型室性心动过速，后者可能致命，似乎只发生在极少数患者中。大多数报告的心脏事件发生在存在易感因素或剂量不当的患者中。因此，在 HF 是唯一治疗选择的罕见情况下，在仔细检查有无用药禁忌（如潜在的心脏疾病、心动过缓、代谢紊乱、个人或家族长 QT 间期病史或同时使用另一种延长 QT 间期的药物[如甲氟喹]）后，仍可使用 HF，尤其是在女性患者中。
