Kurita Tomoko, Kitaichi Tomomi, Nagao Takako, Miura Toshiyuki, Kitazono Yoshifumi
ViiV Healthcare K. K., Tokyo, 151-8566, Japan.
Pharmacoepidemiol Drug Saf. 2014 Apr;23(4):361-71. doi: 10.1002/pds.3589. Epub 2014 Mar 3.
Abacavir is a nucleoside reverse transcriptase inhibitor indicated for human immunodeficiency virus (HIV) infection. In Japan, Ziagen® (300-mg abacavir sulfate) has been marketed since 1999. To obtain safety data on Ziagen, a mandatory postmarketing surveillance was conducted between September 1999 and September 2009.
A joint survey [HIV-related Drug Surveys (HRD)] has been conducted involving manufacturers of drugs for HIV treatment in Japan. Safety data from total 643 cases (1345.7 person-years) registered to the HRD surveys and received Ziagen were obtained. Adverse drug reaction (ADR) was defined as adverse event of which association with abacavir could not be "ruled out."
It was found that the overall frequency of ADR was 47.6% (306/643); the common ADRs were "hyperlipidemia," "nausea," "increased γ-glutamyltransferase level," "increased blood triglycerides," "abnormal hepatic function," and so on. Serious adverse events were reported in 65 subjects; however, none of the three fatal cases were clearly associated with Ziagen use. The survey-defined hypersensitivity has been infrequently reported in 15 subjects (2.3%). Although some studies had indicated of the association between abacavir and myocardial infarction, no ischemic heart diseases were reported in the present survey. Two of the three pregnant cases delivered normal neonates (one induced abortion).
During the mandatory postmarketing survey of Ziagen, there were no cases of ischemic heart diseases, and the incidence of hypersensitivity was considerably low. These indicated that abacavir can be safely used in Japanese HIV+ population. However, the safety profile of Ziagen should be continued to be monitored through pharmacovigilance.
阿巴卡韦是一种核苷类逆转录酶抑制剂，用于治疗人类免疫缺陷病毒（HIV）感染。在日本，自1999年以来齐多夫定（Ziagen®，300毫克硫酸阿巴卡韦）已上市销售。为获取齐多夫定的安全性数据，于1999年9月至2009年9月开展了一项强制性上市后监测。
日本开展了一项联合调查[HIV相关药物调查（HRD）]，涉及HIV治疗药物制造商。获取了总共643例登记至HRD调查并接受齐多夫定治疗的病例（1345.7人年）的安全性数据。药物不良反应（ADR）定义为不能“排除”与阿巴卡韦有关联的不良事件。
发现ADR的总体发生率为47.6%（306/643）；常见的ADR有“高脂血症”“恶心”“γ-谷氨酰转移酶水平升高”“血甘油三酯升高”“肝功能异常”等。65名受试者报告了严重不良事件；然而，3例死亡病例均未明确与使用齐多夫定有关。调查定义的超敏反应在15名受试者中报告较少（2.3%）。尽管一些研究表明阿巴卡韦与心肌梗死有关，但本次调查中未报告缺血性心脏病。3例妊娠病例中有2例分娩出正常新生儿（1例人工流产）。
在齐多夫定的强制性上市后调查期间，未出现缺血性心脏病病例，超敏反应发生率相当低。这些表明阿巴卡韦可在日本HIV阳性人群中安全使用。然而，应通过药物警戒继续监测齐多夫定的安全性。
