Dutkowski Regina, Thakrar Bharat, Froehlich Enrico, Suter Pia, Oo Charles, Ward Penny
Hoffmann-La Roche, Nutley, New Jersey 07110, USA.
Drug Saf. 2003;26(11):787-801. doi: 10.2165/00002018-200326110-00004.
Oseltamivir is a novel agent approved for the treatment and prevention of influenza infection and illnesses in adults and children. Assessment of data from the clinical trial programme, a US health insurance database study and postmarketing surveillance allowed a comprehensive review of the safety of oseltamivir in clinical use in subjects >1 year of age. Oseltamivir has been studied over the course of a 5-year development programme in >11000 subjects from North America, Europe and the Southern Hemisphere, including otherwise healthy adults, approximately 500 elderly/high-risk subjects, and children (>1000) aged 1-12 years. Safety evaluations included treatment-emergent adverse events, hospitalisations and deaths, as well as haematological and biochemical laboratory safety tests. The data reveals that oseltamivir has simple, uncomplicated pharmacology and lacks potential for drug-drug interactions. Electrocardiogram parameters, including corrected QT interval, were unaffected by oseltamivir even at high doses. Postmarketing studies confirmed that transient gastrointestinal disturbance is the major adverse effect of oseltamivir and that this can be reduced by taking oseltamivir after a light snack. On treatment serious adverse events were reported in 1.3% of oseltamivir 75mg twice daily, 0.7% of oseltamivir 150 mg twice daily and 1.2% of placebo recipients, respectively, in the clinical trial programme. Postmarketing, it is estimated that, to date, over 4 million oseltamivir prescriptions have been dispensed worldwide. Approximately 2300 spontaneous reports were received by the manufacturer over the three winter seasons of use. As these events are reported infrequently and from an unknown number of users, it is not possible to definitively assess causality or frequency of reported events. Most reports were of gastrointestinal and skin reactions. However, a clear association between the skin reactions and oseltamivir has not been established. A large study of insurance records, which permitted the assessment of the relative risk of medical events treated in the month following prescription of oseltamivir in general use, showed no evidence of increased risk of cardiac, neuropsychiatric or respiratory events for those receiving oseltamivir compared with those who did not. To conclude, no important safety concerns have evolved which might limit the suitability of oseltamivir for the treatment and prevention of influenza in all patient populations.
奥司他韦是一种已获批准用于治疗和预防成人及儿童流感感染和疾病的新型药物。对临床试验项目、一项美国医疗保险数据库研究及上市后监测数据的评估，使得对奥司他韦在1岁以上受试者临床使用中的安全性进行了全面审查。在一项为期5年的研发项目中，对来自北美、欧洲和南半球的11000多名受试者进行了奥司他韦研究，其中包括健康的成年人、约500名老年/高危受试者以及1000多名1至12岁的儿童。安全性评估包括治疗中出现的不良事件、住院和死亡情况，以及血液学和生化实验室安全性检测。数据显示，奥司他韦的药理学特性简单、不复杂，且不存在药物相互作用的可能性。即使在高剂量情况下，包括校正QT间期在内的心电图参数也不受奥司他韦影响。上市后研究证实，短暂的胃肠道不适是奥司他韦的主要不良反应，并且在吃少量点心后服用奥司他韦可减轻这种不适。在临床试验项目中，接受每日两次75mg奥司他韦治疗的受试者中，有1.3%报告了严重不良事件；接受每日两次150mg奥司他韦治疗的受试者中，有0.7%报告了严重不良事件；接受安慰剂治疗的受试者中，有1.2%报告了严重不良事件。在上市后阶段，据估计，迄今为止全球已开出超过400万份奥司他韦处方。在三个使用季节里，制造商收到了约2300份自发报告。由于这些事件报告不频繁且使用者数量不明，因此无法明确评估所报告事件的因果关系或发生频率。大多数报告涉及胃肠道和皮肤反应。然而，尚未确定皮肤反应与奥司他韦之间存在明确关联。一项对保险记录的大型研究，该研究能够评估在开具奥司他韦常规处方后的一个月内所治疗医疗事件的相对风险，结果显示，与未接受奥司他韦治疗的患者相比，接受奥司他韦治疗的患者发生心脏、神经精神或呼吸事件的风险没有增加。总之，尚未出现可能限制奥司他韦在所有患者群体中用于治疗和预防流感适用性的重大安全问题。
