Fogg Carole, Kasliwal Rachna, Shakir Saad A W
Drug Safety Research Unit, Bursledon Hall, Southampton, UK.
Drug Saf. 2009;32(3):229-37. doi: 10.2165/00002018-200932030-00005.
Pioglitazone is an antidiabetic drug that belongs to the thiazolidinedione (TZD) class of insulin-sensitizing agents. Adverse events to pioglitazone of potential severity are listed in the 'special warnings and special precautions for use' section of the pioglitazone summary of product characteristics (SPC), with recommendations for monitoring and management.
To describe the risk management and outcomes of recognized TZD class effects in patients prescribed pioglitazone.
An observational study of risk management and event outcomes for the adverse events of cardiac failure, fluid retention/oedema, weight gain, anaemia and abnormal liver function tests (LFTs) was performed. Patients were identified from within a prescription-event monitoring (PEM) postmarketing cohort of first-users of pioglitazone. Patients with pre-existing events or alternative causes, or with no possibility of collecting further information, were excluded. Outcomes included (i) the method of detection of the adverse event, i.e. whether the patient or the prescriber identified the problem; (ii) whether responsibility for risk management was taken at a primary- or secondary-care level; (iii) interventions taken to manage the event, including discontinuation of treatment; (iv) resolution and/or other outcomes of the event; and (v) general practitioner (GP) opinion of relatedness of the event to pioglitazone.
Acute events such as cardiac failure and oedema were more likely to be detected by the patient presenting with the event rather than at regular follow-up. GPs were more likely to take responsibility for management of abnormal LFTs, anaemia and oedema events, whereas hospital admissions occurred mainly in patients with cardiac failure (45.3%). Pioglitazone was stopped in more than 50% of each type of event, apart from anaemia. Oedema events were the most likely to resolve (87.6%) and anaemia the least likely (42.9%). Oedema events were the most likely to be attributed to the drug by GPs, whereas cardiac failure was the event least attributed to pioglitazone.
Timely drug withdrawal and/or interventions such as corrective treatment or referral to a specialist can lead to successful resolution of class-effect adverse events of pioglitazone. Regular follow-up of patients on antidiabetic agents is essential to detect certain events, but more acute events are more likely to be reported spontaneously. Treatment options for patients with diabetes mellitus and cardiovascular risk factors are limited, requiring careful benefit-risk assessment of pioglitazone use in these patients and careful monitoring for signs of worsening cardiac function.
吡格列酮是一种抗糖尿病药物，属于噻唑烷二酮（TZD）类胰岛素增敏剂。吡格列酮产品特性摘要（SPC）的“特殊警告和特殊使用注意事项”部分列出了具有潜在严重性的吡格列酮不良事件，并给出了监测和管理建议。
描述使用吡格列酮的患者中已确认的TZD类效应的风险管理及结果。
对心力衰竭、液体潴留/水肿、体重增加、贫血和肝功能检查异常（LFTs）等不良事件的风险管理和事件结果进行了一项观察性研究。从吡格列酮首次使用者的处方事件监测（PEM）上市后队列中识别患者。排除已有事件或有其他原因，或无法收集更多信息的患者。结果包括：（i）不良事件的检测方法，即患者还是开处方者发现问题；（ii）风险管理责任是在初级保健还是二级保健层面承担；（iii）为管理该事件采取的干预措施，包括停药；（iv）事件的解决和/或其他结果；（v）全科医生（GP）对该事件与吡格列酮相关性的看法。
心力衰竭和水肿等急性事件更有可能由出现该事件的患者发现，而非在定期随访中发现。全科医生更有可能负责管理肝功能检查异常、贫血和水肿事件，而住院主要发生在心力衰竭患者中（45.3%）。除贫血外，每种类型的事件中超过50%的患者停用了吡格列酮。水肿事件最有可能得到解决（87.6%），而贫血事件最不可能得到解决（42.9%）。水肿事件最有可能被全科医生归因于药物，而心力衰竭事件最不可能归因于吡格列酮。
及时停药和/或采取如纠正治疗或转诊至专科医生等干预措施可成功解决吡格列酮的类效应不良事件。对使用抗糖尿病药物的患者进行定期随访对于发现某些事件至关重要，但更急性的事件更有可能自发报告。糖尿病合并心血管危险因素患者的治疗选择有限，需要对这些患者使用吡格列酮进行仔细的效益风险评估，并密切监测心脏功能恶化的迹象。
