Safety Notices
September 28, 2009
ST LOUIS (MD Consult) - On September 25, 2009, the US Food and Drug Administration (FDA) announced revisions to the prescribing information for Januvia (sitagliptin) and Janumet (sitagliptin/metformin) to include adverse-event information about acute pancreatitis. This action was prompted by the results of an analysis of 88 postmarketing cases of acute pancreatitis that occurred in patients taking these medications. These reports were received by the FDA between October 2006 and February 2009 and included 2 cases of hemorrhagic or necrotizing pancreatitis.
Hospitalization was reported in 58/88 (66%) of the patients affected by acute pancreatitis, and 4 were admitted to an intensive care unit. The most common adverse events reported in the all cases were abdominal pain, nausea, and vomiting.
Additionally, the FDA's analysis revealed that 19 (21%) of the reported cases of pancreatitis occurred within 30 days of starting sitagliptin or sitagliptin/metformin. Furthermore, 47 (53%) of these cases resolved after sitagliptin was discontinued. Prescribers should also be aware that 45 cases (51%) were associated with at least one other risk factor for developing pancreatitis (eg, diabetes, obesity, and high cholesterol and/or high triglyceride levels).
Health care professionals should monitor their patients taking Januvia or Janumet for the emergence of signs and symptoms of pancreatitis such as nausea, vomiting, anorexia, and persistent severe abdominal pain, sometimes radiating to the back. If pancreatitis is suspected, sitagliptin or sitagliptin/metformin should be discontinued. Affected patients should be monitored closely using appropriate laboratory studies such as determination of amylase/creatinine clearance ratios and, measurement of electrolyte, glucose, lipase, serum calcium, and serum and urine amylase levels. The FDA recommends that clinicians heighten their awareness of the possible emergence of pancreatitis after sitagliptin or sitagliptin/metformin therapy is initiated and when dose increases are implemented.
Sitagliptin has not been studied in patients with a history of pancreatitis. Therefore, it is not known whether these patients are at an increased risk for developing pancreatitis. Sitagliptin products should therefore be used with caution and with appropriate monitoring in patients with a history of pancreatitis.
Sitagliptin is included in a class of diabetic drugs known as dipeptidyl peptidase-4 inhibitors. The drug is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
安全须知
2009年9月28日
圣路易斯（MD Consult）——美国食品药品管理局（FDA）于2009年9月25日宣布对Januvia （西他列汀，sitagliptin）和Janumet（西他列汀和二甲双胍复方）的处方信息进行修订，增加有关急性胰腺炎的不良事件信息。美国FDA自2006年10月到2009年2月共收到88例胰腺炎上市后不良反应报告，其中包括2例出血性或坏死性胰腺炎，对这些报告进行分析，其结果促成了此次修订。
报告发生急性胰腺炎的88例患者中住院的有58例（66%），其中4例被送往重症监护室。所有报告中最常见的不良事件为腹痛、恶心和呕吐。
此外，FDA的分析显示，报告病例中有19例（21%）患者的胰腺炎是在服用西他列汀或西他列汀和二甲双胍复方30天内出现。另有47例（53%）患者的不良反应在停药后消失。处方医师尚需了解有45例（51%）患者至少有一个其他的胰腺炎风险因素，包括糖尿病、肥胖、高胆固醇和（或）高甘油三酯水平。
医护专业人士应监测服用Januvia或Janumet的患者发生胰腺炎的症状和体征，如恶心、呕吐、厌食、持续剧烈腹痛、有时有背部放射痛。如果怀疑是胰腺炎，应停止使用西他列汀或西他列汀和二甲双胍复方，采用淀粉酶和肌酐清除率测定等恰当的实验室检查手段密切监测受累患者，并测定电解质、血糖、脂肪酶、血清钙离子、血清和尿淀粉酶水平。FDA建议临床医师在西他列汀或西他列汀和二甲双胍复方治疗开始后及剂量增加时注意观察患者是否出现胰腺炎。
由于目前尚未在胰腺炎病史患者中进行西他列汀的研究，我们无从得知此类患者发生胰腺炎的风险是否会增高。因此，有胰腺炎病史的患者应谨慎使用西他列汀，并在服用后进行适当的监测。
西他列汀属于二肽基肽酶-4（DPP-4）抑制剂类糖尿病治疗药物。该药物获批作为2型糖尿病成年患者饮食和运动的辅助用药，以改善其血糖控制。
