奥美沙坦新标签强调口炎性腹泻样肠病风险

圣路易斯(MD Consult)——2013年7月3日，美国食品药品管理局(FDA)宣布，已要求更新含有奥美沙坦酯的血管紧张素Ⅱ受体阻断剂(ARB)类药物的标签。这些药物的商品名包括Benicar、Benicar HCT、Azor和Tribenzor等，还有相应的仿制药。新标签将包含使用该产品可导致口炎性腹泻样肠病的警示信息。口炎性腹泻样肠病的症状包括严重慢性腹泻伴体重明显下降。这种肠病可在开始使用奥美沙坦后数月至数年时发生，可能涉及住院。

FDA已审查了与不良事件和使用奥美沙坦酯有关的多个来源的数据。调查者找到了使用奥美沙坦与口炎性腹泻样肠病相关的明确证据。尽管二者发生关联的机制尚不清楚，但可能与局部迟发型超敏反应或对前体药奥美沙坦酯的细胞介导性免疫应答有关。

FDA不良事件报告系统(FAERS)中收录了23例严重迟发型腹泻伴明显体重下降的报告。在某些患者中，活检证实发生了肠绒毛萎缩。所有患者在停用奥美沙坦之后均病情改善，其中10例患者激发试验结果为阳性。

2012年6月，梅奥医院的研究人员发表了一篇系列病例报告，涉及22例发生奥美沙坦相关性口炎性腹泻样肠病的患者，其临床表现与FAERS收录的病例类似。梅奥医院的病例在使用奥美沙坦期间发生了腹泻、体重下降和肠绒毛萎缩，停药后临床情况好转。其中18例患者接受了随访肠道活检，结果证实十二指肠在停用奥美沙坦后得以复原或改善。

2013年5月，一篇文章称在有肠绒毛萎缩且乳糜泻血清学检查结果为阴性的患者中，一部分患者肠绒毛萎缩病因不明而表现为未分类的口炎性腹泻。后者中又有若干患者被证实肠绒毛萎缩与使用奥美沙坦有关。

应告知患者，假如在服用含奥美沙坦药物后发生严重慢性腹泻伴体重明显下降，即使症状的出现与服药间隔数月甚至数年之久，均应当寻求治疗。假如在接受奥美沙坦治疗期间出现症状，应分析是否存在乳糜泻等其他病因。如果确定没有其他病因，应停用奥美沙坦而改用另一种降压治疗。尚未在使用非奥美沙坦ARB类药物的患者中发现口炎性腹泻样肠病。

奥美沙坦适用于治疗高血压。

应将与使用奥美沙坦产品相关的不良事件报告至FAERS。

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ST LOUIS (MD Consult) - On July 3, 2013, the US Food and Drug Administration (FDA) announced that it has ordered updates to the labels for angiotensin II receptor blockers (ARBs) containing olmesartan medoxomil. These drugs are marketed as Benicar, Benicar HCT, Azor, Tribenzor, and generics. Updated labels will contain warnings that use of the product can cause sprue-like enteropathy. Symptoms of sprue-like enteropathy include severe, chronic diarrhea with substantial weight loss. The enteropathy may occur months to years after starting olmesartan, and may involve hospitalization.

The FDA has reviewed data from several sources related to adverse events and the use of olmesartan medoxomil. The investigation found that clear evidence of an association exists between olmesartan use and sprue-like enteropathy. Although the mechanism for olmesartan-associated sprue-like enteropathy is uncertain, a localized delayed hypersensitivity or cell-mediated immune response to the pro-drug olmesartan medoxomil has been suggested.

Through the FDA's Adverse Event Reporting System (FAERS), 23 serious cases of late-onset diarrhea with significant weight loss were identified. In some cases, intestinal villous atrophy was found on biopsy. All patients improved clinically after discontinuation of olmesartan, and a positive rechallenge was seen in 10 of the cases.

In June 2012, Mayo Clinic researchers published a case series of sprue-like enteropathy associated with olmesartan in 22 patients whose clinical presentation was similar to that of the FAERS cases. Patients in the Mayo Clinic case series experienced diarrhea, weight loss, and villous atrophy while receiving olmesartan, and drug discontinuation resulted in clinical improvement. Eighteen patients underwent follow-up intestinal biopsies histologically demonstrating recovery or improvement of the duodenum after discontinuation of olmesartan.

In May 2013, an article describing patients with villous atrophy and negative serologies for celiac disease reported that some patients without definitive etiologies for villous atrophy were characterized as having unclassified sprue. Some of these patients were later found to have villous atrophy associated with olmesartan use.

Patients should be told to seek treatment if they experience severe, chronic diarrhea with substantial weight loss while taking an olmesartan-containing product, even if it takes months to years for symptoms to develop. If symptoms occur during treatment with olmesartan, other etiologies, such as celiac disease, should be investigated. If no other etiology is identified, olmesartan should be discontinued and another antihypertensive treatment started. Sprue-like enteropathy has not been detected with ARBs other than olmesartan.

Olmesartan is used in the treatment of hypertension.

Adverse events related to use of olmesartan products should be reported to FAERS.