Nitrofurantoin Contraindication in Patients with a Creatinine Clearance Below 60 mL/min: Looking for the Evidence
Nitrofurantoin Contraindication in Patients with a Creatinine Clearance Below 60 mL/min: Looking for the Evidence
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DOI：
10.1345/aph.1r352
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发表时间：
2013-01-01
影响因子：
2.9
通讯作者：
Andrews, Carlota O.
中科院分区：
文献类型：
--
作者：
Oplinger, Mandy;Andrews, Carlota O.
目的：应用计算机检索PubMed(1965-2012-06)相关文献，检索词：呋喃妥因与呋喃妥因联合治疗尿路感染的药物治疗、慢性肾功能不全、肾脏疾病、药代动力学、安全性和有效性。文章仅限于英文。参考文献还包括食品和药物管理局批准的产品信息包、药物信息资源和药理学书籍。数据综合：1988年至2003年的某个时候，产品信息包中包含了呋喃妥因的禁忌症。1988年的Macrodantin产品信息显示，CrCl的截止浓度为40毫升/分钟，但2003年的MacroBid产品信息中发现了当前低于60毫升/分钟的禁忌。目前尚不清楚这种变化发生的时间和原因，但它可能遵循了萨克斯和他的同事在1968年的工作，他们报告说，CrCl60毫升/分钟以下的患者的尿液中几乎没有药物回收。这项研究和以前的研究都有几个严重的局限性，例如纳入少数患者，确定氯化铬和肾脏损害的方法不明确或定义不明确，测量尿中呋喃妥因的排泄量而不是尿液浓度，以及最重要的是，缺乏临床疗效终点。最近，一份关于呋喃妥因治疗尿路感染临床治愈的图表综述为进一步研究这种药物对CrCl60毫升/分钟或更低的患者的有效性提供了依据。对肾功能减退患者严重不良反应风险增加的担忧进一步限制了呋喃妥因的使用。然而，虽然不完全清楚，但这些并发症似乎最常与长期治疗、遗传变异和过敏倾向有关。结论：目前尚不存在支持呋喃妥因禁忌症的数据，对于CrCl值低于60mL/min的患者。在不同程度的肾损害患者身上，非常需要设计良好的临床试验，提供尿液浓度信息和临床终点。在这样的研究出现之前，现有的有限数据将支持考虑在CrCl40毫升/分钟或更高的患者中使用该药物。
OBJECTIVE: To investigate the evidence leading to nitrofurantoin contraindication in patients with a creatinine clearance (CrCl) below 60 mL/min.DATA SOURCES: Literature was searched in PubMed (1965-June 2012) by using the key words and MeSH terms urinary tract infections-drug therapy, chronic kidney insufficiency, kidney diseases, pharmacokinetics, safety, and efficacy, combined with nitrofurantoin. Articles were limited to the English language. References from the identified studies, Food and Drug Administration-approved product information packets, drug information resources, and pharmacology books were also reviewed.DATA SYNTHESIS: The contraindication of nitrofurantoin in patients with a CrCl below 60 mL/min was included in the product information packets sometime between 1988 and 2003. The 1988 Macrodantin product information indicated a CrCl cutoff level of 40 mL/min, but the current contraindication of less than 60 mL/min is found in the 2003 Macrobid product information. It is unclear when and why this change occurred, but it may have followed the work of Sachs and colleagues in 1968, who reported very little drug recovery in the urine of patients with a CrCl below 60 mL/min. This and previous studies have several and severe limitations, such as the inclusion of a small number of patients, an undefined or poorly defined method to determine CrCl and renal impairment, measurement of amounts of nitrofurantoin excreted in the urine instead of urinary concentrations, and most importantly, a lack of clinical efficacy end points. More recently, a chart review on clinical cure of urinary tract infections treated with nitrofurantoin provided grounds for further investigations on the utility of this drug for patients with a CrCl of 60 mL/min or lower. Concerns of increased risks of serious adverse reactions in patients with reduced renal function have further limited the use of nitrofurantoin. However, although not completely clear, these complications seem to be linked most often to prolonged treatment, genetic variability, and predisposition to hypersensitivity.CONCLUSIONS: Data supporting the contraindication of nitrofurantoin for patients with a CrCl less than 60 mL/min are nonexistent. Well-designed clinical trials with urinary concentration information and clinical end points on patients with various degrees of renal impairment are much needed. Until such a study becomes available, the limited data available would support considering using this drug in patients with a CrCl of 40 mL/min or higher.