title: Nitrofurantoin contraindication in patients with a creatinine clearance below 60 mL/min: looking for the evidence.
abstract: OBJECTIVE
  To investigate the evidence leading to nitrofurantoin contraindication in patients with a creatinine clearance (CrCl) below 60 mL/min.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors: Wegmans School of Pharmacy, St. John Fisher College, Rochester, NY, USA.
authors: Mandy
authors: M
authors: Oplinger
authors: Carlota O
authors: CO
authors: Andrews
mesh_terms: D000892:Anti-Infective Agents, Urinary / Q000009:adverse effects / Q000627:therapeutic use; D000075202:Contraindications; D003404:Creatinine / Q000097:blood / Q000652:urine; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology*; D007677:Kidney Function Tests; D009582:Nitrofurantoin / Q000009:adverse effects / Q000627:therapeutic use; D014552:Urinary Tract Infections / Q000188:drug therapy
chemical_list: D000892:Anti-Infective Agents, Urinary; D009582:Nitrofurantoin; D003404:Creatinine