Adverse Events Associated With Sodium Phosphate (Saline) Enema in Adults: A 46-Year Database and Clinical Survey

Abstract

Introduction: Sodium phosphate enemas are marketed in the U.S. for treatment of occasional constipation and as a bowel preparation. In January 2014, the FDA issued a Safety Communication warning that use of more than one sodium phosphate enema [SPE] in a 24-hour period could cause rare but serious cardiac and renal effects. This study sought to evaluate U.S. adverse event reporting for SPE among adults and to assess U.S. gastroenterologists' [USGI] knowledge regarding the dosing of SPE. Methods: All U.S. adverse event [AE] reports associated with SPE use in adults > 12 yrs were reviewed during the period from June 1968 through December 2014. Sources included an enema manufacturer's safety database, medical literature, and FDA MedWatch reports. Events associated with oral sodium phosphate were excluded. Serious AEs [SAE] and non-serious AEs [NSAE] were defined by the FDA Code of Federal Regulations. Overdose was defined as use of more than the labeled amount of SPE/24 hrs. A survey evaluating USGI knowledge regarding SPE dosing was conducted in January 2015 using a nationally diverse sample. Results: AEs were reported in 608 subjects (Table 1), including 56 SAE and 552 NSAE. The most frequent SAE was electrolyte disturbance and/or acute kidney injury, occurring in 20/56 cases. Fatality was recorded in 12 cases, including electrolyte disturbance (7) and arrhythmia (3). Overdose was more frequent in SAE compared to NSAE (p < 0.00001). Among fatal SAE, overdose was reported in 8/12 cases (75%) vs. 8/44 non-fatal cases (18.2%; p < 0.001). Only 24% of USGI knew that the maximum recommended SPE dose is one bottle/24 hrs (Table 2). In 15/16 SAE cases identified as overdose, a health care provider improperly dosed the enema.Table 1: Adverse Events Associated with Sodium Phosphate (Saline) Enema (1968-2014)Table 2: Survey of U.S. Gastroenterologists on Sodium Phosphate (Saline) Enema (n=50)Conclusion: Overdose of sodium phosphate enema was significantly associated with both serious adverse events and fatality when compared to non-serious adverse events. A majority of U.S. gastroenterologists are unaware of appropriate enema dosing guidelines. Efforts to educate consumers and clinicians on the proper use of sodium phosphate (saline) enema should be undertaken to reduce the risk of adverse events.