Adverse Event Reports for Oral Sodium Phosphate and Polyethylene Glycol
Background: Screening colonoscopy exposes healthy patients to the risk of serious adverse events associated with bowel preparation. Randomized controlled trials are not an effective method for evaluating this risk.
Aim: To search published literature in order to characterize the risk of adverse events associated with oral polyethylene glycol (PEG) or sodium phosphate (NaP).
Methods: A systematic review identified case reports of any serious events associated with PEG or NaP. Reports to the Food and Drug Administration (FDA) were also examined.
Results: Fifty-eight publications of significant events in 109 patients using NaP and 22 patients using PEG were identified. As the total number of prescriptions issued is unknown, rates for the two agents cannot be directly compared. Most commonly reported were electrolyte disturbances, renal failure and colonic ulceration for NaP and Mallory–Weiss tear, electrolyte disturbances and allergic reactions for PEG between January 2006 and December 2007; there were 171 cases of renal failure reported to the FDA following use of NaP and 10 following PEG.
Conclusions: Adverse events following bowel preparation are uncommon, but potentially serious. Given that many of these patients are healthy individuals undergoing screening, the benefit/risk ratio must be carefully considered when deciding which preparation to prescribe in individual patients.

In the past 10 years, three systematic reviews have compared the efficacy of polyethylene glycol (PEG) and oral sodium phosphate (NaP). One of these analysed the results of eight studies (n = 1286) and found no difference between agents in the chances of adequate preparation (RR random effects = 1.06; 95% CI 0.95-1.19). The second, looking at 16 studies (n = 3484), identified a result in favour of NaP (OR fixed effects = 0.75; CI 0.65-0.88). The third, based on 24 studies (n = 4091), showed no significant difference (OR random effects = 0.94; CI 0.64-1.39). In none of the analyses, however, was any significant difference in adverse events identified. Indeed, in the largest analysis, there were no clinically significant serious adverse events recorded in either treatment group. This was not an unexpected result - relatively small numbers of patients, coupled with tight control of inclusion criteria and treatment dosage means that serious adverse events are rarely apparent in randomized controlled trials, especially if the events in question are uncommon.

Within the context of broader clinical practice, however, uncommon but potentially serious adverse events are likely to come to light. Since its first widespread use in bowel preparation regimes in the early 1990s, the propensity of NaP to trigger significant and potentially fatal electrolyte disturbances has been well recognized, with the Australian Adverse Drugs Reactions Advisory Committee first highlighting the issue in 1997. Subsequent publications from Spanish, Austrian, Canadian and US authorities have further underlined the problem and emphasized the importance of caution in using NaP, particularly in those patients with potentially compromised renal phosphate handling capacity.

In the past few years, new concerns have arisen around the occurrence of irreversible renal damage from nephrocalcinosis (acute phosphate nephropathy). As for the previously described electrolyte disturbances, the risk of this rare adverse event appears to be related to baseline renal function, as well as the use of renally acting drugs, such as diuretics and angiotensin converting enzyme (ACE) inhibitors.

Although there are no such systematic concerns associated with the use of PEG, data from clinical trials suggest that its use is also potentially associated with electrolyte disturbances, albeit to a lesser extent than that seen with NaP.

The purpose of this review was to identify adverse event reports for both NaP and PEG from all available published sources, to assess the risks associated with both forms of bowel preparation.