Impact of a warning CPOE system on the inappropriate pill splitting of prescribed medications in outpatients

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The article was published in 2014 in PLOS ONE, the world’s first multidisciplinary Open Access journal.


  • Background:Prescribing inappropriate pill splitting is not rare in clinical practice. To reduce inappropriate pill splitting, we developed an automatic warning system linked to a computerized physician order entry (CPOE) system for special oral formulation drugs in outpatient settings. We examined the impact of the warning system on inappropriate prescribing of pill splitting and assess prescribers' responses to the warnings.
  • Methods:Drugs with extended-release or enteric-coated formulations that were not originally intended to be split were recognized as “special oral formulations”. A hard-stop system which could examine non-integer doses of drugs with special oral formulations, provide warnings to interrupt inappropriate prescriptions was integrated in CPOE in a medical center since June 2010. We designed an intervention study to compare the inappropriate splitting before and after the implementation of the warning system (baseline period 2010 January to May vs. intervention period 2010 June to 2011 August). During the intervention period, prescription changes in response to a warning were logged and analyzed.
  • Results:A total of 470,611 prescribed drug items with 34 different drugs with special oral formulations were prescribed in the study period. During the 15-month intervention period, 909 warnings for 26 different drugs were triggered among 354,523 prescribed drug items with special oral formulations. The warning rate of inappropriate splitting in the late intervention period was lower than those in baseline period (0.16% vs. 0.61%, incidence rate ratio 0.27, 95% CI 0.23–0.31, P<0.001). In respond to warnings, physicians had to make adjustments, of which the majority was changing to an unsplit pill (72.9%).
  • Conclusions:The interruptive warning system could avoid the prescriptions with inappropriate pill splitting. Accordingly, physicians changed their behavior of prescribing special oral formulations regarding inappropriate pill splitting. We suggest the establishment of such system to target special oral formulations with warnings to prevent inappropriate pill splitting.



Splitting of extended-release (ER) or enteric-coated (EC) oral drugs can lead to adverse drug events (ADE). To reduce inappropriate pill splitting, the authors developed an automatic warning system within CPOE in an outpatient setting of a hospital. The study assessed the impact of the system and physicians responses. [1]


The authors designed a real time pop up on the CPOE screen. The message was “Drug should not be split. Please revise the prescription.” Physicians were prompted to either change the prescription or select another medication. The study compared inappropriate splitting before and after the implementation of the warning system.


The duration of the intervention period was 15 months, during which 909 warnings were triggered for 26 different drugs. In the late intervention period, the rate of pill splitting was lower than that in the baseline period (0.61% vs 0.16%). The physician' responses to the warning message were changing to the whole pill by adjusting dose or frequency (72.9%), switching to same-ingredient with different formulation(11.8%), switching to an alternative (10.3%), and cancelling the drug.


The study demonstrated that the warning system for prescriptions had a clear learning effect on physician prescribing behavior. After the introduction of the system, the rates of the inappropriate pill splitting were significantly reduced. The authors recommend developing and implementation of interruptive warning system.


This study was conducted in Taiwan. In the USA, FDA does not have a clear policy on pill splitting but advises against such practice. "Not all pills are safe to split. Patients may mistakenly think that any pill can be split. But some pills, such as capsules and time-released drugs, should always be taken whole. For example, some tablets are coated with a substance that helps to release the medicine slowly. Splitting these tablets destroys the coating, which means you might absorb the medicine too fast or not at all." [2]

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Can Utilizing a Computerized Provider Order Entry (CPOE) System Prevent Hospital Medical Errors and Adverse Drug Events


  1. Hsu C-C, Chou C-Y, Chou C-L, et al. Impact of a Warning CPOE System on the Inappropriate Pill Splitting of Prescribed Medications in Outpatients.
  2. FDA. Tablet Splitting: A Risky Practice.