Tablet splitting of narrow therapeutic index drugs: a nationwide survey in Taiwan


Background Tablet splitting or pill splitting frequently occurs in daily medical practice. For drugs with special pharmacokinetic characters, such as drugs with narrow therapeutic index (NTI), unequal split tablets might lead to erroneous dose titration and it even cause toxicity. Objective The aim of this study was to investigate the frequency of prescribing split NTI drugs at ambulatory setting in Taiwan. Setting A population-based retrospective study was conducted using the National Health Insurance Research Database in Taiwan. All ambulatory visits were analyzed from the longitudinal cohort datasets of the National Health Insurance Research Database. Methods The details of ambulatory prescriptions containing NTI drugs were extracted by using the claims datasets of one million beneficiaries from National Healthcare Insurance Research Database in 2010 in Taiwan. The analyses were stratified by dosage form, patient age and the number of prescribed tablets in a single dose for each NTI drugs. Main outcome measures Number and distinct dosage forms of available NTI drug items in Taiwan, number of prescriptions involved split NTI drugs, and number of patients received split NTI drugs. Results A total of 148,548 patients had received 512,398 prescriptions of NTI drugs and 41.8 % (n = 62,121) of patients had received 36.3 % (n = 185,936) of NTI drug prescriptions in form of split tablets. The percentage of splitting was highest in digoxin prescriptions (81.0 %), followed by warfarin (72.0 %). In the elderly patients, split tablets were very prevalent with digoxin (82.4 %) and warfarin (84.5 %). Conclusion NTI drugs were frequently prescribed to be taken in split forms in Taiwan. Interventions may be needed to provide effective and convenient NTI drug use. Further studies are needed to evaluate the clinical outcome of inappropriate split NTI drugs.

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This study is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health and managed by National Health Research Institutes, Taiwan. The interpretation and conclusions contained herein do not represent those of Bureau of National Health Insurance, Department of Health or National Health Research Institutes.


This study was supported by Grants from Taipei Veterans General Hospital (V102C-160) and National Science Council in Taiwan (NSC 99-2410-H-004-029-MY3).

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The authors declare that they have no conflicts of interest.

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Correspondence to Yueh-Ching Chou.

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Chou, C., Hsu, C., Chou, C. et al. Tablet splitting of narrow therapeutic index drugs: a nationwide survey in Taiwan. Int J Clin Pharm 37, 1235–1241 (2015) doi:10.1007/s11096-015-0194-0

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  • Narrow therapeutic index drugs
  • Prescribing patterns
  • Splitting frequency
  • Tablet splitting
  • Taiwan