Abstract
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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References
Chou CY, Hsu CC, Chiang SC, Ho CC, Chou CL, Wu MS, et al. Association between physician specialty and risk of prescribing inappropriate pill splitting. PLoS One. 2013;8(7):e70113. doi:10.1371/journal.pone.0070113 (eCollection 2013).
Quinzler R, Gasse C, Schneider A, Kaufmann-Kolle P, Szecsenyi J, Haefeli WE. The frequency of inappropriate tablet splitting in primary care. Eur J Clin Pharmacol. 2006;62(12):1065–73.
Quinzler R, Schmitt SP, Pritsch M, Kaltschmidt J, Haefeli WE. Substantial reduction of inappropriate tablet splitting with computerised decision support: a prospective intervention study assessing potential benefit and harm. BMC Med Inform Decis Mak. 2009;9:30. doi:10.1186/1472-6947-9-30 (eCollection 2009).
Olliaro PL, Vaillant M, Hayes DJ, Montresor A, Chitsulo L. Practical dosing of praziquantel for schistosomiasis in preschool-aged children. Trop Med Int Health. 2013;18(9):1085–9.
van Santen E, Barends DM, Frijlink HW. Breaking of scored tablets: a review. Eur J Pharm Biopharm. 2002;53(2):139–45.
Choe HM, Stevenson JG, Streetman DS, Heisler M, Sandiford CJ, Piette JD. Impact of patient financial incentives on participation and outcomes in a statin pill-splitting program. Am J Manag Care. 2007;13(6):298–304.
Miller DP, Furberg CD, Small RH, Millman FM, Ambrosius WT, Harshbarger JS, et al. Controlling prescription drug expenditures: a report of success. Am J Manag Care. 2007;13(8):473–80.
Peek BT, Al-Achi A, Coombs SJ. Accuracy of tablet splitting by elderly patients. JAMA. 2002;288(4):451–2.
McDevitt JT, Gurst AH, Chen Y. Accuracy of tablet splitting. Pharmacotherapy. 1998;18(1):193–7.
Jiang W, Yu LX. Bioequivalence for narrow therapeutic index drugs. In: Yu L, Li B, editors. FDA bioequivalence standards. New York: Springer; 2014. p. 191–216.
Neidecker M, Patel AA, Nelson WW, Reardon G. Use of warfarin in long-term care: a systematic review. BMC Geriatr. 2012;12:14. doi:10.1186/1471-2318-12-14 (eCollection 2012).
Clark NP, Witt DM, Delate T, Trapp M, Garcia D, Ageno W, et al. Warfarin-associated research projects and other endeavors consortium. Thromboembolic consequences of subtherapeutic anticoagulation in patients stabilized on warfarin therapy: the low INR study. Pharmacotherapy. 2008;28(8):960–7.
Blix HS, Viktil KK, Moger TA, Reikvam A. Drugs with narrow therapeutic index as indicators in the risk management of hospitalised patients. Pharm Pract (Internet). 2009;8(1):50–55. PMCID: PMC4140577.
Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clin Ther. 2013;35(5):694–700.
Paveliu MS, Bengea S, Paveliu FS. Generic substitution issues: brand-generic substitution, generic-generic substitution, and generic substitution of narrow therapeutic index (nti)/critical dose drugs. Maedica. 2011;6(1):52–8.
Helmy SA. Tablet splitting: is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting. J Manag Care Spec Pharm. 2015;21(1):76–86.
Shah RB, Collier JS, Sayeed VA, Bryant A, Habib MJ, Khan MA. Tablet splitting of a narrow therapeutic index drug: a case with levothyroxine sodium. AAPS Pharm Sci Tech. 2010;11(3):1359–67.
Bureau of National Health Insurance, Department of Health, Executive Yuan, “The National Health Insurance Statistics,” 2010. http://www.nhi.gov.tw/English/webdata/webdata.aspx?menu=11&menu_id=296&WD_ID=296&webdata_id=4010. Accessed Aug 3 2015.
Chen YC, Yeh HY, Wu JC, Haschler I, Chen TJ, Wetter T. Taiwan’s national health insurance research database: administrative health care database as study object in bibliometrics. Scientometrics. 2010;86(2):365–80.
Narrow therapeutic index drugs designated by the north carolina secretary of human resources. North Carolina Register. 2013;27(13):1263.
Fischbach MS, Gold JL, Lee M, Dergal JM, Litner GM, Rochon PA. Pill-splitting in a long-term care facility. CMAJ. 2001;164(6):785–6.
Berg C, Ekedahl A. Dosages involving splitting tablets: common but unnecessary? J Pharm Health Serv Res. 2010;1(3):137–41.
Vivo RP, Krim SR, Perez J, Inklab M, Tenner T Jr, Hodgson J. Digoxin: current use and approach to toxicity. Am J Med Sci. 2008;336:423–8.
Ehle M, Patel C, Giugliano RP. Digoxin: clinical highlights: a review of digoxin and its use in contemporary medicine. Crit Pathw Cardiol. 2011;10(2):93–8.
Information Product. Lanoxin, digoxin 2006. Greenville: GlaxoSmith-Kline; 2006.
Bressler R, Bahl JJ. Principles of drug therapy for the elderly patient. Mayo Clin Proc. 2003;78(12):1564–77.
Currie GM, Wheat JM, Kiat H. Pharmacokinetic considerations for digoxin in older people. Open Cardiovasc Med J. 2011;5:130–5.
Leendertse AJ, Van den Bemt PMLA, Poolman JB, Stoker LJ, Egberts ACG, Postma MJ. Preventable hospital admissions related to medication (HARM): cost analysis of the HARM study. Value Health. 2011;14(1):34–40.
Bachynsky J, Wiens C, Melnychuk K. The practice of splitting tablets: cost and therapeutic aspects. Pharmacoeconomics. 2002;20(5):339–46.
Powell EC, Reynolds SL, Rubenstein JS. Theophylline toxicity in children: a retrospective review. Pediatr Emerg Care. 1993;9(3):129–33.
Hocaoğlu N, Yıldıztepe E, Bayram B, Aydın B, Tunçok Y, Kalkan Ş. Demographic and clinical characteristics of theophylline exposures between 1993 and 2011. Balkan Med J. 2014;31(4):322–7.
Shannon M. Life-threatening events after theophylline overdose: a 10-year prospective analysis. Arch Intern Med. 1999;159:989–94.
Hsu CC, Chou CY, Chou CL, Ho CC, Chen TJ, Chiang SC, et al. Impact of a warning CPOE system on the inappropriate pill splitting of prescribed medications in outpatients. PLoS ONE. 2014;9(12):e114359. doi:10.1371/journal.pone.0114359 (eCollection 2014).
Wang BR, Chou CL, Hsu CC, Chou YC, Chen TJ, Chou LF. Drugs cheaper than threepenny: the market of extremely low-priced drugs within the National Health Insurance in Taiwan. ScientificWorldJournal. 2014;2014:234941. doi:10.1155/2014/234941 (eCollection 2014).
Elliott I, Mayxay M, Yeuichaixong S, Lee SJ, Newton PN. The practice and clinical implications of tablet splitting in international health. Trop Med Int Health. 2014;19(7):754–60.
Acknowledgments
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.
Funding
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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Chou, CL., Hsu, CC., Chou, CY. et al. Tablet splitting of narrow therapeutic index drugs: a nationwide survey in Taiwan. Int J Clin Pharm 37, 1235–1241 (2015). https://doi.org/10.1007/s11096-015-0194-0
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DOI: https://doi.org/10.1007/s11096-015-0194-0