The practice of dividing tablets: An uncertain act

Abstract

Background and Aims: Tablets can be split by patients for a number of reasons, using various instruments. Tablets can be scored or unscored; if scored, they may be split into pieces, and in spite of guidelines to do so patients are still at risk of re- sultant drug dose fluctuations, or being exposed to toxic or subtherapeutic doses. The aim of this study was to investigate differences in weight between halves of tablets, split by different populations and with different devices. Methods: 3-factor full factorial design (3 runs) was used with participants: patients, caregivers, nurses, medical doctors, and pharmacists; instruments: scissors, tablet cutters, knives, hand; drugs: losartan, clonidine, metoprolol, and warfarin. The risk of unequal tablet splitting was estimated and analyzed for each factor and their interaction with linearized general- ized models. Results: Differences in weight were found to be above 15% and 25% of the theoretical weight as in general, the highest weight variations after splitting were found in clonidine with patients using scissors. The overall risk of non-equal tablet splitting was 22.5% for deviations > 15% and for > 25%. Conclusion: In this study, no tablet was split into halves of equal weight; based on these findings, splitting tablets is a ques- tionable practice.

Keywords

• Splitting tablets
• Equal weight
• Amount
• Patients
• Risk

References

1. Arnet, I., & Hersberger, K. E. (2010). Misleading score-lines on tab- lets: Facilitated intake or fractional dosing? Swiss Medical Weekly, 140(7-8), 105-110. https://doi.org/smw-12953
2. Cook, T. J., Edwards, S., Gyemah, C., Shah, M., Shah, I., & Fox, T. (2004). Variability in tablet fragment weights when splitting unscored cyclobenzaprine 10 mg tablets. Journal of the Ameri- can Pharmacists Association: JAPhA, 44(5), 583-586. https://doi. org/10.1331/1544-3191.44.5.583.cook
3. Elliott, I., Mayxay, M., Yeuichaixong, S., Lee, S. J., & Newton, P. N. (2014). The practice and clinical implications of tablet splitting in international health. Tropical Medicine & International Health: TM & IH, 19(7), 754-760. https://doi.org/10.1111/tmi.12309
4. FDA. (2013). Best Practices for Tablet Splitting. https://www.fda.gov/ drugs/ensuring-safe-use-medicine/best-practices-tablet-splitting
5. Haywood, A., & Glass, B. D. (2011). Pharmaceutical excipients – where do we begin? Australian Prescriber, 34(4), 112-114. https:// doi.org/10.18773/austprescr.2011.060
6. Johnson, J. A. (2012). Warfarin pharmacogenetics: A rising tide for its clinical value. Circulation, 125(16), 1964-1966. https://doi. org/10.1161/CIRCULATIONAHA.112.100628
7. Palcsó, B., & Zelkó, R. (2018). Different types, applications and lim- its of enabling excipients of pharmaceutical dosage forms. Drug Discovery Today. Technologies, 27, 21-39. https://doi.org/10.1016/j. ddtec.2018.04.002
8. Rowley F. (s. f.). Minimize Bisect Risk: Part I. Oct 06, 2006. https:// www.pharmamanufacturing.com/articles/2006/188/

9. Shah, R. B., Collier, J. S., Sayeed, V. A., Bryant, A., Habib, M. J., & Khan, M. A. (2010). Tablet splitting of a narrow therapeutic index drug: A case with levothyroxine sodium. AAPS PharmSciTech, 11(3), 1359- 1367. https://doi.org/10.1208/s12249-010-9515-8
10. Spiller, H. A., Klein-Schwartz, W., Colvin, J. M., Villalobos, D., John- son, P. B., & Anderson, D. L. (2005). Toxic clonidine ingestion in children. The Journal of Pediatrics, 146(2), 263-266. https://doi. org/10.1016/j.jpeds.2004.09.027
11. Thompson, C. A. (2012). New term will distinguish tablets known to split in half. American Journal of Health-System Pharmacy: AJHP: Official Journal of the American Society of Health-System Pharma- cists, 69(19), 1619-1621. https://doi.org/10.2146/news120071
12. United States Pharmacopeial Convention Inc. (2018). USP 41-NF 36. En United States Pharmacopeia and National For- mulary. https://www.deutscher-apotheker-verlag.de/shop/ produkt/9783769270228/usp-41-nf-36-the-united-states-phar- macopeia-and-national-formulary-2018
13. Veronin, M. A., & Youan, B.-B. C. (2004). Medicine. Magic bullet gone astray: Medications and the Internet. Science (New York, N.Y.), 305(5683), 481. https://doi.org/10.1126/science.1097355
14. Verrue, C., Mehuys, E., Boussery, K., Remon, J.-P., & Petrovic, M. (2011). Tablet-splitting: A common yet not so innocent practice. Journal of Advanced Nursing, 67(1), 26-32. https://doi.org/10.1111/ j.1365-2648.2010.05477.x