Prevalence of tablet splitting in a Brazilian tertiary care hospital
Background: Although a highly common practice in hospital care, tablet splitting can cause dose variation and reduce drug stability, both of which impair drug therapy.
Objective: To determine the overall prevalence of tablet splitting in hospital care as evidence supporting the rational prescription of split tablets in hospitals.
Methods: Data collected from inpatients’ prescriptions were analyzed using descriptive statistics and used to calculate the overall prevalence of tablet splitting and the percentage of split tablets that had at least one lower-strength tablet available on the market. The associations between the overall prevalence and gender, age, and hospital unit of patients were also assessed. The results of laboratory tests, performed with a commercial splitter, allowed the calculation of the mass loss, mass variation, and friability of the split tablets.
Results: The overall prevalence of tablet splitting was 4.5%, and 78.5% of tablets prescribed to be split had at least one lower-strength tablet on the market. The prevalence of tablet splitting was significantly associated with the patient’s age and hospital unit. Laboratory tests revealed mean values of mass loss and variation of 8.7% (SD 1.8) and 11.7% (SD 2.3), respectively, both of which were significantly affected by the presence of coating and scoreline. Data from laboratory tests indicated that the quality of 12 of the 14 tablets deviated in at least one parameter examined.
Conclusions: The high percentage of unnecessary tablet splitting suggests that more regular, rational updates of the hospital’s list of standard medicines are needed. Also, inappropriate splitting behavior suggests the need to develop tablets with functional scores.
Darji MA, Lalge RM, Marathe SP, Mulay TD, Fatima T, Alshammari A, Lee HK, Repka MA, Narasimha Murthy S. Excipient Stability in Oral Solid Dosage Forms: A Review. AAPS PharmSciTech. 2018;19(1):12‐26. https://doi.org/10.1208/s12249-017-0864-4
Mascarenhas Starling F, Medeiros-Souza P, Francisco de Camargos E, Ferreira F, Rodrigues Silva A, Homem-de-Mello M. Tablet splitting of psychotropic drugs for patients with dementia: a pharmacoepidemiologic study in a Brazilian sample. Clin Ther. 2015;37(10):2332‐2338. https://doi.org/10.1016/j.clinthera.2015.08.015
Teixeira MT, Sá-Barreto LCL, Gratieri T, Gelfuso GM, Silva ICR, Cunha-Filho MSS. Key Technical Aspects Influencing the Accuracy of Tablet Subdivision. AAPS PharmSciTech. 2017;18(4):1393‐1401. https://doi.org/10.1208/s12249-016-0615-y
Fischbach MS, Gold JL, Lee M, Dergal JM, Litner GM, Rochon PA. Pill-splitting in a long-term care facility. CMAJ. 2001;164(6):785‐786.
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. https://doi.org/10.18553/jmcp.2015.21.1.76
Bachynsky J, Wiens C, Melnychuk K. The practice of splitting tablets: cost and therapeutic aspects. Pharmacoeconomics. 2002;20(5):339‐346. https://doi.org/10.2165/00019053-200220050-00005
Habib WA, Alanizi AS, Abdelhamid MM, Alanizi FK. Accuracy of tablet splitting: Comparison study between hand splitting and tablet cutter. Saudi Pharm J. 2014;22(5):454‐459. https://doi.org/10.1016/j.jsps.2013.12.014
Tahaineh LM, Gharaibeh SF. Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice. J Pharm Pract. 2012;25(4):471‐476. https://doi.org/10.1177/0897190012442716
Arnet I, von Moos M, Hersberger KE. Wrongly prescribed half tablets in a swiss university hospital. Int J Clin Med. 2012;3(7):637-643. http://dx.doi.org/10.4236/ijcm.2012.37114
van Riet-Nales DA, Doeve ME, Nicia AE, Teerenstra S, Notenboom K, Hekster YA, van den Bemt BJ. The accuracy, precision and sustainability of different techniques for tablet subdivision: breaking by hand and the use of tablet splitters or a kitchen knife. Int J Pharm. 2014;466(1-2):44‐51. https://doi.org/10.1016/j.ijpharm.2014.02.031
Stegemann S, Ecker F, Maio M, Kraahs P, Wohlfart R, Breitkreutz J, Zimmer A, Bar-Shalom D, Hettrich P, Broegmann B. Geriatric drug therapy: neglecting the inevitable majority. Ageing Res Rev. 2010;9(4):384‐398. https://doi.org/10.1016/j.arr.2010.04.005
Verrue C, Mehuys E, Boussery K, Remon JP, Petrovic M. Tablet-splitting: a common yet not so innocent practice. J Adv Nurs. 2011;67(1):26‐32. https://doi.org/10.1111/j.1365-2648.2010.05477.x
Gharaibeh SF, Tahaineh L. Effect of different splitting techniques on the characteristics of divided tablets of five commonly split drug products in Jordan. Pharm Pract (Granada). 2020;18(2):1776. https://doi.org/10.18549/pharmpract.2020.2.1776
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 PharmSciTech. 2010;11(3):1359‐1367. https://doi.org/10.1208/s12249-010-9515-8
Brasil. [Resolution 466 of 12 December 2012]. 2012: 59. Available from: http://conselho.saude.gov.br/resolucoes/2012/Reso466.pdf (accessed Apr 11, 2020).
Brasil. [List A of reference medicines]. Agência Nacional de Vigilância Sanitária (Anvisa). 2017.
Brasil. [Drug market regulation chamber]. Vol. 504, Agência Nacional de Vigilância Sanitária (Anvisa). 2017. p. 1–504.
Food and Drug Administration. Guidance for Industry- Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation. 2013.
Green G, Berg C, Polli J, Barends D. Pharmacopeial standards for the subdivision characteristics of scored tablets. Pharmacopeial Forum. 2009; 35:1598-1603
Rosenberg JM, Nathan JP, Plakogiannis F. Weight variability of pharmacist-dispensed split tablets. J Am Pharm Assoc (Wash). 2002;42(2):200‐205. https://doi.org/10.1331/108658002763508498
USP. United States Pharmacopeia. 37 ed. Rockville: United States Pharmacopeial Convention, 2014.
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. https://doi.org/10.1186/1472-6947-9-30
Lima-Dellamora EC, Caetano R, Osorio-de-Castro CGS. [Selection or standardization? Wrings and rights that may (des)orientate the essential medicines selection process]. Rev Bras Farm. 2014; 95(1):415-435.
World Health Organization. Drug and Therapeutics Committees: A Practical Guide Department of Essential Drugs and Medicines Policy. 2003.
Marin N. [Pharmaceutical Management for municipal managers]. Organização Panamericana de Saúde (OPAS); 2003.
Wannmacher L. [Essential medicines selection: purposes and consequences]. Rev Tempus Actas Saúde Colet 2010; 4(3): 23-29.
Tóth K, Csukly G, Sirok D, et al. Optimization of Clonazepam Therapy Adjusted to Patient's CYP3A Status and NAT2 Genotype. Int J Neuropsychopharmacol. 2016;19(12):pyw083. https://doi.org/10.1093/ijnp/pyw083
Hill SW, Varker AS, Karlage K, Myrdal PB. Analysis of drug content and weight uniformity for half-tablets of 6 commonly split medications. J Manag Care Pharm. 2009;15(3):253‐261. https://doi.org/10.18553/jmcp.2009.15.3.253
Kimmel SE. Warfarin therapy: in need of improvement after all these years. Expert Opin Pharmacother. 2008;9(5):677‐686. https://doi.org/10.1517/14656518.104.22.1687
Marriott JL, Nation RL. Splitting tablets. Aust Prescr. 2002;25(6):133-135.
Brasil 2010. [Resolution RDC Num. 31, of 11 August 2010]. Agência Nac Vigilância Sanitária. 2010;36–8.
Temer AC, Teixeira MT, Sa-Barreto LL, Gratieri T, Gelfuso GM, Silva IC, Taveira SF, Marreto RN, Cunha-Filho M. Subdivision of tablets containing modified delivery technology: the case of orally disintegrating tablets. J Pharm Innov. 2018;13(3):261-269. https://doi.org/10.1007/s12247-018-9323-3
Rodenhuis N, De Smet PA, Barends DM. The rationale of scored tablets as dosage form. Eur J Pharm Sci. 2004;21(2-3):305‐308. https://doi.org/10.1016/j.ejps.2003.10.018
van Santen E, Barends DM, Frijlink HW. Breaking of scored tablets: a review. Eur J Pharm Biopharm. 2002;53(2):139‐145. https://doi.org/10.1016/s0939-6411(01)00228-4
Allemann SS, Bornand D, Hug B, Hersberger KE, Arnet I. Issues around the Prescription of Half Tablets in Northern Switzerland: The Irrational Case of Quetiapine. Biomed Res Int. 2015;2015:602021. https://doi.org/10.1155/2015/602021
Brotto V, Rafferty K. Clinical Dosage Calculations: For Australian and New Zealand. Australia: Cengage Learning Australia, 2011.
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):754‐760. https://doi.org/10.1111/tmi.12309
McDevitt JT, Gurst AH, Chen Y. Accuracy of tablet splitting. Pharmacotherapy. 1998;18(1):193‐197. https://doi.org/10.1002/j.1875-9114.1998.tb03838.x
Teng J, Song CK, Williams RL, Polli JE. Lack of medication dose uniformity in commonly split tablets. J Am Pharm Assoc (Wash). 2002;42(2):195‐199. https://doi.org/10.1331/108658002763508489
Gupta A, Hunt RL, Khan MA. Influence of tablet characteristics on weight variability and weight loss in split tablets. Am J Health Syst Pharm. 2008;65(24):2326‐2328. https://doi.org/10.2146/ajhp080371
Pereira GRS, Taveira SF, Cunha-Filho M, Marreto RN. The Effects of Fillers and Binders on the Accuracy of Tablet Subdivision. AAPS PharmSciTech. 2018;19(7):2929‐2933. https://doi.org/10.1208/s12249-018-1144-7
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