Off-label drug use in an adult intensive care unit of a Brazilian hospital

Authors

  • Elana Figueiredo Chaves Pharmacy service, Walter Cantídio University Hospital, Federal University of Ceara, Fortaleza, Ceará, Brasil https://orcid.org/0000-0002-5817-0999
  • Pedro Henrique Quintela Soares de Medeiros Department of Pathology and Legal Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceará, Brasil
  • Paulo Andrei Milen Firmino Faculty of Pharmacy, Odontology and Nursing, Federal University of Ceara, Fortaleza, Ceará, Brasil
  • Gabriela Araújo de Abreu Pharmacy service, Walter Cantídio University Hospital, Federal University of Ceara, Fortaleza, Ceará, Brasil
  • Angelina Almeida Bastos Pharmacy service, Walter Cantídio University Hospital, Federal University of Ceara, Fortaleza, Ceará, Brasil
  • José Martins de Alcântara Neto Pharmacy service, Walter Cantídio University Hospital, Federal University of Ceara, Fortaleza, Ceará, Brasil
  • Lívia Maria Porto Moreira Pharmacy service, Walter Cantídio University Hospital, Federal University of Ceara, Fortaleza, Ceará, Brasil https://orcid.org/0000-0001-6429-2557
  • Arnaldo Aires Peixoto Junior Faculty of Pharmacy, Odontology and Nursing, Federal University of Ceara, Fortaleza, Ceará, Brasil
  • Marjorie Moreira Guedes Pharmacy service, Walter Cantídio University Hospital, Federal University of Ceara, Fortaleza, Ceará, Brasil

DOI:

https://doi.org/10.1590/

Keywords:

Off-label use, Intensive Care Units, Critical Care, High-alert medication

Abstract

The objective of this study was to determine the prevalence and describe the factors associated with off-label drug use in an adult intensive care unit (ICU) of a Brazilian hospital. An analytical, cross-sectional, prospective study was conducted in the adult ICU population from March 2018 to May 2018. Off-label use of medication was classified by indication, dosage, route of administration, type and volume of diluent, and duration of administration. Most patients were female (57.89%), non-elderly (56.14%), and had a mean age of 54.44 ± 17.15 years. The prevalence of off-label drug use was 70.31%, but was not associated with the clinical severity of the patients. A statistically significant association was observed between label use of drugs and prescribing potentially inappropriate medicines (PIM). The most common reasons for off-label drug use were therapeutic indication (19.58%) and volume of diluent (23.30%). Drug administration by enteral tubes accounted for the largest number of off-label uses due to route of administration (90.85%). There was a higher prevalence of off-label use of systemic antimicrobials (14.44%) and norepinephrine (9.28%). Our study provided a broad characterization of off-label drug use in an adult ICU and showed why it is important for health professionals to evaluate the specific risks and benefits of this practice.

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References

Aronson JK, Ferner RE. Unlicensed and off-label uses of medicines: definitions and clarification of terminology. Br J Clin Pharmacol. 2017;83(12):2615-25.

Barletta JF, Lat I, Micek ST, Cohen H, Olsen KM, Haas CE. Off-label use of gastrointestinal medications in the intensive care unit. J Intensive Care Med. 2015;30(4):217-25.

Besen BA, Gobatto AL, Melro LM, Maciel AT, Park M. Fluid an electrolyte overload in critically ill patients: an overview. World J Crit Care Med. 2015;4(2):116-29.

Cajanding JMR. Administering and monitoring high-alert medications in acute care. Nurs Stand. 2017;31(47):42-52.

Carvalho CG, Ribeiro MR, Bonilha MM, Jr. MF, Procianoy RS, Silveira RC. Use of off-label and unlicensed drugs in the neonatal intensive care unit and its association with severity scores. J Pediatr. 2012;88(6):465-70.

Casañ VA, Escribano BC, Garrido-Corro B, De la Cruz Murie P, Blázquez Álvarez MJ, De la Rubia Nieto MªA. Off-label and unlicensed drug use in a Spanish Neonatal Intensive Care Unit. Farm Hosp. 2017;41(3):371-81.

Closset M, Hecq JD, Soumoy L, Simar J, Gonzalez E, Charlet L, et al. Physical stability of highly concentrated injectable drugs solutions used in intensive care units. Ann Pharm Fr. 2017;75(3):185-8.

Dhaese SAM, Farkas A, Colin P, Lipman J, Stove V, Verstraete AG, et al. Population pharmacokinetics and evaluation of the predictive performance of pharmacokinetic models in critically ill patients receiving continuous infusion meropenem: a comparison of eight pharmacokinetic models. J Antimicrob Chemother. 2018;74(2):432-41.

Dummitt B, Zeringue A, Palagiri A, Veremakis C, Burch B, Yount B. Using survival analysis to predict septic shock onset in ICU patients. J Crit Care. 2018;48:339-44.

Eguale T, Buckeridge DL, Verma A, Winslade NE, Benedetti A, Hanley JA, et al. Association of off-label drug use and adverse drug events in an adult population. JAMA Intern Med. 2016;176(1)55-63.

European Medicines Agency. Evidence of harm from off-label or unlicensed medicines in children. 2004. http://www.ema.europa.eu/docs/en_GB/…/Other/…/WC500004021.pdf Accessed 14 March 2018.

» http://www.ema.europa.eu/docs/en_GB/…/Other/…/WC500004021.pdf

Falagas ME, Tansarli GS, Ikawa K, Vardakas KZ. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/ tazobactam: A systematic review and meta-analysis. Clin Infect Dis. 2013;56:272-82.

Ferreira AL, Ibiapina CC, Machado MGP, Fagundes EDT. A alta prevalência de prescrições de medicamentos off-label e não licenciados em unidade de terapia intensiva pediátrica brasileira. Rev Assoc Med Bras. 2012;58(1):82-7.

Gonçalves AC de S, Reis AMM, Marçal ACG, Bouzada MCF. Use of unlicensed and off-label drugs in neonates in a Brazilian university hospital. Braz J Pharm Sci. 2018;53(3):1-10.

Gonçalves MG, Heineck I. Frequency of prescriptions of off-label drugs and drugs not approved for pediatric use in primary health care in a southern municipality of Brazil. Rev Paul Pediatr. 2016;34(1):11-17.

Instituto para Práticas Seguras no Uso de Medicamentos. Medicamentos Potencialmente Perigosos de Uso Hospitalar e Ambulatorial - Listas Atualizadas 2015. Boletim ISMP Brasil. 2015;4(3). Disponível em: http://www.ismp-brasil.org/site/wp-content/uploads/2015/12/V4N3.pdf >. Accessed 12 Out 2018.

» http://www.ismp-brasil.org/site/wp-content/uploads/2015/12/V4N3.pdf

Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1995;13(10):818-29.

Lat I, Micek S, Janzen J, Cohen H, Olsen K, Haas C. Off-label medication use in adult critical care patients. J Crit Care . 2011;26(1):89-94.

Lin Liu, Hong-Yu Yang, Yan Lou, Jing Miao, Xiao-Yang Lu, Qing-Wei Zhao, et al. Off-label prescriptions in intensive care unit: the Chinese experience. Ther Clin Risk Manag. 2018;14:195-202.

Loureiro CV, Loureiro CV, Néri EDR, Mascarenhas MBJ, Fonteles MMF. Uso de medicamentos off-label ou não licenciado para pediatria em hospital público brasileiro. Rev Bras Farm Hosp Serv Saude. 2013;4(1):17-21.

Matysiak-Luśnia K, Łysenko L. Drug administration via enteral feeding tubes in intensive therapy - terra incognita? Anaesth Intens Care. 2014;46(4)307-11.

Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence. 2014;5(1):1-11.

Ministério da Saúde (BR), Fundação Oswaldo Cruz, Agência Nacional de Vigilância Sanitária. Documento de referência para o Programa Nacional de Segurança do Paciente. Brasília (DF): Ministério da Saúde; 2014.

Ogbu OC, Murphy DJ, Martin GS. How to avoid fluid overlaod. Curr Opin Crit Care. 2015;21(4):315-21.

Patel P, Cerqueira DM, Santos GML, de Lima Soares R, Sousa VD, Liberti L, et al. A Baseline Analysis of Regulatory Review Timelines for ANVISA: 2013-2016. Ther Innov Regul Sci. 2020;54(6):1428-35.

Rigatto MH, Falci DR, Lopes NT, Zavascki AP. Clinical features and mortality of patients on renal replacement therapy receiving polymyxin B. Int J Antimicrob Agents. 2016;47(2):146-50.

Sandri AM, Landersdorfer CB, Jacob J, Boniatti MM, Dalarosa MG, Falci DR, et al. Population pharmacokinetics of intravenous Polymyxin B in critically Ill patients: implications for selection of dosage regimens. Clin Infect Dis . 2013;57(4):524-31.

Shoulders BR, Smithburger PL, Tchen S, Buckley M, Lat I, Kane-Gill SL. Characterization of Guideline Evidence for Off-label Medication Use in the Intensive Care Unit Ann Pharmacother. 2017;51(7):529-42.

Smithburger PL, Buckley MS, Culver MA, Sokol S, Lat I, Handler SM, et al. A multicenter evaluation of off-label medication use and associated adverse drug reactions in adult medical ICUs. Crit Care Med . 2015;43(8):1612-21.

Souza AS, Dos Santos DB, Rey LC, Medeiros MG, Vieira MG, Coelho HLL. Off-label use and harmful potential of drugs in a NICU in Brazil: A descriptive study. BMC Pediatrics. 2016;16(1):1-10.

Tansarli GS, Rafailidis PI, Kapaskelis A, Falagas ME. Frequency of the off-label use of antibiotics in clinical practice: a systematic review. Expert Rev Anti Infect Ther. 2012;10(12):1383-92.

Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med. 1996;22(7):707-10.

Walker SE, Law S, Garland J, Fung E, Iazzetta J. Stability of Norepinephrine Solutions in Normal Saline and 5% Dextrose in Water. Can J Hosp Pharm. 2010;63(2):113-18.

Wittich CM, Burkle CM, Lanier WL. Ten common questions (and their answers) about off-label drug use. Mayo Clin Proc. 2012;87(10):982-90.

World Health Organization (WHO). The anatomical therapeutic chemical classification system with defined daily doses (ATC/DDD). Norway: WHO. 2006. https://www.whocc.no/atc_ddd_index/ Accessed 01 Jan 2018.

» https://www.whocc.no/atc_ddd_index/

Yapa WS, Li J, Patel K, Wilson JW, Dooley MJ, George J, et al. Pulmonary and systemic pharmacokinetics of inhaled and intravenous colistin methanesulfonate in cystic fibrosis patients: targeting advantage of inhalational administration. Antimicrob Agents Chemother. 2014;58(5):2570-79.

Zheng Z, Yang M, Wu J. Ethical Off-label Drug use: Need for a Rethink? Indian Pediatr. 2017;54(6):447-50.

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Published

2023-01-23 — Updated on 2023-01-23

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How to Cite

Off-label drug use in an adult intensive care unit of a Brazilian hospital. (2023). Brazilian Journal of Pharmaceutical Sciences, 58. https://doi.org/10.1590/