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VOLUME 25 , ISSUE 8 ( August, 2021 ) > List of Articles

Original Article

Off-label Drug Prescription Pattern and Related Adverse Drug Reactions in the Medical Intensive Care Unit

Asawari Raut, Kavita Krishna, Utkarsha Adake, Apurva A Sharma, Anitta Thomas

Keywords : Adverse drug reactions, Cohort study, FDA-approved drug, Intensive care unit, Off-label drug prescription

Citation Information : Raut A, Krishna K, Adake U, Sharma AA, Thomas A. Off-label Drug Prescription Pattern and Related Adverse Drug Reactions in the Medical Intensive Care Unit. Indian J Crit Care Med 2021; 25 (8):872-877.

DOI: 10.5005/jp-journals-10071-23909

License: CC BY-NC 4.0

Published Online: 12-08-2021

Copyright Statement:  Copyright © 2021; The Author(s).


Introduction: The utilization of prescription drugs as off-label is common. While this practice can be beneficial to some patients, it can raise a safety concern when scientific evidence is lacking; hence, this study was conducted to evaluate the off-label drug consumption and its adverse drug reactions (ADRs) in the medical intensive care unit (ICU). Materials and methods: In the prospective cohort study conducted for a duration of 6 months, data pertaining to ICU patients’ (age ≥18 years) demography, diagnosis, treatment, and laboratory investigation were collected to assess for off-label use as well as the strength of evidence and the occurrence of ADRs by using MICROMEDEX 2017 version (Healthcare Series Thomson Reuter, Greenwood, CO). Results: Of total 3574 drugs prescribed, 1453 (41%) were off-label indications and 65 (1.81%) were off-label dose. On the evaluation of off-label indication use, 1279 (88%) were evidence-based and 174 (12%) were low/no evidence-based medications (EBMs); 59 (91%) were evidence-based and 6 (9%) were low/no EBMs for off-label dose. Most commonly prescribed evidence-based off-label drug belonged to the gastrointestinal class while low/no evidence drugs were mostly of anti-infective class. A total of 383 ADRs were identified and 139 (36.2%) were implicated due to off-label medications, of which ADRs with evidence off-label medications (87.8%) were higher than low/no evidence off-label medication (12.2%) (P < 0.001). Conclusion: Widespread presence of off-label use was observed in medical ICU. Although incidence of ADRs was similar to the FDA-approved use, ongoing monitoring of such practice is needed.

  1. Wittich CM, Burkle CM, Lanier WL. Ten common questions (and their answers) about off-label drug use. Mayo Clin Proc 2012;87(10):982–990. DOI: 10.1016/j.mayocp.2012.04.017.
  2. Gazarian M, Kelly M, McPhee JR, Graudins LV, Ward RL, Campbell TJ. Off-label use of medicines: consensus recommendations for evaluating the appropriateness. Med J Aust 2006;185(10):544–548. DOI: 10.5694/j.1326-5377.2006.tb00689.x.
  3. Goločorbin Kon S, Iliković I, Mikov M. Reasons for and frequency of off - label drug use. Med Pregl 2015;68(1-2):35–40. DOI: 10.2298/mpns1502035g.
  4. 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. DOI: 10.1016/j.jcrc.2010.06.012.
  5. Recommendation. Evidence and efficacy ratings. In: DRUGDEX® system. Greenwood Village: Thomson Micromedex. Available at:
  6. Available at: (accessed 29 June 2019).
  7. The use of the WHO–UMC system for standardised case causality assessment. Available at: (accessed 4 Mar 2019).
  8. Hartwig SC, Siegel J, Schneider PJ. Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm 1992;49:2229–2231. Available at:
  9. Smithburger PL, Buckley MS, Culver MA, Sokol S, Lat I, Handler SM, et al. A multicentre evaluation of off-label medication use and associated adverse drug reactions in adult medical ICUs. Crit Care Med 2015;43(8):1612–1621. DOI: 10.1097/CCM.0000000000001022.
  10. Spirt MJ. Stress-related mucosal disease: risk factors and prophylactic therapy. Clin Ther 2004;26(2):197–213. DOI: 10.1016/s0149-2918(04)90019-7.
  11. Joshua L, Devi P, Guido S. Adverse drug reactions in intensive care unit of a tertiary care hospital. Pharmacoepidemiol Drug Saf 2009;18(7):639–45. DOI: 10.1002/pds.1761.
  12. Saravanan SS, Kavitha P, Ponnuswamy TK. Patterns of adverse drug reactions in the intensive care unit of an Indian tertiary care hospital. Int J Pharm Biol Arch 2014;5(3):64–68. DOI: 10.18203/2319-2003.ijbcp20192569.
  13. Kane-Gill SL, Jacobi J, Rothschild JM. Adverse drug events in intensive care units: risk factors, impact, and the role of team care. Crit Care Med 2010;38(6 Suppl):S83–S89. DOI: 10.1097/CCM.0b013e3181dd8364.
  14. Strom BL, Schinnar R. Hospital pharmacoepidemiology. 4th ed. West Sussex: John & Wiley Sons Ltd., 2005, pp. 539–553.
  15. Ohta Y, Sakuma M, Koike K, Bates DW, Morimoto T. Influence of adverse drug events on morbidity and mortality in intensive care unit: the JADE study. Int J Qual Health Care 2014;26(6):573–578. DOI: 10.1093/intqhc/mzu081.
  16. Seynaeve S, Verbrugghe W, Claes B, Vandenplas D, Reyntiens D, Jorens PG. Adverse drug events in intensive care unit: a cross-sectional study of prevalence and risk factors. Am J Crit Care 2011; 20(6):e131–e140. DOI: 10.4037/ajcc2011818.
  17. Roque KE, Tonini T, Melo EC. Adverse events in the intensive care unit: impact on mortality and length of stay in a prospective study. Cad Saude Publica 2016;32(10):e00081815. doi: 10.1590/0102-311X00081815.
  18. Good CB, Gellad WF. Off-label drug use and adverse drug events: turning up the heat on off-label prescribing. JAMA Intern Med 2016;176(1):63–64. DOI: 10.1001/jamainternmed.2015.6068.
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