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European Journal of Clinical Pharmacology

, Volume 74, Issue 7, pp 939–943 | Cite as

Safety of brotizolam in hospitalized patients

  • Ophir Lavon
  • Shmuel Bejel
Pharmacoepidemiology and Prescription

Abstract

Purpose

The objective of this study was to evaluate the safety of brotizolam in hospitalized patients.

Methods

A single-center, comparative retrospective cohort analysis of patients hospitalized in internal medicine wards. Patients treated with brotizolam were compared to patients not treated with any benzodiazepines during hospitalization. Primary outcome was any of the following safety events: mechanical ventilation, delirium, and falls.

Results

Six hundred patients were included after exclusion in the final analysis; 300 treated with brotizolam (treatment) and 300 not treated with any benzodiazepines (comparator). The brotizolam-treated patients were older with more comorbidities and psychotropic medications. After adjustment using multivariate logistic regression analysis with propensity score, the primary outcomes occurred at significantly higher rates in treated patients than in untreated patients (17 vs. 2 events; OR = 7.33). Any psychotropic medication administered during hospitalization was found by logistic regression to be the main independent risk factor for the studied safety outcomes while age, comorbidities, and the cause of hospitalization were not.

Conclusions

Treatment with brotizolam during hospitalization in internal medicine wards is linked to a higher risk of respiratory deterioration, delirium, and falls. Use of psychotropic medications during hospitalization is the main independent risk factor of safety outcomes. Further research is needed to fully evaluate the risks and benefits of sleep induction medications in hospitals.

Keywords

Brotizolam Safety Inpatients Adverse reactions 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the institutional review committee of Carmel Medical Center.

Supplementary material

228_2018_2447_MOESM1_ESM.docx (119 kb)
ESM 1 (DOCX 118 kb)

References

  1. 1.
    Shochat T, Umphress J, Israel AG, Ancoli-Israel S (1999) Insomnia in primary care patients. Sleep 22(Suppl 2):S359PubMedGoogle Scholar
  2. 2.
    Mellinger GD, Balter MB, Uhlenhuth EH (1985) Insomnia and its treatment: prevalence and correlates. Arch Gen Psychiatry 42:225–229CrossRefPubMedGoogle Scholar
  3. 3.
    NIH state-of-the science conference statement on manifestations and management of chronic insomnia in adults (2005) NIH Consens Sci Statements 22:1–30Google Scholar
  4. 4.
    Meissner HH, Riemer A, Santiago SM, Stein M, Goldman MD, Williams AJ (1998) Failure of physician documentation of sleep complaints in hospitalized patients. West J Med 169:146–149PubMedPubMedCentralGoogle Scholar
  5. 5.
    Young JS, Bourgeois JA, Hilty DM, Hardin KA (2008) Sleep in hospitalized medical patients, part 1: factors affecting sleep. J Hosp Med 3:473–482CrossRefPubMedGoogle Scholar
  6. 6.
    Ueki S, Watanabe S, Yamamoto T, Shibata S, Shibata K (1984) Behavioral effects of brotizolam, a new thienotriazolodiazepine derivative. Jpn J Pharmacol 35:287–299CrossRefPubMedGoogle Scholar
  7. 7.
    Langley MS, Clissold SP (1988) Brotizolam: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as a hypnotic. Drugs 35:104–122CrossRefPubMedGoogle Scholar
  8. 8.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefPubMedGoogle Scholar
  9. 9.
    Evans D, Hodgkinson B, Lambert L, Wood J (2001) Falls risk factors in the hospital setting: a systematic review. Int J Nurs Prac 7:38–45CrossRefGoogle Scholar
  10. 10.
    Norton D (1962) Geriatric nursing problems. Nurs Times 58:236–238PubMedGoogle Scholar
  11. 11.
    Israel Ministry of Health. Patient Admission Regulation number 0.5.1. Version July 2007. https://www.health.gov.il/download/ng/0_5_1.pdf. Accessed January 11, 2018
  12. 12.
    Jochemsen R, Nandi KL, Corless D, Wesselman JG, Breimer DD (1983) Pharmacokinetics of brotizolam in the elderly. Br J Clin Pharmacol 16(Suppl 2):299S–307SCrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wahid ZU (2004) Delirium in hospitalized patients: underdiagnosed and undertreated. J Natl Med Assoc 96:414PubMedCentralGoogle Scholar
  14. 14.
    Chin YC, Koh GC, Tay YK, Tan CH, Merchant RA (2016) Underdiagnosis of delirium on admission and prediction of patients who will develop delirium during their inpatient stay: a pilot study. Singap Med J 57:18–21CrossRefGoogle Scholar
  15. 15.
    Foy A, O'Connell D, Henry D, Kelly J, Cocking S, Halliday J (1995) Benzodiazepine use as a cause of cognitive impairment in elderly hospital inpatients. J Gerontol Biol Med Sci 50:99–106CrossRefGoogle Scholar
  16. 16.
    The American Geriatrics Society 2015 Beers Criteria Update Expert Panel (2015) American Geriatrics Society 2015 updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 63:2227–2246CrossRefGoogle Scholar
  17. 17.
    Vasilevskis EE, Han JH, Hughes CG, Ely EW (2012) Epidemiology and risk factors for delirium across hospital settings. Best Pract Res Clin Anaesthesiol 26:277–287CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Liao XY, Yamakawa M, Suto S, Shigenobu K, Makimoto K (2012) Changes in activity patterns after the oral administration of brotizolam in institutionalized elderly patients with dementia. Psychogeriatrics 12:99–105CrossRefPubMedGoogle Scholar
  19. 19.
    Chang CM, Chen MJ, Tsai CY, Ho LH, Hsieh HL, Chau YL, Liu CY (2011) Medical conditions and medications as risk factors of falls in the inpatient older people: a case-control study. Int J Geriatr Psychiatry 26:602–607CrossRefPubMedGoogle Scholar
  20. 20.
    Kolla BP, Lovely JK, Mansukhani MP, Morgenthaler TI (2013) Zolpidem is independently associated with increased risk of inpatient falls. J Hosp Med 8:1–6CrossRefPubMedGoogle Scholar
  21. 21.
    Obayashi K, Araki T, Nakamura K, Kurabayashi M, Nojima Y, Hara K, Nakamura T, Yamamoto K (2013) Risk of falling and hypnotic drugs: retrospective study of inpatients. Drugs R D 13:159–164CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Cohn MA (1984) The effects of brotizolam, a new hypnotic, on cardiac and respiratory function in volunteers. Respiration 45:281–285CrossRefPubMedGoogle Scholar
  23. 23.
    Blatter M, Hoigné R, Hess T, Bickel MH, Zoppi M, Fritschy D, Maibach R (1988) Side-effects of frequently administered hypnotics and sedatives as well as of anxiolytics. Results from a comprehensive hospital drug monitoring (CHDM) program. Schweiz Med Wochenschr 118:1859–1864PubMedGoogle Scholar
  24. 24.
    Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE (2005) Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ 331:1169CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Garrido MM, Prigerson HG, Penrod JD, Jones SC, Boockvar K (2013) Benzodiazepine and sedative-hypnotic use among older seriously ill veterans: choosing wisely? Clin Ther 36:1547–1554CrossRefGoogle Scholar
  26. 26.
    Dauphinot V, Faure R, Omrani S, Goutelle S, Bourguignon L, Krolak-Salmon P, Mouchoux C (2014) Exposure to anticholinergic and sedative drugs, risk of falls, and mortality: an elderly inpatient, multicenter cohort. J Clin Psychopharmacol 34:565–570CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Clinical Pharmacology and Toxicology UnitCarmel Medical CenterHaifaIsrael
  2. 2.Rappaport Faculty of MedicineTechnion-Israel Institute of TechnologyHaifaIsrael

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