A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical ICUs

Smithburger, Pamela L.; Buckley, Mitchell S.; Culver, Mark; Sokol, Sarah; Lat, Ishaq; Handler, Steven M.; Kirisci, Levent; Kane‐Gill, Sandra L.

doi:10.1097/ccm.0000000000001022

Cited by 37 publications

(46 citation statements)

References 50 publications

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“…Off-label use has been studied as a potential contributing factor to preventable adverse drug events (ADEs) (4-7), with the risk for ADEs increased by 44% with off-label use compared to on-label use. This risk was even greater when off-label use was not supported by strong evidence, with off-label use lacking strong evidence found to be 80.9% out of all off-label use prescriptions (4).…”

Section: Introductionmentioning

confidence: 99%

Off-Label Medication Use in the Inpatient Palliative Care Unit

Kwon

Kim

Bruera

et al. 2017

Journal of Pain and Symptom Management

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Context Although off-label medications are frequently prescribed in palliative care, there are no published studies examining their use in the United States. Objectives We examined the frequency of off-label medication use in cancer patients admitted to an acute palliative care unit (APCU). Methods This prospective observational study enrolled consecutive patients with advanced cancer admitted to the APCU of a tertiary care cancer center. We collected data on all prescription events, including indications for use, from admission to discharge. Off-label use was checked against the U.S. Food and Drug Administration approved indications. Results Among the 201 patients, median survival was 10 days (95% confidence interval 7-13), and 85 (42%) patients died in the APCU. We documented 6276 prescription events, and 2199 (35%) were off-label. Among off-label prescriptions, central nervous system agents (n=1606, 73%), hormones and synthetic substitutes (n= 302, 14%), and autonomic drugs (n=183, 8%) were most commonly prescribed. Haloperidol (n=720, 33%), chlorpromazine (n=292, 13%), dexamethasone (n=280, 13%), glycopyrrolate (n=175, 8%), hydromorphone (n=161, 7%), and morphine (n=156, 7%) were most frequently prescribed off-label. The most common indications for off-label prescribing were delirium (n=783, 36%) and dyspnea (n=449, 20%). 70% of all off-label prescription events had strong evidence supporting use, and 19% of prescription events had moderate or weak evidence for use. Conclusion One-third of prescription events in the APCU were off-label, with majority of off-label use having a strong level of supporting evidence. Our findings highlight the need for more research in key areas such as delirium and dyspnea management.

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Section: Introductionmentioning

confidence: 99%

Off-Label Medication Use in the Inpatient Palliative Care Unit

Kwon

Kim

Bruera

et al. 2017

Journal of Pain and Symptom Management

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“…the off-label use of drugs is very common in pediatrics and oncology (between 20% and 60% according different studies) (8). Off-label use does not necessarily mean a lack of evidence demonstrating the efficacy and safety of the used agent; but the supporting evidence for different off-label indications may vary considerably both in extent and quality (9). These reasons explain the non-randomized design of our study.…”

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confidence: 73%

Dexmedetomidine, agitated delirium, and “off-label” drugs

2016

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We appreciate the comments by Parker et al. (1) and Knauert et al. (2) concerning our recent manuscript entitled "Dexmedetomidine for the treatment of hyperactive delirium refractory to haloperidol in non-intubated ICU patients: A non-randomized controlled trial" (3). We are agreed with the most of reviewer's considerations. However, we would like to add three reflections that may be interesting for the readers. The first relates to the current position of this alpha-2 agonist on the healthcare market. A second comment intends to respond to some interesting assertions from the reviewers that, in our opinion, could be controversial. The third and final comment is addressed to reflect on the future of the research on intensive care unit (ICU) delirium.The first comment refers to the restricted indications of dexmedetomidine in ICUs setting. This drug was approved in the United States by the Food and Drug Administration (FDA) in late 1999 for use in humans as sedation of initially intubated and mechanically ventilated patients during treatment in an ICU setting, and sedation of nonintubated patients prior to and/or during surgical and other procedures. Subsequently this agent was approved also by the European Medicines Agency (EMA) for the same restricted indications. Consequently, dexmedetomidine has been especially studied for sedation in intubated patients. It has been widely compared with standard ICU intravenous sedation (propofol, midazolam lorazepam...) (4,5). Although dexmedetomidine provided some minor advantages (such as longer adequate sedation level) compared with standard ICU sedatives, the available evidence has shown that its main advantage is the control of delirium symptoms in intubated patients (an indication that was not included by authorizing its use). Although agitated delirium in intubated patients is a major problem, in the non-intubated this problem can be even greater. This is due to two reasons. The first is the different prevalence of delirium in these populations. In our environment, agitated delirium does not exceed 8% in intubated patients whilst it is greater than 25% in non-intubated patients (6). A second reason is due to the different hazard presented by these patients. Agitated delirium in intubated patients is rarely a critical problem because the dangerous agitation can be easily treated with standard sedation (propofol, midazolam lorazepam...). Oppositely, higher risk of respiratory depression limits treatment in non-intubated subjects. We wanted to investigate the problem of agitated delirium in non-intubated patients because it represented one of the main therapeutic challenges in our ICU.Strictly speaking, the treatment of delirium with dexmedetomidine could be seen as an «off-label» indication. Off-label drug use refers to the prescription of licensed drugs for clinical indications or in a manner different from that approved by the regulatory authorities and thus not included in the approved labeling for the agents. Use of drugs for a clinical indication, in a patient po...

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“…the US Food and Drug Administration (221). The off label use of medications is common in many clinical areas, such as psychiatry, pediatrics, oncology and intensive care unit (222)(223)(224)(225). In general, no law prohibits the unauthorized use of medicines and the prescription of unauthorized medicines is legally accepted in most legislations (226).…”

Section: Discussionmentioning

confidence: 99%

Are melatonin doses employed clinically adequate for melatonin-induced cytoprotection?

Cardinali

2019

Melatonin Res.

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This review article discusses the special role that melatonin, a molecule with chronobiotic/cytoprotective properties, may have in prevention and treatment of the metabolic syndrome (MS), ischemic and non-ischemic cardiovascular diseases and Alzheimer´s disease (AD). Prevention of these diseases is a major goal for governmental and non-governmental organizations, and melatonin, an unusual phylogenetically conserved molecule present in all aerobic organisms, merits consideration in this respect. In humans, circulating melatonin levels are consistently reduced in MS, ischemic and non-ischemic cardiovascular diseases and AD, the potential therapeutic value of melatonin being suggested by a limited number of clinical trials generally employing melatonin in the 2-5 mg/day range. In animal model studies of MS, ischemic and non-ischemic cardiovascular diseases and AD melatonin was very effective to curtail symptomatology. However, calculations derived from animal studies indicate projected cytoprotective melatonin doses for humans in the 40-100 mg/day range, doses that are rarely employed clinically. Hence, controlled studies employing melatonin doses in this range are urgently needed. Since the pharmaceutical industry is refractive to support them because of the lack of protective patents for a natural compound, only the involvement of governmental and non-profit organizations can achieve that goal. Within this prospect, the off-label use of melatonin is discussed.

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A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical ICUs

Cited by 37 publications

References 50 publications

Off-Label Medication Use in the Inpatient Palliative Care Unit

Off-Label Medication Use in the Inpatient Palliative Care Unit

Dexmedetomidine, agitated delirium, and “off-label” drugs

Are melatonin doses employed clinically adequate for melatonin-induced cytoprotection?

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