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. 2015 May-Jun;20(3):186-96.
doi: 10.5863/1551-6776-20.3.186.

Patterns of Off-Label Prescribing in the Pediatric Intensive Care Unit and Prioritizing Future Research

Angela S Czaja  1 , Pamela D Reiter  2 , M Lynn Schultz  3 , Robert J Valuck  4
Affiliations

Patterns of Off-Label Prescribing in the Pediatric Intensive Care Unit and Prioritizing Future Research

Angela S Czaja et al. J Pediatr Pharmacol Ther. 2015 May-Jun.

Abstract

Objectives: To characterize off-label prescribing among US pediatric intensive care units (PICUs), determine characteristics associated with off-label use, and identify medications in highest need for additional study.

Methods: Medications prescribed for ≥1% PICU patients (age < 18 years) in 2010 were identified from 39 children's hospitals. Use in a patient younger than the Food and Drug Administration (FDA)-approved age for any indication was considered off-label. Hierarchical multivariable modeling was used to identify characteristics associated with off-label use, accounting for center effects. Highest-impact drugs were defined by: 1) high off-label use (off-label use in at least 5% of the PICU cohort), 2) high risk medication, and 3) high priority status by the FDA or Best Pharmaceuticals for Children Act (BPCA).

Results: A total of 66,896 patients received ≥1 medication of interest (n = 162) during their PICU stay. A median of 3 (interquartile range, 2-6) unique drugs per patient were used off-label. Those who received ≥1 drug off-label (85% of the cohort) had longer median PICU (2 days vs 1 day) and hospital (6 days vs 3 days) lengths of stay and higher mortality (3.6% vs 0.7%), p < 0.001. Factors independently associated with off-label drug use included: age 1 to 5 years, chronic conditions, acute organ failures, mechanical ventilation, arterial or venous catheters, dialysis, and blood products. Half of prescribed medications (n = 84) had been used off-label: 26 with significant off-label use, 30 high-risk medications, and 47 with high FDA/BPCA priority. The highest impact medications identified were: dexmedetomidine, dopamine, hydromorphone, ketamine, lorazepam, methadone, milrinone, and oxycodone.

Conclusions: Most PICU patients are exposed to off-label medication use, with uncertain evidence. Future medication research in this population should focus on medications with high impact potential.

Keywords: off label use; pediatric intensive care units; pharmacoepidemiology; research priorities; risk factors.

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