Transition from rectal to intranasal route among mostly pediatric patients with repeated prescriptions of rescue benzodiazepines for seizure emergencies

Objective

To describe the changes in Food and Drug Administration (FDA)-approved non-intravenous rescue benzodiazepine (non-IV-rBZD) use and cost after the introduction of intranasal midazolam and intranasal diazepam.

Methods

Retrospective descriptive study using the MarketScan Database between the years 2016 and 2022. We considered patients who had at least one non-IV-rBZD prescription before the introduction of intranasal rescue medications and at least one non-IV-rBZD prescription after the introduction of intranasal rescue medications.

Results

There were 4,444 patients (45.8 % female, median (p₂₅-p₇₅) age of 10.0 (5.0–15.0) years). 2,255 of 4,444 (50.7 %) patients switched from rectal diazepam to either intranasal midazolam (1,110 (25.0 %)) or intranasal diazepam (1,145 (25.8 %)) as their last non-IV-rBZD. The change from rectal to intranasal non-IV-rBZDs has been increasing over the years from 2019 to 2022. On multivariable analysis, having a non-IV-rBZD for epilepsy (rather than for other reasons including febrile seizures), the year of the last rescue medication, urban (non-rural) patient’s residence, and certain regions of the United States were the factors most strongly associated with a change from rectal diazepam to intranasal non-IV-rBZDs. After adjusting for inflation, the median (p₂₅-p₇₅) average wholesale price (AWP) of the last non-IV-rBZD was higher than that of the first non-IV-rBZD [702 (406–748) versus 417 (406–426), Wilcoxon signed rank test p < 0.0001)]. This difference was mainly driven by the patients who changed from rectal diazepam to intranasal non-IV-rBZD [748 (714–755) versus 417 (406–426), Wilcoxon signed rank test p < 0.0001)]. After adjusting for inflation, the median (p₂₅-p₇₅) patient cost of the last non-IV-rBZD was higher than that of the first non-IV-rBZD [16 (3–55) versus 12 (6–31), Wilcoxon signed rank test p < 0.0001)]. This difference was mainly driven by the patients who changed from rectal diazepam to intranasal non-IV-rBZD [41 (6–83) versus 12 (6–30), Wilcoxon signed rank test p < 0.0001)].

Conclusion

Approximately half of patients changed from rectal diazepam to intranasal midazolam or intranasal diazepam and that transition has been progressively increasing from the year 2019 to the year 2022. The inflation-adjusted AWP and patient cost increased, especially among those patients who changed from rectal to intranasal rescue medication.