Retrospective Analysis of Coadministration of Parenteral Olanzapine With Parenteral Benzodiazepines

INTRODUCTION: Concomitant administration of parenteral olanzapine (OLZ) and benzodiazepines (BZD) is a common practice in the hospital for agitation and nausea and vomiting; however, there is a warning on the OLZ package insert recommending against the coadministration of these agents. The warning is based on limited retrospective data. This analysis sought to evaluate the safety of coadministration of parenteral OLZ with parenteral BZD.

METHODS : This retrospective, single-center analysis included adult patients who received a combination of parenteral OLZ within two hours of parenteral midazolam or lorazepam from July 2018 to January 2021. Patients were excluded if any of the following were true at the time of administration: administration of continuous infusion of propofol or midazolam, required a ventilator or ECMO, or had a code status of “comfort measures only”. The major endpoint was incidence of respiratory depression defined as oxygen saturation < 92%, the need for supplemental oxygen or mechanical ventilation within 4 hours of administration of the second agent of the combination of drugs. Minor outcomes included the incidence of cardiovascular depression (SBP < 90 mmHg, HR < 60 BPM, fluid bolus, initiation of vasopressors or need for additional vasopressor) and dose of each agent.

RESULTS: A total of 112 patients were included in this analysis with 185 concomitant administrations. Respiratory depression occurred in 16 (8.7%) administrations, and of these, 4 patients required intubation (3 needed to be more deeply sedated, 1 was intubated in the setting of airway inflammation). All events were classified as a possible reaction according to the Naranjo algorithm. Cardiovascular depression occurred in 20 (10.9%) patients, of these patients, 1 patient required initiation of vasopressor and 5 patients received a fluid bolus. Most cardiovascular reactions were classified as a possible or doubtful adverse drug reaction, 3 were classified as a probable drug reaction. The median dose of OLZ used was 5 mg (IQR 5-10), and the median BZD dose in lorazepam equivalent was 1 mg (IQR 0.5-4).

CONCLUSIONS: Patients receiving concomitant parenteral OLZ and BZD had a low incidence of significant respiratory and cardiovascular depression. Additional prospective analyses are needed to further elucidate these findings.