What are the implications of administering intramuscular (IM) Ativan (lorazepam) and Zyprexa (olanzapine) concurrently?

From the Guidelines

I strongly advise against administering intramuscular (IM) Ativan (lorazepam) and Zyprexa (olanzapine) simultaneously due to significant safety concerns, as this combination can cause excessive sedation, respiratory depression, hypotension, and potentially life-threatening complications. The primary concern with co-administering these medications is the synergistic effect on the central nervous system, which can lead to increased risk of adverse effects, including respiratory depression and death 1.

Key Considerations

• The combination of benzodiazepines and antipsychotics can potentiate central nervous system depression, increasing the risk of overdose and death 1.
• If both medications are clinically indicated for acute agitation or psychosis, they should be administered at least 1-2 hours apart to monitor for adverse effects between doses.
• Lorazepam typically works quickly (within 15-30 minutes) when given IM, so it's prudent to assess the patient's response before considering additional medication.
• If both medications are deemed necessary, consider using lower doses than would be used individually - perhaps 1-2mg of lorazepam and 5-10mg of olanzapine rather than maximum doses of each.

Recommendations

• Avoid prescribing benzodiazepines and antipsychotics concurrently whenever possible, due to the increased risk of adverse effects and death 1.
• Clinicians should check the PDMP for concurrent controlled medications prescribed by other clinicians and consider involving pharmacists and pain specialists as part of the management team when these medications are co-prescribed.
• In emergency situations where rapid tranquilization is required, many protocols favor using just one agent initially, then reassessing before adding a second medication from a different class.

From the FDA Drug Label

The co-administration of diazepam with olanzapine potentiated the orthostatic hypotension observed with olanzapine [see Drug Interactions (7. 2)]. Diazepam Olanzapine did not influence the pharmacokinetics of diazepam or its active metabolite N-desmethyldiazepam. However, diazepam co-administered with olanzapine increased the orthostatic hypotension observed with either drug given alone [see Drug Interactions (7.1)].

The administration of IM Ativan (lorazepam) and Zyprexa (olanzapine) at the same time may increase the risk of orthostatic hypotension. However, the label does mention that Lorazepam (IM) Administration of intramuscular lorazepam (2 mg) 1 hour after intramuscular olanzapine for injection (5 mg) did not significantly affect the pharmacokinetics of olanzapine, unconjugated lorazepam, or total lorazepam, but it did add to the somnolence observed with either drug alone 2. Caution should be used when administering these drugs together.

From the Research

Administration of IM Ativan and Zyprexa

• The administration of IM Ativan (lorazepam) and Zyprexa (olanzapine) at the same time is a common practice in managing acute agitation, as seen in studies such as 3 and 4.
• According to 3, the combination of lorazepam and haloperidol was superior to either agent alone, but there were no differences between monotherapy with the individual agents.
• However, 4 found that haloperidol in combination with lorazepam does not have added value to lorazepam or haloperidol alone, and olanzapine is comparable in effectiveness to lorazepam or haloperidol.
• A study on intravenous olanzapine for the management of agitation, 5, found that doses from 2.5 to 10 mg given as an IV bolus have been administered, sometimes with rescue medications such as droperidol or parenteral benzodiazepines.

Safety and Efficacy

• The safety and efficacy of combining IM Ativan and Zyprexa are not well-established, as seen in 5, which states that the use of IV olanzapine remains controversial in the absence of clear evidence evaluating safety and efficacy.
• A multicenter retrospective cohort study, 6, compared the efficacy and safety of combination haloperidol, lorazepam, and diphenhydramine to combination haloperidol and lorazepam in treating acute agitation, and found that both combinations infrequently required repeat agitation medication.
• However, the study also found that the combination of haloperidol, lorazepam, and diphenhydramine resulted in more oxygen desaturation, hypotension, physical restraint use, and longer length of stay compared to the combination of haloperidol and lorazepam.

Considerations

• When administering IM Ativan and Zyprexa, it is essential to consider the potential risks and benefits, as well as the individual patient's needs and medical history, as seen in 7, which highlights the increased risk of respiratory depression when combining opioids and benzodiazepines.
• The choice of medication and dosage should be based on the patient's specific condition and the clinical judgment of the healthcare provider, taking into account the findings of studies such as 3, 4, and 6.