Can we give Haldol (haloperidol) 5mg and Ativan (lorazepam) 2mg to a patient who received Zyprexa (olanzapine) 5mg approximately 1 hour and 38 minutes prior?

Management of Acute Agitation in a Patient Recently Given Olanzapine

It is not recommended to administer haloperidol 5mg and lorazepam 2mg to a patient who received olanzapine 5mg less than 2 hours ago due to risk of excessive sedation, respiratory depression, and potential cardiovascular effects. 1

Rationale and Safety Concerns

The FDA drug label for olanzapine specifically warns against combining olanzapine with benzodiazepines, stating that "lorazepam injection should not be used to reconstitute olanzapine intramuscular as this combination results in a delayed reconstitution time" 1. This warning reflects concerns about pharmacological interactions between these medications.

Research has demonstrated that the combination of olanzapine with benzodiazepines can lead to:

• Excessive sedation and respiratory depression, particularly in patients who may have consumed alcohol 2
• Potential cardiovascular effects including orthostatic hypotension 1
• Increased risk of adverse events when multiple sedating medications are administered in close proximity

Time Considerations

The timing is particularly concerning in this case:

• Olanzapine 5mg was administered at 12:30
• Current time is 2:08 (only 1 hour and 38 minutes later)
• Olanzapine has not yet reached its peak effect, which typically occurs 2-4 hours after administration

Alternative Approach

If additional medication is required for ongoing agitation, consider:

1. Wait until at least 2-4 hours after olanzapine administration before considering additional medications 3, 4

2. Reassess the patient's current level of sedation and vital signs before administering any additional medication

3. If absolutely necessary for severe, dangerous agitation:

   • Consider a lower dose of a single agent rather than the combination
   • Haloperidol alone at a reduced dose (2.5mg instead of 5mg) would be safer than the combination with lorazepam 3
   • Monitor closely for respiratory depression and hypotension

Evidence-Based Guidance

The American College of Emergency Physicians clinical policy recommends:

• "The combination of a parenteral benzodiazepine and haloperidol may produce more rapid sedation than monotherapy in the acutely agitated psychiatric patient in the ED" 3

• However, this recommendation does not address situations where another antipsychotic (olanzapine) has already been administered

Research comparing olanzapine and haloperidol with benzodiazepines found:

• "In patients with known alcohol ingestion, haloperidol, haloperidol + benzodiazepines, or olanzapine alone may be better choices for treatment of agitation" 2
• "Olanzapine + benzodiazepines were associated with lower oxygen saturations than haloperidol + benzodiazepines in ETOH+ patients" 2

Key Monitoring Parameters

If any additional medication is deemed absolutely necessary despite these concerns:

• Continuous monitoring of respiratory status and oxygen saturation
• Frequent blood pressure measurements to detect orthostatic hypotension
• Cardiac monitoring for QT prolongation
• Readiness for airway management if respiratory depression occurs

The safest approach is to allow more time for the olanzapine to take effect before considering additional medications for agitation.