Can I use Zyprexa (Olanzapine) IM along with Ativan (Lorazepam)?

Combining Olanzapine IM with Lorazepam: Safety Concerns and Recommendations

The combination of intramuscular olanzapine (Zyprexa) and lorazepam (Ativan) is not recommended due to the risk of excessive sedation, cardiorespiratory depression, and potentially fatal outcomes.

Safety Concerns with Combination Therapy

The FDA label for olanzapine specifically warns against this combination:

• "Concomitant administration of intramuscular olanzapine and parenteral benzodiazepine is not recommended due to the potential for excessive sedation and cardiorespiratory depression" 1

• The risk of adverse effects is particularly concerning because:

  • Both medications can cause sedation, respiratory depression, and hypotension
  • The combination may have synergistic effects on central nervous system depression
  • Patients may experience profound sedation, respiratory compromise, and cardiovascular instability

Clinical Evidence Supporting This Warning

Research studies have documented specific risks with this combination:

• A 2012 study found that patients who received olanzapine plus benzodiazepines and had consumed alcohol exhibited significant oxygen desaturations, with 20% developing hypoxia (O₂ saturation ≤92%) 2

• Another study comparing olanzapine and haloperidol with benzodiazepines found that olanzapine plus benzodiazepines was associated with lower oxygen saturations in patients who had consumed alcohol 3

• The 2018 ESMO Clinical Practice Guidelines explicitly caution: "(Caution: combining with benzodiazepine as risk of oversedation and respiratory depression)" when discussing olanzapine use 4

Alternative Approaches for Acute Agitation

If medication is needed for acute agitation, consider these safer alternatives:

1. Use olanzapine IM alone (2.5-5 mg) without concurrent benzodiazepines 4

2. Use lorazepam alone (1-2 mg IV/IM) if benzodiazepines are preferred 4

3. Consider haloperidol plus benzodiazepines if combination therapy is necessary, as this appears to have a better safety profile, particularly in patients who have consumed alcohol 3

4. Sequential administration with adequate time between medications (at least 1 hour) to assess response before adding a second agent

Monitoring Requirements if Combination Cannot Be Avoided

In rare emergency situations where this combination cannot be avoided:

• Ensure continuous monitoring of vital signs, especially respiratory rate and oxygen saturation
• Have resuscitation equipment immediately available
• Keep patient in a recumbent position to minimize risk of orthostatic hypotension
• Avoid this combination completely in patients who have consumed alcohol 2, 3
• Use reduced doses of both medications (e.g., olanzapine 2.5 mg IM and lorazepam 0.5 mg IM)

Conclusion

The evidence strongly advises against combining intramuscular olanzapine with lorazepam due to significant safety concerns. When managing acute agitation, it is safer to use either medication alone or consider alternative combinations with better safety profiles.