Can Zyprexa (Olanzapine) IM be given together with Ativan (Lorazepam) IM?

Olanzapine IM and Lorazepam IM Should Not Be Administered Together

Olanzapine IM should not be administered together with lorazepam IM due to the significant risk of respiratory depression, oversedation, and potential fatalities. 1, 2

Safety Concerns

The FDA drug label for olanzapine IM specifically warns about increased somnolence when combined with lorazepam IM 1. This combination presents several serious risks:

• Respiratory depression: The combination can lead to dangerous respiratory suppression
• Oversedation: Excessive sedation can occur rapidly and may be difficult to reverse
• Fatalities: Deaths have been reported with concurrent use of benzodiazepines with high-dose olanzapine 2

Clinical Guidelines

The ESMO Clinical Practice Guidelines explicitly caution against combining olanzapine with benzodiazepines due to the risk of oversedation and respiratory depression 2. This warning appears in their medication management recommendations for delirium in adult patients.

Alternative Approaches

When managing acute agitation requiring parenteral medication, consider these safer alternatives:

1. Use either medication alone:

   • Olanzapine IM 2.5-5 mg as monotherapy 2
   • Lorazepam IM 1-2 mg as monotherapy 2

2. Consider alternative combinations:

   • Haloperidol + lorazepam is a safer combination for rapid sedation 2
   • For oral medications in cooperative patients, risperidone + lorazepam is effective 2

3. Other parenteral options:

   • Midazolam as an alternative benzodiazepine 2
   • Ziprasidone IM has shown efficacy for acute agitation 3

Special Considerations

Alcohol Use

The risks are further amplified in patients who have consumed alcohol. Research shows decreased oxygen saturations in patients who received olanzapine after alcohol ingestion, with even greater decreases when benzodiazepines were added 4. Two patients (20%) who received both medications after alcohol consumption developed hypoxia (O₂ saturation ≤92%) 4.

Dosing Adjustments

If either medication must be used individually:

• Reduce olanzapine doses in older patients and those with hepatic impairment 2
• Use lower lorazepam doses (0.25-0.5 mg) in older or frail patients, those with COPD, or if administered with an antipsychotic 2

Monitoring Requirements

When using either medication individually:

• Monitor respiratory status and oxygen saturation
• Have equipment available for airway management
• Monitor for orthostatic hypotension, particularly with olanzapine
• Be prepared to provide supportive care for any adverse effects

Bottom Line

The combination of olanzapine IM and lorazepam IM presents significant risks that outweigh potential benefits. Each medication can be effective when used appropriately as monotherapy, and safer combinations exist when combination therapy is required for severe agitation.