Today, I’m going to touch on the co-administration of olanzapine with benzodiazepines.
Data is controversial regarding this, but the co-administration has not been studied in depth, which is why it is not currently recommended to give both.
What’s the FDA’s stance?
“Concomitant administration of intramuscular olanzapine along with benzodiazepines is not recommended due to the potential for excessive sedation and cardiorespiratory depression.”
This advisory came about after there were 160 adverse events and 29 fatalities associated with IM olanzapine in 2005.
Possible side effects of co-administration: Severe hypotension, respiratory depression
Why the FDA warning?
There was a study (n=29) looking at patient fatalities involving the administration of olanzapine.
3/29 fatalities involved olanzapine monotherapy.
1/29 fatalities involved IM olanzapine + benzodiazepine dual therapy
25/29 fatalities involved IM olanzapine + PO/IM/IV benzodiazepines + many other medications
The interesting thing about the study is that 12 patients died over 24 hours after administration of the medications. So it’s difficult to determine causality.
Some olanzapine quick facts:
Olanzapine is an atypical antipsychotic
Side effect profile includes: neuroleptic malignant syndrome, hyperglycemia, constipation, dry mouth, tachycardia, orthostatic hypotension
Mortalities and increased risk of cerebrovascular accidents have been linked to elderly patients with dementia
IM olanzapine is 5 times more potent than PO olanzapine.
½ life: 21-54 hours
Peak: within 15-45 minutes
Why is this conversation controversial?
Well, if you look at the data regarding co-administration < 60 minutes apart studied in 41 patients, you see that their vitals are actually fine.
**** 4 Key takeaways ****
According to the European Medicines Agency, it’s likely safe to administer olanzapine and a BZD at least 60 minutes apart.
It’s safer to use PO agents over IM agents. Our ED pharmacy team does not recommend administering IM of both.
Avoid co-administration particularly in high risk groups: elderly, dementia, acute alcohol intoxication, or patients requiring polypharmacy.
If you’ve already used olanzapine, and you’re looking for an additional agent, ketamine is likely a safer option.
References:
https://www.aliem.com/combination-parenteral-olanzapine-benzodiazepines-agitation-adverse-events/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125121/
https://foamcast.org/2019/10/29/black-boxed-medications-in-the-ed-acep-2019/