Medications That Cannot Be Given with Lorazepam IM
High-dose olanzapine should not be combined with lorazepam IM due to risk of fatal outcomes, including oversedation and respiratory depression. 1
Critical Drug Interactions with Lorazepam IM
Antipsychotics Requiring Extreme Caution
Olanzapine (high-dose): Fatalities have been reported with concurrent use of benzodiazepines and high-dose olanzapine, specifically due to oversedation and respiratory depression 1
Haloperidol: Apnea, coma, bradycardia, arrhythmia, heart arrest, and death have been reported with concomitant use 2
Clozapine: Marked sedation, excessive salivation, ataxia, and rarely death have been documented 2
Loxapine: Rare reports of significant respiratory depression, stupor, and/or hypotension when combined with lorazepam 2
Other High-Risk Combinations
Scopolamine: Increased incidence of sedation, hallucinations, and irrational behavior when used concomitantly with injectable lorazepam 2
Opioids: The concomitant use significantly worsens opioid-related respiratory depression due to actions at different CNS receptor sites (benzodiazepines at GABA-A sites, opioids at mu receptors) 2
Dosing Adjustments Required (Not Contraindicated, But Mandatory Reduction)
When lorazepam IM must be used with certain medications, reduce the lorazepam dose by 50% in these situations:
Valproate: Decreases total clearance of lorazepam by 40% and lorazepam glucuronide formation by 55%, resulting in approximately two-fold higher plasma concentrations 2
Probenecid: Prolongs lorazepam half-life by 130% and decreases total clearance by 45% 2
Clinical Context and Monitoring
When combining lorazepam with antipsychotics in agitated patients, use lower doses (0.25-0.5 mg) in elderly, frail patients, or those with COPD 1. The ESMO guidelines specifically note that while combination therapy may be used for severe agitation, the risk of respiratory compromise necessitates readiness to support ventilation 1, 3.
For acute agitation management, if rapid sedation is required and combination therapy is deemed necessary, the evidence supports using lorazepam with haloperidol may produce more rapid sedation than monotherapy, but this comes with the documented risks noted above 1.
Common Pitfalls to Avoid
Do not assume all antipsychotics carry equal risk—the evidence specifically identifies haloperidol, clozapine, loxapine, and high-dose olanzapine as having documented severe adverse events including death 2
Do not use standard lorazepam doses when patients are on valproate or probenecid—this is a critical dosing error that will result in excessive sedation 2
Be prepared to support ventilation whenever combining lorazepam with any CNS depressant, particularly in elderly patients or those with respiratory compromise 1, 3