From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Benadryl (diphenhydramine), Haldol (haloperidol), and Lorazepam should be administered as separate injections rather than combined in one syringe. These medications are physically and chemically incompatible when mixed together, which can lead to precipitation, reduced efficacy, or potential adverse effects. When administering these medications for conditions like acute agitation or delirium, they should be given as individual injections at separate injection sites. This approach ensures each medication maintains its stability and intended therapeutic effect. Additionally, giving them separately allows for better dose titration based on patient response and makes it easier to identify which medication might be causing any adverse effects. While some clinicians historically referred to this combination as a "B-52" or "5-2-1" (referring to typical dosages), modern practice standards emphasize the importance of separate administration to maintain medication integrity and patient safety, as supported by studies such as 1 which evaluated the visual compatibility and particle counter evaluations of syringes of intramuscular psychotropic coadministered solutions. However, the most recent and highest quality study, 2, compared the effect of ketamine vs haloperidol/lorazepam/diphenhydramine combination treatment for management of acute agitation in the emergency department, but did not directly address the compatibility of these medications when mixed in one syringe. Despite this, the general principle of administering potentially incompatible medications separately to ensure patient safety and medication efficacy remains a priority, as emphasized in various studies including 3 and 4, which discussed the use of these medications in different contexts but highlighted the importance of careful administration and monitoring. Furthermore, a study on percutaneous absorption, 5, although not directly relevant to the question of intramuscular injection compatibility, underscores the complexity of drug delivery and the need for careful consideration of how medications are administered to achieve the desired therapeutic effect while minimizing risks. Therefore, based on the principle of prioritizing patient safety and medication efficacy, administering Benadryl, Haldol, and Lorazepam as separate injections is the recommended approach.