Can intramuscular (IM) diphenhydramine (Benadryl) and intramuscular (IM) olanzapine be administered together?

From the Guidelines

You should not administer intramuscular (IM) Benadryl (diphenhydramine) and IM olanzapine together due to the increased risk of adverse effects. When considering the administration of these medications, it is crucial to prioritize the patient's safety and well-being, focusing on minimizing the risk of morbidity, mortality, and improving their quality of life. The potential for excessive sedation, respiratory depression, and hypotension is a significant concern when combining these central nervous system depressants 1. Additionally, physical compatibility issues arise when mixing these medications in the same syringe, further supporting the decision to administer them separately. If both medications are clinically indicated, they should be given at different injection sites, with adequate time between injections, typically at least 30-60 minutes apart, and with close monitoring of vital signs, level of consciousness, and potential side effects. Healthcare providers should consult with a physician or pharmacist before administering these medications, taking into account individual patient factors such as age, weight, medical conditions, and other medications that may affect dosing and safety considerations. In the context of real-life clinical medicine, prioritizing caution and patient safety is paramount, and alternative administration methods, such as oral formulations, should be considered when possible. Key considerations include:

• Administering IM Benadryl and IM olanzapine separately to minimize adverse effects
• Monitoring patients closely for signs of excessive sedation, respiratory depression, and hypotension
• Considering alternative administration methods, such as oral formulations, when clinically appropriate
• Consulting with a physician or pharmacist to determine the best course of treatment for each individual patient.

From the FDA Drug Label

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

The FDA drug label does not specifically mention Benadryl (diphenhydramine), but it does mention that concomitant administration of intramuscular olanzapine and parenteral benzodiazepine is not recommended. However, Benadryl is an antihistamine with sedative properties, and its combination with olanzapine may also increase the risk of excessive sedation and cardiorespiratory depression. It is not recommended to administer IM Benadryl and IM olanzapine together 2.

From the Research

IM Benadryl and IM Olanzapine Co-administration

• The co-administration of IM olanzapine and parenteral benzodiazepines, such as Benadryl (which is an antihistamine but can have sedative effects), has been studied in various research papers 3, 4, 5, 6.
• A retrospective review of intramuscular olanzapine and parenteral benzodiazepine coadministration in the emergency department found that the composite primary endpoint of cardiac or respiratory compromise within 2 hours of medication administration occurred in 8 patients (12.5%) 3.
• Another study found that there was limited comparability between studies in drug choice, combination, dose, method of administration, or timing of repeat administrations, making it difficult to determine the safety and efficacy of co-administering IM olanzapine and benzodiazepines 4.
• A medication use evaluation conducted at a county psychiatric hospital found no serious adverse events following the administration of concomitant intramuscular olanzapine and lorazepam in 91 instances 5.
• A policy was developed to warn of the potential for adverse events associated with the use of intramuscular olanzapine in combination with injectable benzodiazepines, and changes were implemented in the areas of order processing and floor-stock provision to prevent co-administration 6.

Safety and Efficacy

• The available evidence does not consistently support a strong cause and effect relationship between olanzapine/benzodiazepine combinations and serious adverse effects 5.
• However, it is recommended that co-administration of IM olanzapine and benzodiazepines should be done with caution and appropriate patient monitoring 3, 5.
• Further controlled research is needed to help define the actual risk of using concomitant intramuscular olanzapine and benzodiazepines 3, 5.

Adverse Effects

• Akathisia is a possible adverse effect of psychopharmacs, including antipsychotics and benzodiazepines, and can be difficult to identify in everyday clinical practice 7.
• The co-administration of IM olanzapine and benzodiazepines may increase the risk of adverse effects such as hypotension, bradycardia, bradypnea, or oxygen desaturation, although the available evidence does not consistently support a strong cause and effect relationship 3, 5.