Drug interactions
Diphenhydramine + Pentobarbital
Severity: Major
Diphenhydramine and Pentobarbital: major interaction.
Last updated Sources: US FDA label
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Both agents cause CNS depression, and combined use can produce deep sedation, impaired coordination and respiratory depression. Pentobarbital also induces liver enzymes, but the main concern is the additive depressant effect.
What this interaction means in plain words
Diphenhydramine and Pentobarbital can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Why it happens
Additive CNS depression from barbiturate GABA-A potentiation and central H1 antagonism.
What to do
Avoid unnecessary combined use and reduce the dose of one or both drugs when co-administration is needed. Monitor level of consciousness and respiratory status.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Diphenhydramine and Pentobarbital, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 7 days on the web. No card needed.
References
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Pentobarbital?
MediHelp rates the interaction as major. Diphenhydramine and Pentobarbital can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Both agents cause CNS depression, and combined use can produce deep sedation, impaired coordination and respiratory depression. Pentobarbital also induces liver enzymes, but the main concern is the additive depressant effect.
How serious is the interaction between Diphenhydramine and Pentobarbital?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid unnecessary combined use and reduce the dose of one or both drugs when co-administration is needed. Monitor level of consciousness and respiratory status.
What other medicines interact with Diphenhydramine?
MediHelp also lists interactions of Diphenhydramine with, for example, Alfentanil, Belladonna and opium, Benzhydrocodone / acetaminophen. The full list is on the Diphenhydramine page.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
