Drug interactions
Diphenhydramine + Phenobarbital
Severity: Major
Diphenhydramine and Phenobarbital: 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
Combining a sedating antihistamine with a barbiturate increases drowsiness, impaired coordination and the risk of respiratory depression. Falls and cognitive impairment are of particular concern in older adults.
What this interaction means in plain words
Diphenhydramine and Phenobarbital 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 combining where feasible, and use an alternative non-sedating antihistamine. If needed, use the lowest doses and monitor sedation and respiration.
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?
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References
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Phenobarbital?
MediHelp rates the interaction as major. Diphenhydramine and Phenobarbital 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. Combining a sedating antihistamine with a barbiturate increases drowsiness, impaired coordination and the risk of respiratory depression. Falls and cognitive impairment are of particular concern in older adults.
How serious is the interaction between Diphenhydramine and Phenobarbital?
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 combining where feasible, and use an alternative non-sedating antihistamine. If needed, use the lowest doses and monitor sedation and respiration.
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.
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