Drug interactions
Benzhydrocodone / acetaminophen + Diphenhydramine
Severity: Major
Benzhydrocodone / acetaminophen and Diphenhydramine: major interaction.
Last updated
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
Diphenhydramine adds to the sedation and respiratory depression of the opioid component. It also inhibits CYP2D6, which could modestly reduce conversion of hydrocodone to hydromorphone, but the clinical effect of this is uncertain.
What this interaction means in plain words
Benzhydrocodone / acetaminophen and Diphenhydramine 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 and respiratory depression, with possible CYP2D6 inhibition by diphenhydramine.
What to do
Use the lowest effective doses and avoid the combination where possible. Monitor sedation and respiratory rate, particularly at initiation and after dose changes.
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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Other interactions of Diphenhydramine
Frequently asked questions
Can I take Benzhydrocodone / acetaminophen with Diphenhydramine?
MediHelp rates the interaction as major. Benzhydrocodone / acetaminophen and Diphenhydramine 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. Diphenhydramine adds to the sedation and respiratory depression of the opioid component. It also inhibits CYP2D6, which could modestly reduce conversion of hydrocodone to hydromorphone, but the clinical effect of this is uncertain.
How serious is the interaction between Benzhydrocodone / acetaminophen and Diphenhydramine?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Use the lowest effective doses and avoid the combination where possible. Monitor sedation and respiratory rate, particularly at initiation and after dose changes.
What other medicines interact with Diphenhydramine?
MediHelp also lists interactions of Diphenhydramine with, for example, Alfentanil, Belladonna and opium, Brexanolone. The full list is on the Diphenhydramine page.
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