Drug interactions
Diphenhydramine + Hydromorphone
Severity: Major
Diphenhydramine and Hydromorphone: 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 an opioid with a sedating antihistamine adds to central nervous system and respiratory depression. Drowsiness, impaired psychomotor performance and, at higher doses, respiratory compromise may occur. Hydromorphone is mainly glucuronidated, so any CYP2D6 effect of diphenhydramine is unlikely to matter clinically.
What this interaction means in plain words
Diphenhydramine and Hydromorphone 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 belongs to Respiratory; Hydromorphone belongs to Musculoskeletal.
Why it happens
Additive CNS and respiratory depression through opioid receptor agonism and central H1 antagonism.
What to do
Use the lowest effective doses and monitor sedation and respiratory rate, especially in older adults or opioid-naive patients. Counsel patients to avoid driving and alcohol.
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 Hydromorphone
- Alvimopan + Hydromorphone Contraindicated
- Bupropion-naltrexone + Hydromorphone Contraindicated
- Hydromorphone + Isocarboxazid Contraindicated
- Hydromorphone + Olanzapine / samidorphan Contraindicated
- Hydromorphone + Phenelzine Contraindicated
- Hydromorphone + Tranylcypromine Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Hydromorphone?
MediHelp rates the interaction as major. Diphenhydramine and Hydromorphone 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 an opioid with a sedating antihistamine adds to central nervous system and respiratory depression. Drowsiness, impaired psychomotor performance and, at higher doses, respiratory compromise may occur. Hydromorphone is mainly glucuronidated, so any CYP2D6 effect of diphenhydramine is unlikely to matter clinically.
How serious is the interaction between Diphenhydramine and Hydromorphone?
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 monitor sedation and respiratory rate, especially in older adults or opioid-naive patients. Counsel patients to avoid driving and alcohol.
What other medicines interact with Hydromorphone?
MediHelp also lists interactions of Hydromorphone with, for example, Alvimopan, Bupropion-naltrexone, Isocarboxazid. The full list is on the Hydromorphone page.
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