Drug interactions
Diphenhydramine + Tramadol
Severity: Moderate
Diphenhydramine and Tramadol: moderate 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 is a CYP2D6 inhibitor and can reduce conversion of tramadol to its more potent active metabolite, which may weaken analgesia. It also adds sedative and anticholinergic effects to opioid CNS depression.
What this interaction means in plain words
Diphenhydramine and Tramadol can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Diphenhydramine belongs to Respiratory; Tramadol belongs to Musculoskeletal.
Why it happens
CYP2D6 inhibition by diphenhydramine reducing O-desmethyltramadol formation, plus additive CNS depression.
What to do
Monitor for reduced pain relief and for excessive sedation or confusion. Consider a non-sedating antihistamine or an alternative analgesic if the combination is needed regularly.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Tramadol
- Isocarboxazid + Tramadol Contraindicated
- Olanzapine / samidorphan + Tramadol Contraindicated
- Phenelzine + Tramadol Contraindicated
- Procarbazine + Tramadol Contraindicated
- Rasagiline + Tramadol Contraindicated
- Safinamide + Tramadol Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Tramadol?
MediHelp rates the interaction as moderate. Diphenhydramine and Tramadol can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Diphenhydramine is a CYP2D6 inhibitor and can reduce conversion of tramadol to its more potent active metabolite, which may weaken analgesia. It also adds sedative and anticholinergic effects to opioid CNS depression.
How serious is the interaction between Diphenhydramine and Tramadol?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for reduced pain relief and for excessive sedation or confusion. Consider a non-sedating antihistamine or an alternative analgesic if the combination is needed regularly.
What other medicines interact with Tramadol?
MediHelp also lists interactions of Tramadol with, for example, Isocarboxazid, Olanzapine / samidorphan, Phenelzine. The full list is on the Tramadol page.
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