Drug interactions
Imipramine + Tramadol
Severity: Major
Imipramine and Tramadol: 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
Both drugs raise synaptic serotonin and norepinephrine, so combining them increases the risk of serotonin syndrome. Both also lower the seizure threshold and cause sedation. Imipramine, a CYP2D6 substrate, may also compete with tramadol for CYP2D6 metabolism, altering tramadol's analgesic effect.
What this interaction means in plain words
Imipramine and Tramadol 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.
Imipramine belongs to Central Nervous System; Tramadol belongs to Musculoskeletal.
Why it happens
Additive serotonergic activity and seizure threshold lowering, with CYP2D6 competition.
What to do
Avoid the combination if possible, or use low doses and monitor for agitation, tremor, hyperthermia, clonus and seizures. Stop both drugs if serotonin syndrome develops.
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 Tramadol
- Isocarboxazid + Tramadol Contraindicated
- Olanzapine / samidorphan + Tramadol Contraindicated
- Phenelzine + Tramadol Contraindicated
- Procarbazine + Tramadol Contraindicated
- Rasagiline + Tramadol Contraindicated
- Safinamide + Tramadol Contraindicated
Other interactions of Imipramine
- Dronedarone + Imipramine Contraindicated
- Imipramine + Isocarboxazid Contraindicated
- Imipramine + Phenelzine Contraindicated
- Imipramine + Pimozide Contraindicated
- Imipramine + Rasagiline Contraindicated
- Imipramine + Safinamide Contraindicated
Frequently asked questions
Can I take Imipramine with Tramadol?
MediHelp rates the interaction as major. Imipramine and Tramadol 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 drugs raise synaptic serotonin and norepinephrine, so combining them increases the risk of serotonin syndrome. Both also lower the seizure threshold and cause sedation. Imipramine, a CYP2D6 substrate, may also compete with tramadol for CYP2D6 metabolism, altering tramadol's analgesic effect.
How serious is the interaction between Imipramine and Tramadol?
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 the combination if possible, or use low doses and monitor for agitation, tremor, hyperthermia, clonus and seizures. Stop both drugs if serotonin syndrome develops.
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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