Drug interactions
Protriptyline + Tramadol
Severity: Major
Protriptyline and Tramadol: 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
Both drugs enhance serotonergic and noradrenergic neurotransmission, so combining them raises the risk of serotonin syndrome. Tricyclic antidepressants may also increase seizure risk with tramadol, and protriptyline as a CYP2D6 substrate and inhibitor may reduce formation of tramadol's active metabolite. Additive sedation can occur as well.
What this interaction means in plain words
Protriptyline 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.
Why it happens
Additive serotonin and norepinephrine reuptake inhibition, additive seizure threshold lowering and CNS depression, with CYP2D6 competition.
What to do
Avoid if possible; if combined use the lowest doses and monitor for agitation, tremor, hyperreflexia, clonus, hyperthermia and seizures. Choose a non-serotonergic analgesic when feasible.
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 Tramadol
- Isocarboxazid + Tramadol Contraindicated
- Olanzapine / samidorphan + Tramadol Contraindicated
- Phenelzine + Tramadol Contraindicated
- Procarbazine + Tramadol Contraindicated
- Rasagiline + Tramadol Contraindicated
- Safinamide + Tramadol Contraindicated
Frequently asked questions
Can I take Protriptyline with Tramadol?
MediHelp rates the interaction as major. Protriptyline 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 enhance serotonergic and noradrenergic neurotransmission, so combining them raises the risk of serotonin syndrome. Tricyclic antidepressants may also increase seizure risk with tramadol, and protriptyline as a CYP2D6 substrate and inhibitor may reduce formation of tramadol's active metabolite. Additive sedation can occur as well.
How serious is the interaction between Protriptyline 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 if possible; if combined use the lowest doses and monitor for agitation, tremor, hyperreflexia, clonus, hyperthermia and seizures. Choose a non-serotonergic analgesic when feasible.
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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