Drug interactions
Amitriptyline + Cyclobenzaprine
Severity: Major
Amitriptyline and Cyclobenzaprine: 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
Cyclobenzaprine is structurally a tricyclic antidepressant, so combining it with amitriptyline duplicates tricyclic effects. This raises the risk of serotonin syndrome, anticholinergic toxicity, sedation and QT or conduction abnormalities. Overdose-type toxicity can occur even at normal doses in susceptible patients.
What this interaction means in plain words
Amitriptyline and Cyclobenzaprine 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.
Amitriptyline belongs to Central Nervous System; Cyclobenzaprine belongs to Musculoskeletal.
Why it happens
Additive serotonergic, anticholinergic and cardiac sodium channel effects from two tricyclic structures, with possible CYP competition.
What to do
Avoid the combination where possible and choose a non-tricyclic muscle relaxant. If used, monitor for serotonin toxicity, anticholinergic effects and ECG 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 Cyclobenzaprine
- Cyclobenzaprine + Isocarboxazid Contraindicated
- Cyclobenzaprine + Linezolid Contraindicated
- Cyclobenzaprine + Phenelzine Contraindicated
- Cyclobenzaprine + Safinamide Contraindicated
- Cyclobenzaprine + Selegiline Contraindicated
- Cyclobenzaprine + Selegiline transdermal Contraindicated
Other interactions of Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide Contraindicated
Frequently asked questions
Can I take Amitriptyline with Cyclobenzaprine?
MediHelp rates the interaction as major. Amitriptyline and Cyclobenzaprine 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. Cyclobenzaprine is structurally a tricyclic antidepressant, so combining it with amitriptyline duplicates tricyclic effects. This raises the risk of serotonin syndrome, anticholinergic toxicity, sedation and QT or conduction abnormalities. Overdose-type toxicity can occur even at normal doses in susceptible patients.
How serious is the interaction between Amitriptyline and Cyclobenzaprine?
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 where possible and choose a non-tricyclic muscle relaxant. If used, monitor for serotonin toxicity, anticholinergic effects and ECG changes.
What other medicines interact with Cyclobenzaprine?
MediHelp also lists interactions of Cyclobenzaprine with, for example, Isocarboxazid, Linezolid, Phenelzine. The full list is on the Cyclobenzaprine page.
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