Cyclobenzaprine and Milnacipran interaction
Cyclobenzaprine and Milnacipran: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Cyclobenzaprine (TONMYA) label · effective 2026-08-14
Immediately discontinue concomitant treatment with TONMYA and a serotonergic agent if serotonin syndrome symptoms occur and initiate supportive symptomatic treatment.
Treatment with TONMYA and any concomitant serotonergic agents should be discontinued immediately if serotonin syndrome symptoms occur and supportive symptomatic treatment should be initiated.
Postmarketing cases of serotonin syndrome have been reported with the concomitant use of oral cyclobenzaprine and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors [see Warnings and Precautions (5.2) ] .
If serotonin syndrome symptoms occur with the use of other serotonergic drugs, immediately discontinue TONMYA.
Other serotonergic Drugs: Serotonin syndrome has been reported ( 5.2 , 7 )
From the Milnacipran (Milnacipran Hydrochloride) label · effective 2026-03-19
• Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents, but also when taken alone.
If concomitant use of milnacipran hydrochloride with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, tramadol, meperidine, methadone, lithium, tryptophan, buspirone, amphetamines, and St.
If it occurs, discontinue milnacipran hydrochloride and any other serotonergic agents, and initiate supportive treatment ( 5.2 ).
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Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.