Cyclobenzaprine and Desipramine interaction

Cyclobenzaprine and Desipramine: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

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

Major

Hyperpyretic crisis seizures and deaths have occurred in patients who received cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitors drugs.

Contraindicationsby drug classView label on DailyMed
Major

Immediately discontinue concomitant treatment with TONMYA and a serotonergic agent if serotonin syndrome symptoms occur and initiate supportive symptomatic treatment.

Warnings and precautionsby drug classView label on DailyMed
Major

Treatment with TONMYA and any concomitant serotonergic agents should be discontinued immediately if serotonin syndrome symptoms occur and supportive symptomatic treatment should be initiated.

Warnings and precautionsby drug classView label on DailyMed
Major

Based on its structural similarity to TCAs, concomitant use of TONMYA with: MAO inhibitors may be life-threatening [see Contraindications (4) ] , Alcohol, barbiturates, and other CNS depressants may increase the risk of adverse reactions associated with these drugs, Tramadol may increase the seizure risk, Guanethidine or other similar acting drugs may block the…

Drug interactionsby drug classView label on DailyMed
Major

If serotonin syndrome symptoms occur with the use of other serotonergic drugs, immediately discontinue TONMYA.

Drug interactionsby drug classView label on DailyMed

From the Desipramine (Norpramin) label · effective 2025-07-03

Minor

…Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with serotonin norepinephrine re-uptake inhibitors (SNRIs) and SSRIs, including NORPRAMIN, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St.

Warningsby drug classView label on DailyMed
Minor

If concomitant use of NORPRAMIN with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St.

Warningsby drug classView label on DailyMed

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Not 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.