Cyclobenzaprine and Venlafaxine interaction

Cyclobenzaprine and Venlafaxine: 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

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) ] .

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 Venlafaxine (Venlafaxine Hydrochloride) label · effective 2025-01-31

Major

If concomitant use of Venlafaxine Extended Release Tablets with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

Warnings and precautionsby drug classView label on DailyMed
Major

If concomitant use of Venlafaxine Extended Release Tablets with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Serotonin Syndrome: Sertotonin syndrome has been reported with SSRIs and SNRIs, including Venlafaxine Extended Release Tablets, both when taken alone, but especially when co-administered with other serotonergic agents.

Warnings and precautionsby drug classView label on DailyMed
Moderate

The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, busipirone, amphetamines, and St.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Monoamine Oxidase Inhibitors (MAOIs) [See Dosage and Administration ( 2.6 and 2.7 ), Contraindications ( 4.1 ), and Warnings and Precautions ( 5.2 ) . ] 7.10 Other Serotonergic Drugs The concomitant use of serotonergic drugs (including other SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St.

Drug interactionsby 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.