Bupropion and Cyclobenzaprine interaction

Bupropion and Cyclobenzaprine: 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

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 interactionsnames BupropionView label on DailyMed
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
Moderate

Tricyclic Antidepressant-like Adverse Reactions: TCAs have been reported to produce arrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke.

Warnings and precautionsby drug classView label on DailyMed
Minor

…Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with cyclobenzaprine when used in combination with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors.

Warnings and precautionsby drug classView label on DailyMed
Minor

Tricyclic Antidepressant-like Adverse Reactions Cyclobenzaprine is structurally related to tricyclic antidepressants (TCAs).

Warnings and precautionsby drug classView label on DailyMed

From the Bupropion (BUPROPION HCl ER (XL)) label · effective 2026-02-04

Minor

Additional predisposing conditions include diabetes mellitus treated with oral hypoglycemic drugs or insulin, use of anorectic drugs, excessive use of alcohol, use of benzodiazepines, sedatives/hypnotics, or opiates.

Warnings and precautionsby 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.