Cyclobenzaprine and Phenelzine interaction

Cyclobenzaprine and Phenelzine: 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

Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after discontinuation of a MAO inhibitor.

Contraindicationsby drug classView 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
Major

Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation ( 4 )

Contraindicationsby drug classView label on DailyMed
Major

The concomitant use of TONMYA with MAO inhibitors is contraindicated [see Contraindications (4) ] .

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

From the Phenelzine (phenelzine sulfate) label · effective 2026-05-21

Major

Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain narcotics.

Contraindicationsby drug classView label on DailyMed
Moderate

…hydrochloride amitriptyline hydrochloride perphenazine and amitriptyline hydrochloride clomipramine hydrochloride desipramine hydrochloride imipramine hydrochloride doxepin carbamazepine cyclobenzaprine HCl amoxapine maprotiline HCl trimipramine maleate protriptyline HCl mirtazapine Phenelzine sulfate should be used with caution in combination with antihypertensive…

Warningsnames CyclobenzaprineView 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.