Phenelzine and Promethazine and dextromethorphan interaction

Phenelzine and Promethazine and dextromethorphan: 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 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.

Contraindicationsnames Promethazine and dextromethorphanView label on DailyMed
Major

OTC Medications To Avoid Cold and cough preparations (including those containing dextromethorphan) Nasal decongestants (tablets, drops, or spray) Hay-fever medications Sinus medications Asthma inhalant medications Antiappetite medicines Weight-reducing preparations "Pep" pills L-tryptophan containing preparations Also, certain prescription drugs should be avoided.

Warningsnames Promethazine and dextromethorphanView label on DailyMed
Minor

Patients should be warned that the use of the above foods, beverages, or medications may cause a reaction characterized by headache and other serious symptoms due to a rise in blood pressure, with the exception of dextromethorphan which may cause reactions similar to those seen with meperidine.

Warningsnames Promethazine and dextromethorphanView label on DailyMed
Minor

Also, there has been a report of an interaction between phenelzine sulfate and dextromethorphan (ingested as a lozenge) causing drowsiness and bizarre behavior.

Warningsnames Promethazine and dextromethorphanView label on DailyMed

From the Promethazine and dextromethorphan (Promethazine Hydrochloride and Dextromethorphan Hydrobromide) label · effective 2025-08-08

Major

Dextromethorphan should not be used in patients receiving a monoamine oxidase inhibitor (see PRECAUTIONS – Drug Interactions ).

Contraindicationsby drug classView label on DailyMed
Major

Drug Interactions Monoamine Oxidase (MAO) Inhibitors – Hyperpyrexia, hypotension, and death have been reported coincident with the co-administration of monoamine oxidase (MAO) inhibitors and products containing dextromethorphan.

Drug interactionsby drug classView label on DailyMed
Major

Thus, concomitant administration of Promethazine Hydrochloride and Dextromethorphan Hydrobromide Oral Solution and MAO inhibitors should be avoided (see CONTRAINDICATIONS ).

Drug interactionsby drug classView label on DailyMed
Major

…prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine.

Drug interactionsby drug classView label on DailyMed
Moderate

…concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine (see PRECAUTIONS – Information for Patients…

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.