Promethazine and dextromethorphan and Trazodone interaction

Promethazine and dextromethorphan and Trazodone: 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 Trazodone (RALDESY TM) label · effective 2026-09-01

Major

Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone.

Warnings and precautionsby drug classView label on DailyMed
Major

If concomitant use of RALDESY 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

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

Warnings and precautionsby drug classView label on DailyMed
Moderate

Other Serotonergic Drugs Clinical Impact: The concomitant use of serotonergic drugs, including RALDESY and other serotonergic drugs increases the risk of serotonin syndrome.

Drug interactionsby drug classView label on DailyMed
Moderate

Intervention: Patients should be counseled that RALDESY may enhance the response to alcohol, barbiturates, and other CNS depressants.

Drug interactionsby drug classView label on DailyMed

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

Moderate

The impairment may be amplified by 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…

Warningsby drug classView label on DailyMed
Moderate

CNS Depressants – Promethazine may increase, 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…

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.