Fluoxetine and Promethazine and dextromethorphan interaction
Fluoxetine 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.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Fluoxetine (Prozac) label · effective 2026-01-08
If concomitant use of PROZAC 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 ( 5.2 )
If concomitant use of PROZAC with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, buspirone, amphetamines, and St.
Use with caution in combination with other drugs that prolong the QT interval ( 4.2 , 5.11 , 7.7 , 7.8 ) 7.1 Monoamine Oxidase Inhibitors (MAOI) [See Dosage and Administration ( 2.9 , 2.10 ), Contraindications ( 4.1 ), and Warnings and Precautions ( 5.2 )] .
Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including PROZAC, both when taken alone, but especially when co-administered with other serotonergic agents.
From the Promethazine and dextromethorphan (Promethazine Hydrochloride and Dextromethorphan Hydrobromide) label · effective 2025-08-08
…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.
…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…
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Open in the checkerNot 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.