Duloxetine and Nortriptyline interaction

Duloxetine and Nortriptyline: 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 Duloxetine (Cymbalta) label · effective 2025-07-21

Major

Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents, but also when taken alone.

Warnings and precautionsby drug classView label on DailyMed
Major

If concomitant use of CYMBALTA 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
Major

If serotonin syndrome occurs, consider discontinuation of CYMBALTA and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.4 )] .

Drug interactionsby drug classView label on DailyMed
Moderate

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

Warnings and precautionsby drug classView label on DailyMed
Moderate

…Metabolized by CYP2D6 — Co-administration of CYMBALTA with drugs that are extensively metabolized by CYP2D6 and that have a narrow therapeutic index, including certain antidepressants (tricyclic antidepressants [TCAs], such as nortriptyline, amitriptyline, and imipramine), phenothiazines and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached…

Warnings and precautionsby drug classView label on DailyMed

From the Nortriptyline (PAMELOR) label · effective 2024-12-04

Major

Anyone considering the use of nortriptyline hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.

Boxed warningby drug classView label on DailyMed
Moderate

Monoamine Oxidase Inhibitors (MAOIs) ( See CONTRAINDICATIONS , WARNINGS , and DOSAGE AND ADMINISTRATION . ) Serotonergic Drugs ( See CONTRAINDICATIONS , WARNINGS , and DOSAGE AND ADMINISTRATION . )

Drug interactionsby drug classView label on DailyMed
Minor

Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Pamelor, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St.

Warningsby drug classView label on DailyMed
Minor

If concomitant use of Pamelor with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St.

Warningsby drug classView label on DailyMed
Minor

Treatment with Pamelor and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

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.