Fluoxetine and Nortriptyline interaction
Fluoxetine 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.
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.
If serotonin syndrome occurs, consider discontinuation of PROZAC and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )] .
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.
Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with PROZAC or when PROZAC has been recently discontinued ( 5.2 , 7.7 )
From the Nortriptyline (PAMELOR) label · effective 2024-12-04
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.
Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other.
Monoamine Oxidase Inhibitors (MAOIs) ( See CONTRAINDICATIONS , WARNINGS , and DOSAGE AND ADMINISTRATION . ) Serotonergic Drugs ( See CONTRAINDICATIONS , WARNINGS , and DOSAGE AND ADMINISTRATION . )
Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).
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.
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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.