Nefazodone and Nortriptyline interaction

Nefazodone 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 Nefazodone (Nefazodone Hydrochloride) label · effective 2025-07-31

Major

Anyone considering the use of nefazodone hydrochloride tablets 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
Major

Nefazodone hydrochloride tablets are also contraindicated in patients who have demonstrated hypersensitivity to nefazodone hydrochloride, its inactive ingredients, or other phenylpiperazine antidepressants.

Contraindicationsby drug classView label on DailyMed
Major

Severe hyperthermia and seizures, sometimes fatal, have been reported in association with the combined use of tricyclic antidepressants and MAOIs.

Warningsby drug classView label on DailyMed
Minor

Such individuals are referred to commonly as “poor metabolizers” of drugs such as debrisoquin, dextromethorphan, and the tricyclic antidepressants.

Drug interactionsby 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
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

The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide).

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.