Doxepin and Nortriptyline interaction

Doxepin 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 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

Close supervision and careful adjustment of the dosage are required when Pamelor is used with other anticholinergic drugs and sympathomimetic drugs.

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

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

From the Doxepin (Silenor) label · effective 2026-04-21

Moderate

Although behaviors such as "sleep-driving" may occur with hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with hypnotics appears to increase the risk of such behaviors, as does the use of hypnotics at doses exceeding the maximum recommended dose.

Warnings and precautionsby drug classView label on DailyMed
Moderate

When taken with SILENOR, the sedative effects of alcoholic beverages, sedating antihistamines, and other CNS depressants may be potentiated [s ee Warnings and Precautions (5.2) and Drug Interactions (7.3 , 7.4) ].

Warnings and precautionsby drug classView label on DailyMed

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

Open in the checker

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.