Naltrexone and bupropion and Nortriptyline interaction

Naltrexone and bupropion 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
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 Naltrexone and bupropion (Contrave Extended-Release) label · effective 2025-11-10

Moderate

…(sulfonylureas and meglitinides) that may cause hypoglycemia concomitant administration of medications that may lower the seizure threshold, including other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, systemic steroids Recommendations for Reducing the Risk of Seizure: Clinical experience with bupropion suggests that the risk of seizure may…

Warnings and precautionsby drug classView label on DailyMed
Moderate

Drugs Metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of antidepressants, (e.g., selective serotonin reuptake inhibitors and many tricyclics), antipsychotics (e.g., haloperidol, risperidone and thioridazine), beta-blockers (e.g., metoprolol) and Type 1C antiarrhythmics (e.g., propafenone and flecainide).

Drug interactionsby drug classView label on DailyMed
Moderate

Coadministration of CONTRAVE with drugs that are metabolized by CYP2D6 isozyme including certain antidepressants (SSRIs and many tricyclics), antipsychotics (e.g., haloperidol, risperidone and thioridazine), beta-blockers (e.g., metoprolol) and Type 1C antiarrhythmics (e.g., propafenone and flecainide), should be approached with caution and should be initiated…

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.