Bupropion with Nortriptyline Interaction Details

Brand Names Associated with Bupropion

Brand Names Associated with Nortriptyline

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 06, 2024

Interaction Effect

Increased plasma levels of nortriptyline

Interaction Summary

Use caution with the concurrent administration of buPROPion (a CYP2D6 inhibitor) and nortriptyline (a CYP2D6 substrate) as this may increase the exposure of the nortriptyline[1]. In a case report, there was a 200% increase in nortriptyline levels when given with buPROPion [2]. Concomitant administration should be initiated at the lower end of the dose range of nortriptyline. If buPROPion is added to an existing regimen with nortriptyline, consideration should be given to reducing the nortriptyline dose [1]. Monitor for nortriptyline toxicity during coadministration.

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concurrent administration of buPROPion (a CYP2D6 inhibitor) and nortriptyline (a CYP2D6 substrate) may increase the exposure of the nortriptyline and should be undertaken with caution. Concomitant administration should be initiated at the lower end of the dose range of nortriptyline. If buPROPion is added to an existing regimen with nortriptyline, consideration should be given to reducing the nortriptyline dose[1]. Monitor for nortriptyline toxicity during coadministration.

Mechanism Of Interaction

Inhibition of CYP2D6-mediated nortriptyline metabolism by buPROPion and its hydroxybupropion metabolite

Literature Reports

A) One patient developed nortriptyline toxicity possibly secondary to buPROPion-induced inhibition of TCA metabolism. An 83-year-old female with a history of recurrent major depression who failed multiple therapies for depression was prescribed nortriptyline. Nortriptyline was initiated at 25 mg at bedtime and titrated to 75 mg at bedtime after several days. Her steady-state nortriptyline plasma level was 96 nanograms/milliliter (ng/mL; 364 nanomoles/L (nmol/L)). buPROPion SR 150 mg twice daily was added to her therapeutic regimen because she was anergic and lacking motivation. Two weeks later she was reported to have fallen three times in several days and was confused and lethargic. Nortriptyline and buPROPion were held and her nortriptyline level was 274 ng/mL (1040 nmol/L), a 200% increase. Nortriptyline was reinitiated several days later and titrated from 25 mg to 75 mg at bedtime. Plasma nortriptyline levels were 98 ng/mL (372 nmol/L) . BuPROPion SR 100 mg/day was reinitiated and ten days later her plasma nortriptyline level was 153 ng/mL (a 50% increase; 581 nmol/L). It was reported that she was becoming unsteady and lethargic again. BuPROPion was discontinued and nortriptyline was maintained at a dose of 75 mg/day. A repeat plasma level six weeks later was 64 ng/mL (243 nmol/L) [2].

B) Coadministration of buPROPion 150 mg twice daily and a single dose of desipramine 50 mg (a CYP2D6 substrate) in healthy volunteers who were extensive 2D6 metabolizers (n=15) resulted in a 2-fold, 5-fold, and 2-fold increase in desipramine Cmax, AUC, and t1/2, respectively. The effect persisted for 7 days following the last dose of buPROPion [1].

References

1 ) Product Information: WELLBUTRIN SR(R) oral sustained-release tablets, bupropion HCl oral sustained-release tablets. GlaxoSmithKline (per FDA), Research Triangle Park, NC, 2013.

2 ) Weintraub D: Nortriptyline toxicity secondary to interaction with bupropion sustained-release. Depress Anxiety 2001; 13(1):50-52.

Bupropion Overview

• Bupropion (Aplenzin, Wellbutrin, Wellbutrin SR, Wellbutrin XL) is used to treat depression. Bupropion (Aplenzin, Wellbutrin XL) is also used to treat seasonal affective disorder (SAD; episodes of depression that occur at the same time each year [usually in the fall and winter but rarely may occur in the spring or summer months]). Bupropion (Zyban) is used to help people stop smoking. Bupropion is in a class of medications called antidepressants. It works by increasing certain types of activity in the brain.

Nortriptyline Overview

• Nortriptyline is used to treat depression. Nortriptyline is in a group of medications called tricyclic antidepressants. It works by increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.