Duloxetine with Bupropion Interaction Details

Brand Names Associated with Duloxetine

Brand Names Associated with Bupropion

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

Interaction Effect

Increased exposure of CYP2D6 substrates; increased risk of seizure

Interaction Summary

BuPROPion is associated with a dose-related risk of seizures and when used concomitantly with other seizure threshold-lowering agents there is an increased risk. Additionally, coadministration of buPROPion (a CYP2D6 inhibitor) and a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Initiate a CYP2D6 substrate at the lower end of the dose range and titrate gradually. If buPROPion is added to an existing regimen with a CYP2D6 substrate, consider decreasing the substrate dose, especially if it has a narrow therapeutic index. Use extreme caution when coadministering buPROPion with drugs that lower seizure threshold; use a low initial buPROPion dose and titrate slowly to reduce the risk of seizures. If a patient experiences a seizure, discontinue buPROPion and do not reinitiate[1][2].

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

BuPROPion is associated with a dose-related risk of seizures and when used concomitantly with other seizure threshold-lowering agents there is an increased risk. Additionally, concurrent administration of buPROPion (a CYP2D6 inhibitor) and a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. The CYP2D6 substrate should be initiated at the lower end of the dose range and titrated gradually. If buPROPion is added to an existing regimen with a CYP2D6 substrate, consider decreasing the CYP2D6 substrate dose, especially if it has a narrow therapeutic index. Use extreme caution when coadministering buPROPion with drugs that lower seizure threshold; begin with a low initial buPROPion dose and titrate slowly to reduce the risk of seizures. If a patient experiences a seizure, discontinue buPROPion and do not reinitiate[1][2].

Mechanism Of Interaction

Inhibition of CYP2D6-mediated metabolism of CYP2D6 substrates by buPROPion; additive lowering of the seizure threshold

Literature Reports

A) Coadministration of buPROPion 150 mg twice daily and a single dose of desipramine 50 mg (a CYP2D6 substrate) in healthy volunteers who were extensive CYP2D6 metabolizers (n=15) resulted in a 2-fold and 5-fold increase in desipramine Cmax and AUC respectively. The effect persisted for 7 days following the last dose of buPROPion [3].

References

1 ) Product Information: APLENZIN(R) oral extended-release tablets, bupropion hydrobromide oral extended-release tablets. Bausch Health US LLC (per FDA), Bridgewater, NJ, 2021.

2 ) Product Information: WELLBUTRIN XL(R) oral extended-release tablets, bupropion HCl oral extended-release tablets. Bausch Health US, LLC (per FDA), Bridgewater, NJ, 2021.

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

Duloxetine Overview

• Duloxetine is used to treat depression in adults and generalized anxiety disorder (GAD; excessive worry and tension that disrupts daily life and lasts for 6 months or longer) in adults and children 7 years of age and older. Duloxetine is also used to treat pain and tingling caused by diabetic neuropathy (damage to nerves that can develop in people who have diabetes) in adults and fibromyalgia (a long-lasting condition that may cause pain, muscle stiffness and tenderness, tiredness, and difficulty falling asleep or staying asleep) in adults and children 13 years of age and older. It is also used to treat ongoing bone or muscle pain such as lower back pain or osteoarthritis (joint pain or stiffness that may worsen over time) in adults. Duloxetine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It works by increasing the amounts of serotonin and norepinephrine, natural substances in the brain that help maintain mental balance and stop the movement of pain signals in the brain.

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.

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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.