From the FDA Drug Label
Drugs Metabolized by CYP2D6 Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors Therefore, coadministration of bupropion hydrochloride extended-release tablets (XL) with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline)
Fluoxetine can be given with bupropion, but it may be necessary to decrease the dose of fluoxetine, particularly for drugs with a narrow therapeutic index, as bupropion is a CYP2D6 inhibitor and fluoxetine is a substrate of CYP2D6 1.
- Use low initial doses and increase the dose gradually.
- Monitor for increased exposure of fluoxetine and adjust the dose as needed.
From the Research
Fluoxetine and bupropion can be used together, but with caution and close monitoring due to the potential risk of serotonin syndrome, as reported in a case study from 2. When considering the combination of fluoxetine and bupropion, it's essential to weigh the benefits against the potential risks. The combination may be prescribed to enhance antidepressant effects or counteract side effects like sexual dysfunction.
- Typical dosing might include fluoxetine 20-40 mg daily with bupropion 150-300 mg daily, though dosages should be individualized based on patient response and tolerance.
- Patients should be aware of the increased risk of seizures and serotonin syndrome, a potentially serious condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and hyperthermia.
- The pharmacological basis for this interaction is that fluoxetine inhibits the CYP2D6 enzyme that metabolizes bupropion, potentially increasing bupropion levels in the blood, as noted in 2.
- A more recent study from 3 highlights the importance of careful monitoring and prompt treatment of serotonin syndrome, which can be a life-threatening condition.
- Patients should report any unusual symptoms promptly, especially agitation, tremors, excessive sweating, or confusion, and starting with lower doses and gradually increasing can help minimize adverse effects.
- The use of bupropion in combination with fluoxetine has been explored in various studies, including one from 4, which found that approximately 60% of patients with major depressive disorder resistant to fluoxetine experienced a full or partial response to bupropion.
- However, the most recent and highest quality study 3 suggests that careful monitoring and management of potential side effects are crucial when using this combination.