From the FDA Drug Label
7.2 Potential for Bupropion Hydrochloride Extended-Release Tablets (XL) to Affect Other Drugs 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 is a substrate of CYP2D6 and bupropion is a CYP2D6 inhibitor.
- When used concomitantly with bupropion, it may be necessary to decrease the dose of fluoxetine, particularly for drugs with a narrow therapeutic index.
- There is no information about naltrexone or topiramate in the provided drug label that suggests a direct interaction with bupropion or fluoxetine.
- Therefore, fluoxetine can be taken with bupropion but the dose of fluoxetine may need to be adjusted.
- The FDA drug label does not provide information about taking fluoxetine with naltrexone or topiramate. 1
From the Research
Fluoxetine can be taken with naltrexone, topiramate, or bupropion (Wellbutrin), but each combination requires careful medical supervision due to potential interactions. When combining fluoxetine with bupropion, there is an increased risk of seizures and serotonin syndrome, as seen in a case report where cyproheptadine was used to treat serotonin syndrome in a patient taking fluoxetine and bupropion 2. The fluoxetine-naltrexone combination is commonly used for weight management or addiction treatment and is generally well-tolerated, though liver function should be monitored. Fluoxetine with topiramate may enhance weight loss effects but can increase the risk of cognitive side effects like memory problems or confusion, as topiramate is known to have a unique pharmacokinetic profile with potential for drug interactions due to induction of its metabolism 3. All these combinations can potentially increase side effects such as dizziness, drowsiness, dry mouth, and insomnia. It's essential to start with lower doses when combining these medications and gradually increase as tolerated. These combinations are sometimes intentionally prescribed for treatment-resistant depression, eating disorders, or addiction disorders, but should only be initiated under close medical supervision with regular follow-up appointments to monitor for adverse effects, as suggested by a study on the safety assessment of combination therapies for obesity treatment 4. A study from 2010 also found that combination of antidepressant medications from treatment initiation can be effective, with fluoxetine and bupropion being one of the combinations used 5. However, the most recent study from 2023 highlights the importance of careful management of serotonin syndrome when combining fluoxetine with other medications 2. Key points to consider when prescribing these combinations include:
- Monitoring for serotonin syndrome and seizures when combining fluoxetine with bupropion
- Regular liver function tests when using fluoxetine with naltrexone
- Assessing cognitive function and adjusting doses as needed when combining fluoxetine with topiramate
- Gradually increasing doses and monitoring for side effects when initiating any of these combinations.