From the Guidelines
Yes, there is a significant interaction between bupropion and methylene blue that can potentially cause serotonin syndrome, a serious and potentially life-threatening condition. These medications should not be used together. Bupropion is an antidepressant that weakly inhibits the reuptake of serotonin, while methylene blue is a dye used for medical purposes that is a potent monoamine oxidase inhibitor (MAOI) 1. When combined, they can lead to excessive serotonin levels in the brain. If you are taking bupropion and need methylene blue for a medical procedure, bupropion should ideally be stopped at least 2 weeks before methylene blue administration. If emergency use of methylene blue is required while on bupropion, close monitoring for signs of serotonin syndrome is essential, including confusion, agitation, muscle rigidity, fever, sweating, shivering, tremor, and diarrhea. If methylene blue treatment has been given, bupropion should not be restarted until at least 24 hours after the last dose of methylene blue. This interaction occurs because both medications affect serotonin metabolism through different mechanisms, creating a dangerous synergistic effect, as methylene blue administration may precipitate serotonin syndrome in individuals receiving selective serotonin reuptake inhibitors and other serotonergic antidepressants, such as bupropion 1. Key considerations for the use of methylene blue include:
- Caution in patients with G6PD deficiency, as methylene blue may induce hemolysis and worsen methemoglobinemia
- Avoidance in pregnant women due to concerns about teratogenicity and possible intestinal atresia
- Use with caution in patients with renal failure and in anesthetized patients, as methylene blue may inhibit guanylate cyclase and decrease nitric oxide-mediated vasodilatation, leading to systemic and pulmonary hypertension 1.
From the FDA Drug Label
Do not start bupropion hydrochloride extended-release tablets (XL) in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg per kg with bupropion hydrochloride extended-release tablets (XL) are unclear.
Interaction between bupropion and methylene blue:
- There is a potential interaction between bupropion and methylene blue, particularly with intravenous methylene blue, which can increase the risk of hypertensive reactions.
- The use of bupropion with intravenous methylene blue is contraindicated.
- The risk of interaction with non-intravenous routes of methylene blue administration is unclear. 2
From the Research
Interaction between Bupropion and Methylene Blue
- There is evidence to suggest a potential interaction between bupropion and methylene blue, which can increase the risk of serotonin syndrome 3, 4.
- A case report describes a patient taking fluoxetine and bupropion who received methylene blue for vasoplegia syndrome, resulting in serotonin syndrome 3.
- Methylene blue has monoamine oxidase inhibiting properties, which can contribute to the development of serotonin syndrome when combined with serotonergic drugs like bupropion 4.
- The combination of bupropion and selective serotonin reuptake inhibitors (SSRIs) has also been reported to cause serotonin syndrome, highlighting the potential for drug-drug interactions involving bupropion 5.
- Drug-drug interactions, including those involving bupropion and methylene blue, can be prevented or minimized by using drug interaction software and collaborating with pharmacists 6, 7.