From the Guidelines
Starting Champix (varenicline) while a patient is already taking Wellbutrin (bupropion) 300mg/day is generally not recommended due to the potential for increased side effects. Both medications work on similar neurotransmitter systems in the brain and are used for smoking cessation, making concurrent use redundant and potentially risky. Patients should typically choose one smoking cessation medication rather than combining them. If a patient on Wellbutrin wants to switch to Champix, they should discuss with their healthcare provider about gradually tapering off Wellbutrin before starting Champix to avoid withdrawal symptoms and adverse effects. The combination could potentially increase the risk of neuropsychiatric side effects such as agitation, depression, suicidal thoughts, and seizures. Additionally, both medications can cause insomnia and other sleep disturbances, which might be exacerbated when used together. If smoking cessation hasn't been successful with Wellbutrin alone, the healthcare provider should evaluate whether to switch completely to Champix rather than adding it to the existing regimen, as evidence suggests that varenicline may be more effective than bupropion SR, with cessation rates increasing from approximately 12% in control groups to 28% in those using varenicline 1.
Some key points to consider:
- The FDA-approved pharmacotherapy interventions for tobacco dependence in adults are bupropion SR, varenicline, and NRT (including nicotine transdermal patches, lozenges, gum, inhalers, or nasal spray) 1.
- Combining behavioral and pharmacotherapy interventions may increase cessation rates from approximately 8% to 14% compared with usual care or minimal behavioral interventions 1.
- The addition of behavioral support to pharmacotherapy also significantly increased cessation rates from approximately 18% in persons using pharmacotherapy alone to 21% in those using a combination of pharmacotherapy and behavioral support 1.
It's essential to weigh the potential benefits and risks of combining these medications and to consider the individual patient's needs and medical history before making a decision. In general, it's recommended to choose one smoking cessation medication and combine it with behavioral support for the best outcomes, as suggested by the U.S. Preventive Services Task Force recommendation statement 1.
From the FDA Drug Label
Based on varenicline characteristics and clinical experience to date, varenicline has no clinically meaningful pharmacokinetic drug interactions [see Clinical Pharmacology(12.3)]. Varenicline (1 mg twice daily) did not alter the steady-state pharmacokinetics of bupropion (150 mg twice daily) in 46 smokers. The safety of the combination of bupropion and varenicline has not been established
The patient can start Champix (varenicline) while already on Wellbutrin (bupropion) 300mg/day, but it is crucial to note that:
- The pharmacokinetic interaction between varenicline and bupropion is not significant.
- However, the safety of the combination of bupropion and varenicline has not been established 2 2. It is recommended to exercise caution and closely monitor the patient for potential adverse effects when using these medications together.
From the Research
Safety of Combining Varenicline and Bupropion
- The safety of combining varenicline (Champix) and bupropion (Wellbutrin) for smoking cessation has been evaluated in several studies 3, 4, 5.
- A study published in 2022 found that varenicline and bupropion had similar risks of neuropsychiatric adverse events in smokers with major depressive disorder 3.
- Another study published in 2025 found that varenicline was effective for smoking cessation in individuals with current or past major depressive disorder, with no increased risk of neuropsychiatric adverse events compared to bupropion 4.
- A Phase II clinical trial published in 2009 found that combination therapy with varenicline and bupropion SR was effective for smoking cessation, with a 71% 7-day point-prevalent smoking abstinence rate at 3 months and a 58% rate at 6 months 5.
Potential Interactions and Adverse Events
- A study published in 2020 found that varenicline was associated with a lower risk of cardiovascular hospitalization and a lower risk of neuropsychiatric hospitalization compared to nicotine replacement therapy, while bupropion was associated with a lower risk of cardiovascular hospitalization but a higher risk of neuropsychiatric hospitalization 6.
- A pharmacovigilance study published in 2025 found that nicotine replacement therapy, bupropion, and varenicline were associated with various adverse events, including psychiatric, nervous system, and gastrointestinal disorders, with varenicline having a higher risk of serious adverse events associated with psychiatric disorders 7.
Considerations for Patients on Bupropion 300mg/Day
- When considering starting varenicline in a patient already on bupropion 300mg/day, it is essential to weigh the potential benefits of combination therapy against the potential risks of adverse events 5.
- Close monitoring of the patient's mental health and cardiovascular status is recommended, as well as regular follow-up to assess the effectiveness of the treatment and potential side effects 3, 4, 6, 7.