Management of Wellbutrin (Bupropion)-Induced Rash
Discontinue bupropion immediately upon recognition of a rash and do not rechallenge with the medication. 1
Immediate Actions
Stop bupropion as soon as rash develops, as this represents a hypersensitivity reaction that can progress to serious conditions including erythema multiforme, drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, or Stevens-Johnson syndrome. 1, 2
- The FDA drug label explicitly instructs patients to discontinue bupropion and consult a healthcare provider if they develop skin rash, pruritus, hives, chest pain, edema, or shortness of breath during treatment. 1
- Rash occurred in 5% of patients taking bupropion sustained-release 300 mg/day and 4% at 400 mg/day in controlled trials, compared to 1% with placebo. 1
Symptomatic Treatment
Initiate antihistamine therapy with cetirizine 10 mg daily for management of pruritus and urticaria while tapering bupropion. 3
- In documented cases, complete resolution of hives and pruritus occurred after bupropion discontinuation and antihistamine treatment. 3
- For severe hypersensitivity reactions including DRESS syndrome with systemic involvement (hepatitis, eosinophilia, myositis), prolonged systemic corticosteroid therapy may be required. 4
Discontinuation Strategy
Taper bupropion over 7 days rather than abrupt cessation to minimize withdrawal symptoms, though the urgency of the allergic reaction takes priority. 3
- Monitor closely during the taper period for progression of dermatologic symptoms. 2
- Watch for systemic symptoms including fever, arthralgia, myalgia, and signs of serum sickness, which suggest delayed hypersensitivity. 1
Critical Monitoring Parameters
Aggressively follow up patients with any rash or urticaria, as delayed allergic reactions can appear 2 or more weeks after bupropion initiation (median onset day 28 in reported cases). 3, 2
- The risk of delayed hypersensitivity may be highest in males aged 17-40 years and those with a history of allergic reactions. 3
- Erythema multiforme can progress to life-threatening conditions including Stevens-Johnson syndrome or toxic epidermal necrolysis. 1, 2
- In patients with psoriasis, bupropion can trigger erythrodermic psoriasis, a potentially life-threatening exacerbation. 5
Alternative Antidepressant Selection
Transition to a different antidepressant class such as venlafaxine or an SSRI, as rechallenge with bupropion is contraindicated. 3
- Complete resolution of allergic symptoms should occur within days to weeks after bupropion discontinuation and appropriate symptomatic treatment. 3, 4
- Do not use other formulations of bupropion (SR, XL, or combination products like naltrexone-bupropion) as cross-reactivity is expected. 1
Special Considerations
Severe hypersensitivity reactions occur in approximately 0.1% of patients taking bupropion at recommended doses. 6
- DRESS syndrome with multisystem involvement (hepatitis, obstructive lung disease, myositis) has been reported and requires aggressive management with systemic corticosteroids. 4
- The FDA black box warning emphasizes that hypersensitivity reactions can include serum sickness-like symptoms with arthralgia, myalgia, and fever with rash. 1