What should I do if I develop a skin rash while taking Wellbutrin (bupropion)?

Wellbutrin Skin Rash Management

If you develop a skin rash while taking Wellbutrin (bupropion), stop the medication immediately and contact your healthcare provider, as this can represent a serious allergic reaction requiring prompt discontinuation. 1

Immediate Assessment Required

When a rash develops on Wellbutrin, you must first determine severity:

• Assess for severe features immediately: Look for blistering, skin sloughing, mucosal involvement (mouth, eyes, genitals), facial or tongue swelling, or respiratory symptoms 2
• These severe features indicate Stevens-Johnson syndrome, toxic epidermal necrolysis, or anaphylaxis and require immediate emergency care 2
• Evaluate body surface area affected and presence of systemic symptoms such as fever, malaise, joint pain, or muscle aches 2, 3

Critical Action: Discontinue Bupropion

The FDA label explicitly states to stop bupropion and call your healthcare provider right away if you develop rash, itching, hives, fever, swollen lymph glands, painful mouth sores, swelling of lips or tongue, chest pain, or breathing difficulty 1. These are signs of a serious allergic reaction that can progress to life-threatening conditions.

Understanding Bupropion-Associated Rashes

Bupropion can cause several types of skin reactions:

• Delayed hypersensitivity reactions including urticaria and pruritus, which may appear 2-4 weeks after starting the medication 4
• Erythema multiforme, a potentially serious condition requiring immediate drug discontinuation 5
• Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, which includes fever, organ involvement (hepatitis, lung disease, myositis), and eosinophilia 3
• Subacute cutaneous lupus erythematosus, presenting as photosensitive annular plaques 6
• Serum sickness, with fever, myalgia, arthralgia, and rash developing within 24 hours to days 7

Treatment Based on Severity

For Mild Rashes (if medication already discontinued):

• Apply topical corticosteroids: Use 1-2.5% hydrocortisone or moderate-potency topical steroids to affected areas 8
• Oral antihistamines: Non-sedating agents like cetirizine, loratadine, or fexofenadine for daytime; sedating antihistamines like diphenhydramine for nighttime pruritus 8, 4
• Emollients: Apply at least once daily to prevent xerosis 8
• Acetaminophen or ibuprofen for associated fever or discomfort 8

For Severe Reactions:

• Immediate hospitalization for any signs of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome 2
• IV methylprednisolone 1-2 mg/kg for severe cutaneous reactions, with slow taper when toxicity resolves 2
• Prolonged systemic corticosteroid therapy may be required for DRESS syndrome with complete resolution of symptoms 3
• Burn unit admission may be necessary for extensive skin sloughing 2

Critical Pitfalls to Avoid

• Never continue bupropion through a rash: Unlike some mild antibiotic rashes that can be monitored, bupropion-induced rashes require immediate discontinuation due to risk of progression to severe reactions 1, 5
• Do not rechallenge with bupropion after a significant allergic reaction 1
• Avoid hot showers and excessive soap, which worsen skin irritation 8
• Do not apply topical acne medications or retinoids, as they cause further irritation 8
• Recognize that delayed reactions can occur 2-4 weeks after starting bupropion, so temporal association may not be immediately obvious 4

Special Populations at Higher Risk

Males aged 17-40 years and those with a history of allergic reactions may be at highest risk for delayed hypersensitivity reactions to bupropion 4.

Alternative Treatment

After bupropion discontinuation and rash resolution, transition to an alternative antidepressant such as an SSRI or SNRI (e.g., venlafaxine) that does not cross-react 4. Do not attempt to restart bupropion.