Are Wellbutrin (bupropion) SR (Sustained Release) and XL (Extended Release) interchangeable?

Wellbutrin SR and XL Are Not Interchangeable

Wellbutrin SR (Sustained Release) and XL (Extended Release) formulations are not interchangeable due to their different pharmacokinetic profiles and dosing schedules. While they contain the same active ingredient (bupropion), their release mechanisms and dosing requirements differ significantly 1.

Key Differences Between Wellbutrin SR and XL

Pharmacokinetic Differences

• SR (Sustained Release):

  • Administered twice daily (BID) 2
  • Peak plasma concentration (Tmax) occurs at approximately 3 hours 3
  • Requires 12-hour interval between doses

• XL (Extended Release):

  • Administered once daily (QD) 3
  • Peak plasma concentration (Tmax) occurs at approximately 5 hours 3
  • Provides 24-hour coverage with a single dose

Clinical Implications of These Differences

1. Dosing Schedule:

   • SR formulation: 150 mg twice daily (morning and evening) 2
   • XL formulation: 150-300 mg once daily (morning only) 2

2. Bioequivalence:

   • While the formulations are bioequivalent in terms of total systemic exposure, they have different absorption rates and peak concentration times 3
   • This affects the drug's concentration throughout the day and potentially its side effect profile

3. Therapeutic Considerations:

   • Switching between formulations requires dosage adjustment and monitoring
   • Abrupt substitution may lead to altered efficacy or increased side effects

Clinical Decision-Making Algorithm

When considering which formulation to use:

1. For patients requiring twice-daily dosing:

   • Use SR formulation (150 mg BID)
   • Consider for patients who need more even coverage throughout the day

2. For patients preferring once-daily dosing:

   • Use XL formulation (300 mg QD)
   • Better for adherence and convenience

3. When switching between formulations:

   • Convert total daily dose (e.g., 300 mg total daily dose remains 300 mg)
   • Adjust dosing schedule (SR: divide into two doses; XL: give as single dose)
   • Monitor for efficacy and side effects for 1-2 weeks after switching

Important Cautions and Considerations

• Seizure risk: Both formulations carry a dose-related seizure risk; abrupt changes in formulation could potentially affect seizure threshold 1

• Side effect profile: Common side effects include dry mouth, insomnia, headache, nausea, and anxiety with both formulations, but the timing of these effects may differ based on the release profile 1

• Specific patient scenarios:

  • Patients with adherence issues may benefit from XL (once-daily dosing)
  • Patients with sensitivity to peak drug levels may tolerate SR better (less pronounced peaks)

• Hypersensitivity reactions: There have been case reports of patients developing hypersensitivity to one formulation but tolerating another 4, suggesting that the excipients or release mechanisms may play a role in some adverse reactions

In summary, while both formulations contain the same active ingredient, their different pharmacokinetic profiles and dosing requirements make them non-interchangeable without appropriate clinical consideration and dosage adjustment.