How do I switch from Wellbutrin (bupropion) XL to SR?

Switching from Wellbutrin XL to SR

When switching from Wellbutrin XL to SR, give the same total daily dose when possible—if a patient is on 300 mg XL once daily, switch directly to 150 mg SR twice daily (300 mg total) without a washout period or dose adjustment. 1

Direct Switching Strategy

• The FDA label explicitly states that when switching between bupropion formulations, you should give the same total daily dose when possible 1
• No tapering or washout period is required when switching between XL and SR formulations 1
• All three bupropion formulations (IR, SR, and XL) are bioequivalent in terms of systemic exposure to bupropion, meaning they deliver the same amount of active drug to the body 2, 3

Practical Conversion Examples

For patients on 300 mg XL once daily:

• Switch directly to bupropion SR 150 mg twice daily (morning and early afternoon) 4, 1
• The total daily dose remains 300 mg 1

For patients on 150 mg XL once daily:

• Switch directly to bupropion SR 150 mg once daily in the morning 1
• Alternatively, consider 75 mg SR twice daily if available, though this is less common 4

Critical Timing Considerations for SR Formulation

• The first dose of SR should be taken in the morning 4
• The second dose must be administered before 3 PM to minimize insomnia risk 4, 5
• This timing is crucial because bupropion has activating properties that can interfere with sleep if taken late in the day 4

Monitoring During the Switch

• Close monitoring is necessary in the first weeks after the medication switch, particularly when switching between brand and generic formulations 4
• Historical bioequivalence issues with some generic bupropion SR formulations mean that some patients may experience loss of antidepressant effect when switching 4
• Schedule follow-up within 2 weeks to assess for any changes in efficacy or side effects 5
• Monitor for neuropsychiatric adverse effects, especially in patients younger than 24 years 4, 5

Pharmacokinetic Differences to Anticipate

• The SR formulation has a shorter time to peak concentration (Tmax approximately 3 hours) compared to XL (Tmax approximately 5 hours) 3
• Despite this difference in absorption profile, the formulations are bioequivalent and deliver the same systemic exposure 2, 3
• Patients may notice slightly different timing of effects or side effects due to the different release profiles, but overall efficacy should remain equivalent 3

Common Pitfalls to Avoid

• Do not reduce the total daily dose when switching unless there are specific safety concerns 1
• Do not introduce a washout period between formulations—this is unnecessary and may lead to symptom recurrence 1
• Ensure patients understand the twice-daily dosing schedule and the importance of the before-3-PM timing for the second dose 4, 5
• Be aware that some patients may have been on generic XL formulations that were not truly bioequivalent, so switching to SR may actually improve response in these cases 4

Special Population Considerations

For patients with hepatic impairment:

• If moderate to severe hepatic impairment (Child-Pugh score 7-15), the maximum total daily dose should not exceed 150 mg, regardless of formulation 4, 1
• This would mean 150 mg SR once daily rather than twice daily 1

For patients with renal impairment:

• Reduce the total daily dose by half for moderate to severe renal impairment (GFR <90 mL/min) 4, 1
• For a patient on 300 mg XL, this would mean switching to 75 mg SR twice daily (150 mg total) 4

For older adults:

• Consider starting at approximately 50% of the standard dose and titrating more gradually 4
• This may mean switching from 300 mg XL to 150 mg SR once daily initially, then increasing to twice daily if tolerated 4

Reasons Patients May Prefer SR Over XL

• Better adherence may occur with once-daily XL dosing, but some patients prefer SR for more flexible dosing 4, 6
• SR allows for dose adjustments throughout the day if side effects occur 4
• Some patients report better tolerability with the SR formulation due to its different release profile 3
• Cost considerations may favor SR in some insurance formularies 7