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

Switching from Wellbutrin SR to XL

When switching from Wellbutrin SR to XL, give the same total daily dose when possible. 1

Direct Conversion Strategy

The FDA-approved approach is straightforward:

• If currently taking bupropion SR 150 mg twice daily (300 mg total), switch directly to bupropion XL 300 mg once daily in the morning 1
• If currently taking bupropion SR 150 mg once daily (150 mg total), switch directly to bupropion XL 150 mg once daily in the morning 1
• No titration period or dose adjustment is required during the switch 1

Bioequivalence and Formulation Differences

The switch is seamless because:

• All three bupropion formulations (IR, SR, and XL) are bioequivalent in terms of systemic exposure to bupropion 2, 3, 4
• The primary difference is absorption kinetics: XL has a Tmax of approximately 5 hours versus SR's Tmax of approximately 3 hours 4
• Both formulations produce the same active metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion) with similar steady-state profiles 4

Timing Considerations

Administer bupropion XL once daily in the morning 1:

• XL can be taken with or without food 1
• The tablet must be swallowed whole and not crushed, divided, or chewed 1
• Morning administration leverages bupropion's activating properties while minimizing insomnia risk 5

Clinical Advantages of XL Formulation

The once-daily XL formulation offers practical benefits:

• Improved adherence due to reduced dosing frequency 2, 3
• Similar efficacy and tolerability profile to SR formulation 2, 3
• Maintains the same advantages over SSRIs: less somnolence and sexual dysfunction 2, 3

Common Pitfalls to Avoid

• Do not split or crush XL tablets—this destroys the extended-release mechanism and increases seizure risk 1
• Do not take XL late in the day, as this increases insomnia risk despite the extended-release formulation 5
• Remember that the maximum dose for XL is 450 mg/day (versus 400 mg/day for SR) to minimize seizure risk 5

Special Population Considerations

If your patient has hepatic or renal impairment:

• For moderate to severe hepatic impairment, the maximum XL dose is 150 mg every other day 1
• For renal impairment (GFR <90 mL/min), consider reducing dose and/or frequency 1
• These restrictions apply regardless of formulation 5, 1