How do I switch a patient from immediate‑release bupropion to extended‑release bupropion, including dose conversion and monitoring?

Switching from Immediate-Release to Extended-Release Bupropion

When switching from bupropion immediate-release (IR) to extended-release (XL), give the same total daily dose when possible. 1

Direct Conversion Strategy

The FDA-approved approach is straightforward: match the total daily dose. 1 For example:

• If a patient is taking bupropion IR 100 mg three times daily (300 mg total), switch to bupropion XL 300 mg once daily in the morning 1
• If taking bupropion IR 150 mg twice daily (300 mg total), switch to bupropion XL 300 mg once daily 1

The switch can be made immediately without tapering or overlap, as all three formulations (IR, SR, and XL) are bioequivalent in terms of systemic exposure to bupropion. 2, 3

Key Pharmacokinetic Considerations

The formulations differ in absorption timing but deliver equivalent drug exposure. 3 The XL formulation has a prolonged absorption with Tmax at approximately 5 hours compared to approximately 1.5 hours for IR, but this does not require dose adjustment. 3

All formulations produce the same active metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion) with similar steady-state concentrations when total daily doses are matched. 3

Administration Guidelines for XL Formulation

Bupropion XL must be taken once daily in the morning and swallowed whole—never crushed, divided, or chewed. 1 It may be taken with or without food. 1

The once-daily dosing of XL offers improved convenience and potentially better adherence compared to the three-times-daily IR regimen. 2

Dose Titration After Switching

For major depressive disorder, start with 150 mg XL once daily for 4 days, then increase to the target dose of 300 mg once daily if needed. 1 However, if the patient was already stable on 300 mg total daily of IR, you can switch directly to 300 mg XL. 1

The maximum dose for XL is 450 mg per day, compared to 400 mg per day for SR formulation. 4

Critical Monitoring During Transition

Monitor closely for loss of antidepressant effect when switching between formulations, as historical bioequivalence issues have been reported with some generic versions. 4 While the branded products are bioequivalent, vigilance is warranted during the first 1-2 weeks after switching. 4

Assess for:

• Return of depressive symptoms 4
• Changes in energy levels (bupropion has activating properties) 4
• Blood pressure and heart rate, especially in the first 12 weeks 4
• Neuropsychiatric symptoms including suicidal ideation, particularly in patients under 24 years old 4

Special Population Adjustments

For patients with hepatic impairment, the maximum XL dose is 150 mg every other day in moderate to severe impairment (Child-Pugh 7-15). 1 In mild hepatic impairment, consider reducing dose and/or frequency. 1

For renal impairment (GFR <90 mL/min), reduce the dose and/or frequency by half. 4, 1

Common Pitfalls to Avoid

Do not exceed 450 mg/day of XL formulation, as seizure risk increases substantially above this dose. 4, 5 The seizure risk at therapeutic doses is approximately 0.1% (1 in 1,000). 4

Do not split or crush XL tablets, as this destroys the extended-release mechanism and can lead to immediate release of the full dose, increasing seizure risk. 1

Ensure the second dose timing issue from IR/SR is no longer relevant—with XL's once-daily morning dosing, there is no concern about late-day administration causing insomnia. 4

Expected Timeline for Efficacy

Allow 6-8 weeks at an adequate dose before determining treatment response after any formulation switch. 4 However, improvements in energy levels may occur within the first few weeks. 4