Is 200mg twice daily of Wellbutrin (Bupropion) SR equivalent to 300mg once daily of Wellbutrin (Bupropion) XL?

Equivalence of Bupropion SR 200mg Twice Daily and Bupropion XL 300mg Once Daily

Yes, 200mg twice daily of Wellbutrin SR is equivalent to 300mg once daily of Wellbutrin XL in terms of total daily dose and systemic exposure. 1

Pharmacokinetic Differences Between Formulations

Bupropion is available in three oral formulations with different release mechanisms:

• Immediate Release (IR): Administered three times daily
• Sustained Release (SR): Administered twice daily
• Extended Release (XL): Administered once daily

While the total daily dose is the same (400mg SR vs 300mg XL), there are important pharmacokinetic differences:

• Absorption rate: XL formulation has a more prolonged absorption compared to SR (Time to peak concentration [Tmax] ~5 hours for XL vs ~3 hours for SR) 2
• Peak plasma levels: XL formulation produces lower peak concentrations but maintains more consistent blood levels throughout the day 3
• Bioequivalence: All three formulations are bioequivalent in terms of systemic exposure to bupropion and its metabolites 3, 2

Clinical Implications of Formulation Differences

The FDA drug label specifically addresses switching between formulations:

• When switching from Wellbutrin SR to Wellbutrin XL, give the same total daily dose when possible 1
• The 300mg XL once-daily dosing was specifically designed to provide equivalent systemic exposure to 150mg SR twice daily 1

Advantages of XL Formulation:

• Convenience: Once-daily dosing may improve adherence
• Smoother blood levels: May reduce peak-related side effects
• Evening dosing avoidance: XL is administered in the morning, avoiding evening doses that could contribute to insomnia 4

Proper Administration Guidelines

For optimal effectiveness and safety:

• XL tablets: Should be swallowed whole and not crushed, divided, or chewed 1
• Morning administration: XL formulation should be taken in the morning 1
• Food considerations: May be taken with or without food 1

Switching Between Formulations

When switching between formulations:

1. Direct conversion: 300mg XL once daily can directly replace 150mg SR twice daily 1
2. Timing: Begin the XL formulation the morning after the last SR dose
3. Monitoring: Watch for any changes in efficacy or side effects during the transition

Common Pitfalls to Avoid

• Crushing or splitting XL tablets: This destroys the extended-release mechanism and can lead to rapid absorption, increasing side effect risk and seizure potential 1
• Evening dosing of XL: Can increase insomnia risk 4
• Abrupt discontinuation: When discontinuing treatment with 300mg XL, decrease to 150mg once daily prior to complete discontinuation 1

Special Considerations

• Hepatic impairment: In moderate to severe impairment, maximum dose should be 150mg every other day 1
• Renal impairment: Consider reducing dose and/or frequency 1
• Seizure risk: Bupropion lowers seizure threshold; dose should be increased gradually 1

The clinical evidence supports that 200mg twice daily of Wellbutrin SR provides equivalent systemic exposure to 300mg once daily of Wellbutrin XL, making them therapeutically equivalent options for treating depression.