Can Wellbutrin XL (bupropion) be dosed twice daily?

Dosing of Wellbutrin XL (Bupropion Extended-Release)

Wellbutrin XL should NOT be dosed twice daily as it is specifically formulated for once-daily administration in the morning. 1

Proper Administration of Wellbutrin XL

Wellbutrin XL is an extended-release formulation designed specifically for once-daily dosing, with distinct pharmacokinetic properties that differentiate it from other bupropion formulations:

• Wellbutrin XL should be administered once daily in the morning 1
• The tablet should be swallowed whole and not crushed, divided, or chewed 1
• May be taken with or without food 1
• Standard dosing for major depressive disorder (MDD):
  • Starting dose: 150 mg once daily in the morning
  • After 4 days, may increase to target dose of 300 mg once daily 1

Different Bupropion Formulations and Their Dosing

It's important to understand the differences between bupropion formulations:

1. Immediate Release (IR): Administered three times daily 2
2. Sustained Release (SR): Administered twice daily 2
3. Extended/Modified Release (XL/XR): Administered once daily 2

All three formulations are bioequivalent in terms of systemic exposure to bupropion, but have different absorption profiles:

• XL formulation has prolonged absorption (T₍max₎ 5 hours) compared to IR (1.5 hours) and SR (~3 hours) 3

Why XL Should Not Be Dosed Twice Daily

Twice-daily dosing of Wellbutrin XL would be inappropriate for several reasons:

• The FDA-approved labeling specifically indicates once-daily morning dosing 1
• The extended-release mechanism is designed to provide 24-hour coverage with a single dose 3
• Studies in both adults and adolescents confirm that once-daily dosing of bupropion XL provides appropriate 24-hour coverage 3, 4
• Twice-daily dosing could potentially increase the risk of adverse effects, particularly insomnia, due to evening administration 5

Switching Between Formulations

When switching between bupropion formulations:

• The same total daily dose should be maintained when possible 1
• For example, patients on bupropion SR 150 mg twice daily could be switched to bupropion XL 300 mg once daily
• The FDA label specifically provides guidance on switching from IR or SR to XL formulations 1

Potential Adverse Effects and Precautions

Common side effects of bupropion include:

• Insomnia, dry mouth, anxiety/jitteriness, decreased appetite, headache 5
• Potential for increased blood pressure and heart rate 5
• Risk of seizures (dose-dependent) 5, 1

Taking Wellbutrin XL twice daily could potentially increase these risks, particularly:

• Insomnia if the second dose is taken later in the day 5
• Increased seizure risk due to higher peak concentrations 1

Special Populations

For patients with impaired hepatic or renal function:

• Moderate to severe hepatic impairment: Maximum dose is 150 mg every other day 1
• Mild hepatic impairment: Consider reducing dose and/or frequency 1
• Renal impairment: Consider reducing dose and/or frequency 1

Conclusion

The pharmacokinetic profile and FDA-approved labeling clearly indicate that Wellbutrin XL should be administered once daily in the morning. Twice-daily dosing would be contrary to the product's design and could potentially increase adverse effects without providing additional therapeutic benefit.