What is the recommended renal dosing for bupropion (Wellbutrin) in a patient with impaired renal function, specifically a creatinine clearance of 47 ml/min?

From the Guidelines

For a patient with a creatinine clearance of 47 ml/min, the total daily dose of bupropion should be reduced by one-half, as indicated for patients with moderate to severe renal impairment 1. This recommendation is based on the guidance provided for naltrexone-bupropion ER, which contains bupropion, and suggests that in patients with moderate to severe renal impairment, the dose should be adjusted to minimize potential adverse effects. Given that the standard dose for bupropion can vary depending on the formulation (immediate-release, sustained-release, or extended-release), a general approach would be to reduce the dose by half from the typical starting dose. For example, if the standard starting dose for a patient with normal renal function is 150 mg twice daily for immediate-release formulations, a patient with a creatinine clearance of 47 ml/min might start with 150 mg once daily. Similarly, for extended-release formulations, the dose could be adjusted to 150 mg every other day or 100 mg daily, depending on the specific formulation and the patient's response to the medication. It's crucial to monitor these patients closely for both efficacy and adverse effects, as renal impairment can affect the pharmacokinetics of bupropion, potentially leading to increased levels and risk of side effects such as seizures. Regular assessment of renal function and adjustment of the bupropion dose as needed is essential to balance the therapeutic benefits with the risk of adverse effects in patients with impaired renal function. The primary concern in managing patients with renal impairment is to prevent accumulation of the drug and its metabolites, which could exacerbate side effects, thus a cautious and individualized approach to dosing is necessary 1.

From the FDA Drug Label

Consider a reduced dose and/or dosing frequency of bupropion hydrochloride extended-release tablets (XL) in patients with renal impairment (glomerular filtration rate: <90 mL/min). Bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures

The recommended renal dosing for bupropion in a patient with impaired renal function and a creatinine clearance of 47 ml/min is to consider a reduced dose and/or dosing frequency of bupropion hydrochloride extended-release tablets (XL) and to monitor closely for adverse reactions 2.

From the Research

Renal Dosing for Bupropion

To determine the recommended renal dosing for bupropion in a patient with impaired renal function, specifically a creatinine clearance of 47 ml/min, we need to consider the pharmacokinetics of bupropion and its metabolites in patients with renal impairment.

• The study by 3 found that bupropion AUC was 126% higher, C(max) 86% higher, CL/F 63% lower, and t(1/2) 140% longer in renally impaired patients compared to healthy subjects.
• However, the same study noted that only minor changes were detected in the concentrations of the metabolites, and the hydroxybupropion : bupropion AUC ratio was decreased by 66% in renally impaired subjects.
• Another study by 4 suggested that a dose of 150 mg bupropion every 3 days in patients receiving haemodialysis may be more appropriate than the current manufacturer's recommendation of 150 mg daily.

Dosing Recommendations

Based on the available evidence, it appears that dosage adjustments may be necessary for patients with renal impairment. However, the exact dosing recommendations are not clearly established.

• The study by 3 suggests that the CL/F of bupropion is significantly lower in subjects with renal impairment, which may require a reduction in dose or an increase in dosing interval.
• The study by 4 provides some guidance on dosing in patients with end-stage renal disease receiving haemodialysis, but more research is needed to determine the optimal dosing strategy for patients with varying degrees of renal impairment.

Considerations for Renal Impairment

When considering renal dosing for bupropion, it is essential to take into account the patient's individual renal function and the potential for accumulation of the drug and its metabolites.

• The study by 5 found that pentamidine pharmacokinetics were not significantly affected by renal function in patients with creatinine clearances above 35 ml/min, but this may not be directly applicable to bupropion.
• The study by 3 highlights the importance of considering the pharmacokinetics of bupropion and its metabolites in patients with renal impairment, as the metabolites may accumulate and contribute to the overall pharmacological effect.