What is the dose reduction of bupropion in patients with Chronic Kidney Disease (CKD) based on Creatinine Clearance Rate (CrCl) or Estimated Glomerular Filtration Rate (eGFR)?

From the Guidelines

Bupropion dose should be reduced in patients with moderate to severe kidney impairment, with adjustments based on eGFR rather than creatinine clearance (CrCl) alone, as recommended by the KDIGO 2024 clinical practice guideline 1. When dosing bupropion in patients with chronic kidney disease (CKD), it is essential to consider the patient's eGFR, as it is a more accurate measure of kidney function than CrCl alone.

• For patients with mild renal impairment (eGFR 60-89 mL/min), no dose adjustment is necessary.
• For moderate impairment (eGFR 30-59 mL/min), the maximum recommended dose is 150 mg once daily.
• For severe impairment (eGFR <30 mL/min), the maximum dose should be limited to 150 mg every other day. These adjustments are necessary because kidney dysfunction leads to decreased clearance of bupropion and its metabolites, potentially increasing blood levels and the risk of adverse effects, particularly seizures, as highlighted in the KDIGO 2024 guideline 1. The extended-release formulations (SR, XL) should be used with caution in renal impairment as the altered pharmacokinetics may lead to unpredictable drug levels.
• Close monitoring for side effects such as insomnia, headache, dry mouth, and neuropsychiatric symptoms is recommended when using bupropion in patients with kidney disease.
• If dialysis is required, supplemental doses are not typically needed as bupropion is not significantly removed by hemodialysis. It is crucial to consider the individual patient's factors, such as body weight and volume of distribution, when adjusting the bupropion dose, as emphasized in the KDIGO 2024 guideline 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

• Dose reduction is recommended for patients with renal impairment (glomerular filtration rate: <90 mL/min) when taking bupropion.
• The dose and/or dosing frequency should be reduced in these patients.
• It is essential to monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures in patients with renal impairment 2.

From the Research

Bupropion Dose Reduction in CKD

• Bupropion dose reduction in patients with chronic kidney disease (CKD) should be based on creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) 3.
• The Kidney Disease: Improving Global Outcomes (KDIGO) conference highlighted the importance of accurate estimation of kidney function in patients with CKD and the need for dosage adjustments of drugs cleared renally 4.
• eGFR can be estimated using serum markers such as serum creatinine (SCr) or cystatin C, and the estimation of GFR by SCr differs in health and in CKD due to differences in GFR range and in creatinine production between these two populations 5.

Comparison of CrCl and eGFR

• A study compared CKD-EPI eGFR and measured creatinine clearance (CLCR) in critically ill patients with normal plasma creatinine concentrations and found significant bias and imprecision between the two methods 6.
• The study suggested that clinicians should consider carefully which value they employ in clinical practice, particularly for drug dose modification.
• The Chronic Kidney Disease Epidemiology Collaboration developed a new equation in 2009 that is more accurate than the MDRD Study equation at values above 60 mL/min/1.73 m2, and equations for eGFR based on standardized cystatin C alone and with creatinine are now available 7.

Dose Reduction Considerations

• Dosages of drugs cleared renally, such as bupropion, should be adjusted according to CrCl or eGFR and should be calculated using online or electronic calculators 3.
• Recommended methods for maintenance dosing adjustments are dose reductions, lengthening the dosing interval, or both.
• Physicians should be familiar with commonly used medications that require dosage adjustments in patients with CKD.