Can bupropion (Wellbutrin) cause impaired renal function or kidney failure?

From the Guidelines

Bupropion is not typically associated with causing kidney failure in most patients, but it should be used with caution in those with pre-existing renal impairment. When considering the use of bupropion, particularly in the context of naltrexone-bupropion ER for obesity management, it's crucial to assess the patient's renal function. According to the guideline evidence 1, in patients with moderate to severe renal impairment, the total daily dose of naltrexone-bupropion ER should be reduced by one-half, and it should be avoided in end-stage renal disease. This suggests that while bupropion itself may not directly cause kidney failure, its use in patients with compromised renal function requires careful consideration and dose adjustment to prevent potential exacerbation of renal impairment.

Key points to consider include:

• Bupropion's primary metabolism by the liver reduces its direct impact on kidney function compared to renally eliminated drugs.
• Patients with pre-existing kidney disease may require dosage adjustments due to the renal excretion of some bupropion metabolites.
• Rare cases of acute kidney injury associated with bupropion have been reported, often in the context of hypersensitivity reactions, seizures, or rhabdomyolysis following overdose.
• Regular monitoring of kidney function is not routinely necessary unless the patient has underlying kidney disease or is taking other medications that may affect renal function 1.

In clinical practice, the decision to use bupropion should prioritize the patient's overall health status, including their renal function, to minimize the risk of adverse effects while maximizing the potential benefits of the medication. Given the potential for renal impairment to affect the dosing and safety profile of bupropion, particularly in combination with naltrexone for obesity management, healthcare providers should carefully evaluate each patient's individual risk factors and adjust treatment plans accordingly 1.

From the FDA Drug Label

The elimination of the major metabolites of bupropion may be affected by reduced renal or hepatic function, because they are moderately polar compounds and are likely to undergo further metabolism or conjugation in the liver prior to urinary excretion Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and subsequently excreted by the kidneys. The elimination of the major metabolites of bupropion may be reduced by impaired renal function Bupropion hydrochloride extended-release tablets (XL) should be used with caution in patients with renal impairment, and a reduced frequency and/or dose should be considered [see Dosage and Administration (2.7)and Use in Specific Populations (8. 6)].

Bupropion and Kidney Function: Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and subsequently excreted by the kidneys. The elimination of the major metabolites of bupropion may be reduced by impaired renal function.

• Key Points:
  • The drug label does not directly state that bupropion causes kidney failure.
  • However, it does indicate that impaired renal function may affect the elimination of bupropion's major metabolites.
  • Bupropion should be used with caution in patients with renal impairment, and a reduced frequency and/or dose should be considered. 2

From the Research

Bupropion and Kidney Function

• Bupropion is a medication used to treat depression and seasonal affective disorder, but its effects on kidney function are not well understood.
• A study published in 2007 3 found that bupropion pharmacokinetics are altered in patients with impaired kidney function, with a 126% increase in bupropion AUC and a 63% decrease in CL/F.
• Another study published in 2012 4 found that drug clearance in CKD3-5 was markedly reduced for bupropion, and dose reduction is necessary for patients with renal impairment.

Impaired Renal Function and Bupropion

• The same study published in 2012 4 found that bupropion is one of the antidepressants that require dose reduction in patients with CKD3-5.
• A review of pharmacokinetics, efficacy, and safety of antidepressant drugs in patients with CKD3-5 4 found that bupropion is effective in treating depression, but its use in patients with renal impairment requires careful consideration.

Kidney Failure and Bupropion

• There is no direct evidence to suggest that bupropion can cause kidney failure.
• However, a study published in 2007 3 found that bupropion pharmacokinetics are altered in patients with impaired kidney function, which may increase the risk of adverse effects.
• A review of the literature on albuminuria, serum creatinine, and estimated glomerular filtration rate as predictors of cardio-renal outcomes in patients with type 2 diabetes mellitus and kidney disease 5 found that kidney decline is a complex process, and multiple factors contribute to the risk of kidney disease progression.

Renal Impairment and Bupropion Metabolism

• A study published in 2007 3 found that the hydroxybupropion : bupropion AUC ratio was decreased by 66% in renally impaired subjects, suggesting that bupropion metabolism is altered in patients with renal impairment.
• The same study found that the CL/F of bupropion was significantly lower in subjects with renal impairment, which may increase the risk of adverse effects.