Can bupropion cause impaired renal function?

From the Guidelines

Bupropion is not directly known to cause kidney disease, but it should be used with caution in patients with moderate to severe renal impairment, and the total daily dose should be reduced by one-half in these cases, as indicated in the 2022 clinical practice guideline on pharmacological interventions for adults with obesity 1.

Key Considerations

• The medication is primarily metabolized by the liver, which reduces its potential impact on kidney function.
• Patients with pre-existing kidney disease may require dose adjustments as the medication and its metabolites are partially eliminated through the kidneys.
• In patients with end-stage renal disease, bupropion should be avoided, according to the guideline 1.
• Regular monitoring of kidney function through blood tests is advisable for patients on long-term medication regimens, including bupropion, especially for those with risk factors for kidney disease.

Important Precautions

• Bupropion may lower the seizure threshold and should be avoided in patients with epilepsy or used with caution in patients with a history of seizures or with clinical factors that may increase the risk of seizures, as noted in the guideline 1.
• Patients should be observed for neuropsychiatric adverse effects, including suicidal thoughts and behaviors, especially in individuals younger than 24 years.
• Vital signs should be monitored in patients treated with bupropion, and it should be avoided in patients with uncontrolled hypertension or those treated with, or within 14 days of, monoamine oxidase inhibitors.

From the FDA Drug Label

Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. The risk of adverse reactions may be greater in patients with impaired renal function. 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

Bupropion may not cause kidney disease directly, but it can accumulate in patients with impaired renal function, which may increase the risk of adverse reactions.

• The drug label recommends considering a reduced dose and/or dosing frequency in patients with renal impairment.
• It is essential to monitor patients with renal impairment closely for adverse reactions that could indicate high bupropion or metabolite exposures 2.
• The elimination of the major metabolites of bupropion may be reduced by impaired renal function 2.

From the Research

Bupropion and Kidney Disease

• There is no direct evidence to suggest that bupropion causes kidney disease, but studies have investigated the effect of renal impairment on bupropion pharmacokinetics 3, 4.
• A study published in the British Journal of Clinical Pharmacology 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 3.
• Another study published in Nephrology, Dialysis, Transplantation found that drug clearance in CKD3-5 was markedly reduced for bupropion, and dose reduction in CKD3-5 is necessary 4.
• The pharmacokinetics of bupropion are altered in patients with kidney disease, which may necessitate dose adjustment 4.
• However, there is no evidence to suggest that bupropion is nephrotoxic or causes kidney disease 3, 4, 5, 6, 7.

Pharmacokinetics and Pharmacodynamics

• Bupropion undergoes extensive stereoselective metabolism, and its major active metabolites reach higher plasma concentrations than bupropion 6.
• Bupropion exerts its effects mainly by inhibiting dopamine and norepinephrine reuptake and by blocking several nicotinic receptors 6.
• The characterization of the polymorphic enzymes involved in the metabolism of bupropion is essential to understand factors that may influence the interindividual and intraindividual variability in bupropion metabolite exposure 6.

Clinical Use and Safety

• Bupropion is a safe and effective antidepressant, suitable for first-line use, with a unique pharmacology and a low risk of sexual dysfunction and weight gain 5, 7.
• Bupropion is effective in helping people quit tobacco smoking and has demonstrated comparable efficacy to other antidepressants in clinical trials 5, 7.
• However, bupropion can cause seizures, insomnia, agitation, headache, dry mouth, and nausea, and its use requires careful management of potential side effects 6.