From the Guidelines
In patients with moderate to severe renal impairment, the total daily dose of bupropion should be reduced by one-half. According to the most recent evidence from 2022, as stated in the study published in Gastroenterology 1, this dose adjustment is crucial to minimize potential adverse effects. The recommended dose reduction applies to bupropion when used in combination with naltrexone for obesity treatment, and it is essential to avoid the medication in patients with end-stage renal disease. Key considerations for dose adjustment in CKD include:
- Reducing the total daily dose by one-half in patients with moderate to severe renal impairment
- Avoiding the medication in patients with end-stage renal disease
- Monitoring patients closely for adverse effects, such as seizures, agitation, or insomnia, which can be exacerbated by the accumulation of bupropion and its metabolites in renal impairment. It is also important to note that the pharmacokinetics of bupropion are altered in renal impairment, as the parent drug is primarily metabolized by the liver, but some active metabolites are eliminated by the kidneys and can accumulate when renal function is compromised, as mentioned in the study 1.
From the FDA Drug Label
2.7 Dose Adjustment in Patients with Renal Impairment Consider reducing the dose and/or frequency of bupropion hydrochloride extended-release tablets (XL) in patients with renal impairment (glomerular filtration rate less than 90 mL/min) [seeUse in Specific Populations (8.6)and Clinical Pharmacology (12.3)].
The recommended dose adjustment for bupropion in patients with Chronic Kidney Disease (CKD) is to consider reducing the dose and/or frequency of bupropion hydrochloride extended-release tablets (XL) in patients with renal impairment (glomerular filtration rate less than 90 mL/min) 2.
- The exact dose reduction is not specified in the label.
- Key considerations for dose adjustment include the patient's glomerular filtration rate and the potential for increased risk of adverse effects in patients with renal impairment.
From the Research
Package Insert Dose Adjustment in CKD for Bupropion
- The pharmacokinetics of bupropion are affected in patients with chronic kidney disease (CKD), with a 126% higher AUC, 86% higher C(max), 63% lower CL/F, and 140% longer t(1/2) in renally impaired patients compared to healthy subjects 3.
- However, the study found 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 3.
- Due to the altered pharmacokinetics, dosage recommendations for patients with renal impairment cannot be given, and a direct effect of renal impairment on CYP2B6 activity could not be demonstrated 3.
- Another study suggested that health care providers should be aware of renal dose adjustments for antidepressants, including bupropion, in patients with CKD 4.
- A systematic review of pharmacokinetics, efficacy, and safety of antidepressant drugs in patients with CKD3-5 found that dose reduction is necessary for bupropion in CKD3-5 5.
- A modified Delphi study identified bupropion as one of the medications that require dose adjustment in people with CKD 6.
- However, there is limited evidence on the effectiveness of antidepressants, including bupropion, in patients with CKD, and more research is needed to inform dosage recommendations 5.
- It is essential to consider the kidney function of patients when prescribing bupropion, as lower kidney function is associated with a reduced dose 7.