Can Wellbutrin Be Started in a Male in His Early 60s with eGFR 53?
Yes, Wellbutrin (bupropion) can be started in this patient, but use a reduced dose and/or reduced dosing frequency due to moderate renal impairment, with close monitoring for signs of drug accumulation and toxicity. 1
FDA-Approved Dosing Guidance for Renal Impairment
The FDA label explicitly recommends dose reduction in patients with renal impairment (GFR <90 mL/min):
- Bupropion should be used with caution in patients with renal impairment, and a reduced frequency and/or dose should be considered 1
- Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures 1
Pharmacokinetic Rationale for Dose Adjustment
The concern with renal impairment stems from metabolite accumulation rather than parent drug accumulation:
- In moderate-to-severe renal impairment (GFR 30.9 ± 10.8 mL/min), bupropion exposure was approximately 2-fold higher after a single 150 mg dose 1
- The major metabolites (hydroxybupropion and threohydrobupropion) had 2.3- and 2.8-fold increases in AUC in end-stage renal failure 1
- These metabolites are moderately polar compounds that undergo further metabolism or conjugation in the liver prior to urinary excretion, making them susceptible to accumulation when renal clearance is impaired 1
Research confirms these findings, showing that bupropion AUC was 126% higher and clearance 63% lower in renally impaired patients, though the metabolite-to-parent drug ratios were actually decreased 2
Practical Dosing Recommendations
For this patient with eGFR 53 mL/min (moderate renal impairment):
- Start with a lower dose than standard (consider 150 mg once daily of extended-release formulation rather than 150 mg twice daily) 1
- Consider reducing dosing frequency (e.g., every other day or once daily instead of twice daily) 1
- Titrate slowly if dose increases are needed, allowing adequate time to assess for accumulation 1
Critical Monitoring Parameters
Watch closely for neurologic and psychiatric toxicity, which may indicate drug or metabolite accumulation:
- Progressive tremor, truncal ataxia, myoclonic jerks, visual hallucinations, vertigo, slurred speech, and delirium have been reported in an elderly patient with stage III CKD after bupropion initiation 3
- Symptoms improved 36-48 hours after dose reduction, confirming dose-related toxicity 3
- Acute psychotic and parkinsonian symptoms can occur with bupropion, particularly in vulnerable populations 3
Age as Additional Risk Factor
This patient's age (early 60s) compounds the renal impairment concern:
- Elderly patients are more likely to have decreased renal function, and the risk of adverse reactions may be greater 1
- Limited pharmacokinetic data in the elderly and those with renal impairment suggest reduced clearance 3
- Greater sensitivity in older individuals cannot be ruled out 1
Common Pitfalls to Avoid
- Do not use standard dosing without adjustment - the FDA label is clear that dose reduction should be considered for GFR <90 mL/min 1
- Do not assume safety based solely on parent drug levels - the active metabolites accumulate significantly and contribute to both efficacy and toxicity 1, 2
- Do not ignore subtle neurologic changes - these may be early signs of toxicity requiring immediate dose reduction 3
- Do not forget that adherence with renal dosing guidelines at hospital discharge is poor (only 53.9%), and 71.4% of non-adherence cases have potential to cause moderate to severe harm 4