Is Buproprion (bupropion) safe to use in a patient with end-stage renal disease (ESRD) on hemodialysis?

Bupropion Use in End-Stage Renal Disease on Hemodialysis

Bupropion can be used cautiously in ESRD patients on hemodialysis, but requires significant dose reduction to 150 mg every 3 days (not daily) due to substantial accumulation of active metabolites that are renally cleared. 1, 2

Critical Dosing Modifications Required

For patients with renal impairment (GFR <90 mL/min), the FDA label mandates reduced dose and/or frequency, with close monitoring for adverse reactions indicating high bupropion or metabolite exposures. 1

Specific ESRD Dosing Recommendations

• The most appropriate dose for hemodialysis patients is 150 mg every 3 days, not the manufacturer's recommendation of 150 mg daily. 2
• The American Gastroenterological Association recommends reducing the total daily dose by 50% in moderate to severe renal impairment, and avoiding bupropion entirely in end-stage renal disease when used as naltrexone-bupropion combination. 3, 4
• For hemodialysis patients specifically, a single-dose pharmacokinetic study demonstrated that while parent bupropion levels remain similar to those with normal renal function, hydroxybupropion and threohydrobupropion metabolites show 2.3-fold and 2.8-fold increased AUC respectively. 1

Pharmacokinetic Rationale

The concern in ESRD stems from metabolite accumulation rather than parent drug:

• Bupropion itself shows comparable Cmax and AUC in ESRD patients versus normal subjects, but active metabolites accumulate significantly. 1, 2
• Hydroxybupropion has approximately 10 times the peak level of parent drug at steady state and an elimination half-life of 20 hours in normal renal function. 1
• Threohydrobupropion and erythrohydrobupropion have even longer half-lives (33 and 37 hours respectively) and achieve steady-state AUCs 1.5 and 7 times that of bupropion. 1
• Hemodialysis clearance of hydroxybupropion is unlikely, meaning dialysis does not effectively remove accumulated metabolites. 2

Critical Safety Monitoring

Baseline Assessment Required

• Screen for absolute contraindications: seizure history, uncontrolled hypertension, eating disorders, current MAOI use, or abrupt discontinuation of alcohol/benzodiazepines/antiepileptics. 4
• Measure baseline blood pressure and heart rate, as bupropion can elevate both parameters. 4
• Assess for conditions predisposing to seizures, as maximum seizure risk is 0.1% at 300 mg/day in normal renal function but may be higher with metabolite accumulation. 4

Ongoing Monitoring Parameters

• Monitor closely for neuropsychiatric adverse effects including agitation, restlessness, behavioral changes, and suicidal ideation, particularly in patients under 24 years. 4
• Monitor blood pressure and heart rate periodically, especially in the first 12 weeks of treatment. 4
• Watch for signs of metabolite toxicity including confusion, tremor, or seizures, which may indicate excessive accumulation. 1, 2

Clinical Context and Alternatives

When Bupropion May Be Appropriate in ESRD

• Patients with comorbid depression and low energy, apathy, or hypersomnia may benefit from bupropion's activating properties. 4
• Patients concerned about sexual dysfunction or weight gain associated with SSRIs may prefer bupropion, which has lower rates of these side effects. 4
• Smokers with ESRD who want to quit may benefit from bupropion's dual indication for depression and smoking cessation. 4

Critical Timing Considerations

• If used, administer bupropion after hemodialysis sessions to facilitate directly observed therapy and avoid premature drug removal. 3
• The second daily dose (if splitting doses) must be given before 3 PM to minimize insomnia risk. 4

Important Caveats

The clinical importance of metabolite accumulation and toxic plasma levels in ESRD patients remains incompletely characterized. 2 The single-dose pharmacokinetic study in hemodialysis patients suggests 150 mg every 3 days is more appropriate than daily dosing, but multi-dose studies are needed to confirm optimal dosing strategies. 2

Given the European hepatitis C guidelines explicitly recommend avoiding sofosbuvir in patients with eGFR <30 mL/min or ESRD until more data is available, and the AGA guidelines recommend avoiding naltrexone-bupropion in ESRD, a conservative approach favoring alternative antidepressants with better-established safety profiles in ESRD may be prudent. 3

Safer Alternatives in ESRD

Consider antidepressants that do not rely on renal clearance or have inactive metabolites, though specific recommendations for ESRD are beyond the scope of bupropion-specific evidence provided. The key principle is that any medication with active metabolites cleared renally poses accumulation risk in ESRD and requires either dose reduction, extended dosing intervals, or avoidance. 3, 1