What is the recommended dosage and treatment plan for bupropion (Zyban) in adult patients with impaired renal function or liver disease for smoking cessation?

Bupropion Dosing for Smoking Cessation in Renal and Hepatic Impairment

In patients with impaired renal function, reduce bupropion to 150 mg once daily or every other day with close monitoring; in moderate-to-severe hepatic impairment (Child-Pugh 7-15), the maximum dose is 150 mg every other day, while mild hepatic impairment (Child-Pugh 5-6) requires dose reduction and/or frequency adjustment. 1

Renal Impairment Dosing Algorithm

For patients with any degree of renal impairment (GFR <90 mL/min):

• Reduce dose and/or frequency from the standard 150 mg twice daily regimen 1
• Recommended approach: Start with 150 mg once daily, as bupropion and its metabolites accumulate significantly in renal impairment 1
• Monitor closely for adverse reactions indicating high bupropion or metabolite exposures, including agitation, tremor, insomnia, or seizure risk 1
• The standard initiation protocol (150 mg daily for 3 days, then 150 mg twice daily) should be modified—consider maintaining 150 mg once daily throughout treatment rather than escalating 2, 1

Hepatic Impairment Dosing Algorithm

For moderate-to-severe hepatic impairment (Child-Pugh score 7-15):

• Maximum dose is 150 mg every other day 1
• This represents the most restrictive dosing due to extensive hepatic metabolism 1
• Do not attempt dose escalation in this population 1

For mild hepatic impairment (Child-Pugh score 5-6):

• Consider reducing dose and/or frequency below standard dosing 1
• Reasonable approach: 150 mg once daily rather than twice daily 1
• Elderly patients are more likely to have decreased hepatic function and may require similar dose adjustments 1

Standard Treatment Protocol (for patients WITHOUT organ impairment)

For context, the standard regimen is 2, 3:

• Initiation: Start 1-2 weeks before quit date 2, 3
• Days 1-3: 150 mg once daily 2
• Day 4 onward: 150 mg twice daily (maximum 300 mg/day) 2
• Duration: 7-12 weeks minimum, can extend to 6-12 months for relapse prevention 2, 3

Critical Safety Monitoring in Organ Impairment

Seizure risk is the primary concern:

• Baseline seizure risk with bupropion is approximately 1 in 1,000 2, 4
• Risk increases substantially with dose accumulation in renal/hepatic impairment 1
• Absolute contraindications: Any seizure disorder, eating disorders, abrupt alcohol/benzodiazepine discontinuation 2, 4
• Use extreme caution with any factors lowering seizure threshold 4, 5

Additional monitoring parameters:

• Neuropsychiatric symptoms including depression, suicidal ideation (especially in patients <24 years) 6, 1
• Blood pressure elevation—avoid in uncontrolled hypertension 6
• Allergic/hypersensitivity reactions (approximately 1 in 1,000 to 1 in 10,000) 2, 5

Behavioral Support Integration

Bupropion must be combined with behavioral counseling for optimal outcomes:

• Pharmacotherapy alone achieves ~19% abstinence vs. 11% with placebo 6
• Adding behavioral support increases cessation from 18% to 21% 6
• Minimum effective counseling: At least 4 sessions totaling 91-300 minutes of contact 6, 3
• Include practical problem-solving skills, identifying high-risk situations, and social support 6, 3

Follow-Up Schedule

• Week 2-3: Assess medication tolerance, side effects, and smoking status 3
• Week 4: Evaluate response; if quit attempt continuing, provide additional month of treatment 2
• Week 12: Primary outcome assessment 2, 3
• Months 6 and 12: Long-term follow-up for successful quitters 3

Alternative Strategies if Bupropion Fails or Is Contraindicated

First-line alternatives:

• Varenicline: Superior efficacy (28% vs. 19% abstinence) but requires dose adjustment in severe renal impairment (GFR <30 mL/min) 6, 7
• Combination NRT: Patch plus short-acting form (gum/lozenge) achieves 20.6% abstinence vs. 15.6% for single NRT 6
• NRT has minimal contraindications and no dose adjustment needed for organ impairment 8, 9

Common Pitfalls to Avoid

• Failing to reduce dose in organ impairment: This dramatically increases seizure risk and other adverse effects 1
• Inadequate behavioral support: Bupropion trials demonstrating efficacy included frequent counseling sessions 2, 4
• Premature discontinuation: Minimum 7-12 weeks needed; longer duration prevents relapse 2, 3
• Ignoring drug interactions: Avoid MAO inhibitors (within 14 days), use caution with medications lowering seizure threshold 6, 1
• Prescribing to patients requiring opioid therapy: The naltrexone-bupropion combination (used for obesity, not smoking cessation) blocks opioid effects, but standard bupropion SR for smoking does not contain naltrexone 6