What is the recommended protocol for prescribing varenicline (Chantix) and Nicotine Replacement Therapy (NRT) to a patient seeking to quit smoking?

Prescribing Varenicline and Nicotine Replacement Therapy for Smoking Cessation

Primary Treatment Approach

Both varenicline and combination NRT (nicotine patch + short-acting form) are equally effective first-line options for smoking cessation, and both must be combined with behavioral counseling for optimal outcomes. 1

Varenicline Prescribing Protocol

Standard Dosing Regimen:

• Begin varenicline 1-2 weeks before the quit date using a titration schedule to minimize nausea 2, 3
• Days 1-3: 0.5 mg once daily
• Days 4-7: 0.5 mg twice daily
• Week 2 through Week 12: 1 mg twice daily 2, 3
• Take after eating with a full glass of water 3

Treatment Duration:

• Standard course: 12 weeks 1, 2
• For patients who successfully quit during initial 12 weeks: Add an additional 12-week course (total 24 weeks) to significantly increase long-term abstinence rates 2
• May extend to 6-12 months to promote continued cessation 1

Efficacy:

• Varenicline increases quit odds almost 3-fold compared to placebo (RR 2.24,95% CI 2.06-2.43) 2
• Superior to bupropion (RR 1.39,95% CI 1.25-1.54) and single forms of NRT (RR 1.25,95% CI 1.14-1.37) 2
• Continuous abstinence rates at weeks 9-12: 43.9% with varenicline vs 17.6% with placebo 2

Combination NRT Prescribing Protocol

Standard Dosing Regimen:

• Nicotine patch: Start with 21 mg/24-hour patch for smokers consuming ≥10 cigarettes per day 4, 5
• For lighter smokers (<10 cigarettes/day): Start with 14-15 mg patch 4
• Plus short-acting NRT: Add nicotine gum (2 mg for lighter smokers, 4 mg for highly dependent smokers who smoke within 30 minutes of waking), lozenge, nasal spray, or inhaler 1, 4

Treatment Duration:

• Minimum 12 weeks for initial quit attempt 4, 5
• Longer duration (>14 weeks) shows superior results to standard 8-12 week courses 4
• May extend to 6-12 months to prevent relapse 4

Efficacy:

• Combination NRT achieves 36.5% abstinence at 6 months vs 23.4% for patch alone (RR 1.25,95% CI 1.15-1.36) 4
• Nearly doubles cessation success compared to single-form NRT 4

Behavioral Counseling Requirements

All pharmacotherapy must be combined with behavioral support: 1, 2

• Minimum of 4 counseling sessions during the 12-week treatment course 1, 2
• Sessions should last 10-30+ minutes, with longer and more frequent sessions linked to higher success rates 2
• First session within 2-3 weeks of starting treatment 1, 2
• Use the "5 A's" framework: Ask, Advise, Assess, Assist, Arrange 1

Follow-Up Schedule

Structured monitoring is essential for both varenicline and NRT: 1, 4

• First follow-up: Within 2-3 weeks after starting pharmacotherapy 1, 2, 4
• Assess smoking status and medication side effects/tolerability 1, 2
• Additional follow-up at 12 weeks 1, 2
• At end of therapy if extended beyond 12 weeks 1, 2
• Minimum follow-up intervals of every 12 weeks during therapy 2

Side Effects and Safety Monitoring

Varenicline

Common Side Effects:

• Nausea occurs in 28-40% of patients, typically peaks in weeks 1-2 and diminishes over time 2
• Insomnia (14%) and abnormal dreams (10-13%) 2
• The titration schedule is specifically designed to minimize dose-dependent nausea 2

Safety Monitoring:

• Monitor for neuropsychiatric symptoms including depression, agitation, behavioral changes, and suicidal ideation throughout treatment 2
• However, the large EAGLES trial found no significant increase in neuropsychiatric events with varenicline compared to placebo or nicotine patch 2
• No significant link between varenicline and increased cardiovascular adverse events 2

Contraindications:

• History of serious hypersensitivity or skin reactions to varenicline 2, 3
• Avoid in patients with brain metastases due to seizure risk 1, 2

Nicotine Replacement Therapy

Common Side Effects:

• Local skin reactions at patch site 5
• Nausea, vomiting, sweating 5
• Mood changes and sleep disturbances 5

Safety Profile:

• NRT is safe even in patients with cardiovascular disease 1, 4
• Blood nicotine levels from combination NRT remain significantly lower than from smoking cigarettes, making toxicity rare 4
• Very few people become addicted to NRT itself 4

Management of Treatment Failure or Relapse

After Combination NRT Failure:

• Continue/resume combination NRT with additional behavior therapy 1
• Or switch to varenicline 1

After Varenicline Failure:

• Continue/resume varenicline with additional behavior therapy 1
• Or switch to combination NRT + bupropion 1
• Bupropion alone is category 2B recommendation 1

Key Principles for Retreatment:

• Identify and address factors contributing to previous treatment failure (frequent cravings, elevated anxiety/stress/depression, living/working with smokers, drug/alcohol use) 2
• Progressively intensify behavioral therapy with referral to specialty care as indicated 2
• Patients who previously failed varenicline can be re-treated once contributing factors are addressed 2

Special Considerations

Renal Impairment (Varenicline):

• No adjustment needed for mild-moderate renal impairment 3
• Severe renal impairment (CrCl <30 mL/min): Start 0.5 mg once daily, titrate to maximum 0.5 mg twice daily 3
• End-stage renal disease on hemodialysis: Maximum 0.5 mg once daily 3

Cardiovascular Disease:

• NRT is safe with no increased cardiovascular risk 1, 4
• Varenicline has favorable risk/benefit ratio with no significant cardiovascular adverse events 2

Pregnancy:

• For NRT: Benefits likely outweigh risks of continued smoking, but consult obstetrician before initiating 4

Cancer Patients:

• Nausea from varenicline may need careful management, especially during chemotherapy 1
• Avoid varenicline in patients with brain metastases due to seizure risk 1

Common Pitfalls to Avoid

For both varenicline and NRT: 4

• Inadequate dosing: Ensure sufficient doses to control withdrawal symptoms
• Premature discontinuation: Encourage continued therapy even through brief slips (nicotine withdrawal symptoms peak within 1-2 weeks) 1
• Insufficient treatment duration: Maintain treatment for at least 12 weeks
• Failure to combine with behavioral support: Always provide counseling

For NRT specifically: 4

• Not using combination therapy when indicated (patch + short-acting form is more effective than patch alone)
• Improper gum technique: Chew slowly until peppery taste emerges, then "park" between cheek and gum 4
• Avoid food/beverages 15 minutes before and after using nicotine gum 4