How should varenicline (Champix) be initiated in an adult smoker who wants to quit, ensuring no contraindications (hypersensitivity, pregnancy, breastfeeding, severe renal impairment, uncontrolled psychiatric illness), reviewing cardiovascular and psychiatric history, and applying appropriate dosing and renal adjustments?

How to Initiate Varenicline (Champix) for Smoking Cessation

Begin varenicline 1-2 weeks before the patient's chosen quit date, using a standardized titration schedule: 0.5 mg once daily for days 1-3, then 0.5 mg twice daily for days 4-7, then 1 mg twice daily for weeks 2-12. 1, 2, 3

Pre-Treatment Assessment and Contraindications

Before prescribing varenicline, you must screen for absolute contraindications and risk factors:

Absolute Contraindications:

• History of serious hypersensitivity or skin reactions to varenicline 3
• Brain metastases or active seizure disorder (due to seizure risk) 1, 2
• Pregnancy and breastfeeding (not FDA-approved for these populations) 1

Severe Renal Impairment Requires Dose Adjustment:

• For creatinine clearance <30 mL/min: start 0.5 mg once daily, titrate to maximum 0.5 mg twice daily 3
• For end-stage renal disease on hemodialysis: maximum 0.5 mg once daily if tolerated 3

Psychiatric History Assessment:

• Take a complete psychiatric history and suicide risk assessment before prescribing 4
• However, psychiatric history alone is NOT a contraindication—the large EAGLES trial demonstrated no increased neuropsychiatric adverse events in over 4,000 patients with diagnosed psychiatric disorders compared to placebo 2
• Document current severity of any depression or anxiety symptoms at baseline 4

Standard Dosing Regimen

The FDA-approved titration schedule minimizes nausea while achieving therapeutic dosing: 3

• Days 1-3: 0.5 mg once daily
• Days 4-7: 0.5 mg twice daily
• Weeks 2-12: 1 mg twice daily (target dose)

Key timing considerations:

• Start varenicline 1-2 weeks BEFORE the quit date 1, 2, 3
• The quit date should fall between day 8 and day 35 of treatment 3
• This allows the medication to reach steady-state levels before nicotine withdrawal begins 2

Treatment Duration

Standard course is 12 weeks, but successful quitters should receive an additional 12 weeks (total 24 weeks) to maximize long-term abstinence. 1, 2

• Initial 12-week course for all patients 1, 2
• For patients who achieve abstinence during the first 12 weeks, an additional 12-week course significantly increases long-term abstinence rates (continuous abstinence rate 70.5% vs 49.6% with placebo at 24 weeks) 2
• Therapy may be extended to 6-12 months in select cases to promote continued cessation 2

Mandatory Behavioral Counseling Integration

Varenicline must ALWAYS be combined with behavioral counseling—pharmacotherapy alone is insufficient. 1, 2, 4

Minimum counseling requirements:

• At least 4 counseling sessions during the 12-week treatment period 2
• First session within 2-3 weeks of starting medication 2
• Each session should last 10-30+ minutes (longer sessions linked to higher success rates) 2
• Sessions should include skills training, social support, and motivational interviewing 4

Brief counseling framework (5 A's strategy):

• Ask about tobacco use at every visit
• Advise to quit through clear, personalized messages
• Assess willingness to make a quit attempt
• Assist with quit plan and medication
• Arrange follow-up and support 1, 2

Follow-Up Schedule

Intensive early monitoring is critical for success and safety: 2, 4

• First follow-up: Within 2-3 weeks after starting varenicline (mandatory) 2, 4
• Second follow-up: At 12 weeks (end of initial treatment) 2
• Ongoing: Minimum every 12 weeks during extended therapy 2

At each follow-up, assess:

• Smoking status (continuous abstinence vs. lapses)
• Medication side effects and tolerability
• Neuropsychiatric symptoms (see monitoring section below)
• Risk of relapse
• Need for dose adjustments or therapy modifications 2, 4

Common Side Effects and Management

Nausea is the most common side effect, occurring in 28-40% of patients, but is usually manageable: 2, 5, 6

• Nausea typically peaks in weeks 1-2 and diminishes over time 2
• The titration schedule is specifically designed to minimize nausea 2
• Reassure patients that nausea usually improves after the first 2 weeks 2
• If nausea is intolerable, consider flexible dosing (0.5 mg/day to 1 mg twice daily) allowing patients to self-regulate based on tolerability 1, 2

Other common side effects:

• Insomnia (14% of patients) 2, 5
• Abnormal/vivid dreams (10-13% of patients) 2, 5
• Headache (14% of patients) 5

For patients with cancer receiving chemotherapy, nausea may require especially careful management. 1, 2

Critical Safety Monitoring: Neuropsychiatric Symptoms

Monitor for neuropsychiatric symptoms throughout treatment, though the risk is not significantly elevated compared to placebo: 1, 2, 3

Symptoms requiring immediate discontinuation and provider contact:

• Depression or worsening of pre-existing depression
• Suicidal ideation or behavior
• Agitation or behavioral changes
• Anxiety or panic attacks
• Hostility or aggression 1, 4, 3

Important context: The EAGLES trial (over 8,000 participants) found no significant increase in neuropsychiatric events with varenicline compared to nicotine patch or placebo in patients with or without psychiatric disorders 1, 2

Special Populations and Precautions

Patients with cardiovascular disease:

• Varenicline has a favorable cardiovascular safety profile with no significant link to increased cardiovascular adverse events 2
• Can be used safely in patients with cardiovascular disease 2

Patients with seizure history or conditions lowering seizure threshold:

• Use cautiously and monitor closely 3
• Absolutely contraindicated if brain metastases present 1, 2

Alcohol interaction:

• Increased effects of alcohol have been reported 3
• Instruct patients to reduce alcohol consumption until they know how varenicline affects them 3

Management of Treatment Failure or Relapse

If the patient fails to quit or relapses after initial varenicline therapy: 2, 4

1. Identify and address factors contributing to failure:

   • Frequent or intense cravings
   • Elevated anxiety, stress, or depression
   • Living or working with smokers
   • Drug or alcohol use/abuse
   • Inadequate behavioral therapy support 4

2. Consider restarting varenicline using the same dosing regimen if factors have been addressed 2, 4

3. Progressively intensify behavioral therapy with referral to specialty care as indicated 4

4. If second course of varenicline fails, switch to combination nicotine replacement therapy (NRT) before trying other options 4

Alternative Dosing Strategy for Flexible Approach

For patients unable or unwilling to quit abruptly, consider a gradual reduction approach: 3

• Begin varenicline with standard titration
• Reduce smoking by 50% from baseline within first 4 weeks
• Reduce by additional 50% in next 4 weeks
• Achieve complete abstinence by 12 weeks
• Continue treatment for additional 12 weeks (total 24 weeks) 3

Clinical Pitfalls to Avoid

Do not start varenicline without:

• Setting a specific quit date with the patient 4
• Establishing behavioral support structure (minimum 4 sessions scheduled) 2, 4
• Screening for contraindications (especially brain metastases, seizure history, severe renal impairment) 1, 2, 3

Do not continue varenicline if:

• Serious neuropsychiatric symptoms develop or worsen 1, 4, 3
• Seizures occur 3
• Serious skin reactions develop 3

Do not dismiss treatment failure as patient non-compliance:

• Systematically identify barriers to success 4
• Intensify behavioral support before abandoning pharmacotherapy 4
• Consider that varenicline can be successfully used for retreatment once barriers are addressed 2, 4