Varenicline Titration Schedule and Dosing
Begin varenicline 1 week before the quit date with 0.5 mg once daily for days 1-3, increase to 0.5 mg twice daily for days 4-7, then maintain 1 mg twice daily from day 8 through week 12. 1
Standard Titration Protocol
The FDA-approved dosing regimen follows a specific 1-week titration schedule designed to minimize nausea and other dose-dependent adverse effects 1, 2:
- Days 1-3: 0.5 mg once daily
- Days 4-7: 0.5 mg twice daily
- Day 8 through week 12: 1 mg twice daily (maintenance dose)
Take varenicline orally after eating with a full glass of water to reduce gastrointestinal side effects. 1
Treatment Duration and Extended Therapy
Standard treatment duration is 12 weeks, which is sufficient for most patients to achieve initial abstinence 1, 2
For patients who successfully quit during the initial 12 weeks, prescribe an additional 12-week course (total 24 weeks) to significantly increase long-term abstinence rates 2, 1. This maintenance strategy was validated in a trial of 1,236 smokers showing improved sustained abstinence 3
Alternative Dosing Strategies
Gradual Reduction Approach
For patients unable or unwilling to quit abruptly 1, 2:
- Begin standard titration schedule
- Reduce smoking by 50% from baseline within first 4 weeks
- Reduce by another 50% in weeks 5-8
- Achieve complete abstinence by week 12
- Continue treatment for additional 12 weeks (total 24 weeks)
Flexible Dosing Option
Recent evidence suggests flexible dosing (0.5 mg/day to 1 mg twice daily) may reduce adverse effects while maintaining efficacy, allowing patients to self-regulate based on tolerability 2. However, do not exceed the standard 2 mg/day maximum dose, as doses up to 5 mg/day showed no additional benefit but significantly increased nausea and vomiting 3
Dose Adjustments for Special Populations
Severe Renal Impairment (CrCl <30 mL/min) 1:
- Start: 0.5 mg once daily
- Maximum: 0.5 mg twice daily (if tolerated)
End-Stage Renal Disease on Hemodialysis 1:
- Maximum: 0.5 mg once daily
Mild-to-Moderate Renal Impairment:
- No adjustment necessary 1
Hepatic Impairment:
- No adjustment necessary 1
Behavioral Support Requirements
Combine varenicline with at least 4 counseling sessions during the 12-week treatment period, with the first session within 2-3 weeks of starting medication 2. Sessions should last 10-30+ minutes, as longer and more frequent sessions correlate with higher success rates 2
Monitoring and Follow-Up Schedule
- Week 2-3: First follow-up to assess smoking status, medication side effects, and tolerability 2
- Week 12: Assessment at end of initial treatment course 2
- Additional periodic follow-up during therapy and after completion 2
Managing Common Side Effects
Nausea occurs in 28-40% of patients, typically peaks in weeks 1-2, and diminishes over time 3, 4, 5. The titration schedule specifically addresses this by gradually increasing the dose 2. If nausea is intolerable:
- Consider temporary dose reduction to 0.5 mg twice daily 1
- Ensure medication is taken after meals with full glass of water 1
- Reassure patients that nausea typically improves after the first 2 weeks 3
Other common side effects include insomnia (14%) and abnormal dreams (10-13%) 3, 4
Critical Safety Monitoring
Monitor for neuropsychiatric symptoms including depression, agitation, behavioral changes, and suicidal ideation throughout treatment 2. However, large-scale trials including the EAGLES study (n=8,144) found no significant increase in neuropsychiatric events with varenicline compared to placebo or nicotine patch 3
Re-treatment Considerations
Patients who previously failed varenicline therapy can be re-treated once factors contributing to the failed attempt are identified and addressed 1. An RCT of 498 patients demonstrated varenicline remains effective and well-tolerated for re-treatment 3
Common Pitfalls to Avoid
- Do not skip the titration week - starting directly at 1 mg twice daily significantly increases nausea and discontinuation rates
- Do not start varenicline on the quit date - begin 1 week before to allow proper titration and drug accumulation 1
- Do not discontinue prematurely for mild nausea - this side effect typically resolves within 2 weeks 3
- Do not exceed 2 mg/day total dose - higher doses provide no additional benefit and increase adverse events 3