Varenicline Dosing for Smoking Cessation
The standard varenicline regimen is 0.5 mg once daily for days 1-3, then 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily for weeks 2-12, with treatment starting 1 week before the quit date. 1
Standard Dosing Regimen
The FDA-approved titration schedule is designed to minimize nausea while achieving therapeutic efficacy:
- Days 1-3: 0.5 mg once daily 1
- Days 4-7: 0.5 mg twice daily 1
- Day 8 through week 12: 1 mg twice daily (maintenance dose) 1
Varenicline should be taken orally after eating with a full glass of water to reduce gastrointestinal side effects. 1
Treatment Duration and Extended Therapy
The standard treatment course is 12 weeks, but patients who successfully quit should receive an additional 12-week course (total 24 weeks) to significantly increase long-term abstinence rates. 2, 1 This extended therapy approach was validated in a trial of 1,236 smokers and increases continuous abstinence rates from 49.6% to 70.5% at 24 weeks. 2
Timing Relative to Quit Date
Begin varenicline 1 week before the target quit date. 1 Alternatively, patients can start varenicline and then quit smoking between days 8-35 of treatment if they prefer a more flexible approach. 1
Alternative Dosing Strategies
Gradual Reduction Approach
For patients unable or unwilling to quit abruptly, a gradual reduction strategy is available:
- Start varenicline and reduce smoking by 50% within the first 4 weeks 1
- Reduce by an additional 50% in the next 4 weeks 1
- Achieve complete abstinence by week 12, then continue treatment for an additional 12 weeks (total 24 weeks) 1
Lower Dose Option
A reduced maintenance dose of 0.5 mg twice daily may be considered for patients who cannot tolerate the standard 1 mg twice daily dose, though this is less effective. 2, 1 One randomized trial of 484 smokers found similar 1-year abstinence rates between 1 mg twice daily (46.5%) and 0.5 mg twice daily (46.4%), though the standard dose remains preferred based on broader evidence. 3
Flexible dosing allowing patients to self-regulate between 0.5 mg daily and 1 mg twice daily may reduce adverse effects while maintaining efficacy, though doses exceeding 2 mg/day provide no additional benefit and significantly increase nausea and vomiting. 2
Special Populations
Severe Renal Impairment
For patients with creatinine clearance <30 mL/min:
- Start with 0.5 mg once daily 1
- May titrate to maximum of 0.5 mg twice daily if tolerated 1
- For end-stage renal disease on hemodialysis: maximum 0.5 mg once daily 1
Normal Renal and Hepatic Function
No dose adjustment is necessary for mild-to-moderate renal impairment or any degree of hepatic impairment. 1
Elderly Patients
No dose adjustment required, but monitor renal function as elderly patients are more likely to have decreased renal clearance. 1
Behavioral Support Requirements
Varenicline should be combined with behavioral counseling for optimal outcomes. 2, 1 The National Comprehensive Cancer Network recommends:
- Four or more counseling sessions during the 12-week treatment course 2
- First session within 2-3 weeks of starting treatment 2
- Sessions lasting 10-30+ minutes, with longer and more frequent sessions associated with higher success rates 2
Efficacy Data
Varenicline is the most effective single pharmacotherapy for smoking cessation, increasing quit odds almost 3-fold compared to placebo (RR 2.24,95% CI 2.06-2.43). 2 It demonstrates superior efficacy compared to bupropion (RR 1.39,95% CI 1.25-1.54) and single forms of nicotine replacement therapy (RR 1.25,95% CI 1.14-1.37). 2
In the pivotal trial, continuous abstinence rates during weeks 9-12 were 43.9% with varenicline versus 29.8% with bupropion and 17.6% with placebo. 4 At 52 weeks, abstinence rates were 23% with varenicline versus 14.6% with bupropion and 10.3% with placebo. 4
Common Side Effects and Management
Nausea occurs in 28-40% of patients, typically peaks in weeks 1-2, and diminishes over time. 2, 5 The gradual titration schedule is specifically designed to minimize this dose-dependent effect. 2 Other common side effects include insomnia (14-15%) and abnormal dreams (10-13%). 2, 5
Monitor for neuropsychiatric symptoms including depression, agitation, behavioral changes, and suicidal ideation throughout treatment. 2, 5, 1 However, the large EAGLES trial found no significant increase in neuropsychiatric events with varenicline compared to nicotine patch or placebo. 6, 5
Contraindications and Precautions
Avoid varenicline in patients with brain metastases or history of seizures due to rare but significant seizure risk. 6, 2, 5 The medication is contraindicated in patients with history of serious hypersensitivity or skin reactions to varenicline. 1
Recent systematic reviews have not identified a significant link between varenicline and increased cardiovascular adverse events, and the National Comprehensive Cancer Network considers it to have a favorable risk/benefit ratio. 6, 5
Retreatment After Failed Attempt
Patients who fail initial varenicline therapy can be retreated once factors contributing to the failed attempt are identified and addressed. 2, 1 Varenicline remains effective and well-tolerated for retreatment, as demonstrated in a trial of 498 patients. 2