Champix

Champix

varenicline

Manufacturer:

Pfizer

Distributor:

Zuellig
Full Prescribing Info
Contents
Varenicline tartrate.
Description
Varenicline tartrate (Champix) 500 mcg film-coated tablet: Each film-coated tablet contains varenicline tartrate equivalent to 500 mcg of varenicline.
Varenicline tartrate (Champix) 1 mg film-coated tablet: Each film-coated tablet contains varenicline tartrate equivalent to 1 mg of varenicline.
Varenicline tartrate (Champix) film-coated tablets contain the active ingredient, varenicline (as the tartrate salt), which is a partial agonist selective for α4β2 nicotinic acetylcholine receptor subtypes.
Varenicline, as the tartrate salt, is a powder which is a white to off-white to slightly yellow solid with the following chemical name: 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3] benzazepine, (2R,3R)-2,3-dihydroxybutanedioate (1:1). It is highly soluble in water.
Varenicline tartrate has a molecular weight of 361.35 Daltons, and a molecular formula of C13H13N3•C4H6O6.
Action
Pharmacology: Pharmacodynamics: Varenicline tartrate (Champix) binds with high affinity and selectivity at the α4β2 neuronal nicotinic acetylcholine receptors, where it acts as a partial agonist - a compound that has both agonist activity, with lower intrinsic efficacy than nicotine, and antagonist activities in the presence of nicotine.
Electrophysiology studies in vitro and neurochemical studies in vivo have shown that varenicline tartrate (Champix) binds to the α4β2 neuronal nicotinic acetylcholine receptors and stimulates receptor-mediated activity, but at a significantly lower level than nicotine. Nicotine competes for the same human α4β2 nAChR binding site for which varenicline tartrate (Champix) has higher affinity. Therefore, varenicline tartrate (Champix) can effectively block nicotine's ability to fully activate α4β2 receptors and the mesolimbic dopamine system, the neuronal mechanism underlying reinforcement and reward experienced upon smoking. Varenicline tartrate (Champix) is highly selective and binds more potently to the α4β2 receptor subtype (Ki = 0.15 nM) than to other common nicotinic receptors (α3β4 Ki = 84 nM, α7 Ki = 620 nM, α1βγδ Ki = 3,400 nM), or to non-nicotinic receptors and transporters (Ki >1M, except to 5-HT3 receptors: Ki = 350 nM).
The efficacy of varenicline tartrate (Champix) in smoking cessation is a result of varenicline's partial agonist activity at the α4β2 nicotinic receptor where its binding produces an effect sufficient to alleviate symptoms of craving and withdrawal (agonist activity), while simultaneously resulting in a reduction of the rewarding and reinforcing effects of smoking by preventing nicotine binding to α4β2 receptors (antagonist activity).
Clinical Efficacy and Safety: The efficacy of varenicline tartrate (Champix) in smoking cessation was demonstrated in 3 pre-marketing clinical trials involving chronic cigarette smokers (≥10 cigarettes per day). 2,619 patients received varenicline tartrate (Champix) 1 mg BID (titrated during the first week), 669 patients received bupropion 150 mg BID (also titrated) and 684 patients received placebo.
Comparative Clinical Studies: Two identically designed double-blind clinical trials prospectively compared the efficacy of varenicline tartrate (Champix) (1 mg twice daily), sustained release bupropion (150 mg twice daily) and placebo in smoking cessation. In these 52-week duration studies, patients received treatment for 12 weeks, followed by a 40-week non-treatment phase.
In all studies, patients were provided with an educational booklet on smoking cessation and received up to 10 minutes of smoking cessation counseling at each weekly treatment visit according to Agency for Healthcare Research and Quality guidelines. Patients set a date to stop smoking (target quit date, TQD) with dosing starting 1 week before this date.
The primary endpoint of the two studies was the carbon monoxide (CO) confirmed, 4-week continuous quit rate (4W-CQR) from week 9 through week 12. The primary endpoint for varenicline demonstrated statistical superiority to bupropion and placebo.
After the 40-week non-treatment phase, a key secondary endpoint for both studies was the Continuous Abstinence Rate (CA) at week 52. CA was defined as the proportion of all subjects treated who did not smoke (not even a puff of a cigarette) from Week 9 through Week 52 and did not have an exhaled CO measurement of >10 ppm. The 4W-CQR (weeks 9 through 12) and CA rate (weeks 9 through 52) from studies 1 and 2 are included in the following table: See Table 1.

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Patient reported craving, withdrawal and reinforcing effects of smoking: Across both Studies 1 and 2 during active treatment, Patient Reported Outcomes measures demonstrated that craving and withdrawal were significantly reduced in patients randomized to varenicline tartrate (Champix) in comparison with placebo. Varenicline tartrate (Champix) also significantly reduced reinforcing effects of smoking that can perpetuate smoking behavior in patients who smoke during treatment compared with placebo. The effect of varenicline tartrate (Champix) on craving, withdrawal and reinforcing effects of smoking were not measured during the non-treatment long-term follow-up phase.
Maintenance of Abstinence Study: The third study assessed the benefit of an additional 12 weeks of varenicline tartrate (Champix) therapy on the maintenance of abstinence. Patients in this study (n = 1,927) received open-label varenicline tartrate (Champix) 1 mg twice daily for 12 weeks. Patients who stopped smoking by Week 12 were then randomized to receive either varenicline tartrate (Champix) (1 mg twice daily) or placebo for an additional 12 weeks for a total study duration of 52 weeks.
The primary study endpoint was the CO-confirmed continuous abstinence rate from week 13 through week 24 in the double-blind treatment phase. A key secondary endpoint was the continuous abstinence (CA) rate for week 13 through week 52.
This study showed the benefit of an additional 12-week treatment with varenicline tartrate (Champix) 1 mg twice daily for the maintenance of smoking cessation compared to placebo. The odds of maintaining abstinence at week 24, following an additional 12 weeks of treatment with varenicline tartrate (Champix), were 2.47 times those for placebo (p <0.0001). Superiority to placebo for CA was maintained through week 52 (Odds Ratio=1.35, p = 0.0126).
The key results are summarized in the following table: See Table 2.

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Flexibility in Setting a Quit Date: The effect of varenicline tartrate (Champix) 1 mg BID in a flexible, patient-selected quit date setting was assessed in a double-blind, placebo-controlled study of 651 subjects. Subjects were randomized 3:1 to varenicline tartrate (Champix) or placebo for a treatment of 12 weeks and a followed up post-treatment for another 12 weeks. In this study, 486 subjects received varenicline tartrate (Champix) and 165 received placebo. Patients were instructed to select a quit date after the initial week of dose titration and before the clinical visit at the end of week 5 of treatment. Patients treated with varenicline tartrate (Champix) had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (53.94%) compared to patients treated with placebo (19.4%) (odds ratio 6.03; 95% CI 3.80, 9.56; p <0.0001) and from week 9 through 24 (35.2%) compared to subjects treated with placebo (12.73%) (odds ratio 4.45; 95% CI 2.62, 7.55; p <0.0001). Adverse events in this study were quantitatively and qualitatively similar to those observed in pre-marketing studies.
The key results are summarized in the following table: See Table 3.

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Study in Subjects Re-treated with Varenicline tartrate (Champix): Varenicline tartrate (Champix) was evaluated in a double-blind, placebocontrolled trial of 494 patients who had made a previous attempt to quit smoking with varenicline tartrate (Champix), and either did not succeed in quitting or relapsed after treatment. Subjects were randomized 1:1 to varenicline tartrate (Champix) 1 mg twice daily (N=249) or placebo (N =245) for 12 weeks of treatment and followed for up to 40 weeks post-treatment. Patients included in this study had taken varenicline tartrate (Champix) for a smoking-cessation attempt in the past (for a total treatment duration of a minimum of two weeks), at least three months prior to study entry, and had been smoking for at least four weeks.
Patients treated with varenicline tartrate (Champix) had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (45.0%) compared to patients treated with placebo (11.8%) (odds ratio 7.08; 95% CI 4.34, 11.55; p <0.0001) and from weeks 9 through 52 (20.1%) compared to subjects treated with placebo (3.3%) (odds ratio 9.00; 95% CI 3.97, 20.41; p <0.0001).
Adverse events in this study were quantitatively and qualitatively similar to those observed in pre-marketing studies.
The key results are summarized in the following table: See Table 4.

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Gradual approach to quitting smoking: Varenicline tartrate (Champix) was evaluated in a 52-week double-blind placebo-controlled study of 1,510 subjects who were not able or willing to quit smoking within four weeks, but were willing to gradually reduce their smoking over a 12-week period before quitting. Subjects were randomized to either varenicline tartrate (Champix) 1 mg twice daily (n = 760) or placebo (n = 750) for 24 weeks and followed up post-treatment through week 52. Subjects were instructed to reduce the number of cigarettes smoked by at least 50 percent by the end of the first four weeks of treatment, followed by a further 50 percent reduction from week four to week eight of treatment, with the goal of reaching complete abstinence by 12 weeks. After the initial 12-week reduction phase, subjects continued treatment for another 12 weeks. Subjects treated with varenicline tartrate (Champix) had a significantly higher Continuous Abstinence Rate compared with placebo at weeks 15 through 24 (32.1% vs. 6.9%; odds ratio 8.74; 95% CI 6.09, 12.53; p <0.0001) and weeks 21 through 52 (27.0% vs. 9.9%; odds ratio 4.02; 95% CI 2.94, 5.50; p <0.0001).
The varenicline tartrate (Champix) safety profile in this study was consistent with the premarketing studies.
The key results are summarized in the following table: See Table 5.

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Study in Subjects with Cardiovascular Disease: Varenicline tartrate (Champix) was evaluated in a randomized, double-blind, placebo-controlled study of 703 subjects with stable, documented cardiovascular disease (other than or in addition to hypertension) that had been diagnosed for more than 2 months. Subjects aged 35 to 75 years were randomized to varenicline tartrate (Champix) 1 mg BID or placebo for a treatment of 12 weeks and then were followed for 40 weeks post-treatment. Subjects treated with varenicline tartrate (Champix) had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (47.3%) compared to subjects treated with placebo (14.3%) (odds ratio 6.05; 95% CI 4.13, 8.86; p <0.0001) and from week 9 through 52 (19.8%) compared to subjects treated with placebo (7.4%) (odds ratio 3.19; 95% CI 1.97, 5.18; p <0.0001). Deaths and serious cardiovascular events occurring over the 52 weeks of the study (treatment-emergent and non-treatment- emergent) were adjudicated by a blinded, independent committee. The following treatment-emergent adjudicated events occurred with a frequency ≥1% in either treatment group: non-fatal myocardial infarction (1.1% vs. 0.3% for varenicline tartrate (Champix) and placebo, respectively), and hospitalization for angina pectoris (0.6% vs. 1.1%). During non-treatment follow-up to 52 weeks, adjudicated events with a frequency ≥1% included need for coronary revascularization (2.0% vs. 0.6%), hospitalization for angina pectoris (1.7% vs. 1.1%), and new diagnosis of peripheral vascular disease (PVD) or admission for a PVD procedure (1.4% vs. 0.6%). Some of the patients requiring coronary revascularization underwent the procedure as part of management of non-fatal MI and hospitalization for angina. Cardiovascular death occurred in 0.3% of patients in the varenicline tartrate (Champix) arm and 0.6% of patients in the placebo arm over the course of the 52 week study. (See Precautions.)
The key results are summarized in the following table: See Table 6.

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Cardiovascular Safety Assessment Study in Subjects with and without a History of Psychiatric Disorder: The cardiovascular (CV) safety of varenicline tartrate (Champix) was evaluated in the Cardiovascular Safety Assessment Study in subjects with and without a history of psychiatric disorder (parent study) and in a nontreatment extension study. In the parent study (N=8058), subjects aged 18-75 years, smoking 10 or more cigarettes per day were randomized 1:1:1:1 to varenicline tartrate (Champix) 1 mg BID, bupropion SR 150 mg BID, nicotine replacement therapy patch (NRT) 21 mg/day with taper or placebo for a treatment period of 12 weeks; they were then followed for another 12 weeks post-treatment. The non-treatment extension study enrolled 4595 of the 6293 subjects who completed the parent study and followed them through week 52. Of all treated subjects, 1749 (21.7%) had a medium CV risk and 644 (8.0%) had a high CV risk, as defined by Framingham score.
The primary CV endpoint was the time to major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke during treatment. Deaths and cardiovascular events were adjudicated by a blinded, independent committee. The following table shows the incidence of MACE and Hazard Ratios vs. placebo for all treatment groups during treatment, and cumulative for treatment plus 30 days and through end of study. (See Table 7.)

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Incidence of MACE + (defined as any MACE or a new onset or worsening peripheral vascular disease (PVD) requiring intervention, a need for coronary revascularization, or hospitalization for unstable angina) and all cause deaths are shown for all treatment groups during treatment, and cumulative for treatment plus 30 days and through end of study in the following table. (See Table 8.)

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The use of varenicline tartrate (Champix), bupropion, and NRT was not associated with an increased risk of CV AEs in smokers treated for up to 12 weeks and followed for up to 1 year compared to placebo, although because of the relatively low number of events overall, an association cannot be entirely ruled out. The number of subjects with MACE, MACE + and all cause deaths was similar or lower for the varenicline-treated subjects compared to those treated with placebo. (See Precautions.)
Study in Subjects with Chronic Obstructive Pulmonary Disease: Varenicline tartrate (Champix) was evaluated in a randomized, double-blind, placebo-controlled study of 499 subjects with mild-to-moderate Chronic Obstructive Pulmonary Disease with post-bronchodilator FEV1/FVC <70% and FEV1 ≥50% of predicted normal value. Subjects aged ≥35 years were randomized to varenicline tartrate (Champix) 1 mg BID or placebo for a treatment of 12 weeks and then were followed for 40 weeks post-treatment. Subjects treated with varenicline tartrate (Champix) had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (42.3%) compared to subjects treated with placebo (8.8%) (odds ratio 8.40; 95% CI 4.99, 14.14; p <0.0001) and from week 9 through 52 (18.6%) compared to subjects treated with placebo (5.6%) (odds ratio 4.04; 95% CI 2.13, 7.67; p <0.0001). Adverse events in this study were quantitatively and qualitatively similar to those observed in pre-marketing studies.
The key results are summarized in the following table: See Table 9.

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Study in Subjects with Major Depressive Disorder: Varenicline tartrate (Champix) was evaluated in a randomized, double-blind, placebo-controlled study of 525 subjects with major depressive disorder without psychotic features (DSM-IV TR), on stable antidepressant treatment and/or who experienced a major depressive episode in the past 2 years and were successfully treated. Subjects aged 18 to 75 years were randomized to varenicline tartrate (Champix) 1 mg BID or placebo for a treatment of 12 weeks and then followed for 40 weeks post-treatment. Subjects treated with varenicline tartrate (Champix) had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (35.9%) compared to subjects treated with placebo (15.6%) (odds ratio 3.35; 95% CI 2.16, 5.21; p <0.0001) and from week 9 through 52 (20.3%) compared to subjects treated with placebo (10.4%) (odds ratio 2.36; 95% CI 1.40, 3.98; p = 0.0011).
The most common adverse events (≥10%) in subjects taking varenicline tartrate (Champix) were nausea (27.0% vs. 10.4% on placebo), headache (16.8% vs. 11.2%), abnormal dreams (11.3% vs. 8.2%), insomnia (10.9% vs. 4.8%) and irritability (10.9% vs. 8.2%). Additionally, the following psychiatric AEs were reported in ≥2% of patients in either treatment group (varenicline or placebo, respectively): anxiety (7.0% vs. 9.3%), agitation (6.6% vs. 4.1%), depression (6.6% vs. 4.8%), tension (3.5% vs. 3.0%), depressed mood (2.7% vs. 3.7%), sleep disorder (2.7% vs. 1.5%), hostility (2.0% vs. 0.4%) and restlessness (2.0% vs. 1.9%). Psychiatric scales showed no differences between the varenicline tartrate (Champix) and placebo groups and no overall worsening of depression during the study in either treatment group.
The percentage of subjects with suicidal ideation and/or behavior was similar between the varenicline tartrate (Champix) and placebo groups during treatment (6.0% and 7.5%, respectively) and the non-treatment follow-up (6.2% and 5.8%, respectively). There was one event of intentional self injury/possible suicide attempt during treatment (Day 73) in a subject with history of alcohol abuse in the placebo group. A possible suicide could not be ruled out in one subject who died by an overdose of illicit drugs 76 days after last dose of study drug in the varenicline tartrate (Champix) group.
The key efficacy results are summarized in the following table: See Table 10.

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Study in Subjects with Stable Schizophrenia or Schizoaffective Disorder: Varenicline tartrate (Champix) safety and tolerability was assessed in a double-blind study of 128 smokers with stable schizophrenia or schizoaffective disorder, on antipsychotic medication, randomized 2:1 to varenicline tartrate (Champix) (1 mg twice daily) or placebo for 12 weeks with 12-week non-drug follow-up.
The most common adverse events in subjects taking varenicline tartrate (Champix) were nausea (23.8% vs. 14.0% on placebo), headache (10.7% vs. 18.6% on placebo) and vomiting (10.7% vs. 9.3% on placebo). Among reported neuropsychiatric adverse events, insomnia was the only event reported in either treatment group in ≥5% of subjects at a rate higher in the varenicline group than in placebo (9.5% vs. 4.7%).
Overall, there was no worsening of schizophrenia in either treatment group as measured by psychiatric scales and there were no overall changes in extra-pyramidal signs.
In the varenicline group compared to placebo, a higher proportion of subjects reported suicidal ideation or behavior prior to enrollment (lifetime history) and after the end of active treatment period (on Days 33 to 85 after the last dose of drugs). During the active treatment period, the incidence of suicide-related events was similar between the varenicline-treated and the placebo-treated subjects (11% vs. 9.3%, respectively). The percentage of subjects with suicide-related events in the active treatment phase compared to post-treatment phase was unchanged in the varenicline group; in the placebo group, this percentage was lower in the post-treatment phase. There were no completed suicides. There was one suicidal attempt in a varenicline-treated subject whose lifetime history included several similar attempts. The limited data available from this single smoking cessation study is not sufficient to allow definitive conclusions to be drawn. However, these data do not suggest that varenicline treatment causes or worsens suicidality in subjects with stable schizophrenia or schizoaffective disorder.
Neuropsychiatric Safety Study in Subjects with and without a History of Psychiatric Disorder: Varenicline tartrate (Champix) was evaluated in a randomized, double-blind, active and placebo-controlled study that included subjects with a history of psychiatric disorder (psychiatric cohort, N=4074) and subjects without a history of psychiatric disorder (non-psychiatric cohort, N=3984). Subjects aged 18-75 years, smoking 10 or more cigarettes per day were randomized 1:1:1:1 to varenicline tartrate (Champix) 1 mg BID, bupropion SR 150 mg BID, nicotine replacement therapy patch (NRT) 21 mg/day with taper or placebo for a treatment period of 12 weeks; they were then followed for another 12 weeks post-treatment.
The primary safety endpoint was a composite of the following neuropsychiatric (NPS) adverse events: severe events of anxiety, depression, feeling abnormal, or hostility, and moderate or severe events of agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, suicidal behavior or completed suicide. (See Precautions.)
The following table shows the rates of the composite NPS adverse event primary end point by treatment group and the risk differences (RDs) (95% CI) vs. placebo in the non-psychiatric cohort. The individual components of the endpoint are also shown. In addition, the table shows the subset of the endpoint comprised of only events of severe intensity: See Table 11.

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In the non-psychiatric cohort, the rates of events in the composite endpoint were low across all treatment groups and were similar or lower for each of the active treatments compared to placebo: risk differences (RDs (95% Confidence Interval [CI])) vs. placebo were -1.28% (-2.40, -0.15) for varenicline tartrate (Champix), -0.08% (-1.37, 1.21) for bupropion and - 0.21% (-1.54, 1.12) for NRT. The use of varenicline tartrate (Champix), bupropion and NRT in the non-psychiatric cohort was not associated with an increased risk of NPS adverse events in the composite primary endpoint compared with placebo (95% CIs were lower than or included zero). Similarly, the use of varenicline tartrate (Champix) was not associated with an increased risk of NPS adverse events in the composite primary endpoint compared with bupropion or NRT in the non-psychiatric cohort (-1.19% (-2.30, -0.09) and -1.07 (-2.21, 0.08), respectively).
In non-psychiatric cohort, the percentage of subjects with suicidal ideation and/or behavior based on the Columbia-Suicide Severity Rating Scale (C-SSRS) was similar between the varenicline tartrate (Champix) and placebo groups during treatment and in the non-treatment follow-up, as shown in the following table: See Table 12.

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There was one completed suicide, which occurred during treatment in a subject treated with placebo in the non-psychiatric cohort.
The following table shows the rates of the composite NPS adverse event primary end point by treatment group and the risk differences (RDs) (95% CI) vs. placebo in the psychiatric cohort. The individual components of the endpoint are also shown. In addition, the table shows the subset of the endpoint comprised of only events of severe intensity: See Table 13.

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There were more events reported in patients in the psychiatric cohort in each treatment group compared with the non-psychiatric cohort. In the psychiatric cohort, the incidence of events in the composite endpoint was higher for each of the active treatments compared to placebo: RDs (95%CI) vs. placebo were 1.59% (-0.42, 3.59) for varenicline tartrate (Champix), 1.78% (-0.24, 3.81) for bupropion and 0.37% (-1.53, 2.26) for NRT. The use of varenicline tartrate (Champix), bupropion and NRT in the psychiatric cohort was not associated with an increased risk of NPS adverse events in the composite primary endpoint compared with placebo (95% CIs included zero). Similarly, the use of varenicline tartrate (Champix) was not associated with an increased risk of NPS adverse events in the composite primary endpoint compared with bupropion or NRT in the psychiatric cohort (-0.20% (-2.34, 1.95) and 1.22% (-0.81, 3.25), respectively).
In the psychiatric cohort, the percentage of subjects with suicidal ideation and/or behavior based on the Columbia-Suicide Severity Rating Scale (C-SSRS) was similar between the varenicline tartrate (Champix) and placebo groups during treatment and in the non- treatment follow-up, as shown in the following table: See Table 14.

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There were no completed suicides reported in the psychiatric cohort.
The most commonly reported adverse events in subjects treated with varenicline tartrate (Champix) in this study were similar to those observed in premarketing studies. Adverse events reported in ≥10% of subjects treated with varenicline tartrate (Champix) in the entire study population were nausea (25.3% vs. 6.8% on placebo) and headache (12.2% vs. 9.9% on placebo).
In both cohorts, subjects treated with varenicline tartrate (Champix) had a superior rate of CO-confirmed abstinence during weeks 9 through 12 and 9 through 24 compared to subjects treated with bupropion, nicotine patch and placebo.
The key efficacy results are summarized in the following table: See Table 15.

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Neuropsychiatric Safety Meta-analyses and Observational Studies: Analyses of clinical trial data did not show evidence of an increased risk of serious neuropsychiatric events with varenicline tartrate (Champix) compared to placebo. In addition, independent observational studies have not supported an increased risk of serious neuropsychiatric events in patients treated with varenicline tartrate (Champix) compared to patients prescribed nicotine replacement therapy (NRT) or bupropion.
Analyses of Clinical Trials: A meta-analysis of 5 randomized, double-blind, placebo-controlled trials, including 1907 patients (1130 varenicline, 777 placebo), was conducted to assess suicidal ideation and behavior as reported on the Columbia-Suicide Severity Rating Scale (C-SSRS). This meta analysis included one trial (N = 127) in patients with a history of schizophrenia or schizoaffective disorder and another trial (N = 525) in patients with a history of depression. The results showed no increase in the incidence of suicidal ideation and/or behavior in patients treated with varenicline compared to patients treated with placebo, with a Risk Ratio (RR) of 0.79 (95% Confidence Interval [CI]: 0.46, 1.36), as shown in the table below. Forty-eight (48) of the 55 patients who reported suicidal ideation or behavior (24 varenicline, 24 placebo) were from the two trials that enrolled patients with a history of schizophrenia, schizoaffective disorder, or depression. Few patients reported these events in the other three trials (4 varenicline tartrate (Champix), 3 placebo).
Number of Patients and Risk Ratio for Suicidal Ideation and/or Behavior Reported on C-SSRS from a Meta-Analysis of 5 Clinical Trials Comparing Varenicline tartrate (Champix) to Placebo: See Table 16.

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A meta-analysis of 18 double-blind, randomized, placebo-controlled clinical trials was conducted to assess the neuropsychiatric safety of varenicline tartrate (Champix). These trials included the 5 trials described above that used the C-SSRS, and a total of 8521 patients (5072 varenicline, 3449 placebo), some of which had psychiatric conditions. The results showed a similar incidence of combined neuropsychiatric adverse events, other than sleep disorders, in patients treated with varenicline tartrate (Champix) compared to patients treated with placebo, with a risk ratio (RR) of 1.01 (95% CI: 0.88, 1.15). Pooled data from these 18 trials showed a similar incidence rate of individual categories of psychiatric events in patients treated with varenicline tartrate (Champix) compared to patients treated with placebo. The table below describes the most frequently (≥1%) reported categories of adverse events related to psychiatric safety other than sleep disorders and disturbances.
Psychiatric Adverse Events Occurring in ≥1% of Patients from Pooled Data from 18 Clinical Trials: See Table 17.

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Observational Studies: Four observational studies, each including 10,000 to 30,000 users of varenicline tartrate (Champix) in the adjusted analyses, compared the risk of serious neuropsychiatric events, including neuropsychiatric hospitalizations and fatal and non-fatal self-harm, in patients treated with varenicline tartrate (Champix) versus patients prescribed NRT or bupropion. All studies were retrospective cohort studies and included patients with and without a psychiatric history. All studies used statistical methods to control for confounding factors, including preferential prescribing of varenicline tartrate (Champix) to healthier patients, although there is the possibility of residual confounding.
Two of the studies found no difference in risk of neuropsychiatric hospitalizations between varenicline tartrate (Champix) users and nicotine patch users (Hazard Ratio [HR] 1.14; 95% Confidence Interval [CI]: 0.56– 2.34 in the first study, and 0.76; 95% CI: 0.40-1.46 in the second study). The power to detect differences in these two studies was limited. The third study reported no difference in risk of psychiatric adverse events diagnosed during an emergency department visit or inpatient admission between varenicline users and bupropion users (HR 0.85; 95% CI: 0.55- 1.30). Based on post-marketing reports, bupropion may be associated with neuropsychiatric adverse events. The fourth study showed no evidence of a higher risk of fatal and non-fatal self- harm (HR of 0.88; 95% CI: 0.52- 1.49) in patients prescribed varenicline tartrate (Champix) compared to patients prescribed NRT. The occurrence of detected suicide was rare during the three months after patients initiated any drug treatment (two cases in 31,260 varenicline tartrate (Champix) users and six cases in 81,545 NRT users).
Other Observational Studies: Pregnancy Cohort Study: A population-based cohort study compared infants exposed to varenicline in utero (N=335) with infants born to mothers who smoked during pregnancy (N=78,412) and infants born to non-smoking mothers (N=806,438). In this study, infants exposed to varenicline in utero were no more likely to have major congenital malformations (3.6%) than infants born to mothers who smoked during pregnancy (4.3%) or to non-smoking mothers (4.2%). Similarly, infants exposed to varenicline in utero, as compared to infants of smoking and non-smoking mothers, were not at increased risk of stillbirth, (0.3%, 0.5%, 0.3%, respectively), small for gestational age (12.5%, 17.1%, 9.1%), preterm birth (7.5%, 7.9%, 5.8%), or premature rupture of membrane (3.6%, 5.4%, 3.8%). (See Use in Pregnancy & Lactation.)
Pharmacokinetics: Absorption: Maximum plasma concentrations of varenicline tartrate (Champix) occur typically within 3-4 hours after oral administration. Following administration of multiple oral doses to healthy volunteers, steady-state conditions were reached within 4 days. Absorption is virtually complete after oral administration and systemic availability is high. Oral bioavailability of varenicline tartrate (Champix) is unaffected by food or time-of-day dosing.
Distribution: Varenicline tartrate (Champix) distributes into tissues, including the brain. Apparent volume of distribution averaged 415 liters (%CV = 50) at steady state. Plasma protein binding of varenicline tartrate (Champix) is low (≤20%) and independent of both age and renal function.
Metabolism: Varenicline tartrate (Champix) undergoes minimal metabolism with 92% excreted unchanged in the urine and less than 10% excreted as metabolites. Minor metabolites in urine include varenicline N-carbamoylglucuronide and hydroxyvarenicline. In circulation, varenicline tartrate (Champix) comprises 91% of drug-related material. Minor circulating metabolites include varenicline tartrate (Champix) N-carbamoylglucuronide and N-glucosylvarenicline.
Excretion: The elimination half-life of varenicline tartrate (Champix) is approximately 24 hours. Renal elimination of varenicline tartrate (Champix) is primarily through glomerular filtration along with active tubular secretion via the organic cationic transporter, OCT2.
Linearity/Non-linearity: Varenicline tartrate (Champix) exhibits linear kinetics when given as single (0.1 to 3 mg) or repeated (1 to 3 mg/day) doses.
Pharmacokinetics in special patient populations: There are no clinically meaningful differences in varenicline tartrate (Champix) pharmacokinetics due to age, race, gender, smoking status, or use of concomitant medications, as demonstrated in specific pharmacokinetic studies and in population pharmacokinetic analyses.
Patients with hepatic impairment: Due to the absence of significant hepatic metabolism, varenicline tartrate (Champix) pharmacokinetics should be unaffected in patients with hepatic impairment (see Patients with hepatic impairment under Dosage & Administration).
Patients with renal insufficiency: Varenicline tartrate (Champix) pharmacokinetics were unchanged in subjects with mild renal impairment (estimated creatinine clearance >50 ml/min and 80 ml/min). In patients with moderate renal impairment (estimated creatinine clearance ≥30 ml/min and ≤50 ml/min), varenicline tartrate (Champix) exposure increased 1.5-fold compared with subjects with normal renal function (estimated creatinine clearance >80 ml/min). In subjects with severe renal impairment (estimated creatinine clearance <30 ml/min), varenicline tartrate (Champix) exposure was increased 2.1-fold. In subjects with end-stage-renal disease (ESRD), varenicline tartrate (Champix) was efficiently removed by hemodialysis (see Patients with renal insufficiency under Dosage & Administration).
Use in elderly patients: The pharmacokinetics of varenicline tartrate (Champix) in elderly patients with normal renal function (aged 65-75 years) is similar to that of younger adult subjects. In elderly patients with severe renal impairment, dosage adjustment is recommended (see Patients with renal insufficiency under Dosage & Administration).
Use in pediatric patients: Single and multiple-dose pharmacokinetics of varenicline tartrate (Champix) have been investigated in pediatric patients aged 12 to 17 years old (inclusive) and were approximately dose-proportional over the 0.5 mg to 2 mg daily dose range studied. Steady-state systemic exposure in adolescent patients of bodyweight >55 kg, as assessed by AUC(0-24), was comparable to that noted for the same doses in the adult population. When 0.5 mg BID was given, steady-state daily exposure of varenicline tartrate (Champix) was, on average, higher (by approximately 40%) in adolescent patients with bodyweight ≤55 kg compared to that noted in the adult population (see Use in pediatric patients under Dosage & Administration).
Toxicology: Preclinical safety data: Carcinogenesis, Mutagenesis, Impairment of Fertility: Lifetime carcinogenicity studies were performed in CD-1 mice and Sprague-Dawley rats. There was no evidence of a carcinogenic effect in mice administered varenicline tartrate (Champix) by oral gavage for 2 years at doses up to 20 mg/kg/day (47 times the maximum recommended human daily exposure based on AUC). Rats were administered varenicline tartrate (Champix) (1, 5, and 15 mg/kg/day) by oral gavage for 2 years. In male rats (n = 65 per sex per dose group), incidences of hibernoma (tumor of the brown fat) were increased at the mid dose (1 tumor, 5 mg/kg/day, 23 times the maximum recommended human daily exposure based on AUC) and maximum dose (2 tumors, 15 mg/kg/day, 67 times the maximum recommended human daily exposure based on AUC). The clinical relevance of this finding to humans has not been established. There was no evidence of carcinogenicity in female rats.
Varenicline tartrate (Champix) was not genotoxic, with or without metabolic activation, in the following assays: Ames bacterial mutation assay; mammalian CHO/HGPRT assay; and tests for cytogenetic aberrations in vivo in rat bone marrow and in vitro in human lymphocytes.
There was no evidence of impairment of fertility in either male or female Sprague-Dawley rats administered varenicline succinate up to 15 mg/kg/day (67 and 36 times, respectively, the maximum recommended human daily exposure based on AUC at 1 mg BID). However, a decrease in fertility was noted in the offspring of pregnant rats who were administered varenicline succinate at an oral dose of 15 mg/kg/day (36 times the maximum recommended human daily exposure based on AUC at 1 mg BID). This decrease in fertility in the offspring of treated female rats was not evident at an oral dose of 3 mg/kg/day (9 times the maximum recommended human daily exposure based on AUC at 1 mg BID).
Teratogenesis: Varenicline succinate was not teratogenic in rats and rabbits at oral doses up to 15 and 30 mg/kg/day, respectively (36- and 50-times the maximum recommended human daily exposure based on AUC at 1 mg BID, respectively).
Non-teratogenic Effects: Varenicline succinate has been shown to have an adverse effect on the fetus in animal reproduction studies. Administration of varenicline succinate to pregnant rabbits resulted in reduced fetal weights at an oral dose of 30 mg/kg/day (50 times the human AUC at 1 mg BID); this reduction was not evident following treatment with 10 mg/kg/day (23 times the maximum recommended daily human exposure based on AUC). In addition, in the offspring of pregnant rats treated with varenicline succinate there were decreases in fertility and increases in auditory startle response at an oral dose of 15 mg/kg/day (36 times the maximum recommended human daily exposure based on AUC at 1 mg BID).
Non-clinical data indicate varenicline has reinforcing properties albeit with lower potency than nicotine. Moreover, in clinical studies in humans, varenicline showed low abuse potential.
Indications/Uses
Varenicline tartrate (Champix) is indicated as an aid to smoking cessation treatment.
Dosage/Direction for Use
Smoking cessation therapies are more likely to succeed for patients who are motivated to stop smoking and who are provided with additional advice and support.
The recommended dose of varenicline tartrate (Champix) is 1 mg twice daily following a 1-week titration as follows: See Table 18.

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The patient should set a date to stop smoking. Varenicline tartrate (Champix) dosing should start 1 week before this date. Alternatively, a flexible approach to quitting may be adopted: the patient can begin varenicline dosing and then quit smoking between days 8 and 35 of treatment (see Pharmacology: Pharmacodynamics: Flexibility in Setting a Quit Date under Actions). Patients should be treated with varenicline tartrate (Champix) for 12 weeks.
For patients who have successfully stopped smoking at the end of 12 weeks, an additional course of 12 weeks treatment with varenicline tartrate (Champix) at 1 mg twice daily is recommended for the maintenance of abstinence (see Pharmacology: Pharmacodynamics: Maintenance of Abstinence Study under Actions).
A gradual approach to quitting smoking with varenicline tartrate (Champix) should be considered for patients who are not able or willing to quit abruptly. Patients should reduce smoking during the first 12 weeks of treatment and quit by the end of that treatment period. Patients should then continue taking varenicline for an additional 12 weeks for a total of 24 weeks of treatment (see Pharmacology: Pharmacodynamics: Gradual approach to quitting smoking under Actions).
Patients who are motivated to quit and who did not succeed in stopping smoking during prior varenicline therapy, or who relapsed after treatment, should be encouraged to make another attempt with varenicline tartrate (Champix) (see Pharmacology: Pharmacodynamics: Study in Subjects Re-treated with Varenicline under Actions).
Patients who cannot tolerate adverse effects of varenicline tartrate (Champix) may have the dose lowered temporarily or permanently.
Varenicline tartrate (Champix) tablets should be swallowed whole with water. Varenicline tartrate (Champix) can be taken with or without food.
Patients with renal insufficiency: No dosage adjustment is necessary for patients with mild (estimated creatinine clearance >50 ml/min and ≤80 ml/min) to moderate (estimated creatinine clearance ≥30 ml/min and ≤50 ml/min) renal impairment.
For patients with severe renal impairment (estimated creatinine clearance <30 ml/min), the recommended dose of varenicline tartrate (Champix) is 1 mg once daily. Dosing should begin at 0.5 mg once daily for the first 3 days then increased to 1 mg once daily. There is insufficient clinical experience with varenicline tartrate (Champix) in patients with end stage renal disease (see Pharmacology: Pharmacokinetics: Patients with renal insufficiency under Actions).
Patients with hepatic impairment: No dosage adjustment is necessary for patients with hepatic impairment (see Pharmacology: Pharmacokinetics: Patients with hepatic impairment under Actions).
Use in elderly patients: No dosage adjustment is necessary for elderly patients. Because elderly patients are more likely to have decreased renal function, prescribers should consider the renal status of an elderly patient (see above Patients with renal insufficiency and Pharmacology: Pharmacokinetics: Patients with renal insufficiency and Use in elderly patients under Actions).
Use in pediatric patients: Varenicline tartrate (Champix) is not recommended for use in pediatric patients below 18 years of age due to insufficient data on safety and efficacy (see Pharmacology: Pharmacokinetics: Use in pediatric patients under Actions).
Overdosage
No cases of overdose were reported in pre-marketing clinical trials.
In case of overdose, standard supportive measures should be instituted as required.
Varenicline tartrate (Champix) has been shown to be dialyzed in patients with end stage renal disease, however, there is no experience in dialysis following overdose (see Pharmacology: Pharmacokinetics: Patients with renal insufficiency under Actions).
Contraindications
Known hypersensitivity to varenicline or to any of the excipients in the product (microcrystalline cellulose, dibasic calcium phosphate, anhydrous, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, Opadry Blue/White and Opadry Clear).
Special Precautions
Effect of smoking cessation: Physiological changes resulting from smoking cessation, with or without treatment with varenicline tartrate (Champix), may alter the pharmacokinetics or pharmacodynamics of some medicinal products, for which dosage adjustment may be necessary (examples include theophylline, warfarin and insulin) (see Warfarin under Interactions).
At the end of treatment, discontinuation of varenicline tartrate (Champix) was associated with an increase in irritability, urge to smoke, depression, and/or insomnia in up to 3% of patients.
There have been post-marketing reports of neuropsychiatric symptoms, some serious, including changes in behavior or thinking, anxiety, psychosis, mood swings, aggressive behavior, agitation, depressed mood, suicidal ideation and suicidal behavior, in patients attempting to quit smoking with varenicline tartrate (Champix) (see Adverse Reactions).
A large randomized, double-blind, active and placebo-controlled study was conducted to compare the risk of serious neuropsychiatric events in patients with and without a history of psychiatric disorder treated for smoking cessation with varenicline, bupropion, nicotine replacement therapy patch (NRT) or placebo. The primary safety endpoint was a composite of neuropsychiatric adverse events that have been reported in post-marketing experience. The use of varenicline tartrate (Champix) in patients with or without a history of psychiatric disorder was not associated with an increased risk of serious neuropsychiatric adverse events in the composite primary endpoint compared with placebo (see Pharmacology: Pharmacodynamics: Study in Subjects with and without a History of Psychiatric Disorder under Actions).
A causal relationship between serious neuropsychiatric events and varenicline tartrate (Champix) has not been established. Physicians should observe patients attempting to quit smoking with or without varenicline tartrate (Champix) for the occurrence of serious neuropsychiatric symptoms and should instruct patients to contact a healthcare professional if they experience such symptoms.
In clinical trials and post-marketing experience there have been reports of seizures in patients with or without a history of seizures, treated with varenicline tartrate (Champix). Varenicline tartrate (Champix) should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold. Causal relationship between these reports and varenicline tartrate (Champix) use has not been established.
There have been post-marketing reports of hypersensitivity reactions including angioedema in patients treated with varenicline tartrate (Champix). Clinical signs included swelling of the face, mouth (tongue, lips, and gums), neck (throat and larynx) and extremities. There were rare reports of life-threatening angioedema requiring urgent medical attention due to respiratory compromise. Patients experiencing these symptoms should discontinue treatment with varenicline tartrate (Champix) and contact a health care provider immediately.
There have also been post-marketing reports of rare but severe cutaneous reactions, including Stevens-Johnson Syndrome and Erythema Multiforme in patients using varenicline tartrate (Champix). As these skin reactions can be life threatening, patients should discontinue treatment at the first sign of rash or skin reaction and contact a healthcare provider immediately.
In a smoking cessation study in patients with stable cardiovascular (CV) disease and in a meta-analysis of 15 clinical trials, some CV events were reported more frequently in patients treated with varenicline tartrate (Champix) compared to placebo. These events occurred primarily in patients with known CV disease. No causal relationship between these events and varenicline tartrate (Champix) has been established. In a large smoking cessation trial that assessed CV safety in patients with and without a history of psychiatric disorder, major CV events (CV death, nonfatal MI, non-fatal stroke) were reported less frequently in patients treated with varenicline tartrate (Champix) compared to placebo. In these studies, major CV events were infrequent overall and all-cause and CV mortality was lower in patients treated with varenicline tartrate (Champix) compared to patients treated with placebo. Smoking is an independent and major risk factor for CV disease. Patients should be instructed to notify their health care providers of new or worsening cardiovascular symptoms and to seek immediate medical attention if they experience signs and symptoms of myocardial infarction or stroke. (See Pharmacology: Pharmacodynamics: Study in Subjects with Cardiovascular Disease, Cardiac Assessment Study under Actions.)
Effects on ability to drive and use machines: Patients should be advised to use caution driving or operating machinery until they know how quitting smoking and/or varenicline tartrate (Champix) may affect them.
Use In Pregnancy & Lactation
Pregnancy: A moderate amount of data on pregnant women (between 300-1,000 pregnancy outcomes) indicated no malformative or fetal/neonatal toxicity of varenicline tartrate (Champix) (see Pharmacology: Pharmacodynamics under Actions).
Animal studies have shown reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions). As a precautionary measure, it is preferable to avoid the use of varenicline tartrate (Champix) during pregnancy (see Pharmacology: Pharmacodynamics under Actions).
Lactation: It is unknown whether varenicline tartrate (Champix) is excreted in human breast milk. Animal studies suggest that varenicline tartrate (Champix) is excreted in breast milk. A decision on whether to discontinue breast-feeding or to discontinue therapy with varenicline tartrate (Champix) should be made taking into account the benefit of breast-feeding to the child and the benefit of varenicline tartrate (Champix) therapy to the woman.
Adverse Reactions
Smoking cessation with or without treatment is associated with various symptoms. For example, dysphoric or depressed mood; insomnia, irritability, frustration or anger; anxiety; difficulty concentrating; restlessness; decreased heart rate; increased appetite or weight gain have been reported in patients attempting to stop smoking. Smoking cessation, with or without pharmacotherapy, has also been associated with the exacerbation of underlying psychiatric illness. No attempt has been made in either the design or the analysis of the varenicline tartrate (Champix) studies to distinguish between adverse events associated with study drug treatment or those possibly associated with nicotine withdrawal.
Pre-marketing development clinical trials included approximately 4,000 patients treated with varenicline tartrate (Champix) for up to 1 year (average exposure 84 days). In general, when adverse reactions occurred, onset was in the first week of therapy; severity was generally mild to moderate and there were no differences by age, race or gender with regard to the incidence of adverse reactions.
In patients treated with the recommended dose of 1 mg BID following an initial titration period the adverse event most commonly reported was nausea (28.6%). In the majority of cases nausea occurred early in the treatment period, was mild to moderate in severity and seldom resulted in discontinuation.
The treatment discontinuation rate due to adverse events was 11.4% for varenicline tartrate (Champix) compared with 9.7% for placebo. In this group, the discontinuation rates for the most common adverse events in varenicline tartrate (Champix) treated patients were as follows: nausea (2.7% vs. 0.6% for placebo), headache (0.6% vs. 1.0% for placebo), insomnia (1.3% vs. 1.2% for placebo), and abnormal dreams (0.2% vs. 0.2% for placebo).
All adverse drug reactions (ADRs) listed in the following table are presented by the Medical Dictionary for Regulatory Activities (MedDRA, Version 16) System Organ Class (SOC), based on evaluation of data from premarketing phase 2-3 studies and updated based on pooled data from 18 placebo-controlled pre -and post-marketing studies, including approximately 5,000 patients treated with varenicline tartrate (Champix). Within each category, the ADRs are presented in order of frequency, and then by decreasing order of clinical importance. (See Table 19.)

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Post-Marketing Experience: The following adverse events have been reported during post-approval use of varenicline tartrate (Champix). Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
There have been reports of depressed mood, agitation, changes in behavior or thinking, anxiety, psychosis, mood swings, aggressive behavior, suicidal ideation and suicide in patients attempting to quit smoking while taking varenicline tartrate (Champix). (See Precautions).
There have also been reports of hypersensitivity reactions, such as angioedema and of rare but severe cutaneous reactions, including Stevens-Johnson Syndrome and Erythema Multiforme in patients taking varenicline tartrate (Champix) (see Precautions).
Drug Interactions
Based on varenicline tartrate (Champix) characteristics and clinical experience to date, no clinically meaningful drug interactions have been identified. No dosage adjustment of varenicline tartrate (Champix) or co-administered drugs listed below is recommended.
In vitro studies indicate that varenicline tartrate (Champix) is unlikely to alter the pharmacokinetics of compounds that are primarily metabolized by cytochrome P450 enzymes.
In vitro studies demonstrate that varenicline tartrate (Champix) does not inhibit cytochrome P450 enzymes (IC50 >6,400 ng/ml). The P450 enzymes tested for inhibition were: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4/5. Also, in human hepatocytes in vitro, varenicline tartrate (Champix) was shown to not induce the activity of cytochrome P450 enzymes 1A2 and 3A4. Therefore, varenicline tartrate (Champix) is unlikely to alter the pharmacokinetics of compounds that are primarily metabolized by cytochrome P450 enzymes.
In vitro studies demonstrate that active renal secretion of varenicline tartrate (Champix) is mediated by the human organic cation transporter, OCT2. Co-administration with inhibitors of OCT2 does not require a dose adjustment of varenicline tartrate (Champix) as the increase in systemic exposure to varenicline tartrate (Champix) is not expected to be clinically meaningful (see cimetidine interaction below). Furthermore since metabolism of varenicline tartrate (Champix) represents less than 10% of its clearance, active substances known to affect the cytochrome P450 system are unlikely to alter the pharmacokinetics of varenicline tartrate (Champix) (see Pharmacology: Pharmacokinetics: Metabolism under Actions) and therefore, a dose adjustment of varenicline tartrate (Champix) would not be required.
In vitro studies demonstrate that varenicline tartrate (Champix) does not inhibit human renal transport proteins at therapeutic concentrations. Therefore, medicinal products that are cleared by renal secretion (e.g., metformin - see as follows) are unlikely to be affected by varenicline tartrate (Champix).
Metformin: Varenicline tartrate (Champix) (1 mg twice daily) did not affect the pharmacokinetics of metformin (500 mg twice daily), which is a substrate of OCT2. Metformin had no effect on varenicline tartrate (Champix) pharmacokinetics.
Cimetidine: Co-administration of an OCT2 inhibitor, cimetidine (300 mg four times daily), with varenicline tartrate (Champix) (2 mg single dose) increased the systemic exposure of varenicline tartrate (Champix) by 29% due to a reduction in varenicline tartrate (Champix) renal clearance.
Digoxin: Varenicline tartrate (Champix) (1 mg twice daily) did not alter the steady-state pharmacokinetics of digoxin administered as a 0.25 mg daily dose.
Warfarin: Varenicline tartrate (Champix) (1 mg twice daily) did not alter the pharmacokinetics of a single 25 mg dose of (R, S) warfarin. Prothrombin time (INR) was not affected by varenicline tartrate (Champix). Smoking cessation itself may result in changes to warfarin pharmacokinetics (see Effect of smoking cessation under Precautions).
Alcohol: There are limited clinical data on any potential interaction between alcohol and varenicline tartrate (Champix). There have been post-marketing reports of increased intoxicating effects of alcohol in patients treated with varenicline tartrate (Champix). A causal relationship between these events and varenicline tartrate (Champix) use has not been established.
Use with other therapies for smoking cessation: Bupropion: Varenicline tartrate (Champix) (1 mg twice daily) did not alter the steady-state pharmacokinetics of bupropion (150 mg twice daily).
Nicotine replacement therapy (NRT): When varenicline tartrate (Champix) (1 mg twice daily) and NRT (transdermal 21 mg/day) were co-administered to smokers (N=24) for 12 days, there was a statistically significant decrease in average systolic blood pressure (mean 2.6 mmHg) measured on the final day of the study. In this study, the incidence of nausea, headache, vomiting, dizziness, dyspepsia, and fatigue was greater for the combination than for NRT alone.
Safety and efficacy of varenicline tartrate (Champix) in combination with other smoking cessation therapies have not been studied.
Caution For Usage
Special precautions for disposal and other handling No special requirements for disposal.
Storage
Store at temperatures not exceeding 30°C.
ATC Classification
N07BA03 - varenicline ; Belongs to the class of drugs used in the management of nicotine dependence.
Presentation/Packing
FC tab 500 mcg (capsular biconvex, white to off-white, debossed with "Pfizer" on one side and "CHX 0.5" on the other side) x 55's. 1 mg (capsular biconvex, light blue, debossed with "Pfizer" on one side and "CHX 1" on the other side) x 56's.
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