Chantix (Varenicline) is indicated for use as an aid to smoking cessation treatment.

Smoking cessation therapies are more likely to succeed for patients who are motivated to stop smoking and who are provided additional advice and support. Provide patients with appropriate educational materials and counseling to support the quit attempt.

The patient should set a date to stop smoking. Begin Chantix (Varenicline) dosing one week before this date. Alternatively, the patient can begin Chantix (Varenicline) dosing and then quit smoking between days 8 and 35 of treatment.
Chantix (Varenicline) should be taken after eating and with a full glass of water.

The recommended dose of Chantix (Varenicline) is 1 mg twice daily following a 1-week titration as follows:

Patients should be treated with Chantix (Varenicline) for 12 weeks. For patients who have successfully stopped smoking at the end of 12 weeks, an additional course of 12 weeks' treatment with Chantix (Varenicline) is recommended to further increase the likelihood of long-term abstinence.

Patients who do not succeed in stopping smoking during 12 weeks of initial therapy, or who relapse after treatment, should be encouraged to make another attempt once factors contributing to the failed attempt have been identified and addressed.

Consider a temporary or permanent dose reduction in patients who cannot tolerate the adverse effects of Chantix (Varenicline) .

Capsular, biconvex tablets: 0.5 mg (white to off-white, debossed with "" on one side and "CHX 0.5" on the other side) and 1 mg (light blue, debossed with "" on one side and "CHX 1.0" on the other side)

Chantix (Varenicline) is contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to Chantix (Varenicline)

Serious neuropsychiatric symptoms have been reported in patients being treated with Chantix (Varenicline) . These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Some reported cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking. Depressed mood may be a symptom of nicotine withdrawal. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these symptoms have occurred in patients taking Chantix (Varenicline) who continued to smoke. When symptoms were reported, most were during Chantix (Varenicline) treatment, but some were following discontinuation of Chantix (Varenicline) therapy.

These events have occurred in patients with and without pre-existing psychiatric disease; some patients have experienced worsening of their psychiatric illnesses. All patients being treated with Chantix (Varenicline) should be observed for neuropsychiatric symptoms or worsening of pre-existing psychiatric illness. Patients with serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder did not participate in the premarketing studies of Chantix (Varenicline) , and the safety and efficacy of Chantix (Varenicline) in such patients has not been established.

Advise patients and caregivers that the patient should stop taking Chantix (Varenicline) and contact a healthcare provider immediately if agitation, depressed mood, changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. In many postmarketing cases, resolution of symptoms after discontinuation of Chantix (Varenicline) was reported, although in some cases the symptoms persisted, therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.

The risks of Chantix (Varenicline) should be weighed against the benefits of its use. Chantix (Varenicline) has been demonstrated to increase the likelihood of abstinence from smoking for as long as one year compared to treatment with placebo. The health benefits of quitting smoking are immediate and substantial.

In a controlled clinical trial of Chantix (Varenicline) administered to patients with stable cardiovascular disease, with approximately 350 patients per treatment arm, certain cardiovascular events were reported more frequently in patients treated with Chantix (Varenicline) than in patients treated with placebo . These included treatment-emergent events (on-treatment or 30 days after treatment) of angina pectoris (13 patients in the varenicline arm vs. 7 in the placebo arm), and the serious cardiovascular events of nonfatal MI (4 vs. 1) and nonfatal stroke (2 vs. 0). During non-treatment follow up to 52 weeks, serious cardiovascular events included nonfatal myocardial infarction (3 vs. 2), need for coronary revascularization (7 vs. 2), hospitalization for angina pectoris (6 vs. 4), transient ischemic attack (1 vs. 0), new diagnosis of peripheral vascular disease (PVD) or admission for a PVD procedure (5 vs. 2). Serious cardiovascular events occurring over the 52 weeks of the study (treatment emergent and non-treatment emergent) were adjudicated by an independent blinded committee. Chantix (Varenicline) was not studied in patients with unstable cardiovascular disease or cardiovascular events occurring within two months before screening. Patients should be advised to notify a health care provider of new or worsening symptoms of cardiovascular disease. The risks of Chantix (Varenicline) should be weighed against the benefits of its use in smokers with cardiovascular disease. Smoking is an independent and major risk factor for cardiovascular disease. Chantix (Varenicline) has been demonstrated to increase the likelihood of abstinence from smoking for as long as one year compared to treatment with placebo.

The following serious adverse reactions were reported in postmarketing experience and are discussed in greater detail in other sections of the labeling:

In the placebo-controlled studies, the most common adverse events associated with Chantix (Varenicline) (>5% and twice the rate seen in placebo-treated patients) were nausea, abnormal (vivid, unusual, or strange) dreams, constipation, flatulence, and vomiting.

The treatment discontinuation rate due to adverse events in patients dosed with 1 mg twice daily was 12% for Chantix (Varenicline) , compared to 10% for placebo in studies of three months' treatment. In this group, the discontinuation rates that are higher than placebo for the most common adverse events in Chantix (Varenicline) -treated patients were as follows: nausea (3% vs. 0.5% for placebo), insomnia (1.2% vs. 1.1% for placebo), and abnormal dreams (0.3% vs. 0.2% for placebo).

Smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illness.

Based on varenicline characteristics and clinical experience to date, Chantix (Varenicline) has no clinically meaningful pharmacokinetic drug interactions

A combined single- and multiple-dose pharmacokinetic study demonstrated that the pharmacokinetics of 1 mg varenicline given once daily or twice daily to 16 healthy elderly male and female smokers (aged 65–75 yrs) for 7 consecutive days was similar to that of younger subjects. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Varenicline is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [].

No dosage adjustment is recommended for elderly patients.

In case of overdose, standard supportive measures should be instituted as required.

Varenicline has been shown to be dialyzed in patients with end stage renal disease however, there is no experience in dialysis following overdose.

Chantix (Varenicline) tablets contain varenicline (as the tartrate salt), which is a partial agonist selective for αβnicotinic 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-6-pyrazino[2,3- h][3]benzazepine, (2,3)-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 CHN • CHO. The chemical structure is:

Chantix (Varenicline) is supplied for oral administration in two strengths: a 0.5 mg capsular biconvex, white to off-white, film-coated tablet debossed with "" on one side and "CHX 0.5" on the other side and a 1 mg capsular biconvex, light blue film-coated tablet debossed with "" on one side and "CHX 1.0" on the other side. Each 0.5 mg Chantix (Varenicline) tablet contains 0.85 mg of varenicline tartrate equivalent to 0.5 mg of varenicline free base; each 1mg Chantix (Varenicline) tablet contains 1.71 mg of varenicline tartrate equivalent to 1 mg of varenicline free base. The following inactive ingredients are included in the tablets: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, Opadry® White (for 0.5 mg), Opadry® Blue (for 1 mg), and Opadry® Clear.

Varenicline binds with high affinity and selectivity at α4β2 neuronal nicotinic acetylcholine receptors. The efficacy of Chantix (Varenicline) in smoking cessation is believed to be the result of varenicline's activity at α4β2 sub-type of the nicotinic receptor where its binding produces agonist activity, while simultaneously preventing nicotine binding to these receptors.

Electrophysiology studies and neurochemical studies have shown that varenicline binds to α4β2 neuronal nicotinic acetylcholine receptors and stimulates receptor-mediated activity, but at a significantly lower level than nicotine. Varenicline blocks the ability of nicotine to activate α4β2 receptors and thus to stimulate the central nervous mesolimbic dopamine system, believed to be the neuronal mechanism underlying reinforcement and reward experienced upon smoking. Varenicline is highly selective and binds more potently to α4β2 receptors than to other common nicotinic receptors (>500-fold α3β4, >3500-fold α7, >20,000-fold α1βγδ), or to non-nicotinic receptors and transporters (>2000-fold). Varenicline also binds with moderate affinity (Ki = 350 nM) to the 5-HT3 receptor.

The efficacy of Chantix (Varenicline) in smoking cessation was demonstrated in six clinical trials in which a total of 3659 chronic cigarette smokers (≥10 cigarettes per day) were treated with Chantix (Varenicline) . In all clinical studies, abstinence from smoking was determined by patient self-report and verified by measurement of exhaled carbon monoxide (CO≤10 ppm) at weekly visits. Among the Chantix (Varenicline) -treated patients enrolled in these studies, the completion rate was 65%. Except for the dose-ranging study (Study 1) and the maintenance of abstinence study (Study 6), patients were treated for 12 weeks and then were followed for 40 weeks post-treatment. Most patients enrolled in these trials were white (79–96%). All studies enrolled almost equal numbers of men and women. The average age of patients in these studies was 43 years. Patients on average had smoked about 21 cigarettes per day for an average of approximately 25 years. Patients set a date to stop smoking (target quit date) with dosing starting 1 week before this date.

Three additional studies were conducted in patients with cardiovascular disease, in patients with chronic obstructive pulmonary disease and in patients instructed to select their quit date within days 8 and 35 of treatment .

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.

Chantix (Varenicline) is supplied for oral administration in two strengths: a 0.5 mg capsular biconvex, white to off-white, film-coated tablet debossed with "" on one side and "CHX 0.5" on the other side and a 1 mg capsular biconvex, light blue film-coated tablet debossed with "" on one side and "CHX 1.0" on the other side. Chantix (Varenicline) is supplied in the following package configurations:

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Inform patients that nausea and insomnia are side effects of Chantix (Varenicline) and are usually transient; however, advise patients that if they are persistently troubled by these symptoms, they should notify the prescribing physician so that a dose reduction can be considered.

Inform patients that some drugs may require dose adjustment after quitting smoking