Varenicline

CHANTIX is indicated for use as an aid to smoking-cessation treatment. CHANTIX is a nicotinic receptor partial agonist indicated for use as an aid to smoking-cessation treatment. ( 1 and 2.1 )

Varenicline binds with high affinity and selectivity at α4β2 neuronal nicotinic acetylcholine receptors. The efficacy of CHANTIX 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 in vitro and neurochemical studies in vivo 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.

• Begin CHANTIX dosing one week before the date set by the patient to stop smoking. Alternatively, the patient can begin CHANTIX dosing and then quit smoking between days 8 and 35 of treatment. • Starting Week: 0.5 mg once daily on days 1–3 and 0.5 mg twice daily on days 4–7. • Continuing Weeks: 1 mg twice daily for a total of 12 weeks. • An additional 12 weeks of treatment is recommended for successful quitters to increase likelihood of long-term abstinence. • Consider a gradual approach to quitting smoking with CHANTIX for patients who are sure that they are not able or willing to quit abruptly. Patients should begin CHANTIX dosing and reduce smoking by 50% from baseline within the first four weeks, by an additional 50% in the next four weeks, and continue reducing with the goal of reaching complete abstinence by 12 weeks.

CHANTIX is contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to CHANTIX. History of serious hypersensitivity or skin reactions to CHANTIX.

• Neuropsychiatric Adverse Events: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Observe patients attempting to quit smoking with CHANTIX for the occurrence of such symptoms and instruct them to discontinue CHANTIX and contact a healthcare provider if they experience such adverse events. • Seizures: New or worsening seizures have been observed in patients taking CHANTIX. CHANTIX should be used cautiously in patients with a history of seizures or other factors that can lower the seizure threshold. • Interaction with Alcohol: Increased effects of alcohol have been reported.

The following serious adverse reactions were reported in postmarketing experience and are discussed in greater detail in other sections of the labeling: • Neuropsychiatric Adverse Events including Suicidality • Seizures • Interaction with Alcohol • Accidental Injury • Cardiovascular Events • Somnambulism • Angioedema and Hypersensitivity Reactions • Serious Skin Reactions In the placebo-controlled premarketing studies, the most common adverse events associated with CHANTIX (>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, compared to 10% for placebo in studies of three months' treatment.

Based on varenicline characteristics and clinical experience to date, CHANTIX has no clinically meaningful pharmacokinetic drug interactions. • Other Smoking-Cessation Therapies: Safety and efficacy in combination with other smoking-cessation therapies has not been established. Coadministration of varenicline and transdermal nicotine resulted in a high rate of discontinuation due to adverse events. • Effect of Smoking Cessation on Other Drugs: Pharmacokinetics or pharmacodynamics of certain drugs (e.g., theophylline, warfarin, insulin) may be altered, necessitating dose adjustment.

Store at 25ºC (77ºF), excursions permitted to 15ºC to 30ºC (59ºF to 86ºF).