We have completed our review of these applications, as amended, and they are approved, effective on the date of this letter, for use as recommended in the enclosed agreed upon labeling text for the package insert, Medication Guide and modified REMS.

In addition, as required under 21 CFR 314.81(b)(3)(i), you must submit your updated final promotional materials, and the package insert(s), at the time of initial dissemination or publication, accompanied by a Form FDA-2253, directly to the above address.

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).

The Division of Anesthesia, Analgesia, and Rheumatology Products (DAARP) consulted the Maternal Health Team (MHT) to review the Pregnancy and Nursing Mothers sections of the sponsors proposed labeling.

If you, your family, or caregiver notice agitation, hostility, depression or changes in behavior or thinking that are not typical for you, or you develop any of the following symptoms, stop taking CHANTIX and call your healthcare provider right away: thoughts about suicide or dying, or attempts to commit suicide • • new or worse depression, anxiety or panic attacks feeling very agitated or restless • • acting aggressive, being angry, or violent • acting on dangerous impulses • an extreme increase in activity and talking (mania) • abnormal thoughts or sensations seeing or hearing things that are not there (hallucinations) • feeling people are against you (paranoia) •

Pfizer Inc 235 East 42nd Street New York City, NY 10017 Attention: Samantha McNamara Director, US Regulatory Affairs Dear Ms. McNamara: Please refer to your supplemental new drug application dated May 9, 2007, received May 9, 2007, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Chantix (varenicline) Tablets.

• Modification of the patient package insert to address possible drug adverse effects related to sleep and dreaming disturbance, depression, agitation, suicidal thoughts, and problems with driving or operating machinery when beginning treatment with varenicline to attempt to quit smoking.

• Modification of the package insert’s PRECAUTIONS, Information for Patients section to address possible adverse drug effects relating to driving or operating machinery when beginning treatment with varenicline to attempt to quit smoking.

• Modification to the ADVERSE REACTIONS section to address the potential for newly emergent psychiatric illness and the potential for exacerbation of underlying psychiatric illness that may occur following treatment with varenicline to attempt to quit smoking.

We have completed our review of this application, as amended, and it is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling text.

We have completed our review of this application, as amended, and it is approved, effective on the date of this letter, for use as recommended in the agreed-upon labeling text.

All applications for new active ingredients, new dosage forms, new indications, new routes of administration, and new dosing regimens are required to contain an assessment of the safety and

To conduct a study to determine the multiple-dose pharmacokinetics of varenicline in pediatric patients in order to determine the appropriate doses for efficacy and safety evaluations in adolescent smokers, ages 12 through 16, inclusive, to determine the adverse event profile in adolescent patients, and to establish whether there is any age group (or weight group) for whom varenicline is so poorly tolerated that its utility as an aid to smoking cessation treatment should not be evaluated in that group.

To conduct a study to determine whether varenicline, as part of an overall smoking cessation program, is effective in achieving and maintaining smoking cessation in tobacco-addicted adolescents, ages 12 through 16, inclusive, to determine a safe and effective dose, and to document the ability of treating physicians to select appropriate patients.

In addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii), you should include a status summary of each commitment in your annual report to this NDA.