FDA Approves Removal Of Boxed Warning Regarding Serious Neuropsychiatric Events From CHANTIX® (varenicline) Labeling

NEW YORK–(BUSINESS WIRE)– Pfizer announced today that the U.S. Food and Drug Administration (FDA)
approved updates to the CHANTIX^® (varenicline) labeling,
including removal of the boxed warning regarding serious
neuropsychiatric events. The removal of the boxed warning is based on
the outcomes of EAGLES (Evaluating Adverse Events in a Global
Smoking Cessation Study), the largest smoking cessation
clinical trial in patients without and with a history of psychiatric
disorder, and is consistent with the recent recommendation of the FDA
Psychopharmacologic Drugs and Drug Safety and Risk Management Advisory
Committees. Additional labeling revisions based on EAGLES include
updates to the corresponding warning regarding neuropsychiatric safety
and the addition of information on the superior efficacy of CHANTIX
compared to bupropion or nicotine patch.^1,2

“For millions who smoke, stopping smoking is one of the most important
steps they can take to improve their health, and Pfizer is committed to
helping smokers in their quit journey,” said Freda Lewis-Hall, M.D.,
DFAPA, chief medical officer and EVP, Pfizer Inc. “We are pleased with
the FDA’s decision to update the CHANTIX labeling based on EAGLES – the
largest clinical trial of smoking cessation medications – and we expect
this new information may further facilitate an informed discussion about
quitting with CHANTIX between smokers and healthcare providers.”

“While the benefits of quitting are immediate and substantial, few
smokers are able to quit on their own and need the help of counseling
and smoking cessation therapy,” said Dr. A. Eden Evins, director,
Massachusetts General Hospital Center for Addiction Medicine and William
Cox Family Associate Professor of Psychiatry in the Field of Addiction
Medicine, Harvard Medical School. “As healthcare providers work on the
front lines to help people who are struggling to quit smoking, this new
labeling provides clinically relevant information on the safety and
efficacy of CHANTIX to help them and their patients make informed
decisions about smoking cessation treatment.”

In the U.S., smoking is the leading preventable cause of death,
responsible for roughly 540,000 deaths each year.^3,4 Stopping
smoking has significant health benefits, including reducing the risk of
tobacco-related diseases such as lung cancer, heart disease, stroke,
chronic respiratory disease and other conditions.⁵ While
smoking rates have declined overall, some segments of society have not
made the same progress,^6,7 including people living with
mental illness, Veterans, LGBTQ and other minority communities.^8-10

The updated warning in the CHANTIX labeling notes that postmarketing
reports of serious or clinically significant neuropsychiatric adverse
events in patients treated with CHANTIX 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. Patients attempting to quit smoking with CHANTIX
should be observed for the occurrence of such symptoms and instructed to
discontinue CHANTIX and contact a healthcare provider if they experience
such symptoms.¹

In EAGLES, in the cohort of patients without a history of psychiatric
disorder, CHANTIX was not associated with an increased incidence of
clinically significant neuropsychiatric adverse events in a composite
endpoint comprising anxiety, depression, feeling abnormal, hostility,
agitation, aggression, delusions, hallucinations, homicidal ideation,
mania, panic, and irritability.

In the cohort of patients with a history of psychiatric disorder, there
were more events reported in each treatment group compared to the
non-psychiatric cohort, and the incidence of events in the composite
endpoint was higher for each of the active treatments compared to
placebo: Risk Differences (RDs) (95%CI) vs. placebo were 2.7% (-0.05,
5.4) for CHANTIX, 2.2% (-0.5, 4.9) for bupropion, and 0.4% (-2.2, 3.0)
for transdermal nicotine. The neuropsychiatric events of a serious
nature were reported in 0.6% of CHANTIX-treated patients, with 0.5%
involving psychiatric hospitalization. In placebo-treated patients,
serious neuropsychiatric events occurred in 0.6%, with 0.2% requiring
psychiatric hospitalization.

About EAGLES Clinical Trial

EAGLES is a randomized, blinded, active- and placebo-controlled clinical
trial, which was conducted by Pfizer in collaboration with
GlaxoSmithKline at the request of and designed in consultation with the
FDA and the European Medicines Agency (EMA). The trial is the first and
largest to compare the safety and efficacy of CHANTIX, bupropion and
nicotine replacement patch in approximately 8,000 smokers without and
with a history of psychiatric disorder. The trial was designed to
compare the risk of clinically significant neuropsychiatric adverse
events in patients using CHANTIX, bupropion, nicotine replacement
therapy or placebo as smoking cessation aids over 12 weeks of treatment,
and to determine whether smokers with a history of psychiatric disorder
are at a greater risk for developing clinically significant adverse
events compared to smokers without a history of psychiatric disorder.²

About CHANTIX^®

CHANTIX^® (also known as CHAMPIX^® in the EU and
other countries) was approved by the FDA in May 2006 as a prescription
medication that, along with support, helps adults 18 and over stop
smoking. CHANTIX is approved in more than 100 countries and has been
prescribed to over 20 million patients worldwide, including more than 11
million in the U.S.¹¹ Adults who smoke may benefit from
quit-smoking support programs and/or counseling during their quit
attempt.¹² It’s possible that patients might slip up and
smoke while taking CHANTIX. If patients slip up, they can stay on
CHANTIX and keep trying to quit.¹

Important CHANTIX (varenicline) Safety Information

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

Postmarketing reports of serious or clinically significant
neuropsychiatric adverse events have been reported in patients treated
with CHANTIX. These 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.

During clinical trials and the postmarketing experience, there have been
reports of seizures in patients treated with CHANTIX, with or without a
history of seizures. CHANTIX should be used cautiously in patients with
a history of seizures or other factors that can lower the seizure
threshold. Instruct patients to discontinue CHANTIX, and contact a
healthcare provider immediately if they experience a seizure while on
treatment.

There have been postmarketing reports of patients experiencing increased
intoxicating effects of alcohol while taking CHANTIX, including unusual
and sometimes aggressive behavior directed to oneself or to others and
often accompanied by amnesia. Advise patients to reduce the amount of
alcohol they consume while taking CHANTIX until they know whether
CHANTIX affects their tolerance for alcohol.

Cases of somnambulism have been reported in patients taking CHANTIX.
Some cases described harmful behavior to self, others, or property.
Instruct patients to discontinue CHANTIX and notify their healthcare
provider if they experience somnambulism.

Patients should be informed that there have been reports of serious skin
reactions, such as Stevens Johnson Syndrome and Erythema Multiforme and
of angioedema, with swelling of the face, mouth, and neck that can lead
to life-threatening respiratory compromise.

Patients should be instructed to discontinue CHANTIX and immediately
seek medical care if they experience these symptoms or at the first sign
of rash with mucosal lesions or any other signs of hypersensitivity.

In a meta-analysis of clinical trials including a trial in patients with
stable cardiovascular disease, while serious cardiovascular events were
infrequent overall, certain serious cardiovascular events were reported
more frequently in patients treated with CHANTIX than placebo. These
events occurred primarily in patients with known cardiovascular disease.
Instruct patients 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.

The most common adverse reactions include nausea (30%), abnormal dreams,
constipation, flatulence, and vomiting. Patients should be informed that
they may experience vivid, unusual, or strange dreams during treatment
with CHANTIX. Patients should be advised to use caution driving or
operating machinery or engaging in other potentially hazardous
activities until they know how CHANTIX may affect them.

Safety and efficacy of CHANTIX in combination with other smoking
cessation drug therapies have not been studied. Dosage adjustment with
CHANTIX is recommended in patients with severe renal impairment or in
patients undergoing hemodialysis.

Smoking cessation, with or without treatment with CHANTIX, may alter the
pharmacokinetics or pharmacodynamics of some drugs, such as
theophylline, warfarin, and insulin. Dosage adjustment for these drugs
may be necessary.

Click here for full
Prescribing Information and Medication Guide.

About Pfizer Inc.: Working together for a healthier world^®

At Pfizer, we apply science and our global resources to bring therapies
to people that extend and significantly improve their lives. We strive
to set the standard for quality, safety and value in the discovery,
development and manufacture of healthcare products. Our global portfolio
includes medicines and vaccines as well as many of the world’s
best-known consumer health care products. Every day, Pfizer colleagues
work across developed and emerging markets to advance wellness,
prevention, treatments and cures that challenge the most feared diseases
of our time. Consistent with our responsibility as one of the world’s
premier innovative biopharmaceutical companies, we collaborate with
health care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world. For
more than 150 years, Pfizer has worked to make a difference for all who
rely on us. For more information, please visit us at www.pfizer.com.
In addition, to learn more, follow us on Twitter at @Pfizer
and @Pfizer_News,
LinkedIn,
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and like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE: The information contained in this release is as of
December 16, 2016. Pfizer assumes no obligation to update
forward-looking statements contained in this release as the result of
new information or future events or developments.

This release contains forward-looking information about
CHANTIX/CHAMPIX (varenicline), including its potential benefits, that
involves substantial risks and uncertainties that could cause actual
results to differ materially from those expressed or implied by such
statements. Risks and uncertainties include, among other things,
uncertainties regarding the commercial impact of the results of the
EAGLES trial and the updates to the U.S. label for CHANTIX, including
removal of the boxed warning regarding serious neuropsychiatric events;
decisions by regulatory authorities regarding labeling and other matters
that could affect the availability or commercial potential of CHAMPIX
(including uncertainties regarding the impact of the EAGLES trial on the
product labeling for CHAMPIX in other jurisdictions); the risk that
clinical trial data are subject to differing interpretations, including
by regulatory authorities; the uncertainties inherent in research and
development; and competitive developments.

A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2015 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information and Factors That May Affect Future Results”, as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at www.sec.gov
and www.pfizer.com.

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