CardioBrief

The FDA is adding boxed warnings about serious mental health events to prescribing information for varenicline (Chantix) and buproprion (Zyban, Wellbutrin, etc).

“The risk of serious adverse events while taking these products must be weighed against the significant health benefits of quitting smoking,” said Janet Woodcock,  director of the FDA’s Center for Drug Evaluation and Research, in a FDA press release. Woodcock said physicians should monitor patients taking these drugs for any unusual changes in mood or behavior.

The FDA will require the drugs’ manufacturers to conduct a clinical trial “to determine how often serious neuropsychiatric symptoms occur in patients using various smoking cessation therapies.”

Melissa Walton-Shirley, a cardiologist in private practice in Glasgow, Kentucky who has been a strong anti-smoking advocate in her hometown and on TheHeart.Org, provided the following comment to CardioBrief:

“Chantix joins the ranks of commonly utilized black box’ed meds such as birth control pills, lasix and penicillin.  With every compound we prescribe, we have to weigh the risk and benefit for the patient. Personally, when I weigh lung cancer, sudden death and stroke with cigarettes against a small risk of severe nausea or a potential mood swing with Chantix, I’ll take my chances with whatever is in the black box and gladly.  In the case of tobacco addiction, the disease is still worse than the cure.”

“This particular black box warning is probably the largest hoax in pharmaceutical medicine to date.  For two decades, before Chantix ever came on the market, folks became depressed, had mood swings, etc. when they just tried to quit cold turkey.  I had to hospitalize a patient on a psychiatric unit once just from changing to patches, so the warning  was completely predictable.  Nothing and no one is ever going to have an easy go in America when it comes to decreasing the prevalence of smoking because of our proximity to the tobacco company venues.  Now more than ever, we need national legislation to become a smoke free nation, so we will mint fewer and fewer nicotine addicts.  It’s a shame that anyone should have to consider choosing a medication to help with cessation in the first place, so prevention through smoke free legislation is the key.”

Here is the FDA press release:

FDA: Boxed Warning on Serious Mental Health Events to be Required for Chantix and Zyban

The U.S. Food and Drug Administration today announced that it is requiring manufacturers to put a Boxed Warning on the prescribing information for the smoking cessation drugs Chantix (varenicline) and Zyban (buproprion). The warning will highlight the risk of serious mental health events including changes in behavior, depressed mood, hostility, and suicidal thoughts when taking these drugs.

“The risk of serious adverse events while taking these products must be weighed against the significant health benefits of quitting smoking,” said Janet Woodcock, M.D., director, the FDA’s Center for Drug Evaluation and Research. “Smoking is the leading cause of preventable disease, disability, and death in the United States and we know these products are effective aids in helping people quit.”

Similar information on mental health events will be required for buproprion marketed as the antidepressant Wellbutrin and for generic versions of buproprion. These drugs already carry a Boxed Warning for suicidal behavior in treating psychiatric disorders.

Woodcock said health care professionals who prescribe Chantix and Zyban should monitor their patients for any unusual changes in mood or behavior after starting these drugs. She added that patients should immediately contact their health care professional if they experience such changes.

The FDA’s request for the additional warnings is based on a review of reports submitted to the agency’s Adverse Event Reporting System since the time the products were marketed and on an analysis of information from clinical trials and scientific literature.

The analyses revealed that some who have taken Chantix and Zyban have reported experiencing unusual changes in behavior, become depressed, or had their depression worsen, and had thoughts of suicide or dying. In many cases, the problems began shortly after starting the medication and ended when the medication was stopped. However, some people continued to have symptoms after stopping the medication. Also, in a few cases, the problems began after the medication was stopped.

Neither Chantix nor Zyban contain nicotine and some of these symptoms may be a response to nicotine withdrawal. People who stop smoking may experience symptoms such as depression, anxiety, irritability, restlessness, and sleep disturbances. However, some patients who were using these products experienced the reported adverse events while they were still smoking. In addition to the Boxed Warning, the FDA also is requesting more information in the Warnings section of the prescribing information and updated information in the Medication Guide for patients that further discuss the risk of mental health events when using these products.

Manufacturers also will be required to conduct a clinical trial to determine how often serious neuropsychiatric symptoms occur in patients using various smoking cessation therapies, including patients who currently have psychiatric disorders. The FDA’s review of adverse events for patients using nicotine patches did not identify a clear link between those medications and suicidal events.

Chantix is manufactured by New York-based Pfizer Inc. Zyban is manufactured by GlaxoSmithKline, Brentford, Middlesex, United Kingdom.

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Here is the Pfizer press release:

Pfizer Updates CHANTIX ^® (varenicline) Labeling in the United States

NEW YORK–(BUSINESS WIRE)–Pfizer Inc announced that it has updated the U.S. product labeling for CHANTIX^® (varenicline), a prescription aid to smoking cessation treatment, to communicate important safety information in a boxed warning as well as in revised warnings and precautions. These updates are based on post-marketing reports and are being made in agreement with the U.S. Food and Drug Administration (FDA). Pfizer is making this information available immediately to U.S. health care providers and patients through multiple communication channels, including letters to doctors and pharmacists, Web site updates, and the CHANTIX patient Medication Guide.

The updated label highlights safety information about reports of serious neuropsychiatric events in a boxed warning; updates the warning about reports of neuropsychiatric symptoms and suicidality; adds warnings about reports of allergic reactions and serious skin reactions; and updates precautionary information about driving or operating machinery to include details about reports of accidental injury.

“The labeling update underscores the important role of health care providers in treating smokers attempting to quit and provides specific information about CHANTIX and instructions that physicians and patients should follow closely,” said Dr. Briggs W. Morrison, senior vice president, Primary Care Development Group at Pfizer. “Quitting smoking is one of the best things people can do for their health, but the quitting process is both difficult and complex.”

Boxed Warning Highlights Important Safety Information

Certain information on neuropsychiatric symptoms has been included in the CHANTIX label since November 2007 and is based on post-marketing reports. The boxed warning instructs health care providers to observe patients being treated with CHANTIX for the possibility of certain serious neuropsychiatric events and to advise patients to stop taking CHANTIX and contact their doctor immediately if these symptoms occur. It also states that the safety and efficacy of CHANTIX in patients with serious psychiatric illness have not been established. The update advises physicians to provide ongoing monitoring and support for patients who exhibit neuropsychiatric events until symptoms resolve.

The boxed warning also provides important information about the quitting process. It states that some smokers who are making a quit attempt – including those who are not using medication – may experience nicotine withdrawal symptoms, such as depressed mood. Additionally, the boxed warning communicates that the health benefits of quitting smoking are immediate and substantial, the risks of CHANTIX should be weighed against the benefits of its use, and that CHANTIX has been demonstrated to increase the likelihood of quitting for as long as one year compared to placebo.

Pfizer is conducting clinical trials of CHANTIX in multiple populations, including in patients with psychiatric disorders and chronic lung disease.

Safety Information in Warnings and Precautions Sections

The CHANTIX label updates existing warning information regarding serious neuropsychiatric symptoms to include the types of reports received. It also adds warnings about allergic reactions, such as angioedema, and rare, but serious, skin reactions, such as Stevens-Johnson Syndrome. Existing precautionary information about driving and operating machinery has been updated in the CHANTIX label to include details about accidental injury.

“The health benefits of quitting smoking are immediate and substantial,” said Dr. Morrison. “The benefits of CHANTIX outweigh the risks for many patients when used as directed. CHANTIX is an effective treatment option for patients who want to quit smoking. Patients should discuss with their physicians if CHANTIX is right for them.”

About CHANTIX

CHANTIX was approved by the FDA in May 2006 as an aid to smoking cessation treatment in adults 18 and older. Nearly 11 million people have been prescribed CHANTIX worldwide. CHANTIX has been shown to increase the likelihood of abstinence from smoking for as long as one year compared to treatment with placebo. Adults who smoke may benefit from quit smoking support programs and/or counseling during their quit attempt. 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.

About Smoking

Tobacco use is a risk factor for six of the eight leading causes of death in the world, including heart disease, cancer, and chronic obstructive pulmonary disease.^1,2 Smoking-related illness is the leading preventable cause of death in the United States, killing more than 443,000 people each year.^3,4

IMPORTANT SAFETY INFORMATION

Some people have had changes in behavior, hostility, agitation, depressed mood, suicidal thoughts or actions while using CHANTIX to help them quit smoking. Some people had these symptoms when they began taking CHANTIX, and others developed them after several weeks of treatment or after stopping CHANTIX. If you, your family or caregiver notice agitation, hostility, depression or changes in behavior, thinking, or mood that are not typical for you, or you develop suicidal thoughts or actions, anxiety, panic, aggression, anger, mania, abnormal sensations, hallucinations, paranoia or confusion, stop taking CHANTIX and call your doctor right away. Also tell your doctor about any history of depression or other mental health problems before taking CHANTIX, as these symptoms may worsen while taking CHANTIX.

Some people can have serious skin reactions while taking CHANTIX, some of which can become life-threatening. These can include rash, swelling, redness, and peeling of the skin. Some people can have allergic reactions to CHANTIX, some of which can be life-threatening and include: swelling of the face, mouth, and throat that can cause trouble breathing. If you have these symptoms or have a rash with peeling skin or blisters in your mouth, stop taking CHANTIX and get medical attention right away.

The most common side effects include nausea (30%), sleep problems, constipation, gas and/or vomiting. If you have side effects that bother you or don’t go away, tell your doctor. You may have trouble sleeping, vivid, unusual or strange dreams while taking CHANTIX. Use caution driving or operating machinery until you know how CHANTIX may affect you.

CHANTIX should not be taken with other quit smoking products. A lower dose of CHANTIX may be necessary in patients with kidney problems or who get dialysis.

Before starting CHANTIX, patients should tell their doctors if they are pregnant, plan to become pregnant, or if they take insulin, asthma medicines, or blood thinners. Medicines like these may work differently when patients quit smoking.

For more information, please visit www.pfizer.com/files/products/uspi_chantix.pdf for full Prescribing Information and http://www.pfizer.com/files/products/ppi_chantix.pdf for Patient Medication Guide.

Pfizer Inc: Working together for a healthier world™

Founded in 1849, Pfizer is the world’s premier biopharmaceutical company taking new approaches to better health. We discover, develop, manufacture and deliver quality, safe and effective prescription medicines to treat and help prevent disease for both people and animals. We also partner with healthcare providers, governments and local communities around the world to expand access to our medicines and to provide better quality health care and health system support. At Pfizer, more than 80,000 colleagues in more than 90 countries work every day to help people stay happier and healthier longer and to reduce the human and economic burden of disease worldwide.

References:

1. World Health Organization. WHO Report on the Global Tobacco Epidemic, 2008: The MPOWER Package. Geneva, Switzerland: World Health Organization; 2008.

2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Medicine, 2006;3(11):e442. (Additional information obtained from personal communication with CD Mathers).

3. Centers for Disease Control and Prevention. Surgeon General’s 2004 Report: The health consequences of smoking on the human body. Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services, Rockville, MD:2004.

4. Centers for Disease Control and Prevention. Smoking-Attributable Mortality, Years of Potential Life Lost, and Productivity Losses–United States, 2000-2004. MMWR. 2008; 57(45); 1226-1228.

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