Chantix FDA Alerts

Pfizer Expands Voluntary Nationwide Recall to include All Lots of Chantix® (Varenicline) Tablets Due to N-Nitroso Varenicline Content

Pfizer is voluntarily recalling all lots of Chantix 0.5 mg and 1 mg Tablets to the patient (consumer/user) level due to the presence of a nitrosamine, N-nitroso-varenicline, at or above the FDA interim acceptable intake limit. As alternative suppliers have been approved in the United States, Pfizer is undertaking this precautionary measure.

Long-term ingestion of N-nitroso-varenicline may be associated with a theoretical potential increased cancer risk in humans, but there is no immediate risk to patients taking this medication. The health benefits of stopping smoking outweigh the theoretical potential cancer risk from the nitrosamine impurity in varenicline.

Nitrosamines are common in water and foods, including cured and grilled meats, dairy products and vegetables. Everyone is exposed to some level of nitrosamines. These impurities may increase the risk of cancer if people are exposed to them above acceptable levels over long periods of time.ⁱ

Chantix is a treatment to help patients quit smoking and is intended for short term use. People who smoke cigarettes are 15 to 30 times more likely to get lung cancer than people who do not smoke.ⁱⁱ

Smoking is also associated with many other cancers, as well as with cardiovascular disease and lung disease.ⁱⁱⁱ CHANTIX has a safety profile that has been established over 15 years of marketing authorization and through a robust clinical program. Pfizer believes the benefit/risk profile of CHANTIX remains positive. Patients currently taking Chantix should consult with their healthcare provider about alternative treatment options. To date, Pfizer has not received reports of adverse events assessed to be related to this recall.

The NDC, Lot Number, Expiration Date, and Configuration details for Chantix Tablets are indicated in Appendix A. Photos of the products can be found in Appendix B. The products were distributed nationwide to Wholesalers and Distributors in the United States, US Virgin Islands and Puerto Rico from May 2019 to September 2021.

Pfizer places the utmost emphasis on patient safety and product quality at every step in the manufacturing and supply chain process. Pfizer has notified their direct consignees by letter to arrange for return of any recalled product.

Wholesalers and Distributors with an existing inventory of Chantix tablets, should stop use and distribution and quarantine the product immediately.

If you have further distributed the recalled product, please notify any accounts or additional locations which may have received the recalled product from you. Please conduct a sub-recall to those accounts and communicate this recall information immediately. Please request they immediately cease distribution of the product and promptly contact Stericycle at 888-276-6166 (Mon.-Fri. 8:00 am - 5:00 pm ET) to obtain a Business Reply Form (BRF) to initiate the return process.

If you received free product through the Pfizer Patient Assistance Program (PAP) or the Pfizer Institutional Patient Assistance Program (IPAP), please check your stock immediately. If you have any of the product in inventory, please follow the instructions above for returning the product to Stericycle Inc. Additionally, if you are aware of any patients to whom you dispensed the products and who still may have the product in their possession, please ask them to return the product to you and then follow the instructions above for returning the product to Stericycle Inc. For any questions related to Pfizer PAP or Pfizer IPAP product, please contact 833-203-2776 (Mon.-Fri. 8:00 am – 6:00 pm ET).

As communicated by FDA, there is no immediate risk to patients taking Chantix.^iv Patients who are taking this product should consult with their health care provider to determine if alternate treatments are available. Patients with Chantix Tablets should contact Stericycle Inc. at 888-276-6166 (Mon.-Fri. 8:00 am - 5:00 pm ET) for instructions on how to return their product and obtain reimbursement for their cost.

Healthcare Professionals with questions regarding this recall can contact Pfizer using the below information.

Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.

• Complete and submit the report Online
• Regular Mail or Fax: Download form or call 1- 800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

This recall is being executed with the knowledge of the U.S. Food and Drug Administration.

Appendix A: Recalled Product Details

PRODUCT: Chantix Tablets, 0.5 mg NDC: 0069-0468-56
SIZE: Bottle of 56 Tablets
EXPIRATION DATE: January 2022 - May 2023
LOT NUMERS:

PRODUCT: Chantix Tablets, 1 mg NDC: 0069-0469-56
SIZE: Bottle of 56 Tablets
EXPIRATION DATE: September 2021 – December 2023
LOT NUMBERS:

PRODUCT: Chantix Tablets, 1 mg NDC: 0069-0469-03
SIZE: Carton containing 4 blister packs of 14 tablets each
EXPIRATION DATE: September 2021 – June 2023
LOT NUMBERS:

PRODUCT: Chantix Tablets, 0.5/1 mg NDC: 0069-0471-03
SIZE: Carton containing one blister pack of 11 0.5 mg tablets and one blister pack containing 42 1 mg tablets
EXPIRATION DATE: August 2021 – January 2023
LOT NUMBERS:

References:

ⁱhttps://www.fda.gov/drugs/drug-safety-and- availability/information-about-nitrosamine-impurities-medications

ⁱⁱ U.S. Centers for Disease Control and Prevention. What Are the Risk Factors for Lung Cancer?
https://www.cdc.gov/cancer/lung/basic_info/risk_factors.htm
Updated September 2020. Accessed June 2021.

ⁱⁱⁱ U.S. Department of Health and Human Services. Smoking Cessation. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2020.

^ivhttps://www.fda.gov/drugs/drug-safety-and-availability/fda- alerts-health-care-professionals-and-patients-voluntary-recall- varenicline-chantix-warehouse

Expansion Press Release

Original Press Release

Source: FDA

Pfizer Expands Voluntary Nationwide Recall to include Four Additional Lots of Chantix (varenicline) Tablets Due to N- Nitroso Varenicline Content

August 16, 2021 -- Pfizer is voluntarily recalling an additional four lots of Chantix 0.5mg/1 mg Tablets to the patient (consumer/user) level due to the presence of a nitrosamine, N-nitroso-varenicline, above the Pfizer established Acceptable Daily Intake (ADI) level.

Long-term ingestion of N-nitroso-varenicline may be associated with a theoretical potential increased cancer risk in humans, but there is no immediate risk to patients taking this medication. The health benefits of stopping smoking outweigh the theoretical potential cancer risk from the nitrosamine impurity in varenicline.

Nitrosamines are common in water and foods, including cured and grilled meats, dairy products and vegetables. Everyone is exposed to some level of nitrosamines. These impurities may increase the risk of cancer if people are exposed to them above acceptable levels over long periods of time. ⁱ

Chantix is a treatment to help patients quit smoking and is intended for short term use. People who smoke cigarettes are 15 to 30 times more likely to get lung cancer than people who do not smoke. ⁱⁱ Smoking is also associated with many other cancers.ⁱⁱⁱ Chantix has a safety profile that has been established over 15 years of marketing authorization and through a robust clinical program. Pfizer believes the benefit/risk profile of Chantix remains positive. Patients currently taking Chantix should consult with their doctor to confirm if they received an affected lot, and if appropriate, about alternative treatment options. To date, Pfizer has not received any reports of adverse events that have been related to this recall.

The NDC, Lot Number, Expiration Date, and Configuration details for Chantix Tablets is indicated in the table below with the four additional lots. Photos of the products can be found at the end of this press release. The product lots were distributed nationwide to wholesalers and Distributors in the United States and Puerto Rico from June 2019 to June 2021.

Pfizer places the utmost emphasis on patient safety and product quality at every step in the manufacturing and supply chain process. Pfizer has notified their direct consignees by letter to arrange for return of any recalled product.

Wholesalers and distributors with an existing inventory of the lots, listed in the table above, should stop use and distribution and quarantine the product immediately.

If you have further distributed the recalled product, please notify any accounts or additional locations which may have received the recalled product from you. Please conduct a sub-recall to those accounts and communicate this recall information immediately. Please request they immediately cease distribution of the affected product and promptly contact Stericycle at 888-276-6166 (Mon.-Fri. 8:00 am - 5:00 pm ET) to obtain a Business Reply Card (BRC) to initiate the return process.

If you received free product through the Pfizer Patient Assistance Program (PAP) or the Pfizer Institutional Patient Assistance Program (IPAP), please check your stock immediately against the table above. If you have any of the affected product lots in your inventory, please follow the instructions above for returning the product to Stericycle Inc. Additionally, if you are aware of any patients to whom you dispensed the affected lots who still may have the product in their possession, please ask them to return the product to you and then follow the instructions above for returning the product to Stericycle Inc. To request replacement product for any Pfizer PAP or Pfizer IPAP product you return, please contact 833-203-2776 (Mon.-Fri. 8:00 am – 6:00 pm ET).

As communicated by FDA, there is no immediate risk to patients taking Chantix. ^iv Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product lots. Patients with the affected lots should contact Stericycle Inc. at 888-276-6166 (Mon.-Fri. 8:00 am - 5:00 pm ET) for instructions on how to return their product and obtain reimbursement for their cost.

Healthcare Professionals with questions regarding this recall can contact Pfizer using the below information.

Adverse events or product complaints experienced with the use of this product may also be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.

• Complete and submit the report Online
• Regular Mail or Fax: Download form or call 1- 800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

This recall is being executed with the knowledge of the U.S. Food and Drug Administration.

References:

i https://www.fda.gov/drugs/drug-safety-and-availability/information-about-nitrosamine-impurities-medications

ii U.S. Centers for Disease Control and Prevention. What Are the Risk Factors for Lung Cancer? https://www.cdc.gov/cancer/lung/basic_info/risk_factors.htm Updated September 2020. Accessed June 2021.

iii U.S. Department of Health and Human Services. Smoking and Cancer (Fact Sheet). Atlanta, GA: US Dept of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2014.

iv https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-and-patients-voluntary-recall-varenicline-chantix-warehouse

Original Press Release

Source: FDA

Pfizer Issues a Voluntary Nationwide Recall for Twelve Lots of Chantix (Varenicline) Tablets Due to N-Nitroso Varenicline Content

July 19, 2021 -- Pfizer is voluntarily recalling two lots of Chantix 0.5mg Tablets, two lots of Chantix 1 mg Tablets, and eight lots of a Chantix kit of 0.5mg/1 mg Tablets to the patient (consumer/user) level due to the presence of a nitrosamine, N-nitroso-varenicline, above the Pfizer established Acceptable Daily Intake (ADI) level.

Long-term ingestion of N-nitroso-varenicline may be associated with a theoretical potential increased cancer risk in humans, but there is no immediate risk to patients taking this medication. The health benefits of stopping smoking outweigh the theoretical potential cancer risk from the nitrosamine impurity in varenicline.

Nitrosamines are common in water and foods, including cured and grilled meats, dairy products and vegetables. Everyone is exposed to some level of nitrosamines. These impurities may increase the risk of cancer if people are exposed to them above acceptable levels over long periods of time.ⁱ

Chantix is a treatment to help patients quit smoking and is intended for short term use. People who smoke cigarettes are 15 to 30 times more likely to get lung cancer than people who do not smoke.ⁱⁱ Smoking is also associated with many other cancers.ⁱⁱⁱ Chantix has a safety profile that has been established over 15 years of marketing authorization and through a robust clinical program. Pfizer believes the benefit/risk profile of Chantix remains positive. Patients currently taking Chantix should consult with their doctor to confirm if they received an affected lot, and if appropriate, about alternative treatment options. To date, Pfizer has not received any reports of adverse events that have been related to this recall.

The NDC, Lot Number, Expiration Date, and Configuration details for Chantix Tablets is indicated in the table below and photos of the products can be found at the end of this press release. The product lots were distributed nationwide to wholesalers and Distributors in the United States and Puerto Rico from June 2019 to June 2021.

Pfizer places the utmost emphasis on patient safety and product quality at every step in the manufacturing and supply chain process. Pfizer has notified their direct consignees by letter to arrange for return of any recalled product.

Wholesalers and distributors with an existing inventory of the lots, listed in the table above, should stop use and distribution and quarantine the product immediately.

If you have further distributed the recalled product, please notify any accounts or additional locations which may have received the recalled product from you. Please conduct a sub-recall to those accounts and communicate this recall information immediately. Please request they immediately cease distribution of the affected product and promptly contact Stericycle at 888-276-6166 (Mon.-Fri. 8:00 am - 5:00 pm ET) to obtain a Business Reply Card (BRC) to initiate the return process.

If you received free product through the Pfizer Patient Assistance Program (PAP) or the Pfizer Institutional Patient Assistance Program (IPAP), please check your stock immediately against the table above. If you have any of the affected product lots in your inventory, please follow the instructions above for returning the product to Stericycle Inc. Additionally, if you are aware of any patients to whom you dispensed the affected lots who still may have the product in their possession, please ask them to return the product to you and then follow the instructions above for returning the product to Stericycle Inc. To request replacement product for any Pfizer PAP or Pfizer IPAP product you return, please contact 833-203-2776 (Mon.-Fri. 8:00 am – 6:00 pm ET).

As communicated by FDA, there is no immediate risk to patients taking Chantix.^iv Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product lots. Patients with the affected lots should contact Stericycle Inc. at 888-276-6166 (Mon.-Fri. 8:00 am - 5:00 pm ET) for instructions on how to return their product and obtain reimbursement for their cost.

Healthcare Professionals with questions regarding this recall can contact Pfizer using the below information.

Contact Center Contact Information Area of Support

Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.

• Complete and submit the report Online
• Regular Mail or Fax: Download form or call 1- 800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

This recall is being conducted with the knowledge of the U.S. Food and Drug Administration.

References:

ⁱ https://www.fda.gov/drugs/drug-safety-andavailability/information-about-nitrosamine-impurities-medications

ⁱⁱ U.S. Centers for Disease Control and Prevention. What Are the Risk Factors for Lung Cancer? https://www.cdc.gov/cancer/lung/basic_info/risk_factors.htmUpdated September 2020. Accessed June 2021.

ⁱⁱⁱ U.S. Department of Health and Human Services. Smoking and Cancer (Fact Sheet). Atlanta, GA: US Dept of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2014.

^ivhttps://www.fda.gov/drugs/drug-safety-and-availability/fdaalerts-health-care-professionals-and-patients-voluntary-recallvarenicline-chantix-warehouse

Source: FDA

FDA Alerts Health Care Professionals and Patients to a Voluntary Recall of Chantix (varenicline) to the Warehouse Level

July 2, 2021 --  FDA is alerting patients and health care professionals to Pfizer’s voluntary recall of nine lots of the smoking cessation drug, varenicline (brand name Chantix), to the warehouse level. The company is recalling varenicline because it may contain levels of a nitrosamine impurity, called N-nitroso-varenicline, above FDA’s acceptable intake limit. N-nitroso-varenicline may be associated with a potential increased cancer risk in humans, but there is no immediate risk to patients taking this medication. An increased cancer risk would be associated with long-term use, and the health benefits of stopping smoking outweigh the cancer risk from the nitrosamine impurity in varenicline.

Recalled lots:

N-Nitroso-varenicline belongs to the nitrosamine class of compounds, some of which are classified as probable or possible human carcinogens (substances that could cause cancer), based on laboratory tests such as rodent carcinogenicity studies. Although there are no data available to directly evaluate the carcinogenic potential of N-nitroso-varenicline, information available on closely related nitrosamine compounds was used to calculate lifetime exposure limits for N-nitroso-varenicline.

Pfizer is recalling the varenicline lots currently stored in warehouses. FDA recommended Pfizer revise its recall to the consumer level in order to take into account the product currently on the market, but the company has not yet done so.

In addition to the voluntary recall, Pfizer is holding release of varenicline to the U.S. market until it can confirm N-nitroso-varenicline levels below what the company considers to be acceptable.

What patients should know:

• Continue taking your current medicine until your doctor or pharmacist gives you a replacement or a different treatment option.
• Contact your health care professional if you are taking this medication and have questions about your health.

What health care professionals should know:

• FDA has determined the recalled varenicline poses an unnecessary risk to patients. Therefore, FDA recommends health care professionals consider other available treatment options for the patient’s medical condition.
• If you have varenicline samples from this company, quarantine them, and do not provide them to patients.
• Contact Pfizer directly if you have questions regarding product return or disposal.

FDA is actively considering options to help mitigate a shortage of varenicline in the U.S. including working to identify an alternate supplier. The agency is continuing to investigate the presence of N-nitroso-varenicline in varenicline products and will provide more information as it becomes available.

We know impurities in medicines are of great concern to patients and consumers who rely on safe and effective medicines approved by FDA, and we are working with manufacturers and global regulators to provide clear and actionable information. In September 2020, FDA published a guidance for industry entitled “Control of N-Nitrosamine Impurities in Human Drugs.” This guidance recommends steps manufacturers of active pharmaceutical ingredients (APIs) and drug products should take to detect and prevent objectionable levels of nitrosamine impurities in pharmaceutical products.

Today, we have better testing methods than ever before, and we have a better understanding of what to look for in products’ chemical structure and manufacturing processes that may increase the risk of forming low levels of impurities. Improved technology enables us to detect even trace amounts of impurities in drug products and may be the reason why more products have been recently found to have detectable levels of nitrosamines.

FDA continues its ongoing review, surveillance, compliance and pharmaceutical quality efforts across every product area and will continue to work with drug manufacturers to ensure safe, effective and high-quality drugs for the American public.

Patients and health care professionals should report any adverse reactions with varenicline to FDA’s MedWatch program to help the agency better understand the scope of the problem:

• Complete and submit the report online at www.fda.gov/medwatch/report.htm
• Download and complete the appropriate form, then submit it via fax at 1-800-FDA-0178

Source: FDA

Chantix (varenicline) and Zyban (bupropion): Drug Safety Communication - Mental Health Side Effects Revised

ISSUE: Based on an FDA review of a large clinical trial that FDA required the drug companies to conduct, FDA determined the risk of serious side effects on mood, behavior, or thinking with the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) is lower than previously suspected. The risk of these mental health side effects is still present, especially in those currently being treated for mental illnesses such as depression, anxiety disorders, or schizophrenia, or who have been treated for mental illnesses in the past. However, most people who had these side effects did not have serious consequences such as hospitalization. The results of the trial confirm that the benefits of stopping smoking outweigh the risks of these medicines. See the Drug Safety Communication for a data summary.

As a result of the large clinical trial review, FDA is removing the Boxed Warning, FDA’s most prominent warning, for serious mental health side effects from the Chantix drug label. The language describing the serious mental health side effects seen in patients quitting smoking will also be removed from the Boxed Warning in the Zyban label. FDA is also updating the existing warning section in both labels that describes the side effects on mood, behavior, or thinking to include the results from the clinical trial. This decision is consistent with the recommendations of external experts at a September 2016 FDA Advisory Committee meeting. The patient Medication Guide that explains the risks associated with the use of the medicines will continue to be provided with every patient prescription; however, the risk evaluation and mitigation strategy (REMS) that formally required the Medication Guide will be removed.

BACKGROUND: FDA review of the clinical trial results also confirmed that Chantix, Zyban, and nicotine replacement patches were all more effective for helping people quit smoking than was an inactive treatment called a placebo. These medicines were found to better help people quit smoking regardless of whether or not they had a history of mental illness.

RECOMMENDATION: Health care professionals should counsel patients about the benefits of stopping smoking and how they can get help to quit, and discuss the benefits and risks of using medicines to help them quit smoking.

Patients should stop taking Chantix or Zyban and call their health care professionals right away if they notice any side effects on mood, behavior, or thinking. Patients should also talk to their health care professionals for help and information about stopping smoking, including about whether stop-smoking medicines may help or if they have any questions or concerns about taking a medicine (See Related Information for more quit smoking resources).

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[12/16/2016 - Drug Safety Communication - FDA]
 

Chantix (varenicline): Drug Safety Communication - FDA Updates Label to Include Potential Alcohol Interaction

ISSUE: FDA is warning that the prescription smoking cessation medicine Chantix (varenicline) can change the way people react to alcohol. Interactions between alcohol and Chantix have resulted in some patients experiencing increased intoxicating effects of alcohol, sometimes associated with aggressive behavior and/or amnesia. In addition, rare accounts of seizures in patients treated with Chantix have been reported. FDA has approved changes to the Chantix label to warn about these risks. Refer to the Drug Safety Communication for a detailed data summary.

BACKGROUND: Chantix is a prescription medicine that is FDA-approved to help adults quit smoking.

RECOMMENDATION:  Healthcare professionals should weigh the potential risk of seizures against the potential benefits before prescribing Chantix in patients with a history of seizures or other factors that can lower the seizure threshold. Advise patients to immediately stop taking Chantix if they develop agitation, hostility, aggressive behavior, depressed mood, or changes in behavior or thinking that are not typical for them, or if they develop suicidal ideation or behavior.

Until patients know how Chantix affects their ability to tolerate alcohol, they should decrease the amount of alcohol they drink. Patients who have a seizure while taking Chantix should stop the medicine and seek medical attention immediately.

Also refer to the Drug Safety Communication for more information for patients and healthcare professionals.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[03/09/2015 - Drug Safety Communication - FDA]

Chantix (Varenicline): Safety Communication - Updated Safety Review On The Risk of Cardiovascular Adverse Events

ISSUE: FDA is informing the public about the results of a large, combined analysis (called a meta-analysis) of clinical trials that compared patients who received the smoking cessation drug Chantix (varenicline) to patients who received a placebo (an inactive treatment). A higher occurrence of major adverse cardiovascular events (a combined outcome of cardiovascular-related death, nonfatal heart attack, and nonfatal stroke) was observed in patients using Chantix compared to placebo. These events were uncommon in both the Chantix and placebo groups, and the increased risk was not statistically significant, which means it is uncertain whether the excess risk for the Chantix group was due to the drug or due to chance.

BACKGROUND: Chantix is a prescription medicine used to help adults quit smoking that works by blocking the effects of nicotine (from smoking) on the brain. FDA first notified the public about a possible increased risk of cardiovascular adverse events with Chantix in its June 2011 Drug Safety Communication (DSC). FDA required the manufacturer of Chantix to conduct the meta-analysis to further evaluate the cardiovascular safety of the drug, and believes it is important to let health care professionals and patients know about the results of this study. The meta-analysis findings of cardiovascular risk are similar to the findings in the smoking cessation clinical trial of patients with stable cardiovascular disease that was described in FDA’s June 16, 2011 DSC. The Warnings and Precautions section of the Chantix label has been updated to include the results of the meta-analysis.

RECOMMENDATION: Health care professionals are advised to weigh the risks of Chantix against the benefits of its use. It is important to note that smoking is a major risk factor for cardiovascular disease, and Chantix is effective in helping patients to quit smoking and abstain from it for as long as one year. The health benefits of quitting smoking are immediate and substantial.

Patients taking Chantix should contact their health care professional if they experience new or worsening symptoms of cardiovascular disease, such as chest pain, shortness of breath, calf pain when walking, or sudden onset of weakness, numbness, or difficulty speaking. Patients should also contact their health care professional if they have any questions or concerns about Chantix.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[12/12/2012 - Drug Safety Communication - FDA]

Chantix (varenicline)

Audience: Healthcare professionals, consumers

[UPDATE 10/24/2011] FDA has reviewed the results from two FDA-sponsored epidemiological studies that evaluated the risk of neuropsychiatric adverse events associated with the smoking cessation drug Chantix (varenicline). Neither study found a difference in risk of neuropsychiatric hospitalizations between Chantix and nicotine replacement therapy (NRT; e.g., NicoDerm patches). However, both studies had a number of study design limitations, including only assessing neuropsychiatric events that resulted in hospitalization, and not having a large enough sample size to detect rare adverse events (see the 10/24/2011 Drug Safety Communication below for more information).

Healthcare professionals and patients should continue to follow the recommendations in the physician label and the patient Medication Guide, and to monitor for neuropsychiatric symptoms when prescribing or using Chantix. The drug manufacturer is conducting a large safety clinical trial of Chantix to assess neuropsychiatric adverse events, and results from this study are expected in 2017.

[UPDATE 05/16/2008] FDA informed healthcare professionals and patients that as the Agency’s review of Chantix safety data has progressed, it appears increasingly likely that there is an association between Chantix and serious neuropsychiatric symptoms. Prescribing information for Chantix was revised to include this safety information in the WARNINGS and PRECAUTIONS sections of the label, and a Medication Guide for patients is also available. If patients, their families, or caregivers notice agitation, depressed mood, or changes in behavior that are not typical for the patient or if the patient has suicidal thoughts or actions, the patient should stop taking Chantix and contact their healthcare professional.

[Posted 11/20/2007] FDA informed healthcare professionals of reports of suicidal thoughts and aggressive and erratic behavior in patient who have taken Chantix, a smoking cessation product. There are also reports of patients experiencing drowsiness that affected their ability to drive or operate machinery. FDA is currently reviewing these cases, along with other recent reports. A preliminary assessment reveals that many of the cases reflect new-onset of depressed mood, suicidal ideation, and changes in emotion and behavior within days to weeks of initiating Chantix treatment. The role of Chantix in these cases is not clear because smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illness. However, not all patients described in the cases had preexisting psychiatric illness and not all had discontinued smoking.

Healthcare professionals should monitor patients taking Chantix for behavior and mood changes. Patients taking this product should report behavior or mood changes to their doctor and use caution when driving or operating machinery until they know how quitting smoking with Chantix may affect them.

10/24/2011

Chantix (varenicline): Label Change - Risk of Certain Cardiovascular Adverse Events

[UPDATED 07/22/2011] FDA has approved an updated drug label for Chantix (varenicline) to include information about the efficacy and safety of the drug in two patient populations who may benefit greatly from giving up smoking—those with cardiovascular disease and those with chronic obstructive pulmonary disease (COPD). The updated label now also includes alternative directions for patients to select a quit smoking date.

[Posted 06/16/2011]

ISSUE: FDA notified healthcare professionals and patients that the Prescribing Information for this drug product will be strengthened to inform the public that use of varenicline may be associated with a small, increased risk of certain cardiovascular adverse events in patients who have cardiovascular disease. This safety information will be added to the Warnings and Precautions section and the patient Medication Guide.

BACKGROUND: FDA reviewed a randomized, double-blind, placebo-controlled clinical trial of 700 smokers with cardiovascular disease who were treated with Chantix or placebo. While cardiovascular adverse events were infrequent overall, certain events, including heart attack, were reported more frequently in patients treated with Chantix than in patients treated with placebo. The events included angina pectoris, nonfatal myocardial infarction, need for coronary revascularization, and new diagnosis of peripheral vascular disease or admission for a procedure for the treatment of peripheral vascular disease. FDA is continuing to evaluate the cardiovascular safety of Chantix and is requiring the manufacturer to conduct a large, combined analysis (meta-analysis) of randomized, placebo-controlled trials. FDA will update the public when additional information is available.

RECOMMENDATION: See the Data Summary section of the Drug Safety Communication for additional information.

Healthcare professionals should be aware that smoking is an independent and major risk factor for cardiovascular disease, and smoking cessation is of particular importance in this patient population. The known benefits of Chantix should be weighed against its potential risks when deciding to use the drug in smokers with cardiovascular disease.

Patients are encouraged to read the Medication Guide they receive along with their Chantix prescription.

Healthcare professionals and patients are encouraged to report adverse events, side effects, or product quality problems related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[07/22/2011 - Drug Safety Communication - FDA]
[06/16/2011 - Drug Safety Communication - FDA]

Chantix (varenicline): Label Change - Risk of Certain Cardiovascular Adverse Events

[Posted 06/16/2011]

ISSUE: FDA notified healthcare professionals and patients that the Prescribing Information for this drug product will be strengthened to inform the public that use of varenicline may be associated with a small, increased risk of certain cardiovascular adverse events in patients who have cardiovascular disease. This safety information will be added to the Warnings and Precautions section and the patient Medication Guide.

BACKGROUND: FDA reviewed a randomized, double-blind, placebo-controlled clinical trial of 700 smokers with cardiovascular disease who were treated with Chantix or placebo. While cardiovascular adverse events were infrequent overall, certain events, including heart attack, were reported more frequently in patients treated with Chantix than in patients treated with placebo. The events included angina pectoris, nonfatal myocardial infarction, need for coronary revascularization, and new diagnosis of peripheral vascular disease or admission for a procedure for the treatment of peripheral vascular disease. FDA is continuing to evaluate the cardiovascular safety of Chantix and is requiring the manufacturer to conduct a large, combined analysis (meta-analysis) of randomized, placebo-controlled trials. FDA will update the public when additional information is available.

RECOMMENDATION: See the Data Summary section of the Drug Safety Communication for additional information.

Healthcare professionals should be aware that smoking is an independent and major risk factor for cardiovascular disease, and smoking cessation is of particular importance in this patient population. The known benefits of Chantix should be weighed against its potential risks when deciding to use the drug in smokers with cardiovascular disease.

Patients are encouraged to read the Medication Guide they receive along with their Chantix prescription.

Healthcare professionals and patients are encouraged to report adverse events, side effects, or product quality problems related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[06/16/2011 - Drug Safety Communication - FDA]

Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics)

FDA notified healthcare professionals and patients that it has required the manufacturers of the smoking cessation aids varenicline (Chantix) and bupropion (Zyban and generics) to add new Boxed Warnings and develop patient Medication Guides highlighting the risk of serious neuropsychiatric symptoms in patients using these products. These symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. The added warnings are based on the continued review of postmarketing adverse event reports for varenicline and bupropion received by the FDA. These reports included those with a temporal relationship between the use of varenicline or bupropion and suicidal events and the occurrence of suicidal ideation and suicidal behavior in patients with no history of psychiatric disease.

Healthcare professionals should advise patients to stop taking varenicline or bupropion and contact a healthcare provider immediately if they experience agitation, depressed mood, and any changes in behavior that are not typical of nicotine withdrawal, or if they experience suicidal thoughts or behavior.

[07/01/2009 - Public Health Advisory - FDA]

[07/01/2009 - Information for Healthcare Professionals - FDA]

[07/01/2009 - News Release - FDA]

Varenicline (marketed as Chantix)

[Posted 02/01/2008] FDA informed healthcare professionals and consumers of important revisions to the WARNINGS and PRECAUTIONS sections of the prescribing information for Chantix regarding serious neuropsychiatric symptoms experienced in patients taking Chantix. These symptoms include changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide. While some patients may have experienced these types of symptoms and events as a result of nicotine withdrawal, some patients taking Chantix who experienced serious neuropsychiatric symptoms and events had not yet discontinued smoking. In most cases, neuropsychiatric symptoms developed during Chantix treatment, but in others, symptoms developed following withdrawal of Chantix therapy. See the FDA Information for Healthcare Professionals Sheet for recommendations and considerations for healthcare professionals on using Chantix therapy for patients.

[February 01, 2008 - FDA]
[February 01, 2008 - Healthcare Professional Information Sheet - FDA]

Chantix (Varenicline)

[Posted 11/20/2007] FDA informed healthcare professionals of reports of suicidal thoughts and aggressive and erratic behavior in patient who have taken Chantix, a smoking cessation product. There are also reports of patients experiencing drowsiness that affected their ability to drive or operate machinery. FDA is currently reviewing these cases, along with other recent reports. A preliminary assessment reveals that many of the cases reflect new-onset of depressed mood, suicidal ideation, and changes in emotion and behavior within days to weeks of initiating Chantix treatment. The role of Chantix in these cases is not clear because smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illness. However, not all patients described in the cases had preexisting psychiatric illness and not all had discontinued smoking.

Healthcare professionals should monitor patients taking Chantix for behavior and mood changes. Patients taking this product should report behavior or mood changes to their doctor and use caution when driving or operating machinery until they know how quitting smoking with Chantix may affect them.

[November 20, 2007 - Ongoing Safety Review: Varenicline (marketed as Chantix) - FDA]