[Posted 12/12/2012]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 varenicline (Chantix) 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 varenicline compared to placebo. These events were uncommon in both the varenicline and placebo groups, and the increased risk was not statistically significant, which means it is uncertain whether the excess risk for the varenicline group was due to the drug or due to chance.
BACKGROUND:Varenicline 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 varenicline in its June 2011 Drug Safety Communication (DSC). FDA required the manufacturer of varenicline 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 varenicline label has been updated to include the results of the meta-analysis.
RECOMMENDATION:Health care professionals are advised to weigh the risks of varenicline against the benefits of its use. It is important to note that smoking is a major risk factor for cardiovascular disease, and varenicline 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 varenicline 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 varenicline. For more information visit the FDA website at: Web Siteand Web Site.
Some people have had changes in behavior, hostility, agitation, depressed mood, and suicidal thoughts (thinking about harming or killing oneself or planning or trying to do so) while taking varenicline. The role of varenicline in causing these mood changes is unclear since people who quit smoking with or without medication may experience changes in their mental health due to nicotine withdrawal. However, some of these symptoms occurred in people who were taking varenicline and continued to smoke. Some people had these symptoms when they began taking varenicline, and others developed them after several weeks of treatment or after stopping varenicline. These symptoms have occurred in people without a history of mental illness and have worsened in people who already had a mental illness. Tell your doctor if you have or have ever had depression, bipolar disorder (mood that changes from depressed to abnormally excited), schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions), or other mental illnesses. If you experience any of the following symptoms, stop taking varenicline and call your doctor immediately: suicidal thoughts or actions; new or worsening depression, anxiety, or panic attacks; agitation; restlessness; angry or violent behavior; acting dangerously; mania (frenzied, abnormally excited mood or talking); abnormal thoughts or sensations; hallucinations (seeing things or hearing voices that do not exist); feeling that people are against you; feeling confused; or any other sudden or unusual changes in behavior, thinking, or mood. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own. Your doctor will monitor you closely until your symptoms get better.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with varenicline and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website ( Web Site) or the manufacturer's website to obtain the Medication Guide.
Talk to your doctor about the risks and benefits of taking varenicline.
WHY is this medicine prescribed?
Varenicline is used along with education and counseling to help people stop smoking. Varenicline is in a class of medications called smoking cessation aids. It works by blocking the pleasant effects of nicotine (from smoking) on the brain.
HOW should this medicine be used?
Varenicline comes as a tablet to take by mouth. It is usually taken once or twice a day with a full glass of water (8 ounces [240 mL]) after eating. Take varenicline at around the same time(s) every day. If you are taking varenicline twice a day, take one dose in the morning and one dose in the evening. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take varenicline exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Your doctor will probably start you on a low dose of varenicline and gradually increase your dose over the first week of treatment.
Set a quit date to stop smoking, and start taking varenicline 1 week before that date. You may continue to smoke during this first week of varenicline treatment, but make sure to try to stop smoking on the quit date you have chosen. Alternatively, you may start taking varenicline and then quit smoking between 8 and 35 days after starting treatment with varenicline.
It may take several weeks for you to feel the full benefit of varenicline. You may slip and smoke during your treatment. If this happens, you may still be able to stop smoking. Continue to take varenicline and to try not to smoke.
You will probably take varenicline for 12 weeks. If you have completely stopped smoking at the end of 12 weeks, your doctor may tell you to take varenicline for another 12 weeks. This may help keep you from starting to smoke again.
If you have not stopped smoking at the end of 12 weeks, talk to your doctor. Your doctor can try to help you understand why you were not able to stop smoking and make plans to try to quit again.
Are there OTHER USES for this medicine?
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What SPECIAL PRECAUTIONS should I follow?
Before taking varenicline,
- tell your doctor and pharmacist if you are allergic to varenicline or any other medications.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: anticoagulants (''blood thinners'') such as warfarin (Coumadin); insulin; other medications to help you stop smoking such as bupropion (Wellbutrin, Zyban) and nicotine gum, inhaler, lozenges, nasal spray, or skin patches; and theophylline (Theo-24). Your doctor may need to change the doses of some of your medications once you stop smoking.
- tell your doctor if you have ever had withdrawal symptoms when you tried to quit smoking in the past and if you have or have ever had heart, blood vessel, or kidney disease
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking varenicline, call your doctor.
- you should know that varenicline may make you drowsy, dizzy, lose consciousness, or have difficulty concentrating. There have been reports of traffic accidents, near-miss accidents, and other types of injuries in people who were taking varenicline. Do not drive a car or operate machinery until you know how this medication affects you.
- ask your doctor for advice and for written information to help you stop smoking. You are more likely to stop smoking during your treatment with varenicline if you get information and support from your doctor.
What SPECIAL DIETARY instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do IF I FORGET to take a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What SIDE EFFECTS can this medicine cause?
Varenicline may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- bad taste in the mouth
- increased or decreased appetite
- trouble falling asleep or staying asleep
- unusual dreams or nightmares
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS sections, stop taking varenicline and get medical help immediately:
- swelling of the face, throat, tongue, lips, gums, eyes, neck, hands, arms, feet, ankles, or lower legs
- difficulty swallowing or breathing
- swollen, red, peeling, or blistering skin
- blisters in the mouth
- pain, squeezing, or pressure in the chest
- pain or discomfort in one or both arms, back, neck, jaw, or stomach
- difficulty in moving your arms or legs
- shortness of breath
- nausea, vomiting, or lightheadedness
- slow or difficult speech
- weakness or numbness of an arm or leg, especially on one side of the body
Varenicline may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at Web Site] or by phone [1-800-332-1088].
What should I know about STORAGE and DISPOSAL of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
What should I do in case of OVERDOSE?
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
What OTHER INFORMATION should I know?
Keep all appointments with your doctor.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.
Selected Revisions: February 15, 2013.