chantix

Important safety information

Seizures: New or worsening seizures have been observed in patients taking CHANTIX. CHANTIX should be used cautiously in patients with a history of seizures or other factors that can lower the seizure threshold. ( 5.2 ) • Interaction with alcohol: Increased effects of alcohol have been reported. Instruct patients to reduce the amount of alcohol they consume until they know whether CHANTIX affects them. ( 5.3 ) • Accidental injury: Accidental injuries (e.g., traffic accidents) have been reported. Instruct patients to use caution driving or operating machinery until they know how CHANTIX may affect them. ( 5.4 ) • Cardiovascular events: A meta-analysis of 15 clinical trials, including a trial in patients with stable cardiovascular disease, demonstrated that while cardiovascular events were infrequent overall, some were reported more frequently in patients treated with CHANTIX. These events occurred primarily in patients with known cardiovascular disease. In both the clinical trial and meta-analysis, all-cause and cardiovascular mortality was lower in patients treated with CHANTIX. 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. ( 5.5 and 6.1 ) • Angioedema and hypersensitivity reactions: Such reactions, including angioedema, infrequently life threatening, have been reported. Instruct patients to discontinue CHANTIX and immediately seek medical care if symptoms occur. ( 5.6 and 6.2 ) • Serious skin reactions: Rare, potentially life-threatening skin reactions have been reported. Instruct patients to discontinue CHANTIX and contact a healthcare provider immediately at first appearance of skin rash with mucosal lesions. ( 5.7 and 6.2) • Nausea: Nausea is the most common adverse reaction (up to 30% incidence rate). Dose reduction may be helpful. ( 5.8) 5.1 Neuropsychiatric Symptoms and Suicidality Serious neuropsychiatric symptoms have been reported in patients being treated with CHANTIX [see Boxed Warning and Adverse Reactions (6.2) ] . These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Some reported cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking. Depressed mood may be a symptom of nicotine withdrawal. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these symptoms have occurred in patients taking CHANTIX who continued to smoke. When symptoms were reported, most were during CHANTIX treatment, but some were following discontinuation of CHANTIX therapy. These events have occurred in patients with and without pre-existing psychiatric disease; some patients have experienced worsening of their psychiatric illnesses. All patients being treated with CHANTIX should be observed for neuropsychiatric symptoms or worsening of pre-existing psychiatric illness. Patients with serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder did not participate in the premarketing studies of CHANTIX. Limited safety data are available from post-marketing smoking cessation studies in two patient groups: 1) patients with major depressive disorder, and 2) patients with stable schizophrenia or schizoaffective disorder [see Adverse Reactions (6.1) , Clinical Studies (14.5) ] . Some reported neuropsychiatric events, including unusual and sometimes aggressive behavior directed to oneself or others, may have been worsened by concomitant use of alcohol [see Interaction with Alcohol (5.3) , Adverse Reactions (6.2) ] . Advise patients and caregivers that the patient should stop taking CHANTIX and contact a healthcare provider immediately if agitation, depressed mood, changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. In many postmarketing cases, resolution of symptoms after discontinuation of CHANTIX was reported, although in some cases the symptoms persisted, therefore, ongoing monitoring and supportive care should be provided until symptoms resolve. The risks of CHANTIX should be weighed against the benefits of its use. CHANTIX has been demonstrated to increase the likelihood of abstinence from smoking for as long as one year compared to treatment with placebo. The health benefits of quitting smoking are immediate and substantial. Since the initial signal of neuropsychiatric symptoms and suicidality emerged, additional analyses and studies have been conducted to further evaluate this association. Analyses of clinical trials A meta-analysis of 5 randomized, double blind, placebo controlled trials, including 1907 patients (1130 CHANTIX, 777 placebo) was conducted to assess suicidal ideation and behavior as reported on the Columbia-Suicide Severity Rating Scale (C SSRS). This meta-analysis included one trial (N=127) in patients with a history of schizophrenia or schizoaffective disorder and another trial (N=525) in patients with a history of depression. The results showed no increase in the incidence of suicidal ideation and/or behavior in patients treated with CHANTIX compared to patients treated with placebo, with a Risk Ratio (RR) of 0.79 (95% Confidence Interval [CI]: 0.46, 1.36), as shown in Table 1. Forty-eight (48) of the 55 patients who reported suicidal ideation or behavior (24 CHANTIX, 24 placebo) were observed in the two trials that enrolled patients with a history of schizophrenia, schizoaffective disorder, or depression. Few events were observed in the other three trials (4 CHANTIX, 3 placebo). Table 1. Number of Patients and Risk Ratio for Suicidal Ideation and/or Behavior Reported on C-SSRS from a Meta-Analysis of 5 Clinical Trials Comparing CHANTIX to Placebo CHANTIX (N=1130) Placebo (N=777) Patients with Suicidal ideation and/or behavior Of the events, one patient in each treatment arm reported suicidal behavior [n (%)] Patients with events up to 30 days after treatment ; % are not weighted by study 28 (2.5) 27 (3.5) Patient-years of exposure 325 217 Risk Ratio # RR of incidence rates per 100 patient years (RR; 95% CI) 0.79 (0.46, 1.36) A pooled analysis of 18 double-blind, randomized, placebo-controlled clinical trials, which includes the 5 trials that collected C-SSRS described in Table 1, was conducted to assess the psychiatric safety of CHANTIX. This pooled analysis included 8521 patients (5072 CHANTIX, 3449 placebo), some of whom had psychiatric conditions at baseline. Table 2 describes the most frequently (≥ 1%) reported adverse events related to psychiatric safety. The results showed a similar incidence of common psychiatric events in patients treated with CHANTIX compared to patients treated with placebo. Table 2. Psychiatric Adverse Events Occurring in ≥ 1% of Patients from Pooled Analysis of 18 Clinical Trials CHANTIX (N=5072) Placebo (N=3449) Anxiety disorders and symptoms 253 (5.0) 206 (6.0) Depressed mood disorders and disturbances 179 (3.5) 108 (3.1) Mood disorders and disturbances NEC NEC = Not Elsewhere Classified Counts (percentages) corresponds to the number of patients reporting the event 116 (2.3) 53 (1.5) Observational Studies Four observational studies, each including 10,000 to 30,000 users of CHANTIX in the adjusted analyses, compared the risk of selected serious neuropsychiatric events (neuropsychiatric hospitalizations, fatal and non-fatal self-harm), between CHANTIX users and prescription NRT or bupropion users. All studies were retrospective cohort studies and included patients with and without a psychiatric history. Two of the studies found no difference in risk of…