Varenicline: uses, appearance and warnings

Varenicline tablet is indicated for use as an aid to smoking-cessation treatment. Varenicline tablet is a nicotinic receptor partial agonist indicated for use as an aid to smoking-cessation treatment. ( 1 and 2.1 )

Capsular, biconvex tablets: 0.5 mg (white to off-white, debossed with "VC" on one side and "0.5" on the other side) and 1 mg (light blue, debossed with "VC" on one side and "1" on the other side). Tablets: 0.5 mg and 1 mg

Varenicline tablets is supplied for oral administration in two strengths: a 0.5 mg capsular biconvex, white to off-white, film-coated tablet debossed with "VC" on one side and "0.5" on the other side and a 1 mg capsular biconvex, light blue film-coated tablet debossed with "VC" on one side and "1" on the other side. Varenicline tablets is supplied in the following package configurations: Description NDC Packs Starting 4-week card: 0.5 mg x 11 tablets and 1 mg x 42 tablets NDC 67877- 745-54 Continuing 4-week card: 1 mg x 56 tablets NDC 67877- 744-54 Starting Month Box: 0.5 mg x 11 tablets and 1 mg x 42 tablets NDC 67877- 745-54 Continuing Month Box: 1 mg x 56 tablets NDC 67877- 744-54 Bottles 0.5 mg - bottle of 56 NDC 67877-743-95 1 mg - bottle of 56 NDC 67877-744-95 Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15 to 30ºC (59 and 86ºF) (see USP Controlled Room Temperature). Protect from light.

Varenicline tablet is contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to varenicline tablets. History of serious hypersensitivity or skin reactions to varenicline tablets.

Neuropsychiatric Adverse Events: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have 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 varenicline tablets for the occurrence of such symptoms and instruct them to discontinue varenicline tablets and contact a healthcare provider if they experience such adverse events. ( 5.1 ) Seizures: New or worsening seizures have been observed in patients taking varenicline tablets. Varenicline tablets 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 varenicline tablets 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 varenicline tablets may affect them. ( 5.4 ) Cardiovascular Events: Patients with underlying cardiovascular (CV) disease may be at increased risk of CV events; however, these concerns must be balanced with the health benefits of smoking cessation. Instruct patients to notify their healthcare providers of new or worsening CV symptoms and to seek immediate medical attention if they experience signs and symptoms of myocardial infarction (MI) or stroke. ( 5.5 and 6.1 ) Somnambulism: Cases of somnambulism have been reported in patients taking varenicline tablets. Some cases described harmful behavior to self, others, or property. Instruct patients to discontinue varenicline tablets and notify their healthcare provider if they experience somnambulism. ( 5.6 and 6.2 ) Angioedema and Hypersensitivity Reactions: Such reactions, including angioedema, infrequently life-threatening, have been reported. Instruct patients to discontinue varenicline tablets and immediately seek medical care if symptoms occur. ( 5.7 and 6.2 ) Serious Skin Reactions: Rare, potentially life-threatening skin reactions have been reported. Instruct patients to discontinue varenicline tablets and contact a healthcare provider immediately at first appearance of skin rash with mucosal lesions. ( 5.8 and 6.2 ) Nausea: Nausea is the most common adverse reaction (up to 30% incidence rate). Dose reduction may be helpful. ( 5.9 ) 5.1 Neuropsychiatric Adverse Events including Suicidality Serious neuropsychiatric adverse events have been reported in patients being treated with varenicline tablets [see Adverse Reactions ( 6.2 )]. These postmarketing reports have 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. Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking-cessation attempt without medication. However, some of these adverse events occurred in patients taking varenicline tablets who continued to smoke. Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses. Some neuropsychiatric adverse events, including unusual and sometimes aggressive behavior directed to oneself or others, may have been worsened by concomitant use of alcohol [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.2 )]. Observe patients for the occurrence of neuropsychiatric adverse events. Advise patients and caregivers that the patient should stop taking varenicline tablets and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. The healthcare provider should evaluate the severity of the symptoms and the extent to which the patient is benefiting from treatment, and consider options including dose reduction, continued treatment under closer monitoring, or discontinuing treatment. In many postmarketing cases, resolution of symptoms after discontinuation of varenicline tablets was reported. However, the symptoms persisted in some cases; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve. The neuropsychiatric safety of varenicline tablets was evaluated in a randomized, double-blind, active and placebo-controlled study that included patients without a history of psychiatric disorder (non-psychiatric cohort, N=3912) and patients with a history of psychiatric disorder (psychiatric cohort, N=4003). In the non-psychiatric cohort, varenicline tablet 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 psychiatric cohort, 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 varenicline tablets, 2.2% (-0.5, 4.9) for bupropion, and 0.4% (-2.2, 3.0) for transdermal nicotine. …

The following serious adverse reactions were reported in postmarketing experience and are discussed in greater detail in other sections of the labeling: Neuropsychiatric Adverse Events including Suicidality [see Warnings and Precautions ( 5.1 )] Seizures [see Warnings and Precautions ( 5.2 )] Interaction with Alcohol [see Warnings and Precautions ( 5.3 )] Accidental Injury [see Warnings and Precautions ( 5.4 )] Cardiovascular Events [see Warnings and Precautions ( 5.5 )] Somnambulism [see Warnings and Precautions ( 5.6 )] Angioedema and Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] Serious Skin Reactions [see Warnings and Precautions ( 5.8 )] In the placebo-controlled premarketing studies, the most common adverse events associated with varenicline tablets (>5% and twice the rate seen in placebo-treated patients) were nausea, abnormal (vivid, unusual, or strange) dream …

Based on varenicline characteristics and clinical experience to date, varenicline tablets has no clinically meaningful pharmacokinetic drug interactions [see Clinical Pharmacology ( 12.3 )]. • Other Smoking-Cessation Therapies: Safety and efficacy in combination with other smoking-cessation therapies has not been established. Coadministration of varenicline and transdermal nicotine resulted in a high rate of discontinuation due to adverse events. ( 7.1 ) • Effect of Smoking Cessation on Other Drugs: Pharmacokinetics or pharmacodynamics of certain drugs (e.g., theophylline, warfarin, insulin) may be altered, necessitating dose adjustment. ( 7.2 ) 7.1 Use with Other Drugs for Smoking Cessation Safety and efficacy of varenicline tablets in combination with other smoking cessation therapies have not been studied. …