varenicline (Rx)

>10%

Nausea (15-40%; dose related)

Abnormal dreams

Headache

Insomnia

1-10%

Appetite changes

Chest pain

Constipation

Dry mouth

Dyspepsia

Dyspnea

Flatulence

Gastroesophageal reflux disease (GERD)

Fatigue or lethargy

Pruritus

Rash

Somnolence

Rhinorrhea

Vomiting

Upper respiratory tract disorder

Frequency Not Defined (selected)

Abnormal liver function tests

Anemia

Anxiety

Arrhythmia

Arthralgia

Depression

Diarrhea

Dizziness

Epistaxis

Hypertension

Myocardial infarction (MI)

Polyuria

Respiratory disorder

Postmarketing Reports

Depression, mania, psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide, somnambulism

Serious skin reactions, including Stevens-Johnson syndrome

Cerebrovascular accident

Seizures

MI

Cardiovascular: During nontreatment follow-up to 52 weeks, adjudicated events comparing patients with stable cardiovascular disease to premarket studies included need for coronary revascularization (2.0% vs 0.6%), hospitalization for angina pectoris (1.7% vs 1.1%), and new diagnosis of peripheral vascular disease (PVD) or admission for PVD procedure (1.4% vs 0.6%)

Irritability

Agitation

Somnambulism

Contraindications

Documented hypersensitivity or skin reactions to drug or components of formulation

Nonsmokers

Cautions

May cause nausea; reduce dose if nausea occurs

Somnambulism reported, including cases describing harmful behavior to self, others, or property; instruct patients to discontinue varenicline and notify their healthcare professional

Seizures reported; some patients had no history of seizures, whereas others had a history of seizure disorder that was remote or well-controlled; in most cases, the seizure occurred within the first month of therapy; use with caution in patients with history of seizures or with other factors that might lower seizure threshold

May cause CNS depression; use caution when performing tasks requiring mental alertness, such as, operating heavy machinery or driving

Hypersensitivity reactions reported, including angioedema

Rare but serious skin reactions reported, including Stevens-Johnson Syndrome and erythema multiforme

Neuropsychiatric adverse effects

• Serious neuropsychiatric adverse events reported; these postmarketing reports include 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 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
• Advise patients and caregivers that the patient should stop taking varenicline and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical are observed, or if the patient develops suicidal ideation or suicidal behavior

Alcohol interaction

• Patients should reduce amount alcohol they consume when initiating therapy until they know whether it increases intoxicating effects
• Postmarketing reports of patients experiencing increased intoxicating effects of alcohol while taking varenicline; some cases described unusual and sometimes aggressive behavior, and were often accompanied by amnesia for the events

Cardiovascular risk

• May increase risk of cardiovascular events in patients with underlying cardiovascular disease; randomized, double-blind, placebo-controlled study of 700 patients treated with varenicline for smoking cessation found increases in risk of nonfatal MI, need for revascularization, angina pectoris, and peripheral vascular disease
• In FDA meta-analysis, varenicline (compared with placebo) showed nonsignificant increase in risk for major adverse cardiovascular events (ie, combined outcome of cardiovascular-related death, nonfatal heart attack, and nonfatal stroke); these events were uncommon in both groups

Pregnancy

Available data have not suggested increased risk for major birth defects following exposure to varenicline in pregnancy, compared with women who smoke; smoking during pregnancy causes increased risks of orofacial clefts, premature rupture of membranes, placenta previa, placental abruption, ectopic pregnancy, fetal growth restriction and low birth weight, stillbirth, preterm delivery and shortened gestation, neonatal death, sudden infant death syndrome and reduction of lung function in infants; it is not known whether quitting smoking with varenicline during pregnancy reduces these risks

Lactation

Because there are no data on presence of varenicline in human milk and effects on breastfed infant, breastfeeding women should monitor their infant for seizures and excessive vomiting, which are adverse reactions that have occurred in adults that may be clinically relevant in breastfeeding infants

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Agonist at nicotinic receptors; acts on mesolimbic dopamine system associated with nicotine addiction, where it prevents nicotine stimulation; stimulates nicotine activity but to lesser degree than nicotine does

Absorption

Completely absorbed

Bioavailability: High

Peak plasma time: 3-4 hr

Distribution

Protein bound: <20%

Metabolism

Minimally metabolized

Elimination

Excretion: Urine (92%)

Half-life: 24 hr

Excretion: Urine (92%)

Oral Administration

Take dose after eating with full glass of water

Set date to stop smoking, and start varenicline 1 week before that date; alternatively, the patient can begin varenicline dosing and then quit smoking between days 8 and 35 of treatment

Patients who are motivated to quit, and who did not succeed in stopping smoking during prior varenicline therapy for reasons other than intolerability due to adverse events or who relapsed after treatment, should be encouraged to make another attempt with varenicline once factors contributing to the failed attempt have been identified and addressed