varenicline (Chantix)

Dosing and uses of Chantix (varenicline)

• Adult
• Pediatric

 

Adult dosage forms and strengths

tablet

• 0.5mg
• 1mg

 

Smoking Cessation

Set a date to stop smoking and begin varenicline 1 week before this date

Alternatively, the patient can begin varenicline and then quit smoking between days 8 and 35 of treatment

Also see Administration

Quit smoking date regimen

• Initiate regimen 1 week before quit smoking date
• Days 1-3: 0.5 mg PO qDay
• Days 4-7: 0.5 mg PO BID
• Day 8 to end of treatment: 1 mg PO BID
• If quitting is successful after 12 weeks, continue another 12 weeks at 1 mg q12hr

Gradual approach to quitting

• For patients who are sure that they are not able or willing to quit abruptly, consider a gradual approach to quitting smoking with varenicline
• Begin dosing and reduce smoking by 50% from baseline within the first 4 weeks, by an additional 50% in the next 4 weeks, and continue reducing with the goal of reaching complete abstinence by 12 weeks
• Continue varenicline for an additional 12 weeks, for a total of 24 weeks of treatment
• Encourage patients to attempt quitting sooner if they feel ready

 

Dosage modifications

Consider a temporary or permanent dose reduction in patients who cannot tolerate the adverse effects

Renal impairment

• Mild-to-moderate (CrCl ≥30 mL/min): No dosage adjustment required
• Severe (CrCl <30 mL/min): 0.5 mg PO qDay initially; may increase to 0.5 mg PO q12hr
• ESRD on hemodialysis: Not to exceed 0.5 mg PO qDay

 

Pediatric dosage forms and strengths

<18 years: Safety and efficacy not established

 

Chantix (varenicline) adverse (side) effects

>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

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%)

 

Warnings

Black box warnings

Serious neuropsychiatric events reported, including (but not limited to) depression, suicidal ideation, suicide attempt, and completed suicide; some reported cases may have been complicated by symptoms of nicotine withdrawal in patients who stopped smoking

Depressed mood may be symptom of nicotine withdrawal; depression, rarely including suicidal ideation, reported in smokers undergoing smoking cessation attempt without medication; however, some of these symptoms have occurred in patients taking varenicline who continued to smoke

All patients being treated should be observed for neuropsychiatric symptoms, including changes in behavior, hostility, agitation, depressed mood, and suicide-related events, including ideation, behavior, and attempted suicide

These symptoms have been reported in some patients attempting to quit smoking while taking varenicline in postmarketing experience; most often, symptoms occurred during treatment, but some followed discontinuance

These events have occurred in patients with and without preexisting psychiatric disease; safety and efficacy in patients with serious psychiatric illness (eg, schizophrenia, bipolar disorder, major depressive disorder) have not been established

Advise patients and caregivers that patient should stop taking varenicline and contact healthcare provider immediately if agitation, hostility, depressed mood, or atypical changes in behavior or thinking are observed or if patient develops suicidal ideation or suicidal behavior

Ongoing monitoring and supportive care should be provided until symptoms resolve; risks of varenicline therapy should be weighed against benefits

 

Contraindications

Documented hypersensitivity or skin reactions to drug or components of formulation

Nonsmokers

 

Cautions

May cause nausea; reduce dose if nausea occurs

Possibility of serious neuropsychiatric disorder, including changes in mood (eg, depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, anxiety, abnormal dreams, and panic, as well as suicidal ideation, suicide attempt, and completed suicide

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

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 and lactation

Pregnancy category: C

Lactation: Unknown whether drug is excreted in breast milk; discontinue drug, or do not nurse

 

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.

 

Pharmacology of Chantix (varenicline)

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%)

 

Administration

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