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Varenicline

Pronunciation

Pronunciation

(var EN i kleen)

Index Terms

  • Varenicline Tartrate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Chantix: 0.5 mg, 1 mg

Chantix Continuing Month Pak: 1 mg

Chantix Starting Month Pak: 0.5 mg x 11 & 1 mg x 42

Brand Names: U.S.

  • Chantix
  • Chantix Continuing Month Pak
  • Chantix Starting Month Pak

Pharmacologic Category

  • Partial Nicotine Agonist
  • Smoking Cessation Aid

Pharmacology

Partial neuronal α4 β2 nicotinic receptor agonist; prevents nicotine stimulation of mesolimbic dopamine system associated with nicotine addiction. Also binds to 5-HT3 receptor (significance not determined) with moderate affinity. Varenicline stimulates dopamine activity but to a much smaller degree than nicotine does, resulting in decreased craving and withdrawal symptoms.

Absorption

Well absorbed; unaffected by food

Metabolism

Minimal (<10% of clearance is through metabolism)

Excretion

Urine (92% as unchanged drug)

Time to Peak

Plasma: ~3 to 4 hours

Half-Life Elimination

~24 hours

Protein Binding

≤20%

Special Populations: Renal Function Impairment

Moderate Renal Function Impairment (CrCl ≥30 to ≤50 mL/minute)

Drug exposure increased 1.5-fold.

Severe Renal Function Impairment (CrCl <30 mL/minute)

Drug exposure increased 2.1-fold.

End-Stage Renal Disease

Drug exposure increased 2.7-fold.

Moderate renal impairment (CrCl ≥30 to ≤50 mL/minute): Drug exposure increased 1.5-fold.

Severe renal impairment (CrCl <30 mL/minute): Drug exposure increased 2.1-fold.

End-stage renal disease requiring hemodialysis: Drug exposure increased 2.7-fold.

Use: Labeled Indications

Smoking cessation: As an aid to smoking cessation treatment

Contraindications

Serious hypersensitivity reactions or skin reactions to varenicline or any component of the formulation

Dosing: Adult

Smoking cessation: Oral:

Initial:

Days 1 to 3: 0.5 mg once daily

Days 4 to 7: 0.5 mg twice daily

Maintenance (≥ Day 8):

US labeling: 1 mg twice daily for 11 weeks

Canadian labeling: 0.5 to 1 mg twice daily for 11 weeks

Note: Start 1 week (US labeling) or 1 to 2 weeks (Canadian labeling) before target quit date. Alternatively, patients may consider setting a quit date up to 35 days after initiation of varenicline (some data suggest that an extended pretreatment regimen may result in higher abstinence rates [Hajek 2011]). If patient successfully quits smoking at the end of the 12 weeks, may continue for another 12 weeks to help maintain success. Patients who are motivated to quit and do not succeed in stopping smoking during prior therapy, or who relapse after treatment, should be encouraged to make another attempt with varenicline once factors contributing to the failed attempt have been identified and addressed.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: Initiate: 0.5 mg once daily; maximum dose: 0.5 mg twice daily

End-stage renal disease (ESRD) (receiving hemodialysis):

US labeling: Maximum dose: 0.5 mg once daily

Canadian labeling: Use is not recommended (insufficient data)

Dosing: Hepatic Impairment

No dosage adjustment necessary.

Dosing: Adjustment for Toxicity

Patients who cannot tolerate adverse events may require temporary (or permanent) reduction in dose.

Administration

Administer after eating and with a full glass of water.

Dietary Considerations

Take after eating and with a full glass of water to decrease gastric upset.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Alcohol (Ethyl): Varenicline may enhance the adverse/toxic effect of Alcohol (Ethyl). Specifically, alcohol tolerance may be decreased and the risk for neuropsychiatric adverse effects may be increased. Monitor therapy

BuPROPion: May increase the serum concentration of OCT2 Substrates. Monitor therapy

H2-Antagonists: May increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of cimetidine or other H2-antagonists, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy

Nicotine: Varenicline may enhance the adverse/toxic effect of Nicotine. Monitor therapy

Quinolone Antibiotics: May increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concurrent use of levofloxacin or other quinolone antibiotics, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy

Trimethoprim: May increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of trimethoprim, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy

Adverse Reactions

>10%:

Central nervous system: Headache (15% to 19%), insomnia (10% to 19%), abnormal dreams (9% to 13%), irritability (11%), suicidal ideation (11%), depression (4% to 11%)

Gastrointestinal: Nausea (16% to 40%), vomiting (5% to 11%)

1% to 10%:

Cardiovascular: Angina pectoris (4%), chest pain (3%), peripheral edema (2%), myocardial infarction (≤1%)

Central nervous system: Agitation (7%), malaise (7%), sleep disorder (5%), tension (4%), drowsiness (3%), hostility (2% to 3%), lethargy (1% to 2%), nightmares (1% to 2%)

Dermatologic: Skin rash (3%)

Gastrointestinal: Flatulence (6% to 9%), constipation (5% to 8%), dysgeusia (5% to 8%), abdominal pain (7%), diarrhea (6%), xerostomia (6%), dyspepsia (5%), increased appetite (3% to 4%), anorexia (2%), gastroesophageal reflux disease (1%)

Respiratory: Upper respiratory tract infection (5% to 7%), dyspnea (2%), rhinorrhea (≤1%)

<1% (Limited to important or life-threatening): Acute renal failure, amnesia, anemia, atrial fibrillation, Bell's palsy, cataract (subcapsular), cerebrovascular accident, conjunctivitis, cor pulmonale, coronary artery disease, decreased visual acuity, diabetes mellitus, dissociative disorder, dysarthria, dysphagia, ECG abnormality, eczema, enterocolitis, erectile dysfunction, erythema multiforme, gallbladder disease, gastrointestinal hemorrhage, homicidal ideation, hyperhidrosis, hyperlipidemia, hypersensitivity, hypoglycemia, hypokalemia, intestinal obstruction, leukocytosis, loss of consciousness, lymphadenopathy, mania, Meniere's disease, migraine, multiple sclerosis, myositis, nephrolithiasis, nocturnal amblyopia, nystagmus, ophthalmic vascular disease, oral mucosa ulcer, osteoporosis, pancreatitis, panic, photophobia, psychomotor agitation, psychomotor retardation, psychosis, pulmonary embolism, restless leg syndrome, seizure, skin photosensitivity, splenomegaly, Stevens-Johnson syndrome, syncope, tachycardia, thrombocytopenia, thrombosis, thyroid disease, transient blindness, transient ischemic attacks, urinary retention, ventricular premature contractions

ALERT: U.S. Boxed Warning

Serious neuropsychiatric events:

Serious neuropsychiatric events including but not limited to, depression, suicidal ideation, suicide attempt, and completed suicide have been reported in patients taking varenicline. 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 varenicline who continued to smoke.

All patients being treated with varenicline 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, as well as worsening of preexisting psychiatric illness and completed suicide, have been reported in some patients attempting to quit smoking while taking varenicline in the postmarketing experience. When symptoms were reported, most were during varenicline treatment, but some were following discontinuation of varenicline therapy.

These events have occurred in patients with and without preexisting psychiatric disease. Patients with serious psychiatric illness, such as schizophrenia, bipolar disorder, and major depressive disorder, did not participate in the premarketing studies of varenicline.

Advise patients and caregivers that the patient should stop taking varenicline and contact a health care provider immediately if agitation, hostility, 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. In many postmarketing cases, resolution of symptoms after discontinuation of varenicline was reported, although in some cases the symptoms persisted; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.

Risk vs benefit:

The risks of varenicline should be weighed against the benefits of its use. Varenicline has been demonstrated to increase the likelihood of abstinence from smoking for as long as 1 year compared with treatment with placebo. The health benefits of quitting smoking are immediate and substantial.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). There have been postmarketing reports of traffic accidents, near-miss incidents in traffic, or other accidental injuries in patients taking varenicline.

• Hypersensitivity reactions: Postmarketing reports of hypersensitivity reactions (including angioedema) and rare cases of serious skin reactions (including Stevens-Johnson syndrome and erythema multiforme) have been reported. Patients should be instructed to discontinue use and contact healthcare provider if signs/symptoms occur.

• Nausea: Dose-dependent nausea may occur; both transient and persistent nausea has been reported. Dosage reduction may be considered for intolerable nausea.

• Neuropsychiatric effects: [US Boxed Warning]: Post-marketing cases of serious neuropsychiatric events (including depression, suicidal thoughts, and suicide) have been reported in patients with or without preexisting psychiatric disease; some cases may have been complicated by symptoms of nicotine withdrawal following smoking cessation. Subsequent controlled trials in patients with or without psychiatric disorders; however, have not identified significant differences in neuropsychiatric effects for patients taking varencline, bupropion, nicotine patches, or placebo (Anthenelli 2013; Anthenelli 2016; Gibbons 2013; Thomas 2015). Monitor all patients for behavioral changes and psychiatric symptoms (eg, agitation, depression, suicidal behavior, suicidal ideation); inform patients to discontinue treatment and contact their health care provider immediately if they experience any behavioral and/or mood changes. Of post-marketing cases, many resolved following therapy discontinuation.

Disease-related concerns:

• Cardiovascular events: Treatment may increase risk of cardiovascular events. A meta-analysis of 15 clinical trials, including a placebo-controlled trial in patients with stable cardiovascular disease, showed an increased incidence of major cardiovascular events (combined outcome of cardiovascular-related death, nonfatal MI, nonfatal stroke) in patients using varenicline compared with placebo. Cardiovascular events were uncommon in both the varenicline and placebo groups. These findings did not reach statistical significance, although data was consistent. Events occurred primarily in patients with known cardiovascular disease. The meta-analysis also showed a lower incidence of all-cause and cardiovascular mortality in varenicline-treated patients, although this was not statistically significant either.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required with severe impairment.

• Seizures: Seizures have been reported in patients with or without a history of seizures. Seizures generally occurred within the first month of therapy. Consider the risks against the benefits before initiating in patients with a history of seizures or other factors that can lower the seizure threshold; discontinue use if seizures occur during therapy.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Monitor for behavioral changes and psychiatric symptoms (eg, agitation, depression, suicidal behavior, suicidal ideation).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. The Canadian labeling recommends avoiding use during pregnancy.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, flatulence, insomnia, headache, nightmares, constipation, dry mouth, abdominal pain, change in taste, or loss of strength and energy. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, illogical thinking), hallucinations, psychosis, signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), signs of a heart attack (angina; pain in arms, back, neck, jaw, or stomach; shortness of breath; cold sweats; severe dizziness; passing out; severe nausea; or vomiting), shortness of breath, memory impairment, severe nausea, vomiting, seizures, confusion, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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