Chantix

Generic Name: Varenicline tartrate
Class: Autonomic Drugs, Miscellaneous
Chemical Name: 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3- h][3]benzazepine, (2R,3R)-2,3-dihydroxybutanedioate (1:1)
Molecular Formula: C₁₃H₁₃N₃•C₄H₆O₆
CAS Number: 375815-87-5

Special Alerts:

[UPDATED 07/22/2011] FDA has approved an updated drug label for Chantix (varenicline) to include information about the efficacy and safety of the drug in two patient populations who may benefit greatly from giving up smoking—those with cardiovascular disease and those with chronic obstructive pulmonary disease (COPD). The updated label now also includes alternative directions for patients to select a quit smoking date. For more information visit the FDA website at: and .

[Posted 06/16/2011] ISSUE: FDA notified healthcare professionals and patients that the Prescribing Information for this drug product will be strengthened to inform the public that use of varenicline (Chantix) may be associated with a small, increased risk of certain cardiovascular adverse events in patients who have cardiovascular disease. This safety information will be added to the Warnings and Precautions section and the patient Medication Guide.

BACKGROUND: FDA reviewed a randomized, double-blind, placebo-controlled clinical trial of 700 smokers with cardiovascular disease who were treated with varenicline or placebo. While cardiovascular adverse events were infrequent overall, certain events, including heart attack, were reported more frequently in patients treated with varenicline than in patients treated with placebo. The events included angina pectoris, nonfatal myocardial infarction, need for coronary revascularization, and new diagnosis of peripheral vascular disease or admission for a procedure for the treatment of peripheral vascular disease. FDA is continuing to evaluate the cardiovascular safety of varenicline and is requiring the manufacturer to conduct a large, combined analysis (meta-analysis) of randomized, placebo-controlled trials. FDA will update the public when additional information is available.

RECOMMENDATION: See the Data Summary section of the Drug Safety Communication for additional information.

Healthcare professionals should be aware that smoking is an independent and major risk factor for cardiovascular disease, and smoking cessation is of particular importance in this patient population. The known benefits of varenicline should be weighed against its potential risks when deciding to use the drug in smokers with cardiovascular disease.

Patients are encouraged to read the Medication Guide they receive along with their varenicline prescription. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for varenicline tartrate to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of varenicline tartrate and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

• Neuropsychiatric Symptoms and Suicide Risk


• 
  

  Serious neuropsychiatric symptoms (e.g., depression, suicidal ideation, suicide attempt, completed suicide) have been reported in patients receiving varenicline for smoking cessation.^{1 10 11 12 13} (See Neuropsychiatric Symptoms and Suicidality under Cautions.)

  
  


• 
  

  Such effects have occurred in patients with or without psychiatric illnesses.^{1 10 11 12 13} Safety and efficacy of varenicline not established in patients with serious psychiatric illness (e.g., schizophrenia, bipolar disorder, major depressive disorder); such patients may experience recurrence or worsening of symptoms during varenicline therapy.^{1 10 12}

  
  


• 
  

  Depressed mood may be a symptom of nicotine withdrawal; however, some symptoms occurred in varenicline-treated patients who continued to smoke.¹

  
  


• 
  

  Most symptoms occurred during varenicline therapy, but some were reported following discontinuance of drug.^{1 10 13}

  
  


• 
  

  Monitor all patients receiving varenicline for neuropsychiatric symptoms, including changes in behavior, hostility, agitation, depressed mood, and suicide-related events (including ideation, behavior, and attempted suicide).^{1 10 12}

  
  


• 
  

  Patient should discontinue varenicline and immediately contact clinician if agitation, hostility, depressed mood, or changes in thinking or behavior not typical for the patient occur, or if patient develops suicidal ideation or behavior.^{1 10 11 13}

  
  


• 
  

  Symptoms resolved upon drug discontinuance in many cases, but persisted in some.^{1 10 12} Provide ongoing patient monitoring and supportive care until symptoms resolve.^{1 10}

  
  


• 
  

  Weigh risks of varenicline therapy against benefits of its use for smoking cessation.^{1 7 10 13}

  
  

Introduction

Nicotinic acetylcholine receptor partial agonist.¹

Uses for Chantix

Smoking Cessation

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Adjunct in the cessation of cigarette smoking.^{1 3 4 5 7 8}

Urge to smoke was less severe in individuals receiving varenicline than in those receiving placebo.^{1 3 4 5}

Efficacy and safety of varenicline given in conjunction with other smoking cessation therapies (e.g., bupropion, nicotine replacement therapy) have not been established.¹

Chantix Dosage and Administration

Administration

Oral Administration

Administer tablets orally after eating, with a full glass of water.^{1 3 4 5 7}

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as varenicline tartrate; dosage expressed in terms of varenicline.¹

Adults

Smoking Cessation

Oral

0.5 mg once daily on days 1–3, followed by 0.5 mg twice daily on days 4–7, and then 1 mg twice daily from day 8 through the end of 12 weeks of treatment.¹ Initiate 1 week before the target smoking cessation date.¹

Titrate dosage during the initial week of treatment to reduce the incidence of drug-related nausea.¹ Dosage may be reduced temporarily or permanently in patients who experience intolerable adverse effects.¹

In patients who have successfully stopped smoking by the end of 12 weeks of initial treatment, consider an additional 12 weeks of therapy to increase the likelihood of long-term abstinence.¹

Patients unable to quit smoking during 12 weeks of treatment or those who have relapsed after varenicline therapy should make another attempt to quit smoking once factors responsible for such failure have been identified and addressed.¹

Prescribing Limits

Adults

Oral

1 mg twice daily.¹

Special Populations

Hepatic Impairment

No dosage adjustment is needed in patients with hepatic impairment.¹

Renal Impairment

No dosage adjustment needed in patients with mild to moderate renal impairment.¹

If Cl_cr is <30 mL/minute, initially administer 0.5 mg once daily; titrate dosage as needed to a maximum of 0.5 mg twice daily.¹

In patients with end-stage renal disease undergoing hemodialysis, maximum dosage is 0.5 mg once daily.¹

Geriatric Patients

Select dosage carefully and monitor renal function.¹

Cautions for Chantix

Contraindications

No known contraindications to the use of varenicline.¹

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Neuropsychiatric Symptoms and Suicidality

Serious neuropsychiatric symptoms, including changes in mood (e.g., depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, panic, and suicidality (e.g., suicidal ideation, attempted and completed suicides), reported.^{1 10 11 12 13} (See Neuropsychiatric Symptoms and Suicide Risk in Boxed Warning.)

While some patients who stopped smoking have experienced these symptoms as a result of nicotine withdrawal, others who had not yet discontinued smoking also experienced such symptoms.¹

Monitor all patients for neuropsychiatric symptoms or for worsening of preexisting psychiatric conditions.^{1 10 12} Discontinue varenicline in patients who develop agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient or who develop suicidal ideation or suicidal behavior.^{1 10 11 13}

Symptoms resolved after varenicline discontinuance in many cases but persisted in some despite discontinuance.^{1 10 12} Provide ongoing patient monitoring and supportive care until symptoms resolve.^{1 10}

Risk of worsening preexisting psychiatric illness.¹ Safety and efficacy of varenicline in patients with serious psychiatric illness (e.g., schizophrenia, bipolar disorder, major depressive disorder) not established.¹

Discuss risk of developing serious neuropsychiatric effects with patients prior to use of varenicline.^{1 10} (See Advice to Patients.) Weigh such risks against health benefits of smoking cessation (e.g., reduction in the risk of developing pulmonary disease, cardiovascular disease, or certain types of cancer).^{1 7 10 13}

Dermatologic Effects

Serious dermatologic reactions, including Stevens-Johnson syndrome and erythema multiforme, reported; potentially life-threatening.¹ Instruct patients to discontinue varenicline and immediately contact healthcare provider at first appearance of rash with mucosal lesions or any signs of hypersensitivity.¹

Sensitivity Reactions

Angioedema and Hypersensitivity Reactions

Hypersensitivity reactions, including angioedema, reported.¹ Manifestations included swelling of the face, mouth (tongue, lips, and gums), extremities, and neck (pharynx and larynx).¹ Life-threatening angioedema requiring emergent medical attention because of respiratory compromise infrequently reported.¹

Instruct patients to discontinue varenicline and immediately seek medical attention if such symptoms occur.¹

General Precautions

Nausea

Nausea is most commonly reported adverse effect; usually mild or moderate, dose related, and often transient (although may persist for several months).^{1 3 4 8}

Initial titration of varenicline dosage reduces incidence of nausea (see Dosage under Dosage and Administration).¹ Consider dosage reduction in patients experiencing intolerable nausea.¹

Accidental Injury

Traffic accidents, near-miss incidents in traffic, or other accidental injuries reported.¹ In some cases, somnolence, dizziness, loss of consciousness or difficulty concentrating was reported.^{1 7} (See Advice to Patients.)

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk in animals; not known whether varenicline is distributed into human milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.¹

Modification of dosage may be necessary because of age-related decreases in renal function.¹

Renal Impairment

Caution in patients with moderate to severe renal impairment and in patients with end-stage renal disease undergoing hemodialysis.¹ Exposure to the drug was increased in patients with such impairment.¹ Dosage adjustment is recommended for patients with Cl_cr<30 mL/minute.¹ (See Special Populations under Dosage and Administration.)

Common Adverse Effects

Nausea,^{1 3 4 8} abdominal pain,¹ flatulence,^{1 3 4} dyspepsia,^{1 3} vomiting,^{1 3} constipation,^{1 3 4} dry mouth,^{1 3 4} insomnia,^{1 3 4} abnormal dreams,^{1 3 4} sleep disorders,^{1 3 4} headache,^{1 3 4} dysgeusia,¹ fatigue/malaise/asthenia,^{1 3} upper respiratory tract disorders.^{1 9}

Interactions for Chantix

Physiologic changes resulting from smoking cessation (with or without varenicline) may alter the pharmacokinetics or pharmacodynamics of some drugs (e.g., insulin, theophylline, warfarin); dosage adjustment may be required.¹

Does not inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5 in vitro; does not induce CYP isoenzymes 1A2 or 3A4 in vitro.¹ Pharmacokinetic interactions with drugs metabolized by or affecting these isoenzymes unlikely.¹

Specific Drugs

Drug	Interaction	Comments
Bupropion	Pharmacokinetic interaction unlikely1	Safety of combined use not established1
Cimetidine	Possible increased plasma concentration of varenicline secondary to a reduction in renal clearance1
Digoxin	Pharmacokinetic interaction unlikely1
Nicotine	Pharmacokinetic interaction unlikely;1 increased incidence of adverse effects (nausea, headache, vomiting, dizziness, dyspepsia, fatigue) and increased rate of discontinuance of combination (varenicline and transdermal nicotine replacement) therapy compared with those receiving transdermal nicotine and placebo1	Safety and efficacy of varenicline in combination with other smoking cessation therapies not established1
Warfarin	Pharmacokinetic interaction unlikely;1 warfarin pharmacokinetics may be affected by smoking cessation1

Chantix Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, with peak plasma concentration usually attained within 3–4 hours.¹ Time of dosing does not appear to affect oral bioavailability.¹

Food

Food does not appear to affect oral bioavailability.¹

Distribution

Plasma Protein Binding

≤20%; independent of age and renal function.¹

Elimination

Metabolism

Undergoes limited biotransformation.¹

Elimination Route

Excreted in urine principally (92%) as unchanged drug.¹

Half-life

24 hours.¹

Special Populations

No evidence of gender-, age-, race-, smoking status-, or concomitant drug-related pharmacokinetic differences.¹

In patients with moderate (Cl_cr ≤50 mL/minute) to severe (Cl_cr <30 mL/minute) renal impairment or end-stage renal disease undergoing hemodialysis, exposure to the drug was increased. ¹ (See Special Populations under Dosage and Administration.)

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

Actions

• 
  

  Binds with high affinity and selectivity to α₄β₂ nicotinic acetylcholine receptors located in the brain to stimulate receptor-mediated activity, but at a substantially lower level than nicotine.^{1 6}

  
  


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  Stimulation and subsequent moderate, sustained release of mesolimbic dopamine are thought to reduce craving and withdrawal symptoms associated with smoking cessation.^{1 4 6}

  
  


• 
  

  Blocks the ability of nicotine to activate α₄β₂ receptors by preventing nicotine-induced stimulation of the mesolimbic dopaminergic system and thus reducing the reinforcement and reward effects of cigarette smoking.^{1 6}

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of providing educational materials and counseling to support attempt to quit smoking.¹ Patients should be instructed to read the patient medication guide before initiation of varenicline therapy and every time the prescription is refilled since the information may have been revised.^{1 7}

  
  


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  Advise patients to set a date to quit smoking and to start varenicline therapy 1 week prior to the quit date.^{1 7}

  
  


• 
  

  Importance of taking varenicline after eating and with a full glass of water.^{1 7}

  
  


• 
  

  Importance of instructing patients how to titrate varenicline tartrate dosage, starting with a dosage of 0.5 mg daily.^{1 7} (See Smoking Cessation under Dosage and Administration.)

  
  


• 
  

  Advise patients to take the drug exactly as prescribed by clinician.⁷

  
  


• 
  

  Advise patients not to take varenicline while using other smoking cessation treatments.⁷ Importance of informing clinician if using other smoking cessation treatments.⁷

  
  


• 
  

  Advise patients to notify clinician if nausea or insomnia persistently occur; consideration of dosage reduction may be necessary.¹

  
  


• 
  

  Importance of encouraging patients to continue to attempt to quit smoking if they have early lapses after the set quit date.¹

  
  


• 
  

  Importance of informing patients that quitting smoking, with or without use of varenicline, may be associated with symptoms of nicotine withdrawal (e.g., depression, agitation, urge to smoke, difficulty sleeping, irritability, frustration, anger, anxiety, difficulty concentrating, restlessness, decreased heart rate, increased appetite, weight gain) or exacerbation of preexisting psychiatric illness.^{1 7 10 13}

  
  


• 
  

  Importance of advising patients and their caregivers that changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, agitation, aggression, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide, have been reported in patients attempting to quit smoking while receiving varenicline.^{1 7 10 11 12 13} Importance of advising patients to discontinue varenicline and notify a clinician if they or their caregivers observe agitation, depressed mood, or changes in behavior or thinking that are not typical for the patients, or if the patient develops suicidal ideation or suicidal behavior.^{1 7 10 11 13} Importance of informing clinicians of preexisting psychiatric illness.^{1 7}

  
  


• 
  

  Importance of immediately discontinuing varenicline and contacting a clinician at first sign of rash with mucosal lesions (e.g., peeling skin, mouth blisters) or other skin reactions or symptoms of angioedema (e.g., swelling of the face, mouth [lips, gums, tongue], throat).^{1 7}

  
  


• 
  

  Importance of informing clinicians about development of symptoms associated with previous attempts to quit smoking (with or without varenicline).⁷

  
  


• 
  

  Importance of informing patients that they may experience vivid, unusual, or strange dreams during varenicline treatment.^{1 7}

  
  


• 
  

  Somnolence, dizziness, or difficulty concentrating reported.^{1 7} Importance of advising patients to use caution while driving, operating machinery, or engaging in other potentially hazardous activities until the effects of varenicline on the individual are known.^{1 7}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Advise women who are or plan to become pregnant or plan to breast-feed of risks of smoking and risks and benefits of using varenicline to aid in smoking cessation.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., depression or other psychiatric illness, renal disease).^{1 7} Some concomitantly administered drugs may require dosage adjustment due to effects of smoking cessation.^{1 7}

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Varenicline Tartrate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Kit	11 Tablets, film-coated, Varenicline Tartrate 0.5 mg (of varenicline) (Chantix) 42 Tablets, film-coated, Varenicline Tartrate 1 mg (of varenicline) (Chantix)	Chantix Pack (available as dose/cards for first month of therapy)	Pfizer
	Tablets, film-coated	0.5 mg (of varenicline)	Chantix	Pfizer
		1 mg (of varenicline)	Chantix (available as 4 cards of 14 tablets and regular packaging)	Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Chantix 0.5MG Tablets (PFIZER U.S.): 56/$177.65 or 168/$499.17

Chantix 1MG Tablets (PFIZER U.S.): 56/$179.00 or 168/$506.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Pfizer Labs. Chantix (varenicline) tablets prescribing information. New York, NY; 2009 Jul.

2. Kuehn BM. FDA speeds smoking cessation drug review. JAMA. 2006; 295:614. [PubMed 16467225]

3. Jorenby DE, Hays JT, Rigotti NA et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006; 296:56-63. [PubMed 16820547]

4. Gonzales D, Rennard SI, Nides M et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006; 296:47-55. [PubMed 16820546]

5. Tonstad S, Tonnesen P, Hajek P et al. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA. 2006; 296:64-71. [PubMed 16820548]

6. Coe JW, Brooks PR, Vetelino MG et al. Varenicline: an α₄β₂ nicotinic receptor partial agonist for smoking cessation. J Med Chem. 2005; 48:3474-7. [PubMed 15887955]

7. Pfizer Labs. Medication Guide: Chantix (varenicline) tablets. New York, NY; 2009 Jul.

8. Klesges RC, Johnson KC, Somes G. Varenicline for smoking cessation: definite promise, but not panacea. JAMA. 2006; 296:94-5. [PubMed 16820552]

9. Pifzer Inc., Morris Plains, NJ: Personal communication.

10. Food and Drug Administration. FDA Alert: Information for healthcare professionals: varenicline (marketed as Chantix) and bupropion (marketed as Zyban, Wellbutrin, and generics). Rockville, MD; 2009 Jul 1. From the FDA web site: . Accessed 2009 Sep 24.

11. Food and Drug Administration. FDA MedWatch alert: varenicline (marketed as Chantix) and bupropion (marketed as Zyban, Wellbutrin, and generics). Rockville, MD; 2009 Jul 1. From the FDA web site: . Accessed 2009 Sep 25.

12. Pollock M, Lee JH. The smoking cessation aids varenicline (marketed as Chantix) and bupropion (marketed as Zyban and generics): suicidal ideation and behavior. Drug Safety Newsletter. 2009; 2:1–4. From the FDA web site: . Accessed 2009 Sep 25.

13. Food and Drug Administration. Public Health Advisory: FDA requires new boxed warnings for the smoking cessation drugs Chantix and Zyban. Rockville, MD; 2009 Jul 1. From the FDA web site: . Accessed 2009 Sep 25.

More Chantix resources

• Chantix Side Effects (in more detail)
• Chantix Use in Pregnancy & Breastfeeding
• Drug Images
• Chantix Drug Interactions
• Chantix Support Group
• 369 Reviews for Chantix - Add your own review/rating

• Chantix Prescribing Information (FDA)


• Chantix Consumer Overview


• Chantix Advanced Consumer (Micromedex) - Includes Dosage Information


• Chantix MedFacts Consumer Leaflet (Wolters Kluwer)


• Varenicline Professional Patient Advice (Wolters Kluwer)

Compare Chantix with other medications

• Smoking Cessation