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varenicline (Chantix, Champix)

Tradename: Chantix Indications: - smoking cessation - leads to higher smoking cessation rates among smokers who say they're not quite ready to quit (32& vs 7%) [24] - higher smoking cessation rate than with transdermal nicotine or bupropion at 9-12 weeks [28] - has not been studied in the elderly [29] Contraindications: 1) NOT for use with nicotine replacement [2] a) no evidence of efficacy b) increased incidence of adverse effects c) apparently, some specialist do combine nicotine with varenicline [12] 2) caution with renal insufficiency 3) should NOT be used by pilots, air traffic controllers, truckers, & bus drivers Pregnancy Category C Dosage: - Days 1-3: 0.5 mg once daily, Days 4-7: 0.5 mg twice daily then 1 mg twice daily - start one week before the set stop smoking date - continue for 12 weeks. - take after eating & with a full glass of water (to decrease nausea) Tabs: 0.5, 1 mg, bottles of 56 tablets treatment packs - initial: 1 card of 11 X 0.5 mg tablets & 3 cards of 14 X 1 mg tablets - continuing: 4 cards of 14 X 1 mg tablets Adverse effects: 1) nausea (30%) 2) sleep disturbance (18%), insomnia [26] 3) headaches (15%) 4) abnormal dreams (13%) 5) constipation (8%) 6) flatulence (6%) 7) vomiting (5%) 8) dysguesia (5-8%) 9) hostility, aggressive, violent behavior? [4,6,8] 10) suicidal ideation? [4,6,8,14] a) risk if real < 2-fold [9] b) might not increase risk [13] c) label implies no increase in risk [21] - FDA officials recommending varenicline keep its black-box warning regarding potential adverse neuropsychiatric effects* d) not associated with excess risk for suicidal behavior [26] e) not associated with excess risk for neuropsychiatric events [28] 11) somnolence is common 12) depression [8,14]; a) might not increase risk [13] b) safe & effective in patients with treated depression [18] c) no excess risk for depression or self-harm [19] d) label implies no increase in risk [21,26] 13) no increase in risk of neuropsychiatric disorders [21] 14) agitation [8] 15) associated with heart attack, seizures, diabetes, dizziness, confusion 16) linked to arrhythmias & heart attacks a) safe & effective for smoking cessation in patients with stable cardiovascular disease b) long term cardiovascular safety unclear [10,11,15] c) not associated with greater risk for adverse cardiovascular outcomes than bupropion [16] d) associated with greater risk for adverse cardiovascular outcomes than placebo, but increase not statistically significant [17] e) not associated with increased risk of major cardiovascular events [18] f) increased risk of tachycardia & arrhythmia [18] 17) increased risk for cardiovascular hospitalizations [32] 18) not associated with increased risk of death [26] 19) more adverse effects in slow metabolizers of nicotine [23] * Black box warning; potential adverse neuropsychiatric effects including suicidal ideation, seizures, alcohol interaction [25] * FDA in votes (10-9, mixed vote) to remove Black box warning Sept 2016 [30] * risk of serious side effects on mood, behavior, or thinking lower than previously suspected [31] Drug interactions: 1) does not affect cyt P450 system 2) no clinically meaningful drug-drug interactions have been identified 3) varenicline (Chantix) in combination with alcohol (ethanol) may be associated with decreased tolerance, aggressive behavior, & amnesia [25] 4) varenicline in comination with alcohol may increase risk of seizures [25] Mechanism of action: 1) partial nicotine agonist - binds selectively to alpha-4,beta-2 nicotinic acetylcholine receptors 2) blunts pleasurable effects of smoking 3) helps reduce withdrawal symptoms Clinical trials: - neither harmful or effective [11] - smoking cessation 31% for varenicline vs 21% for placebo at 52 weeks [33] Notes: Estimated cost (2006) - $112 for all strengths & packages - $2 per 0.5 mg or 1 mg tablet

Interactions

drug interactions

General

neurologic agent receptor agonist

Database Correlations

PUBCHEM correlations

References

  1. Prescriber's Letter 13(5): 2006 FDA Approves Novel Medication for Smoking Cessation Detail-Document#: 220608 (subscription needed) http://www.prescribersletter.com
  2. Prescriber's Letter 13(8): 2006 New Drug: Chantix (Varenicline) Detail-Document#: 220814 (subscription needed) http://www.prescribersletter.com
  3. Prescriber's Letter 13(12): 2006 Smoking Cessation Drug Therapy Detail-Document#: 221212 (subscription needed) http://www.prescribersletter.com
  4. Prescriber's Letter 14(11): 2007 Behavioral Side Effects with Varenicline (Chantix, Champix) Detail-Document#: 231111 (subscription needed) http://www.prescribersletter.com
  5. Pfizer Inc. http://www.Chantix.com
  6. FDA MedWatch http://www.fda.gov/medwatch/safety/2007/safety07.htm#Chantix http://www.fda.gov/medwatch/safety/2008/safety08.htm#Varenicline - Prescriber's Letter 15(3): 2008 Behavioral Side Effects with Varenicline (Chantix, Champix) Detail-Document#: 240313 (subscription needed) http://www.prescribersletter.com
  7. Prescriber's Letter 15(7): 2008 Comparison of Smoking Cessation Drug Therapy Detail-Document#: 240706 (subscription needed) http://www.prescribersletter.com
  8. FDA Safety Alert Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics) http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm170090.htm
  9. Gunnell D et al Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database BMJ 2009;339:b3805 PMID: 19797344 doi:10.1136/bmj.b3805 http://www.bmj.com/cgi/content/abstract/339/oct01_1/b3805
  10. Prescriber's Letter 17(3): 2010 Varenicline (Chantix, Champix) and Cardiovascular Disease Detail-Document#: 260308 (subscription needed) http://www.prescribersletter.com
  11. Garza D et al. A double-blind randomized placebo-controlled pilot study of neuropsychiatric adverse events in abstinent smokers treated with varenicline or placebo. Biol Psychiatry 2011 Jun 1; 69:1075. PMID: 21295286
  12. FDA MedWatch: 06/16/2011 Chantix (varenicline): Label Change - Risk of Certain Cardiovascular Adverse Events http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm259469.htm - Prescriber's Letter 18(8): 2011 COMMENTARY: Chantix (Varenicline) and Risk of Cardiovascular Events COMMENTARY: Chantix (Varenicline): New Safety Information and Instructions For Use CHART: Smoking Cessation Therapy Detail-Document#: 270820 (subscription needed) http://www.prescribersletter.com
  13. FDA MedWatch: 10/24/2011 Chantix (varenicline) http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm079818.htm
  14. Moore TJ et al. Suicidal behavior and depression in smoking cessation treatments. PLoS ONE 2011 Nov 2; 6:e27016 PMID: 22073240
  15. Prochaska JJ and Hilton JF Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ 2012;344:e2856 PMID: 22563098 http://www.bmj.com/highwire/filestream/582907/field_highwire_article_pdf/0.pdf
  16. Svanstrom H et al. Use of varenicline for smoking cessation and risk of serious cardiovascular events: Nationwide cohort study. BMJ 2012 Nov 8; 345:e7176. PMID: 23138033
  17. FDA MedWatch. 12/12/2012 Chantix (Varenicline): Safety Communication - Updated Safety Review On The Risk of Cardiovascular Adverse Events http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm331626.htm
  18. Anthenelli RM et al. Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: A randomized trial. Ann Intern Med 2013 Sep 16 PMID: 24042367 http://annals.org/article.aspx?articleid=1738491
  19. Thomas KH et al. Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: Prospective cohort study. BMJ 2013 Oct 11; 347:f5704. PMID: 24124105 http://www.bmj.com/content/347/bmj.f5704
  20. Mills EJ et al Cardiovascular Events Associated with Smoking Cessation Pharmacotherapies: A Network Meta-Analysis. Circulation. Dex 9, 2013 PMID: 24323793 http://circ.ahajournals.org/content/early/2013/11/25/CIRCULATIONAHA.113.003961.abstract - Samet J Smoking Cessation: Benefits versus Risks of Using Pharmacotherapy to Quit. Circulation. Dex 9, 2013 PMID: 24323794 http://circ.ahajournals.org/content/early/2013/11/25/CIRCULATIONAHA.113.006928.abstract
  21. Orciari Herman A, Sadoughi S, Saitz R Chantix Label Revision Casts Doubt on Link to Suicidality. Physician's First Watch, Sept 25, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Young K, Fairchild DG, Di Francesco L FDA Staff: Chantix Should Keep Neuropsychiatric Warning on Label Physician's First Watch, Oct 15, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Orciari Herman A, Sadoughi S FDA Advisers Vote to Keep Black-Box Warning on Chantix. Physician's First Watch, Oct 20, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  22. HIGHLIGHTS OF PRESCRIBING INFORMATION CHANTIX (varenicline) Tablets http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021928s032s036s038lbl.pdf
  23. Lerman C et al Use of the nicotine metabolite ratio as a genetically informed biomarker of response to nicotine patch or varenicline for smoking cessation: a randomised, double-blind placebo- controlled trial. Lancet Respir Med. 2015 PMID: 25588294 http://www.thelancet.com/journals/lanres/article/PIIS2213-2600%2814%2970294-2/abstract - Ware JJ, Davies NM, Munafo MR Importance of national context in the translation of personalised treatments for smoking cessation. Lancet Respir Med. 2015 PMID: 25588293 http://www.thelancet.com/journals/lanres/article/PIIS2213-2600%2814%2970319-4/abstract
  24. Ebbert JO, Hughes JR, West RJ et al Effect of Varenicline on Smoking Cessation Through Smoking Reduction: A Randomized Clinical Trial. JAMA. 2015;313(7):687-694. PMID: 25688780 http://jama.jamanetwork.com/article.aspx?articleid=2110968 (industry-sponsored study)
  25. FDA Safety Alert. March 9, 2015 Chantix (varenicline): Drug Safety Communication - FDA Updates Label to Include Potential Alcohol Interaction http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm437415.htm
  26. Thomas KH et al. Risk of neuropsychiatric adverse events associated with varenicline: Systematic review and meta-analysis. BMJ 2015 Mar 12; 350:h1109 PMID: 25767129
  27. Baker TB, Piper ME, Stein JH et al Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks. A Randomized Clinical Trial. JAMA. 2016;315(4):371-379 PMID: 26813210 http://jama.jamanetwork.com/article.aspx?articleid=2484340
  28. Anthenelli RM et al Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo- controlled clinical trial. The Lancet. April 22, 2016 PMID: 27116918 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2816%2930272-0/abstract
  29. Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
  30. Orciari Herman J, Chavey WE FDA Advisers Recommend Removing Chantix Boxed Warning, but Vote Was Mixed. Physician's First Watch, Sept 16, 2016 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  31. FDA Safety Alert. Dec 16, 2016 Chantix (varenicline) and Zyban (bupropion): Drug Safety Communication - Mental Health Side Effects Revised. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm533517.htm - FDA Safety Aommunication. Dec 16, 2016 FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. http://www.fda.gov/Drugs/DrugSafety/ucm532221.htm
  32. Gershon AS, Campitelli MA, Hawken S et al Cardiovascular and Neuropsychiatric Events Following Varenicline Use for Smoking Cessation. Am J Res Critical Care Med. 2018 Apr 1; 197:913. Online Dec 20, 2017. PMID: 29260881 http://www.atsjournals.org/doi/abs/10.1164/rccm.201706-1204OC
  33. Windle SB, Dehghani P, Roy N, et al. Smoking abstinence 1 year after acute coronary syndrome: Follow-up from a randomized controlled trial of varenicline in patients admitted to hospital. CMAJ 2018 Mar 26; 190:E347. PMID: 29581161 Free PMC Article http://www.cmaj.ca/content/190/12/E347