Transcript Slide 1

1
‫מגמות בשיעורי העישון בקרב האוכלוסייה הבוגרת בישראל‪,‬‬
‫לפי קבוצות ומין‪1980-2011 ,‬‬
‫דוח שר הבריאות על עישון בישראל ‪ ,2012‬פורסם במאי ‪2013‬‬
‫‪2‬‬
‫שיעורי העישון באוכלוסייה הבוגרת בישראל (בני ‪ 21‬ומעלה) –‬
‫סקר "‪ KAP“ 2010‬לעומת סקר "אורח חיים פעיל בישראל"‬
‫דוח שר הבריאות על עישון בישראל ‪ ,2012‬פורסם במאי ‪2013‬‬
‫‪3‬‬
‫מבוטחים שעברו תהליך גמילה במסגרת הסל ‪2010-2012‬‬
‫דוח שר הבריאות על עישון בישראל ‪ ,2012‬פורסם במאי ‪2013‬‬
‫‪4‬‬
‫מרבית המעשנים בישראל (‪ )2013‬מנסים להפסיק לעשן ללא‬
‫טיפול וללא תמיכה‬
‫סקר אינטרנטי שנערך בישראל בשנת ‪ 2013‬בקרב ‪ 400‬מעשנים מעל גיל ‪25‬‬
‫שמעשנים מעל ‪ 11‬סיגריות ביום‬
‫נסיונות הפסקת עישון‬
‫‪29%‬‬
‫לא ניסו להפסיק לעשן‬
‫ניסו להפסיק לעשן במהלך ‪ 12‬חודשים אחרונים‬
‫‪50%‬‬
‫‪21%‬‬
‫ניסו להפסיק לעשן בעבר‬
‫‪Pfizer Data on file, Internet survey by Mutagim, May 2013‬‬
‫‪5‬‬
‫מרבית המעשנים בישראל (‪ )2013‬מנסים להפסיק לעשן‬
‫ללא טיפול וללא תמיכה‬
‫‪ 49.5%‬מהמעשנים קיבלו יעוץ מהרופא להפסיק לעשן‬
‫‪ 34.3%‬מתכננים להפסיק לעשן במהלך ששת החודשים הקרובים‬
‫‪ 46.5%‬שוקלים להיעזר בטיפול תרופתי בניסיון הבא שלהם להיגמל‬
‫‪Pfizer Data on file, Internet survey by Mutagim, May 2013‬‬
‫‪6‬‬
)‫ ועל מעשנים פסיביים(עישון כפוי‬,‫השפעת העישון על מעשנים‬
‫ילדים ומבוגרים‬
7
Surgeon General, 2010 How Tobacco Smoke Causes Disease: The Biology and
Behavioral Basis for Smoking-Attributable Disease, chapter 1 page 4
‫מנגנון הפעולה של ניקוטין במערכת העצבים המרכזית‬
a4b2 ‫ בעיקר ל‬,‫) במערכת העצבים המרכזית‬nACh) ‫ניקוטין נקשר לרצפטורים‬
‫ כתוצאה מכך ישנו‬.nicotinic receptor in the Ventral Tegmental Area (VTA)
.)nAcc) ‫שחרור של דופמין באזור‬
b2
a4
b2
a4
b2
a4b2
Nicotinic
Receptor
Nucleus
accumbens
(nAcc)
Ventral tegmental
area (VTA)
Nicotine
Dopamine
• Jarvis MJ. Why people smoke. BMJ 2004; 328: 277-279. 3. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for
Smoking Attributable Disease. A report of the Surgeon General.US Department of Health and Human Services (2010).
9
• West R, et al. Effect of varenicline and bupropion SR on craving, nicotine withdrawal symptoms, and rewarding effects of smoking
during a quit attempt. Psychopharmacology 2008; 197: 371-377
‫תסמיני גמילה כתוצאה ממחסור בניקוטין‬
‫תסמיני גמילה מסיגריות‬
‫סחרחורת (‪)10%‬‬
‫יקיצות בלילה (‪) 25%‬‬
‫חוסר ריכוז (‪)60%‬‬
‫דחף לעשן (‪) 70%‬‬
‫שבועות‬
‫רוגז‪/‬אגרסיביות (‪)50%‬‬
‫חוסר מנוחה (‪)60%‬‬
‫דיכאון (‪)60%‬‬
‫עליה בתאבון (‪)70%‬‬
‫‪12‬‬
‫‪10‬‬
‫‪8‬‬
‫‪6‬‬
‫‪4‬‬
‫‪2‬‬
‫‪0‬‬
‫‪ASH, Stopping smoking: the benefits and aids to quitting ,Dec 2012‬‬
‫‪10‬‬
‫כוח רצון חשוב אבל לא מספיק‬
‫טיפול התנהגותי‬
‫טיפול תרופתי‬
‫‪11‬‬
)EBM( ‫טיפולים קיימים לגמילה מעישון‬
12
( ‫תחליפי ניקוטין‬NRT):‫לכסניות‬/‫משאף‬/‫מדבקות‬/‫מסטיקים‬
•
‫( תרופה אנטי דיכאונית‬Buproprion):‫זייבן‬
•
‫(פותחה במיוחד לגמילה מעישון‬Varenicline): ‫צ'מפיקס‬
•
Silagy C, et al. Cochrane Database Syst Rev. 2004;(3):CD000146. Stead L, et al. Int J Epidemiol.
2005;34:1001–1003. Henningfield JE, et al. CA Cancer J Clin. 2005;55:281-299. Hughes JR et al. Cochrane
Database Syst Rev. 2004;(4):CD000031.
‫התמדה בטיפול תרופתי לגמילה מעישון במשך‬
‫ שבועות הגדילה משמעותית את סיכויי הגמילה‬12
59.40%
60.00%
44.20%
43.10%
Continuous Quit Rate %
50.00%
40.00%
29.80%
30.00%
27%
17.70%
20.00%
10.00%
0.00%
All treated
Varenicline 1.0 mg twice daily
Complete
Bupropion SR 150 mg twice daily
Placebo
All treated= intendment to treat
Completers ≥ 80% days of treatment during the 12-week treatment period
J. Taylor Hays .Et al Adherence to treatment for tobacco dependence: Association with smoking abstinence and predictors of
adherence , Nicotine & Tobacco Research, Volume 12, Number 6 (June 2010) 574–581
‫ שבועות‬24 ‫ צ'מפיקס למשך‬-‫התמדה בטיפול ב‬
‫מעלה את סיכויי הגמילה לאחר שנה‬
Continuously Abstinent Weeks 13–52 (%)
‫ שבועות לפי דפוס התנהגות‬13-52 ‫אחוז המטופלים שהתמידו בגמילה לאורך‬
55.80%
54.10%
60.00%
34.50%
50.00%
23.40%
40.00%
30.00%
20.00%
10.00%
0.00%
Early Quitter (n=537)
Late Quitters (n=671)
Varenicline 1 mg BID
Placebo
‫יש לשים לב שאחוז הגמילה הגבוהים נובע משילוב‬
‫ שבועות טיפול לא עישנו‬12 ‫רק מטופלים שלאחר‬
BID: twice daily oral dosing; OR: odds ratio. Early Quitters: Abstinent from target quit date to randomization at 3 months; Late Quitters: Smoked
after target quit date but achieved abstinence by 3 months. Peter Hajek et al. Varenicline in prevention of relapse to smoking: effect of quit pattern
on response to extended treatment Addiction 2009, 104, 1597–1602
‫השילוב היעיל ביותר להפסקת עישון‬
‫צ'מפיקס‪+‬סדנה‬
‫‪74%‬‬
‫‪80%‬‬
‫ללא טיפול תרופתי‬
‫‪70%‬‬
‫תחליפי ניקוטין‬
‫‪55%‬‬
‫‪52%‬‬
‫‪50%‬‬
‫צ'מפיקס‬
‫‪50%‬‬
‫‪39%‬‬
‫‪37%‬‬
‫‪37%‬‬
‫‪40%‬‬
‫‪32%‬‬
‫‪28%‬‬
‫‪22%‬‬
‫‪25%‬‬
‫‪30%‬‬
‫‪16%‬‬
‫‪20%‬‬
‫‪10%‬‬
‫‪0%‬‬
‫תמיכה קבוצתית‬
‫תמיכה יחידנית (אישית)‬
‫בלי תמיכה‬
‫האפקט היחסי של מגון התערבויות טיפוליות מבוססי עדויות לגמילה מעישון לפי שעור הנגמלים ב ‪ 4‬שבעות‬
‫‪NHS stop smoking services; service and monitoring guidance 2009/10 ;13.‬‬
‫)‪Continuous Abstinence (%‬‬
‫זייבן‬
‫‪60%‬‬
‫ מהחולים שקבלו צ'מפיקס‬56.3% ‫לאחר שנה של מעקב‬
‫במהלך הסדנא נשארו גמולים‬
68.8%
62.5%
70.0%
56.3%
56.3%
Abstinence rate %
60.0%
39.6%
50.0%
33.3%
40.0%
30.0%
20.0%
10.0%
0.0%
3 Month
6 Month
Champix + GCT
12 Month
GCT
GCT- group counseling therapy
M.C. Grassi et al. / Journal of Substance Abuse Treatment, Effectiveness of varenicline for smoking cessation:
A 1-year follow-up study, 2011
Comparisons of high-dose and combination NRT,
varenicline, and Bupropion for smoking cessation:
18
Edward J. Mills, Annals of Medicine, 2012; Early Online: 1–10
Champix(Varenicline) is the most effective treatment for
smoking cessation
Short term
3 months
6 months
12 months
1.52 (1.43–1.61)
1.65 (1.50–1.81)
1.60 (1.45–1.77)
1.48 (1.30–1.69)
1.73 (1.62–1.84)
1.79 (1.44–2.16)
2.10 (1.77–2.47)
1.69 (1.32–2.11)
Combination NRT
1.68 (1.30–2.08
1.29 (0.73–2.07)
1.66 (1.26–2.19)
1.34 (0.96–1.84)
Bupropion
1.71 (1.58–1.83)
1.59 (1.47–1.72)
1.59 (1.45–1.74)
1.40 (1.22–1.60)
Varenicline
2.19 (1.94–2.44)
2.37 (2.04–2.71)
2.19 (1.86–2.56)
2.39 (1.96–2.8
High-dose nicotine patch therapy (> 22 mg) NRT
1.14 (1.07–1.21)
1.09 (0.87–1.33)
1.32 (1.11–1.57)
1.15 (0.91–1.43)
Combination NRT
1.10 (0.85–1.37)
0.77 (0.42–1.29)
1.05 (0.76–1.41)
0.91 (0.62–1.29)
Bupropion
1.12 (1.02–1.22)
0.96 (0.84–1.10)
0.99 (0.86–1.14)
0.94 (0.77–1.15)
Varenicline
1.43 (1.26–1.60)
1.48 (1.23–1.75)
1.38 (1.15–1.64)
1.65 (1.29–2.07)
Control versus
Standard-dose nicotine patch therapy (≤ 22
mg)
High-dose nicotine patch therapy (>22 mg)
NRT
Standard-dose nicotine patch therapy
)≤ 22 mg( versus
19
Edward J. Mills, Annals of Medicine, 2012; Early Online: 1–10
Champix(Varenicline) is the most effective treatment for
smoking cessation
Short term
3 months
6 months
12 months
0.97 (0.73–1.23)
0.68 (0.34–1.25)
0.77 (0.52–1.11)
0.78 (0.50–
High-dose nicotine patch therapy
(> 22 mg) versus
Combination NRT
1.20)
Bupropion
0.98 (0.88–1.09)
0.87 (0.66–1.13)
0.73 (0.58–0.91)
0.81 (0.60–
1.09)
Varenicline
1.29 (1.12–1.46)
1.40 (1.05–1.80)
1.05 (0.80–1.36)
1.47 (1.06–
2.01)
Combination NRT versus
Bupropion
1.01 (0.79–1.25)
1.24 (0.71–1.92)
0.95 (0.69–1.26)
1.04 (0.72–
1.45)
Varenicline
1.28 (1.02–1.53)
1.85 (1.15–2.65)
1.31 (0.95–1.75)
1.78 (1.25–
2.41)
Bupropion versus
Varenicline
20
1.29 (1.12–1.45)
1.43 (1.24–1.63)
For efficacy, RRs higher than 1 favor the row-defining treatment.
Edward J. Mills, Annals of Medicine, 2012; Early Online: 1–10
1.34 (1.13–1.57)
1.61 (1.32–
1.93)
71% of Patients, treated with Champix for 24 weeks, quit
smoking
Adherence to treatment and success rate
71%
29%
6 weeks treatment
duration
Adapted from Nides M, et al.
Arch Intern Med 2006.
49%
12 weeks treatment
duration
Adapted from Oncken C, et al.
Arch Intern Med 2006.
24 weeks quit rate(%)
‡ p<0.01
vs. placebo
12 weeks quit rate(%)
12 weeks quit rate(%)
* p<0.001
vs. placebo
§ p<0.001 vs.
12 weeks
CHAMPIX® +
12 weeks
placebo
24 weeks treatment
duration
Adapted from Tonstad S, et
al. JAMA 2006.
†This analysis included non-titrated and titrated doses of CHAMPIX® 1mg bd
21
†This analysis included non-titrated and titrated doses of CHAMPIX® 1mg bd
Adherence to Varenicline and Associated Smoking
Cessation in a Community-Based Patient Setting
Joshua N. et al, J Manag Care Pharm. 2013;19(2):125-31
METHODS: In this retrospective cohort study, eligible patients were
enrolled with Geisinger Health Plan, had an initial varenicline prescription written
by a Geisinger provider between January 1, 2006, and December 31, 2009, and
had a follow-up clinic visit within the subsequent 12 months.
Adherence was derived from linking 1,477 smokers receiving electronic
prescriptions of with adjudicated pharmacy claims. Smoking status was collected
at each health care encounter.
22
Joshua N. et al, Adherence to Varenicline and Associated Smoking Cessation in a Community-Based Patient
Setting J Manag Care Pharm. 2013;19(2):125-31
Adherent to Varenicline influence success rate
Smoking Cessation by adherence
Adherent to treatment
60.00%
Partially adherent
50.00%
20%
Adherent
24%
50.70%
31.20%
40.00%
56%
nonadherent
28.80%
30.00%
20.00%
10.00%
0.00%
adherent
nonadherent
partially
adherent
No significant difference was found in quit rates between the partially adherent and nonadherent patient
cohorts (adjusted HR 0.88 [95% CI = 0.69-1.13]). However, patients adherent to the varenicline regimen were
almost twice as likely to succeed in quitting smoking compared with completely nonadherent patients (HR
1.93 [95% CI = 1.59-2.33]).
23
Joshua N. et al, Adherence to Varenicline and Associated Smoking Cessation in a Community-Based Patient
Setting J Manag Care Pharm. 2013;19(2):125-31
CONCLUSION
Smoking cessation occurred more often among individuals adherent to
varenicline therapy; however, medication nonadherence was common.
After prescribing varenicline, clinicians and payers could
consider active patient follow-up to maximize adherence and
optimize treatment outcomes.
24
‫בטוח להפסיק לעשן‬
Placebo
N=340
%
9.7
90.9
9.1
0
12.6
3.5
12.4
7.1
Bupropion
N=340
%
7.4
56
40
4
7.9
5.9
21.2
7.4
Varenicline
N=343
%
29.4
71.3
23.8
5
12.8
13.1
14.3
6.4
‫תופעות לוואי‬
‫בחילות‬
‫* קל‬
‫*בינוני‬
‫*חמור‬
‫כאבי ראש‬
(‫חלומות ברורים (חדים‬
‫נדודי שינה‬
‫סחרחורות‬
*Values may not total 100% due to rounding.
Champix(Varenicline) Prescribing Information, as approved by the Israeli Ministry Of Health, 29 Apr 2013
‫בטוח להפסיק לעשן‬
‫‪‬במחקרים קליניים לא נצפו תגובות בין תרופתיות‬
‫משמעותיות‪1‬‬
‫‪‬אין לצ'מפיקס התוויות נגד‪ ,‬למעט רגישות לאחד ממרכיבי‬
‫‪‬אין מניעה לתת צ'מפיקס עם תרופות נגד‬
‫התרופה‪1‬‬
‫דיכאון‪1‬‬
‫‪‬ההבדל בין צ'מפיקס לזייבן בעלייה במשקל התבטא בפחות מקילו לאחר ‪ 3‬חודשי טיפול‪.1‬‬
‫‪‬זמן מחצית החיים של צ'מפיקס ‪ 24‬שעות‬
‫‪ 92%‬מתפנה ללא שינוי דרך הכליות‬
‫‪*Values may not total 100% due to rounding.‬‬
‫‪Champix(Varenicline) Prescribing Information, as approved by the Israeli Ministry Of Health, 29 Apr 2013‬‬
‫פשוט להפסיק לעשן‬
‫•‬
‫הטיפול בצ'מפיקס ל‪ 3-6 -‬חודשים‬
‫•‬
‫יום הפסקת עישון הוא בין ימים ‪ . 8-14‬במידת הצורך ניתן לקבוע את יום ההפסקה‬
‫בין ימים ‪8-35‬‬
‫•‬
‫את הטיפול מומלץ לקחת לאחר אוכל‪ ,‬ולשתות כוס מים מלאה‬
‫•‬
‫גם אם המטופל המשיך לעשן לאחר התאריך שנקבע‪ ,‬מומלץ להמשיך בטיפול‬
‫ולנסות להפסיק לעשן‬
‫•‬
‫המשך טיפול ל‪ 3-‬חודשים נוספים יכול להפחית את הסיכון להישנות העישון‬
‫•‬
‫קיימת אריזת מינון נמוך עבור מקרים מיוחדים‬
‫(אי תפקוד כלייתי חמור(‪X0.5mg56 :‬‬
‫‪Champix(Varenicline) Prescribing Information, as approved by the Israeli Ministry Of Health, 29 Apr 2013‬‬
‫‪27‬‬
Cardiovascular Smokers
Efficacy and safety of treatments
28
Effect of Smoking Relapse on Outcome After
Acute Coronary Syndromes
•
•
1,294 smokers hospitalized for acute coronary syndromes
received a brief in-hospital smoking cessation intervention consisting of
repeated counseling sessions (2-5) , lasting 5 to 20 minutes
•
During follow-up, 813 patients (62.8%) resumed regular smoking
•
Median interval to relapse 19 days, interquartile range 9 to 76
•
Patients enrolled in a cardiac rehabilitation Program and those with diabetes
were more likely to remain abstinent
•
During follow-up, 97 patients died (1-year probability of death 0.075,
95% CI 0.061 to 0.090).
Resumption of smoking was an independent predictor
of total mortality (HR 3.1, 95% CI 1.3 to 5.7, p 0.004).
29
Furio C. et al , Effect of Smoking Relapse on Outcome After Acute Coronary Syndromes The American
Journal of Cardiology 2011
smoking relapse after acute coronary syndromes is
associated with increased mortality (HR 3.1)
Time (Days)
5.3(2.1-6.6)
4.4(2.3-6.1)
3.9(1.9-5.5)
3.4(1.6-5.2)
3.2(1.5-5.8)
3.1(1.3-5.7)
10
20
30
60
90
120
180
210
270
300
330
360
Cumulative number Cumulative number of
of relapsed smokers deaths
230
432
498
555
634
682
783
793
802
806
811
813
7 6 5 4 3 2 1
Multivariable adjusted Hazard Ration (95%CL)
For Total Mortality according to Smoking Relapse
30
Furio C. et al , Effect of Smoking Relapse on Outcome After Acute Coronary Syndromes The American
Journal of Cardiology 2011
29
55
72
78
84
87
90
93
96
97
97
97
The odds ratio of Cardiac patient, treated with Champix to
quit smoking is 6.11 vs. Placebo
OR: 6.11 (95% CI: 4.18 – 8.93)
p < 0.0001
47.00%
Continuous Abstinence (%)
50.00%
OR: 3.92 (95% CI: 2.55, 6.03)
P<0.0001
45.00%
40.00%
OR: 3.14 (95% CI: 1.93 – 5.11)
p < 0.0001
28.20%
35.00%
30.00%
19.20%
25.00%
13.90%
20.00%
9.50%
15.00%
7.20%
10.00%
5.00%
0.00%
Weeks 9-12
Weeks 9-24
Champix
Weeks 9-52
Placebo
OR = Odds ratio; CI = 95% Confidence intervals
31
Rigotti A.R., Pipe L.A. Et all; efficacy and safety of varenicline for smoking cessation in patients with
cardiovascular disease: a randomize trail Circulation. 2010;121:221-229.
Cardiovascular Events and All Deaths*
Varenicline
)n353(,n )%(†
Any adjudicated cardiovascular event‡
Placebo
)n350(,n )%(†
Difference
Between
Groups, %
95% CI
for
Difference
25 (7.1)
20 (5.7)
1.4
-2.3–5.0
Nonfatal MI
7 (2.0)
3 (0.9)
1.1
-0.6–2.9
Need for coronary revascularization
8 (2.3)
3 (0.9)
1.4
-0.4–3.2
Hospitalization for angina pectoris
8 (2.3)
8 (2.3)
-0.02
-2.2–2.2
Hospitalization for congestive heart
failure
0 (0.0)
2 (0.6)
-0.6
-1.5–0.3
Cerebrovascular disease Nonfatal stroke
2 (0.6)
1 (0.3)
0.3
-0.7–1.2
Transient ischemic attack
1 (0.3)
1 (0.3)
-0.0
-0.8–0.8
Peripheral vascular disease
New diagnosis or admission for a
procedure to treat peripheral vascular
disease
5 (1.4)
3 (0.9)
0.6
-1.0–2.1
Death All causes
2 (0.6)
5 (1.4)
-0.8
-2.3–0.6
Cardiovascular death
1 (0.3)
2 (0.6)
-0.3
-1.3–0.7
Noncardiovascular death
1 (0.3)
3 (0.9)
-0.6
-1.7–0.5
Coronary artery disease
32
Rigotti A.R., Pipe L.A. Et all; efficacy and safety of varenicline for smoking cessation in patients with cardiovascular
disease: a randomize trail Circulation. 2010;121:221-229.
.
Cardiovascular Events and all Deaths
Occurring During and Post Treatment (Adjudicated)*
Varenicline
Placebo
(n = 353)
(n = 350)
Study Phase
Treatment a
Non- Treatment
Follow –Up b
Treatment a
Non-Treatment
Follow - Up b
Number (%) of subjects having at least 1 CV event or
any death‡
10 (2.8)
17 (4.8)
10 (2.9)
13 (3.7)
Nonfatal myocardial infarction
4 (1.1)
3 (0.8)
1 (0.3)
2 (0.6)
Need for coronary revascularization
1 (0.3)
7 (2.0)
1 (0.3)
2 (0.6)
Hospitalization for angina pectoris
2 (0.6)
6 (1.7)
4 (1.1)
4 (1.1)
Hospitalization for congestive heart failure
0 (0.0)
0 (0.0)
2 (0.6)
0 (0.0)
Nonfatal stroke
2 (0.6)
0 (0.0)
0 (0.0)
1 (0.3)
Transient ischemic attack
0 (0.0)
1 (0.3)
1 (0.3)
0 (0.0)
New diagnosis or admission for a treatment
procedure for peripheral vascular disease
1 (0.3)
5 (1.4)
1 (0.3)
2 (0.6)
Cardiovascular death
0 (0.0)
1 (0.3)
1 (0.3)
1 (0.3)
Non cardiovascular death
0 (0.0)
1 (0.3)
1 (0.3)
2 (0.6)
33
* Data on File, not included in the manuscript a The treatment phase includes 30 days after last dose of drug b >30 days after last treatment Subjects
with multiple CV events of the same type within a study phase are counted only once for that phase; subjects with the same type of CV event in each
phase are counted in each phase. There was 1 subject in the varenicline arm who reported a PVD event during treatment and had CV death in the
post-treatment phase. ‡Includes non-cardiovascular deaths
FDA-Safety review update of Chantix (varenicline)
and risk of cardiovascular adverse events
•
•
•
•
•
•
•
Health care professionals are advised to weigh the risks of Chantix against the
benefits of its use. It is important to note that smoking is a major risk factor for
cardiovascular disease, and Chantix is effective in helping patients to quit
smoking and abstain from it for as long as one year. The health benefits of
‫• עישון מהווה סיכון משמעותי להתפתחות‬
quitting smoking are ‫קרדיאלית‬
immediate‫מחלה‬
and substantial.
Additional Information for Health Care Professionals
‫ אל מול הסיכוי הגבוה‬,‫• על הרופא לשקול את הסיכון הקטן במתן צ'מפיקס‬
Smoking is an independent and major risk factor for cardiovascular disease, and
‫זמן‬
‫לאורך‬
‫מעישון‬
‫לגמילה‬
Chantix is effective in helping patients quit smoking.
The
health
benefits
of
quitting smoking are immediate and substantial.
‫ומשמעותית‬
‫הינה מידית‬
Weigh the risks of Chantix against
the benefits
of its‫מעישון‬
use. ‫• התועלת בגמילה‬
Counsel patients to seek medical attention if they experience new or worsening
‫לטיפול‬
‫אליו להגיע מידית‬
‫אירוע לבבי‬
‫תסמינים‬
‫• במידה והמטופל חווה‬
symptoms
of cardiovascular
disease
while‫של‬
taking
Chantix.
‫הבריאות‬Guide
‫למשרד‬
‫לדווח‬
‫הרופא‬
‫ ועל‬,with
‫רפואי‬
Encourage patients to read the Medication
they
receive
along
their
Chantix prescription.
Report adverse events involving Chantix to the FDA MedWatch program, using
the information in the "Contact FDA" box at the bottom of this page.
FDA Drug Safety Communication 12/12/12
The estimate risk difference (Varenicline vs. Placebo) was
neither clinically nor statistically significant
– 22 randomized controlled trials of varenicline use for smoking cessation
were identified with 9,232 participants; 8 trials had no CVD events.
The rates of serious treatment-emergent CVD
events
Varenicline
Placebo
0.63%
(34/5,431)
0.47%
(18/3,801)
– The summary estimate for the risk difference, 0.27% (95% confidence
interval −0.10% to 0.63%; P=0.15), based on all 22 trials, was neither
clinically nor statistically significant.
Conclusions:
This meta-analysis found no significant increase in cardiovascular
serious adverse events associated with varenicline use.
Prochaska et al. Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation:
Systematic review and meta-analysis. BMJ 2012;344:e2856 doi: 10.1136/bmj.e2856 (Published 4 May 2012)
Cardiovascular safety Varenicline vs. Bupropion
Objective: To investigate whether Varenicline is associated with
an increased risk of serious cardiovascular events compared with
another drug used for smoking cessation, bupropion.
Setting Denmark, 2007-10.
major cardiovascular
events
cases per 1000
person years
Varenicline
(n=17,926)
57
6.9
Bupropion
(n=17,926)
60
7.1
Varenicline use was not associated with an increased risk of acute
coronary syndrome (1.20, 0.75 to 1.91), ischaemic stroke (0.77, 0.40 to
1.48), and cardiovascular death (0.51, 0.13 to 2.02).
36
Henrik S.S et al. Use of varenicline for smoking cessation and risk of serious cardiovascular events: nationwide
cohort study BMJ 2012;345:e7176 (Published 8 November 2012)
Association of Smoking Cessation and Weight Change With
Cardiovascular Disease Among Adults With and Without Diabetes
Carole C. et al JAMA. 2013;309(10):1014-1021
Objective: To test the hypothesis that weight gain following smoking
cessation does not attenuate the benefits of smoking cessation among
adults with and without diabetes.
38
Carole C. et al, Association of Smoking Cessation and Weight Change With Cardiovascular Disease
Among Adults With and Without Diabetes JAMA. 2013;309(10):1014-1021
Smoking Cessation contributes to minor weight
gain with significant risk reduction of CVD events
After a mean follow-up of 25 (SD, 9.6) years, 631 CVD events
occurred among 3,251 participants.
Median 4-year weight gain
Without diabetes
With Diabetes
recent quitters
2.7 kg
3.9 kg
long-term quitters
0.9 kg
0.0 kg
Rate of CVD events
per 100 person-examinations
Smokers
5.9
Recent quitters
3.1
long-term quitters
2.4
recent quitters – Quit during the last 4 years
long-term quitters –Not smoking more than 4 years
39
Carole C. et al, Association of Smoking Cessation and Weight Change With Cardiovascular Disease Among Adults With
and Without Diabetes JAMA. 2013;309(10):1014-1021
Reduction in mortality achievable through risk factor intervention in
patients with coronary heart disease (CHD)
40
Adapted from Critchley JA and Capewell S. JAMA 2003. Analysis of prospective cohort studies of patients with diagnosed CHD
(previous MI or stable or unstable angina) who were smokers at baseline, provided at least 2 years of follow-up, reported all-cause
mortality as an outcome measure and measured smoking status to determine quit success.
Take home Message
• In all clinical trails, and Meta analysis, there was neither clinically
nor statistically significant different in Champix’s cardiovascular
safety comparing to Zyban or Placebo
• The odd ratio of quitting smoking with Champix is twice than Zyban
or NRT
• Smoking is an independent and major risk factor for cardiovascular
disease
• Counsel patients to seek medical attention if they experience new or
worsening symptoms of cardiovascular disease
41
Smoking & Smoking Cessation in
Psychiatric Illness
Efficacy and safety of treatments
42
Smoking is considerably more common in
persons with mental illness
• 28.3% of population has current mental illness*
• Patients with mental illness are heavier smokers
• Estimate that mentally ill consume 44% of cigarettes in US
No Mental Illness*
Current Mental Illness*
23%
41%
59%
77%
Current Smokers
43
Nonsmokers
Lasser K etal. JAMA. 2000;284:2606-2610
Current Smokers
Nonsmokers
Prevalence of Smoking in Clinical Samples of
Psychiatric and Substance Use Disorders
Psychiatric Disorder (PD)
Substance Use Disorder (SUD)
Smoking Prevalence (%)
100%
80%
60%
40%
20%
0%
SZ
44
BPD
MDD
PD
PTSD
OCD
Clinical Group
Alcohol
Cocaine
Opioid
SZ=schizophrenia, BPD=bipolar disorder, MDD=major depressive disorder, PD=panic disorder, OCD=obsessive
compulsive disorder, PTSD=post-traumatic stress disorder. Adapted from Kalman D et al. Am J Addict. 2005;14:106123.
The percentage of current smokers increases
as depression severity increases
Percentage of adults aged 20 and over who were current smokers,
by age, sex and depression status: United States, 2005-2008
45
*Note: Moderate or severe indicate depression, while mild indicates mild depressive symptoms.
Pratt LA. Depression and Smoking in the U.S. Household Population Aged 20 and Over, 2005–2008.
National Center for Health Statistics. NCHS Data Brief . No. 34 , April 2010
Smoking Increased Risk of Suicides
Relative Riska,b,c (95% CI)
6
4.3
4
2
2.5
1.0
1.4
0
Never
Smoker
Former
Smoker
aThe
Current Smoker,
1-14 Cigarettes/d
(n=1333)
Current Smoker,
15 Cigarettes/d (n=2241)c
probability of an event (developing a disease) occurring in exposed people compared with the
probability of the event in nonexposed people. bTest for trend among current smokers (compared with never
smokers), P=.05. cAdjusted for time period, age, alcohol intake, and marital status. Three cases are missing
information on current smoking status; cP<.001
46
Miller et al. Am J Public Health. 2000;90:768-773.
Smoking prevalence in general population is decreasing,
while Smoking among Serious Psychological patients
does not change
50
47.3
46.6
43.6
43.3
42.2
44.2
44.0
42.6
42.2
42.5
41.9
40.6
42.1
40.1
38.9
40
30
24.1
23.5
23.1
22.8
22.3
21.8
20.9
20
10
20.3
20.2
With Serious Psychological Distress
20.2
19.9
19.2
19.7
18.7
18.2
Without Serious Psychological Distress
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
* Difference between estimate and estimate for 2011 is statistically significant at the .05 level.
47
Adapted from Center for Behavioral Health Statistics and Quality (Feb 5, 2013). NSDU Report: Smoking and
Mental Illness
FDA Update
Serious neuropsychiatric events, including, but not limited to depression, suicidal ideation, suicide attempt
and completed suicide have been reported in patients taking CHAMPIX. 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 CHAMPIX who continued to smoke.
All patients being treated with CHAMPIX 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 pre-existing psychiatric illness and
completed suicide have been reported in some patients attempting to quit smoking while taking CHAMPIX in
the post-marketing experience. When symptoms were reported, most were during CHAMPIX treatment, but
some were following discontinuation of CHAMPIX therapy.
These events have occurred in patients with and without pre-existing psychiatric disease. Patients with
serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder did not
participate in the pre-marketing studies of CHAMPIX and the safety and efficacy of CHAMPIX in such patients
has not been established.
48
Black box WARNING:
•
•
Advise patients and caregivers that the patient should stop taking CHAMPIX and contact a
healthcare provider immediately if agitation, hostility, depressed mood, or changes in
behavior
or thinking
that are‫שינויים‬
not typical
the patient
are observed,
or if the
patient
‫אובדניות‬
‫מחשבות‬
,‫בהתנהגות‬
,‫עוינת‬for‫התנהגות‬
,‫דיכאון‬
,‫מפתח חרדה‬
‫ומטופל‬
‫במידה‬
develops
ideation
or suicidal
behavior.
‫ רפואי‬suicidal
‫מיידית לטיפול‬
‫ולהגיע‬
‫מפיקס‬
'‫או התנהגות אובדנית יש להפסיק את הטיפול בצ‬
•
In many post-marketing cases, resolution of symptoms after discontinuation of CHAMPIX
•
was reported, although in some cases the symptoms persisted; therefore, ongoing monitoring and
‫יש לעקוב אחר המטופל עד להחלמה‬
supportive care should be provided until symptoms resolve.
•
•
•
•
‫ריכוז‬
‫וחוסר‬
‫חוסר מנוחה‬
,‫דיכאון‬
‫ לכלול‬of
‫יכולים‬
‫תמסיני גמילה מניקוטין‬
The risks of CHAMPIX
should
be,weighed
against
the benefits
its use.
CHAMPIX has been demonstrated to increase the likelihood of abstinence from smoking for as
long as one year compared
to treatment
with
‫מול הסיכון‬
‫מפיקס אל‬
'‫ צ‬placebo.
‫יש לשקול את הסיכוי הגבוה להפסיק לעשן עם‬
The health benefits of quitting smoking are immediate and substantial. (See SPECIAL
WARNINGS AND PRECAUTIONS FOR USE, ADVERSE REACTIONS)
49
Champix(Varenicline) Prescribing Information, as approved by the Israeli Ministry Of Health, 29 Apr 2013
CHAMPIX® (varenicline) provides Favorable Benefit-Risk
Profile In Adult Smokers With Major Depressive Disorder
Varenicline was evaluated in a randomized, double-blind, placebocontrolled study of 525 subjects with major depressive disorder
without psychotic features (DSM-IV TR), on stable antidepressant
treatment and/or who experienced a major depressive episode in
the past 2 years and were successfully treated.
Subjects aged 18 to 75 years were randomized to varenicline 1 mg BID
or placebo for a treatment of 12 weeks and then followed for 40
weeks post-treatment.
50
Anthenelli, Morris, Ramey, et al. Ann Intern Med. 2013;159:390-400
Subjects treated with varenicline had a superior
rate of CO-confirmed abstinence
3.35 (2.16, 5.21) p<0.0001)
35.90%
40.00%
2.36 (1.40, 3.98) p=0.0011)
35.00%
30.00%
15.60%
25.00%
20.30%
10.40%
20.00%
15.00%
10.00%
5.00%
0.00%
CA wk 9-12
Varenicline (n=256)
51
CA wk 9-52
Placebo (n=269)
Adapted from:Anthenelli, Morris, Ramey, et al. Ann Intern Med. 2013;159:390-400
Psychiatric scales showed no differences
between the varenicline and placebo groups
No overall worsening of depression during the study in either
treatment group.
Depressed mood disorders and disturbances
Depression
Depressed mood
Depressive symptom
Depression suicidal
Anhedonia
Major depression
Negative thoughts
Anxiety disorders and symptoms
Anxiety
Agitation
Tension
Nervousness
Panic attack
Stress
52
Varenicline, N = 256
n (%) of participants
Placebo, N = 269
n (%) of participants
17 (6.6)
7 (2.7)
2 (0.8)
1 (0.4)
1 (0.4)
1 (0.4)
1 (0.4)
13 (4.8)
10 (3.7)
1 (0.4)
1 (0.4)
0
0
0
18 (7.0)
17 (6.6)
9 (3.5)
2 (0.8)
2 (0.8)
0
25 (9.3)
11 (4.1)
8 (3.0)
1 (0.4)
1 (0.4)
3 (1.1)
Anthenelli, Morris, Ramey, et al. Ann Intern Med. 2013;159:390-400
Smoking cessation treatment and risk of depression,
suicide, and self harm in the Clinical Practice Research
prospective cohort study
•
Objective To compare the risk of suicide, self harm, and depression in
patients prescribed varenicline or bupropion with those prescribed nicotine
replacement therapy.
•
Design Prospective cohort study within the Clinical Practice Research
Datalink.
•
Setting 349 general practices in England.
•
Participants 119 ,546 men and women aged 18 years and over who used a
smoking cessation product between 1 September 2006 and 31 October
2011.
There were 81, 545 users of nicotine replacement products (68.2% of all
users of smoking cessation medicines),
6,741 bupropion (5.6%),
31, 260 varenicline (26.2%) users.
•
•
•
BMJ , 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f5704 (Published 11 October 2013) Cite this as: BMJ 2013;347:f5704
Conclusions
• There is no evidence of an increased risk of suicidal behavior
in patients prescribed varenicline or bupropion compared with
those prescribed nicotine replacement therapy.
• These findings should be reassuring for users and prescribers of
smoking cessation medicines.
54
BMJ , 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f5704 (Published 11 October 2013) Cite this as: BMJ
2013;347:f5704
FDA Safety review update of Chantix (varenicline) and
risk of neuropsychiatric adverse events (24/10/2011)
•
•
FDA sponsored two observational studies of neuropsychiatric adverse
events with Chantix. One was conducted by the Department of Veterans
Affairs’, and the other by the Department of Defense’s.
The VA study was a retrospective cohort study to evaluate the incidence of
mental health hospitalizations
psychiatric hospitalizations
Varenicline
(Event/patients)
NRT
(Event/patients)
Veterans
16/14,131
21/14,131
Department of Defense’s.
18/11,978
16/11,978
There was also no significant difference in psychiatric
hospitalizations for Chantix users compared to NRT
55
Tamra E. et al Neuropsychiatric events in varenicline and nicotine replacement patch users in the
Military Health System, Addiction 2012
Use of Varenicline vs. Bupropion and Risk of
Psychiatric Adverse Events
psychiatric
adverse events
Number of
Patients
Rate events per
1000 personyears
varenicline
0.18% (106)
59,790
22
Bupropion
0.26 %(46 )
17,936
31
The overall rate of psychiatric adverse events was substantially higher
among participants with a history of psychiatric disorder than in patients
without such history; the risk associated with varenicline did not differ
significantly by history of psychiatric disorder.
Registry-based cohort study in Denmark, 2007-2010, comparing new
users of varenicline and bupropion
56
Björn Pasternak; Henrik Svanström; Anders Hviid. 2013 Society for the Study of Addiction
Effects of Varenicline and Bupropion Use Plus
Intensive Smoking Cessation Counseling
58.10%
60.00%
53.50%
46.10%
41.20%
50.00%
40.00%
26.40%
38.40%
26.50%
25.50%
17.90%
30.00%
20.00%
10.00%
0.00%
End of
Treatmente
3-Month
Postquit Follow-up Visitf
Varenicline
Bupropion
6-Month
Postquit Follow-up Visitg
Placebo
Participants: In total, 294 community volunteers who wanted to quit smoking.
Interventions: Twelve weeks of varenicline, bupropion SR, or placebo plus intensive smoking cessation
counseling (10 sessions, for a total of approximately 240 minutes of counseling).
weekly measures of depression, negative affect, and other symptoms of nicotine withdrawal.
57
Adapted from :Paul M, et al, Effects of Varenicline and Bupropion Sustained-Release Use Plus Intensive Smoking Cessation
Counseling on Prolonged Abstinence JAMA Psychiatry , March 27, 2013, doi:10.1001/jamapsychiatry.2013.678
Psychiatric Adverse Event
Irritability
Abnormal dreams
Anxiety symptoms
Depression
Disturbance in
attention
Restlessness
Emotional lability
Panic attack
Elevated mood
Intrusive thoughts
Reduced inhibition
Suicidal ideation
Varenicline
(n = 86)
12 (14.0)
13 (15.1)
7 (8.1)
6 (7.0)
3 (3.5)
1 (1.2)
2 (2.3)
1 (1.2)
0
0
0
0
Bupropion
(n = 102)
16 (15.7)
6 (5.9)
8 (7.8)
8 (7.8)
7 (6.9)
5 (4.9)
3 (2.9)
0
0
0
1 (1.0)
0
Placebo
(n = 106)
17 (16.0)
11 (10.4)
15 (14.2)
14 (13.2)
Total
(N = 294)
45 (15.3)
30 (10.2)
30 (10.2)
28 (9.5)
16 (15.1)
6 (5.7)
4 (3.8)
2 (1.9)
1 (0.9)
1 (0.9)
0
1 (0.9)
26 (8.8)
12 (4.1)
9 (3.1)
3 (1.0)
1 (0.3)
1 (0.3)
1 (0.3)
1 (0.3)
Varenicline exerts a robust and favorable effect on smoking cessation relative to
placebo and may have
a favorable (suppressive) effect on symptoms of depression and other affective
measures, with no clear unfavorable effect on neuropsychiatric adverse events.
58
Adapted from :Paul M, et al, Effects of Varenicline and Bupropion Sustained-Release Use Plus Intensive Smoking
Cessation Counseling on Prolonged Abstinence JAMA Psychiatry , March 27, 2013,doi:10.1001/jamapsychiatry.2013.678
Varenicline safety and tolerability in Stable
Schizophrenic disorder
•
128 smokers with stable schizophrenia or schizoaffective disorder, on
antipsychotic medication, randomized 2:1 to varenicline (1 mg twice daily)
or placebo for 12 weeks with 12-week non-drug follow-up.
•
The most common adverse events in subjects taking varenicline were
nausea (23.8% vs. 14.0% on placebo),
headache (10.7% vs. 18.6% on placebo) and vomiting (10.7% vs. 9.3% on
placebo). Among reported
neuropsychiatric adverse events, insomnia was the only event reported in
either treatment group in ≥ 5% of subjects at a rate higher in the varenicline
group than in placebo (9.5% vs. 4.7%).
•
•
59
Jill M. et al , A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy
of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder. J Clin
Psychiatry. 2012 Jul;73(7):1035.
Varenicline safety and tolerability in Stable
Schizophrenic disorder
•
•
•
•
•
At 12 weeks(End of treatment), 16/84 varenicline treated patients (19%)
Met smoking cessation criteria vs. 2/43 (4.7%) of placebo( p=0.046)
At 24 weeks, 10/84 (11.9%) varenicline treated and 1/43 placebo treated
patients respectively met smoking cessation abstinence criteria
(p=0.09)
Overall, there was no worsening of schizophrenia in either treatment
group as measured by psychiatric scales and there were no overall
changes in extra-pyramidal signs.
During the active treatment period, the incidence of suicide-related events
was similar between the varenicline-treated and the placebo-treated
subjects (11 vs. 9.3 %, respectively).
There were no completed suicides. There was one suicidal attempt in
a varenicline-treated subject whose lifetime
60
Jill M. et al , A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of
varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry.
2012 Jul;73(7):1035.
Effects of Varenicline on Smoking Cessation in Patients
With Mild to Moderate COPD
‫מפלסבו‬
8 ‫ להפסיק לעשן עם צ'מפיקס הוא פי‬COPD ‫הסיכוי של חולי‬
OR: 8.40 (95% CI: 4.99,14.14)
P<0.0001
42.34%
Continuous Abstinence (%)
45.00%
OR: 4.88 (95% CI: 2.75, 8.65)
P<0.0001
40.00%
35.00%
OR: 4.04 (95% CI: 2.13, 7.67)
P<0.0001
25.81%
30.00%
18.55%
25.00%
20.00%
15.00%
8.76%
7.17%
5.58%
10.00%
5.00%
0.00%
weeks 9-12*
weeks 9-24
Varenicline (n=248)
61
Weeks 9-52
Placebo (n=251)
Tashkin D et al. Poster presented at Chest annual meeting, Oct 31st- Nov 5th, 2009, San Diego, California.
‫תוכנית שפותחה ע"י מיטב המומחים לגמילה מעישון בישראל‬
‫כלי עזר לרופאים וצוותים רפואיים המעוניינים ללוות את המעשנים‬
‫לאורך כל התהליך עד לגמילה (כשנה)‬
‫מתאימה למעשנים שבוחרים להיעזר בסדנה וגם לאלו שלא‬
‫‪62‬‬
‫בכל פגישה עם כל מעשן‬
‫ביקור לצורך הפסקת עישון‬
‫יום‪-‬יומיים לאחר הפסקת עישון‬
‫כחודשיים לאחר תחילת טיפול‬
‫בסוף האריזה השנייה‬
‫בסיום הטיפול התרופתי‬
‫‪ 3-6‬חודשים מתחילת התהליך‬
‫‪63‬‬
‫השפעת גמילה מעישון על טיפול תרופתי‬
‫שם התרופה‬
‫השפעה אפשרית של עישון על התרופה‬
‫‪CAFFEINE‬‬
‫מגביר פינוי ב ‪56%‬‬
‫‪CHLORPROMAZINE‬‬
‫ירידה בריכוז בסרום עד ‪24%‬‬
‫‪CLOZAPINE‬‬
‫ירידה בריכוז בסרום עד ‪28%‬‬
‫‪ESTRADIOL‬‬
‫אפשרות לפעילות אנטי אסטרוגנית‬
‫‪FLECAINIDE‬‬
‫מעלה פינוי תרופתי עד ‪61%‬‬
‫‪HALOPERIDOL‬‬
‫ירידה בריכוז בסרום עד ‪70%‬‬
‫‪HEPARIN‬‬
‫מעלה פינוי תרופתי‬
‫‪IMIPRAMINE‬‬
‫ירידה בריכוז בסרום‬
‫‪INSULIN‬‬
‫ספיגה מופחתת בהזרקה תת עורית בשל‬
‫הפרעה אפשרית באספקת הדם לרקמות אלו‬
‫‪OLANZAPINE‬‬
‫מעלה פינוי תרופתי עד ‪98%‬‬
‫‪PROPRANOLOL‬‬
‫מעלה פינוי תרופתי עד ‪77%‬‬
‫‪THEOPHILINE‬‬
‫‪ .‬מעלה פינוי בין ‪ 58%‬ל ‪100%‬‬
‫תוך שבעה ימים מהפסקת עישון ירידה של ‪ 35%‬בפינוי‬
‫‪WARFARIN‬‬
‫מוריד ריכוז בסרום עד ‪ . 13%‬אין השפעה על ‪.PT‬‬
‫‪Ministry of health ,New Zealand Smoking Cessation Guidelines.2007.‬‬
‫‪64‬‬
Indication:
Champix is indicated as an aid to smoking cessation treatment for adults over 18 years of age.
Contraindication:
Hypersensitivity to varenicline or excipients.
Precautions & Warnings:
Physiological change resulting from smoking cessation, with or without treatment of Champix may alter the pharmacology of some drugs, for which dose adjustment may be needed (e.g. Theophylline,
Warfarin, Insulin).
For patients with severe renal impairment, the recommended starting dose is 0.5 mg once daily and the maximum dose should not exceed 0.5 mg twice daily.
Champix is pregnancy category C.
Adverse reaction:
The most common adverse events associated with Champix were: nausea, sleep disturbances, constipation, flatulence and vomiting.
Serious neuropsychiatric events including, but not limited to depression, suicidal ideation, suicide attempt and completed suicide have been reported in patients taking CHAMPIX. 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 CHAMPIX who continued to smoke.
All patients being treated with CHAMPIX 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 pre-existing psychiatric illness and completed suicide have been reported in some patients attempting to quit smoking while taking
CHAMPIX in the post-marketing experience. When symptoms were reported, most were during CHAMPIX treatment, but some were following discontinuation of CHAMPIX therapy. These events have occurred
in patients with and without pre-existing psychiatric disease. Patients with serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder did not participate in the premarketing studies of CHAMPIX. Subsequent CHAMPIX smoking cessation studies provided data in patients with major depressive disorder and limited data in patients with stable schizophrenia or
schizoaffective disorders.
Advise patients and caregivers that the patient should stop taking CHAMPIX and contact a healthcare 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 post-marketing cases, resolution of symptoms after discontinuation of CHAMPIX was reported,
although in some cases the symptoms persisted; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve. The risks of CHAMPIX should be weighed against the benefits of
its use. CHAMPIX has been demonstrated to increase the likelihood of abstinence from smoking for as long as one year compared to treatment with placebo. The health benefits of quitting smoking are
immediate and substantial.
There are also reports of patients experiencing drowsiness that affected their ability to drive or operate machinery.
Healthcare professionals should monitor patients taking Champix for behavior and mood changes. Patients taking this product should report behavior or mood changes to their doctor and use caution when
driving or operating machinery until they know how quitting smoking with Champix may affect them.
There have been post-marketing reports of potentially life-threatening hypersensitivity reactions, such as angioedema, and of rare but severe cutaneous reactions, including Stevens-Johnson Syndrome and
Erythema Multiforme.
In a trial of patients with stable cardiovascular disease while cardiovascular events were infrequent overall, some were reported more frequently in patients treated with varenicline. A meta-analysis of 15
clinical trials, which included the smoking cessation trial of patients with stable cardiovascular disease, had similar results. In both the clinical trial and meta-analysis, all cause and cardiovascular mortality was
lower in patients treated with varenicline. No causal relationship between these events and varenicline has been established. Patients should be instructed to notify their health care providers of new or
worsening cardiovascular symptoms and to seek immediate medical attention if they experience signs and symptoms of myocardial infarction or stroke. Smoking is an independent and major risk factor for
cardiovascular disease.
Adverse events in the trial of COPD patients were similar to those observed in premarketing studies.
65
‫גמילה מעישון = הצלת חיים‬
‫גמילה מעישון –טיפול‬
‫בסיסי בחולים מורכבים‬
‫‪66‬‬