The summary of product characteristics (SPC) for bupropion (Zyban®) has been updated since
publication of the accompanying Bulletin. The initial dosage regimen has been modified and new safety
precautions have been added to the SPC. It is important to consult the current SPC for full prescribing
information. (The rINN has also been changed from amfebutamone to bupropion.)
WeMeReC Bulletin
Providing independent prescribing information
to general practitioners and pharmacists in Wales
Bupropion (Zyban) for smoking cessation
Cigarette smoking is the greatest cause of preventable
death and disability in Wales. It is responsible forapproximately one-fifth of deaths1,2 and an estimated
♦ Bupropion can be an effective smoking cessation
cost to health services of £70 million per annum. 2
aid in appropriately selected patients who receive
The effects of environmental tobacco smoke (passive
smoking) are additional to this. The overall cost ofsmoking to society is even greater.
♦ Bupropion has only been studied in relatively
heavy smokers who were otherwise healthy.
Government policy to combat smoking aims to
Trials of bupropion were conducted in volunteers
prevent people, especially children, from starting to
motivated to stop smoking, and treatment was
smoke; to help adult smokers to stop, particularly
combined with a structured support programme.
pregnant women and those in lower socio-economicgroups; and to raise awareness of the dangers
♦ Bupropion has not been studied in subjects below
associated with passive smoking. Approximately
18 years of age, those who are pregnant or breast-
one-quarter of the adult population in Wales smokes:1
feeding, or those with serious or unstable medical
reducing this figure has been set as a national
♦ Bupropion has been compared with a nicotine
Smoking cessation is beneficial regardless of age or
patch for smoking cessation in one trial; results
smoking history.3 In a 12-month period, about one in
three smokers will attempt to stop,2 of whom only 3%will be abstinent after 12 months using willpoweralone.4 Supportive measures (including provision of
This bulletin does not review all smoking cessation
self-help materials, and advice and counselling from
therapies but provides clinical information on the use
health professionals) are effective in improving
of bupropion [amfebutamone (rINN)]. Bupropion
cessation rates.5 These are cost-effective healthcare
hydrochloride sustained-release (Zyban) is licensed in
interventions4 and guidelines for integrating effective
the UK for use with motivational support as an aid to
smoking cessation measures through the healthcare
smoking cessation in nicotine-dependent patients.
Increased knowledge of the effect of nicotine on
The use of nicotine replacement therapy (NRT) can
neurotransmitters, and links between nicotine-
raise success rates one and a half to two-fold over
dependence and depression, has led to the investigation
those achieved with motivational support alone (some
of many pharmacological agents, including
level of support was always offered in the clinical
antidepressants, to aid smoking cessation.8
trials of NRT).5 The various nicotine products are
Observational reports and two early trials suggested
equally effective, with product choice primarily
that bupropion, an atypical antidepressant (used in the
influenced by personal preference. However, even
USA), may be effective. Bupropion has dopaminergic
with NRT, the majority of dependent smokers rarely
and noradrenergic properties but the precise
succeed in their first attempt to give up, many have to
mechanism by which bupropion aids smoking
make several attempts and many never succeed.
cessation is not firmly established.
Published by the Welsh Medicines Resource Centre, Llandough Hospital, Penarth, Vale of Glamorgan CF64 2XX. Tel: 029 – 2071 6117
WeMeReC Bulletin Vol. 7 No. 2, October 2000 1
Efficacy of bupropion: two clinical trials
Two randomised, double-blind, placebo-controlled,
(6 weeks after the target quit date) and at 3, 6 and 12
multi-centre trials of bupropion for smoking cessation
months. End-of-treatment and 12-month point-
have been conducted in the USA. The trials were
prevalence rates and 6-week continuous abstinence rates
conducted in adult volunteers who smoked at least 15
are presented in Table 1 (trial 1). Continuous abstinence
cigarettes per day and were motivated to stop.9,10
rates at 12 months were not reported.
Subjects had no current depression. Other exclusionsincluded recent use of NRT, a history of, or
In the second study of 893 subjects, sustained-release
predisposition to seizures, eating disorders, pregnancy or
bupropion 300 mg was compared with a nicotine 21-mg
breast-feeding, drug or alcohol abuse, dermatological
patch and a combination of bupropion and the patch.10
disorders and serious or unstable medical or psychiatric
Bupropion treatment began 1 week before the target quit
date and continued for a further 8 weeks. Patch treatmentbegan on the target quit date and continued for
Both year-long studies included a treatment phase, with
8 weeks, however, the dose was reduced in the final 2
day 8 usually set as the “target quit date”. Subjects
received supportive advice before starting treatment andindividual 10-15 minute counselling sessions were
Point-prevalence rates for smoking cessation were
provided each week during treatment. Subjects were also
calculated for 6 and 12 months. The results at
telephoned 3 days after the target quit date. During the
12 months are given in Table 1 along with
follow-up period there were a further four counselling
12-month continuous abstinence rates (trial 2).
sessions and monthly telephone calls.
Bupropion and the combined treatment were associatedwith significantly higher abstinence rates than the
End-points included point-prevalence abstinence rates,
nicotine patch. The combined treatment appeared
which were based on the numbers of subjects who had
superior to, but not significantly better than, bupropion
not smoked for the previous week. Carbon monoxide
alone. With the nicotine patch, only the continuous
abstinence rate differed significantly compared with
self-reports of smoking abstinence. Continuous
abstinence rates were based on the numbers of subjectswho reported not smoking since the target quit date and
In the first trial, weight gain during treatment in subjects
who had negative carbon monoxide measurements at all
who were continuously abstinent (n=103) was
preceding clinic visits. In addition to abstinence rates,
significantly lower with bupropion 300 mg (1.5 kg)
body weight and symptoms of depression and withdrawal
compared with placebo (2.9 kg). This difference had
were monitored. The results were analysed on an
diminished at 6 months. In the second trial, weight gain
intent-to-treat basis; subjects who did not complete the
in subjects at week 7 (n=666) was lower but not
studies were considered to be smoking. Approximately
significantly different in the bupropion group (1.7 kg)
35% of subjects in both studies did not participate for a
compared with the placebo group (2.1 kg).
Withdrawal symptoms were experienced by subjects
receiving bupropion 300 mg but not to the same degree as
sustained-release bupropion taken at daily doses of 100
by those receiving placebo. Bupropion had no effect on
mg, 150 mg and 300 mg (150 mg twice daily) for 7
measures of depressive symptoms in either trial.
weeks.9 Point-prevalence or 7-day abstinence rates weredetermined at the end of treatment
Table 1 Smoking cessation rates* Point-prevalence (7-day abstinence) rates Continuous abstinence rates
* Differences between rates for bupropion and placebo are statistically significant in both trial 19 and trial 2.10
2 WeMeReC Bulletin Vol. 7 No. 2, October 2000
In the trials, dry mouth and insomnia were common
suspected adverse reactions, including serious reactions,
adverse events that were reported significantly more
have been reported to the CSM. Bupropion carries the t
frequently with bupropion than with placebo. In the first
symbol; all suspected adverse reactions should be
trial, 37 (6%) subjects withdrew because of adverse
reported through the Yellow Card Scheme to CSM
events (8 receiving placebo); tremor, headaches, rash and
urticaria were the most common reasons.9 In the secondtrial, 79 (8.8%) subjects withdrew because of adverse
Bupropion and smoking cessation have the potential to
events, with a significantly higher percentage
affect the metabolism of drugs by cytochrome enzymes
withdrawing in the groups receiving bupropion (57
and there are a number of medicines that can potentially
subjects in total) than in the placebo group (6 subjects).10
affect blood levels of bupropion. The summary of
Serious adverse events included three cases of rash and
product characteristics should be consulted about
pruritus, one of which occurred with shortness of breath
potential interactions between bupropion and other
One of the main concerns with bupropion use, which
Patients with recent myocardial infarction or unstable
arose during post-marketing experience in the USA, is
heart disease were not included in clinical trials of
the incidence of seizures. The incidence of seizures is
bupropion, so care is advised in these groups. There have
approximately 0.1%,11 with risk strongly associated with
been reports of cardiovascular effects, including
the presence of predisposing factors. Higher doses of
tachycardia, hypertension and postural hypotension, in
bupropion are associated with a greater risk of seizures.
patients receiving bupropion.11 In the second trial,10 newor worsening hypertension was reported more frequently,
Bupropion is contra-indicated in patients with a current
although not significantly so, in subjects receiving
or previous diagnosis of a seizure disorder or bulimia or
bupropion combined with the nicotine patch than in those
anorexia nervosa, a history of bipolar disorder or those
receiving placebo. In patients receiving combination
taking monoamine oxidase inhibitors. Bupropion is also
treatment, caution must be exercised and blood pressure
contra-indicated in patients with severe hepatic cirrhosis.
It should be used with caution in patients with hepaticimpairment and renal insufficiency. A lower dose (150
The trials of bupropion for smoking cessation did not
mg daily) is recommended in these patients, and in the
include patients with depression. The efficacy of
bupropion for smoking cessation in the trials was notassociated with an antidepressant effect, and a subgroup
Because bupropion can lower the seizure threshold, it
analysis of the first trial found bupropion was equally
should be administered with extreme caution in patients
effective in patients with or without a history of major
who may already be predisposed to a lower seizure
depression.16 Bupropion is not licensed in the UK for use
threshold or a higher risk of seizures. For example,
in the management of depression and depression may
patients with a history of head trauma, those with central
occur during its use for smoking cessation.17
nervous system tumours, or those taking medicines suchas antipsychotics, antidepressants, theophylline or
Discontinuation reactions were not observed in the trials
systemic steroids. It should be used with caution in the
of bupropion but gradual dose reduction may be
presence of alcohol abuse, the abrupt withdrawal of
considered.11 As a centrally-acting drug, bupropion can
alcohol or benzodiazepines, the use of stimulants or
affect the ability to perform tasks requiring judgement or
anorectic products, and diabetes treated with
motor and cognitive skills. Dizziness and light-
headedness have been reported, and patients startingbupropion should be cautioned about driving and using
Relatively rare but serious adverse effects reported with
bupropion include hypersensitivity reactions, serumsickness-like reactions, erythema multiforme and Stevens
Bupropion has not been evaluated in subjects below 18
Johnson syndrome.11-15 Since bupropion has become
years of age and its safety in pregnant or lactating women
has not been established. Bupropion has not been studiedbeyond 9 weeks for use as an aid to smoking cessation.
WeMeReC Bulletin Vol. 7 No. 2, October 2000 1
Prescribing bupropion
Healthcare professionals providing smoking cessation
Bupropion is available in 150-mg sustained-release
advice in primary care should ask about smoking at
tablets. The recommended dosage is 150 mg taken daily
every opportunity; advise all smokers to stop; assist the
for 3 days, increasing to 150 mg twice daily. Doses
smoker to stop and arrange follow-up.6 Before
should be taken at least 8 hours apart. As it takes about
prescribing bupropion, GPs should be confident that
1 week for steady-state blood levels of bupropion to be
patients are committed to quitting and be able to provide,
reached, patients should start the tablets while they are
or refer patients to, a source of face-to-face counselling.
still smoking and set a “target quit date” within thesecond week, usually day 8 of treatment. Treatment
Help with assessment of patients’ motivation and
should be stopped after 7 weeks if no effect is observed.
provision of support may be available locally throughcommunity pharmacies or smoking cessation clinics.
Health authorities and some local health groups have
Information on how to contact your local smoking
issued guidelines on prescribing bupropion. These
cessation co-ordinator can be obtained from the national
telephone helpline. Additional telephone counselling for
1 month only. A second prescription should be issued
patients is available through this national helpline.
only with counselling and assessment of tolerability andcompliance.
Smokers Helpline for Wales: 0800 169-0-169
Cost Zyban costs £85.70 for a 2-month course of treatment.
The manufacturer of bupropion is also advertising a
Costs associated with counselling should also be
support programme that provides patients with self-help
considered. Comparisons with nicotine replacement
materials and access to telephone counselling. Contact
therapy are difficult as costs associated with nicotine
details are provided in the patient information leaflet.
products vary considerably depending on the formulationand dose used, and the route of supply. References 1. Digest of Welsh statistics 1999. The National Assembly for
9. Hurt RD et al. A comparison of sustained-release bupropion
and placebo for smoking cessation. N Engl J Med 1997; 337:
2. Promoting health and well being: a consultation document.
March 2000. Health Promotion Division, The National
10. Jorenby DE et al. A controlled trial of sustained-release
bupropion, a nicotine patch, or both for smoking cessation.
3. Peto R et al. Smoking, smoking cessation, and lung cancer
N Engl J Med 1999; 340: 685-691. Correction: N Engl J
in the UK since 1950: combination of national statistics with
two case-control studies. BMJ 2000; 321: 323-329.
11. Zyban summary of product characteristics. GlaxoWellcome
4. Parrott S et al. A guidence for commissioners on the cost-
effectiveness of smoking cessation interventions. Thorax
12. Tripathi A, Greenberger PA. Bupropion hydrochloride
induced serum sickness-like reaction. Ann Allergy Asthma
5. Lancaster T et al. Effectiveness of interventions to help
people stop smoking: findings from the Cochrane Library.
13. Peloso PM, Baillie C. Serum sickness-like reaction with
6. Raw M et al. Smoking cessation guidelines for health
14. Yolles JC et al. Serum sickness induced by bupropion. Ann
professionals. A guide to effective smoking cessation
interventions for the health care system. Thorax 1998; 53
15. McCollom RA et al. Bupropion-induced serum sickness-like
reaction. Ann Pharmacother 2000; 34: 471-473.
7. Raw M et al. Smoking cessation: evidence based
16. Hayford KE et al. Efficacy of bupropion for smoking cessation
recommendations for the healthcare system. BMJ 1999; 318:
in smokers with a former history of major depression or
alcoholism. Br J Psychiatry 1999; 174: 173-178.
8. Benowitz NL, Peng MW. Non-nicotine pharmacotherapy for
17. Patten CA et al. Development of depression during placebo-
smoking cessation. Mechanisms and prospects. CNS Drugs
controlled trials of bupropion for smoking cessation: case
reports. J Clin Psychiatry 1999; 60: 436-441.
The manufacturer’s summary of product characteristics should be consulted for full prescribing information. Prescribing in pregnancy is the topic for the next WeMeReC bulletin and GP distance-learning module. These will be issued in November.
WeMeReC Bulletin Vol. 7 No. 2, October 2000 3
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Colloque « Santé et mobilités au Nord et au Sud : Circulations des acteurs, évolutions des pratiques » Résumé « Des plantes de la pharmacopée chinoise aux usages et significations multiples au temps de la globalisation économique et culturel e» Evelyne Micollier Structures de rattachement : RD, UMR 145, PUMC/CAMS, BeijingA partir d’une recherche portant sur les usages soc