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JUNIO 2.004
JUNE 2.004
ZYBAN (BUPROPION)
THE DAY AFTER TOMORROW, day in
that he try of stop to smoke and died soon after.
1.) Bupropion (Zyban) toxicity.
2.) Anti-smoking drug deaths triple.
3.) Generalized pustular and erythrodermic psoriasis associated with bupropion treatment.
4.) Acute liver failure with concurrent bupropion and carbimazole therapy.
5.) Bupropion poisoning: a case series.
6.) Antismoking drug comes under scrutiny after deaths.
7.) Fatal bupropion overdose.
8.) Flare of cutaneous lupus erythematosus induced by bupropion (Zyban).
9.) Bupropion (Zyban SR) side effects.
10.) Zyban Anti-Smoking Drug Linked to Suicide.
1.)
BUPROPION (Zyban) TOXICITY.
Ir Med J. 2002 Jan;95(1):23-4.
Tracey JA, Cassidy N, Casey PB, Ali I.
The National Poisons Information Centre, Beaumont Hospital, Dublin, Ireland.
Bupropion is a monocyclic antidepressant structurally related to amphetamine.
Zyban, a sustained-release formulation of bupropion hydrochloride, was recently
released in Ireland, as a smoking cessation aid. In the initial 6 months since
it's introduction, 12 overdose cases have been reported to The National Poisons
Information Centre. 8 patients developed symptoms of toxicity. Common features
included tachycardia, drowsiness, hallucinations and convulsions. Two patients
developed severe cardiac arrhythmias, including one patient who was resuscitated
following a cardiac arrest. All patients recovered without sequelae. We report a
case of a 31 year old female who required admission to the Intensive Care Unit
for ventilation and full supportive therapy, following ingestion of 13.5g
bupropion. Recurrent seizures were treated with diazepam and broad complex
tachycardia was successfully treated with adenosine. Zyban caused significant
neurological and cardiovascular toxicity in overdose. The potential toxic
effects should be considered when prescribing it as a smoking cessation aid.
2.) Anti-smoking drug deaths triple.
Friday, 18 January, 2002, 12:11 GMT
source: http://news.bbc.co.uk/
Zyban : under close review
The number of people who have died after taking the anti-smoking drug Zyban has
more than tripled in a year, official figures show.
By January 10, 57 people had died following suspected adverse reactions to the
drug, compared to 18 the same time last year, the Medicines Control Agency (MCA)
found.
But the MCA said a direct link between the drug, which was launched in June
2000, and the deaths was unproven.
And anti-smoking campaigners said most of the deaths would have occurred anyway.
Data on adverse reactions to the drug was reported by doctors, dentists,
pharmacists, coroners and pharmaceutical companies under the government's "yellow
card" scheme.
There is currently no reason to believe that patients taking Zyban have an
increased risk of death
GlaxoSmithKline spokesman
In a notice published on its website, the MCA said: "There have been 57 reports
of suspected adverse reactions to Zyban which have resulted in a fatal outcome.
"The contribution of Zyban to these fatal cases is unproven and in the majority
of cases the individual's underlying condition may provide an alternative
explanation.
"In 14 of these reports the individual was not taking Zyban at the time of their
death."
Raised awareness
The MCA has received 6,975 reports of suspected adverse reactions to Zyban,
including insomnia, rashes, headache, nausea, vomiting and depression.
Of those, 168 patients suffered seizures suspected as being associated with
Zyban.
As with all new drugs, the safety of Zyban remains under close review
Medicines Control Agency spokesman
A spokesman for the MCA said the figures were an update to keep people aware of
the position.
"As with all new drugs, the safety of Zyban remains under close review."
He added: "Comparing Zyban with other medicines, the proportion of Zyban reports
that have fatal outcomes is much lower - less than 1%."
Doctors and pharmacists will be asked to continue reporting all suspected
adverse reactions to the MCA and the Committee on Safety of Medicines, an expert
advisory group.
A spokesman for pharmaceutical giant GlaxoSmithKline, which makes the drug, said:
"Smoking-related disease claims 320 lives a day in the UK.
"There is currently no reason to believe that patients taking Zyban have an
increased risk of death.
"There is no proven link with deaths and the medicine is used in patients who
are already at risk because of smoking.
Clive Bates, of Action on Smoking and Health, told BBC News Online said: "Most
of these people would have died anyway.
"It's important not to confuse deaths that happen while using the drug with
deaths that happen because of using the drug."
He added that over 400,000 people have used Zyban.
3.) Generalized pustular and erythrodermic psoriasis
associated with bupropion treatment.
Br J Dermatol. 2002 Jun;146(6):1061-3.
Cox NH, Gordon PM, Dodd H.
Department of Dermatology, Cumberland Infirmary, Carlisle CA2 7HY, UK. [email protected]
Severe drug eruptions may cause diagnostic and therapeutic difficulty when they
mimic or provoke endogenous patterns of dermatosis. We report three patients
with known psoriasis in whom use of bupropion (Zyban), prescribed to assist with
cessation of smoking, led to severe pustular or erythrodermic exacerbation of
psoriasis within 3-5 weeks. All patients were systemically unwell and required
hospitalization to control the disease flare.
4.) Acute liver failure with
concurrent bupropion and carbimazole therapy.
Ann Pharmacother. 2003 Feb;37(2):220-3.
Khoo AL, Tham LS, Lee KH, Lim GK.
Department of Pharmacy, National University Hospital, Singapore. [email protected]
OBJECTIVE: To report a case of fatal liver failure possibly associated with
concurrent use of bupropion and carbimazole. CASE SUMMARY: A 41-year-old Chinese
man with a history of hyperthyroidism had been treated with carbimazole and
propranolol for the past 5 years. He received a 10-day course of bupropion as an
aid for smoking cessation 10 weeks prior to presentation. He developed acute
liver failure with rapid deterioration of renal function. Liver biopsy showed
evidence of nonspecific drug-induced acute liver injury. His condition was
further complicated by sepsis and coagulopathy. Death resulted 19 days after the
onset of symptoms. The likelihood that bupropion induced hepatotoxicity in our
patient was possible, based on the Naranjo probability scale. DISCUSSION:
Although there is increasing evidence of hepatotoxicity induced by bupropion,
this is the first case of fatality that could have resulted from acute liver
failure in a patient receiving bupropion while on concomitant treatment with
carbimazole. CONCLUSIONS: Clinicians should be aware of the possibility of acute
liver insult induced by bupropion given concurrently with other hepatotoxic
drugs.
5.) Bupropion poisoning: a case series.
Med J Aust. 2003 Jan 20;178(2):61-3.
Balit CR, Lynch CN, Isbister GK.
NSW Poisons Information Centre, The Children's Hospital at Westmead, Locked Bag
4001, Westmead, NSW 2145, Australia. [email protected]
OBJECTIVE: To investigate the toxicity of bupropion hydrochloride in deliberate
self-poisoning in adults and accidental ingestion by children. DESIGN AND
SETTING: Prospective study of cases identified from calls to the New South Wales
Poisons Information Centre (NSW PIC), with follow-up through hospital medical
records. PARTICIPANTS: Patients with bupropion poisoning managed in hospital,
about whom the NSW PIC was contacted for advice, from 1 November 2000 to 31 July
2001 (59 adults and 10 children). MAIN OUTCOME MEASURES: Clinical effects,
adverse outcomes (including seizures and death) and treatment. RESULTS: 45 of
the 59 adults were followed up (76%), 19 of whom had taken bupropion alone.
Major clinical effects of bupropion included sinus tachycardia (83%),
hypertension (56%), seizures (37%), gastrointestinal symptoms (37%) and
agitation (32%). Seizures were dose-dependent, with those having seizures
ingesting a significantly higher median dose (P = 0.02). All seizures were brief
and self-limiting. 29 patients received decontamination therapy. 10 patients
required pharmacological sedation, 10 were admitted to intensive care and six
were intubated. None died. Eight of 10 accidental ingestions by children were
followed up (80%); one child had symptoms (vomiting and hallucinations).
CONCLUSIONS: Bupropion overdose caused significant clinical effects in adults,
but few in children.
6.) Antismoking drug comes under scrutiny after deaths
BMJ
2001;322:452 ( 24 February ) / News
Roger Dobson, Abergavenny
The manufacturer of the antismoking drug amfebutamone (Zyban), GlaxoSmithKline,
has insisted that no evidence exists of an increased risk of death with its use,
after 18 deaths were linked with suspected adverse drug reactions. The Medicines
Control Agency said that the contribution of amfebutamone to the deaths is
unknown.
"It should be noted that patients may be required to stop smoking because of
underlying diseases and these may well explain some of the reported deaths in
patients taking Zyban," said a spokeswoman for the agency.
She added, "It is important to note that suspected reactions are not necessarily
caused by the drug and may relate to other factors such as nicotine withdrawal,
other illnesses, or other medicines taken concurrently."
Latest figures show that in addition to the 18 deaths there have been 3457 cases
of adverse reactions. Most of these are minorthe most common being dry mouth,
headache, and insomniabut there have also been some involving seizures. About
270000 patients in the United Kingdom have been prescribed the drug, and
amfebutamone has been used by 22 million people worldwide.
The drug is described by GlaxoSmithKline as the first non-nicotine
pharmacological treatment licensed for smoking cessation.
"It is important to note that suspected reports are not necessarily caused by
the drug and may relate to other factors such as other illnesses, other
medicines or more importantly smoking itself," said a spokeswoman for
GlaxoSmithKline. "There is no evidence of an increased risk of death associated
with the use of this medicine. It is, however, well doc umented that 1 in 4
smokers will die in middle age from a smoking related disease."
7.) Fatal bupropion overdose.
J Toxicol Clin Toxicol. 1997;35(3):321-4.
Harris CR, Gualtieri J, Stark G.
Emergency Medicine Department, Ramsey Medical Center, St. Paul, MN 55101-2595,
USA. [email protected]
BACKGROUND: Bupropion is a unique monocyclic antidepressant that has been known
to cause seizures in high therapeutic doses and in acute overdoses. Death due to
ingestion, however, is a rare occurrence. CASE REPORT: We report a case of a 26-year-old
man who ingested 23 g bupropion, developed seizures and hypoxia, and presented
in cardiac arrest. The patient was resuscitated in the emergency department, but
died 4 d after supportive intensive care. CONCLUSIONS: Bupropion overdose may
lead to recurrent seizures, hypoxia and death. Aggressive management of severe
bupropion overdose is recommended.
8.) Flare of cutaneous lupus erythematosus induced by bupropion (Zyban).
Dermatology. 2004;208(4):362.
Jumez N, Dereure O, Bessis D, Guillot B.
Publication Types:
Letter
9.)
Bupropion (Zyban SR) side effects
soruce: http://www.tga.gov.au/
31 August 2001
Bupropion (Zyban SR) was first marketed in Australia late in 2000 as a short-term
aid to giving up smoking and has had very high usage. It was initially developed
as an antidepressant. It is a selective inhibitor of the neuronal re-uptake of
catecholamines in the brain but its mechanism to enhance the ability to quit
smoking is unknown.
New medicines achieve registration on the basis of experience in relatively
limited numbers of patients and some uncommon or rare adverse reactions to the
drug become recognised only after usage has grown, which may take years. In
contrast, the very high usage of bupropion in a short time has highlighted
several possible adverse effects, some of which may be severe.
The assessment of reactions to bupropion use is difficult because many patients
experience the effects of nicotine withdrawal in addition to the effects of
bupropion. Since November 2000 the Adverse Drug Reactions Advisory Committee (ADRAC)
has received 1237 Australian reports of suspected adverse reactions in
connection with the use of Zyban SR. In 1215 of these, Zyban SR was implicated
as the sole suspected drug. The more commonly reported problems involved skin
reactions (499 reports), psychiatric disturbances (427), the nervous system
(406), and the gastrointestinal tract (258) as indicated in Table 1 below.
Table 1: More Commonly Reported Reactions
with Bupropion
Adverse Reaction/No. of Reports
Skin
Urticaria
289
Other rashes
137
Other itch
73
Neurological
Headache
116
Dizziness/ataxia
108
Convulsions/twitching
74
Tremor
71
Paraesthesia/hypoaesthesia
64
Psychiatric
Insomnia
115
Agitation
81
Depression
72
Anxiety
69
Gastrointestinal
Nausea
128
Vomiting
44
Other
Facial/angioedema
89
Chest pain
79
Serum sickness
63
Shortness of breath
51
Increased sweating
41
The profile of the drug is dominated by hypersensitivity reactions and
neurological and psychiatric effects.
The majority of hypersensitivity reactions involve relatively minor skin
reactions but there have also been reports of facial oedema or angioedema and
serum sickness-like reactions. The latter describe a syndrome of a skin rash or
urticaria with joint pain or swelling. The delayed onset ranging from 5 to 44
days (median: 16 days) after commencement of bupropion is also consistent with a
serum sickness-like syndrome. In at least 30 of the cases, steroids were given.
Bupropion can cause seizures and is contraindicated in patients with epilepsy.
It should be used with great caution in those with a predisposition to seizures
including those abusing alcohol or taking another medication that can lower the
seizure threshold. This includes most antidepressant and antipsychotic drugs,
insulin, oral hypoglycaemic drugs and anorectic products.
Care also needs to be taken in prescribing bupropion for patients with a history
of psychiatric conditions, and especially those taking drug therapy, because of
the possibilities of interactions or additive effects. These are identified in
the product information.
Recent media coverage has highlighted a small number of Australian reports to
ADRAC of suspected adverse reactions to bupropion where the patient died. As at
22 June 2001, there had been 18 such reports in patients aged from 30 years to
69 years. The duration of exposure to bupropion ranged from a single dose to 10
weeks in 15 patients: two died three days after ceasing the drug. The death of a
patient may be caused by a drug or may be coincidental. Smokers are at increased
risk of cardiovascular death and early symptoms of cardiovascular disease may
prompt therapy with bupropion.
An ADRAC review of the 18 reports has found that there were a variety of
reported causes of death and not a single consistent mode of death. In addition
to being smokers, several patients had other existing risk factors for
unexpected death such as alcohol abuse, diabetes or cardiomyopathy. Eleven of
the 18 patients had an alternative explanation for death that was at least as
plausible as a possible effect of bupropion. In four reports, the available
information was very limited and it was not possible to assess the cause of
death. Further information is being sought on three cases to aid assessment of
the cause of death.
ADRAC will review each report with a fatal outcome as additional information
becomes available. As with all such reports, ADRAC seeks detailed follow-up
information including post-mortem and coronial reports to aid in assessment of
the individual cases. ADRAC meets every six to seven weeks and is keeping the
drug's safety under close review.
10.) Zyban Anti-Smoking Drug Linked to Suicide
Zyban, an anti-smoking drug, may have been one of
the factors contributing to the suicide death of an 18-year-old college student.
source: Http://www.mercola.com/
The teenager was prescribed Zyban, which is manufactured by pharmaceutical
company GlaxoSmithKline, to help him quit smoking. After taking the drug, he
told family members that he felt “an immediate change within himself.”
Reportedly, the teenager changed from being “outgoing and happy” to suffering
from bouts of depression.
He stopped taking the drug after one week, however six months later was found to
have committed suicide.
According to a psychiatrist who treated the boy, he had a mixed anxiety
depressive disorder that may have been affected by Zyban. The coroner also
stated that the effects of Zyban may have contributed to the student’s suicide,
however mentioned that the boy’s obsessive personality and heavy drinking may
have also played a role.
Another physician and expert of drug effects stated that Zyban could not have
been in the student’s system when he died, however it could have contributed to
his altered state of mind.
A spokeswoman for GlaxoSmithKline said the drug has been tested for safety and
has been used by about 10.5 million people worldwide. She mentioned that mood
changes, including depression and anxiety, often occur when people try to stop
smoking, regardless of whether a drug is used or not.
BBC News February 24, 2003
THE HISTORY
Anti-smoking drug linked to suicide
Mr Hirst took Zyban for a week
A teenage student desperately trying to give up cigarettes by taking the anti-smoking
drug Zyban killed himself after it made him depressed, an inquest has heard.
Nick Hirst, of Prestbury, Cheshire, changed from being an "outgoing and happy"
student after taking the drug to kick his habit, the coroner's court in
Macclesfield was told.
Recording a verdict of suicide, Cheshire coroner Nicholas Rheinberg said the use
of Zyban may have been one of the factors in the death of the 18-year-old.
Mr Hirst, a first-year student at Nottingham Trent University, wanted to give up
smoking to improve his fitness for rugby.
I thought it was likely [Nick] had a mixed anxiety depressive disorder, possibly
precipitated by Zyban
Dr Howard Waring, consultant psychiatrist
The inquest was told that after being prescribed Zyban, made by pharmaceutical
giant GlaxoSmithKline, by a doctor, Mr Hirst told close family and friends that
he felt an immediate "change within himself" and suffered bouts of depression.
He took the drug for a week and then stopped.
Six months later, in May 2001 he was found hanging from a tree in Riverside Park
in Macclesfield after earlier telling his brother Jonathan "I don't want to be
here", the court was told.
Mr Rheinberg said one reason the student committed suicide could have been the
effects of Zyban, but there were other reasons which could have contributed to
his death.
Those included an obsessive personality and heavy drinking.
'Happy, outgoing'
In an outburst in the inquest, Mr Hirst's mother Dianne said: "I just feel that
Zyban stopped him smoking. He didn't want to smoke, he didn't want to drink. He
didn't want anything to do with his car or his dog."
She claimed Zyban not only stopped him smoking, but stopped him wanting to do
anything.
"He loved his rugby," she earlier told the inquest while giving evidence.
"He was a very happy and outgoing young man who didn't have enough hours in the
day to do everything he wanted to do."
Public awareness
Dr Howard Waring, a consultant psychiatrist who treated Mr Hirst, told the
hearing: "I thought it was likely he had a mixed anxiety depressive disorder,
possibly precipitated by Zyban and that he should have anti-depressants.
"But Nick said that the effects of Zyban on him had been so radical that he
wouldn't be willing to take any medication of an anti-depressant type."
Dr Robin Ferner, a consultant physician and an expert on the effects of drugs,
told the hearing it was impossible Zyban was still in Mr Hirst's system at the
time of his death.
"But on balance it's one of the contributors to the alteration in mind that he
suffered in November," he added.
In a statement released after the verdict, Mr Hirst's family said: "We hope this
inquest will raise public awareness about the potential dangers of Zyban."
10.5m users
GlaxoSmithKline offered its condolences to Mr Hirst's family.
But a spokeswoman added the company was "fully confident of the contribution
Zyban makes in helping smokers to successfully stop smoking".
She said the drug had been used by an estimated 10.5m people worldwide after
thorough tests for safety.
"We take all reports of suspected adverse events regarding any of its medicines
very seriously," she said.
"The safety of all medicines is continually monitored by both GlaxoSmithKline
and the Medicines Control Agency.
"When people try to stop smoking, mood changes including depression, agitation,
anxiety and difficulty concentrating are commonly seen - irrespective of whether
nicotine replacement therapy, Zyban or willpower alone is used.
"Clearly is it not appropriate for the coroner to review all the available
evidence for Zyban and as such he has had to base his judgement on the
information available for this one case."
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DATA-MEDICOS/DERMAGIC-EXPRESS /JUNE JOURNAL 2.004/ DR. JOSE
LAPENTA R.
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