Strong controversy surrounding the anti-smoking Zyban

November 5, 2001 – Zyban, launched in 1997 in the United States, was seen as a revolution in tobacco control. Finally, we seemed to have found an effective way to “crush” too many smokers before they die from the effects of their addiction, often fatal in the long term. Remember that tobacco kills approximately 35,000 Canadians per year, 120,000 Britons and hundreds of thousands of Americans.

Nevertheless, concerns started to emerge and grew as Zyban was approved in several other countries. For example, in the spring of 2001, Australia, New Zealand, the Netherlands and Canada joined the United Kingdom in reporting an increasing number of serious side effects related to the consumption of Zyban (see section below ” Some numbers “). In September, Germany also sounded the alarm. And we’re not just talking about insomnia or anxiety here, but seizures, hypoglycemia, serum-like illness, heart attacks, severe hypertension, psychiatric reactions, suicidal ideation and even depression. deaths, including some suicides.

According to spokespersons for GlaxoSmithKline, the manufacturer of Zyban, there is no evidence that these side effects are related to taking this drug; smokers have a five times higher risk of developing cardiovascular problems than non-smokers and people who quit smoking without the help of Zyban also experience withdrawal-related side effects such as chest pain, palpitations and even a depressive state. The company also claims that existing health issues could be the cause of these serious side effects. Yet, according to research from PasseportSanté.net, in February 2001, the United States Food and Drug Administration admitted that cases of severe hypertension had been reported in patients who had no problems previously.¹ . For now, the medical authorities of the various countries concerned are following the Zyban file closely, while affirming that the number of death reports is not really worrying given the high number of users: it is estimated that around 15 million people have taken Zyban so far.

However, health experts are worried around the world and point out that the active ingredient in Zyban, bupropion hydrochloride, is a very powerful molecule. Its mode of action on smoking is not fully understood, but it is believed to increase the production of dopamine and norepinephrine, two neurotransmitters that are involved in brain mechanisms related to pleasure and withdrawal. Since its launch, other studies have confirmed its effectiveness, in particular that published in March 1999 in the prestigious New England Journal of Medicine and covering nearly 900 subjects² : According to the results, Zyban was twice as effective as a transdermal patch. Double-blind research published in June 2001³ and on 450 subjects also concluded that Zyban could also be effective in people who had already tried it without success (12% abstinent after 6 months against 2% in the placebo group). However, eleven people in the placebo group stopped taking their medication because of side effects, while the number was 19 in the Zyban group. During the study of New England Journal of Medicine, the discontinuation rate of subjects receiving Zyban was also much greater than that of the placebo group.

The D^r Biron, the Quebec pharmacovigilance specialist thinks that the cause and effect link between the reported deaths and Zyban has not been established, but he specifies that this drug has documented side effects, including seizures and serum-type illness. The latter is characterized by a rash, fever, and sharp joint and muscle pain. “You must immediately stop taking Zyban in such a case, because there is a risk of complications,” he emphasizes. In addition, according to him, this drug should not be prescribed to someone who has not already tried to quit smoking by other means. “If the support group and then the nicotine substitution have not worked, then we can consider Zyban provided that informed consent is obtained. The patient should be aware that there are rare but serious risks and should receive a copy of the Zyban monograph which, by the way, is an amphetamine derivative and therefore a potent stimulant ”. The D^r Biron also recalls that Zyban has no guaranteed effect (the study of New England Journal of Medicine mentions a success rate of 30%²) and that when prescribed to someone who is not sick, extra care should be taken. Several of the reported deaths occurred in people who were in good health and sometimes very young. A 21-year-old British flight attendant who smoked just 10 cigarettes a day died just over two weeks after starting treatment, as did a 26-year-old Canadian.

In light of the controversy raised by all this information, GlaxoSmithKline wished to remind doctors of the precautions to be taken, as pointed out Medical news of October 17: “Bupropion is contraindicated, among others, in patients who suffer from convulsive disorders as well as bulimia or anorexia nervosa, in those taking another drug containing bupropion as well as in those who do the same. subject to abrupt alcohol withdrawal or sudden withdrawal from benzodiazepines or other sedatives. To minimize the risk of drug interactions, prescribing bupropion in patients who are already taking, especially MAOIs, should be avoided. [inhibiteur de la mono-amine-oxydase] or thioridazine. As for the risks of convulsive seizure, they increase in proportion to the dose. Therefore, 300 mg per day should not be exceeded and no single dose should exceed 150 mg. In addition, extreme caution should be exercised when prescribing bupropion in people with certain factors that lower the seizure threshold or who have severe liver damage. Serious allergic reactions have also been reported [il s’agit de la maladie de type sérique] in rare cases (1 to 3 in 1,000). ”

“Whether or not to take a drug, especially to prevent rather than treat, should always be the subject of a thorough consultation between a doctor and his patient, because there are always risks of adverse effects,” recalls Dr.^r Biron. To learn more about precautions to take before consuming Zyban: RxList. Bupropion.

Some numbers

Note that the figures below should be interpreted with caution for two reasons: firstly, not all reported cases are serious side effects, but secondly, they are not always reported.

Canada (May 2001)

• 2 million prescriptions.
• 1,127 reports of adverse reactions, including 682 considered serious and 19 deaths.

United Kingdom (June 2001)

• 419,000 users.
• 6,110 adverse reaction reports, including 46 deaths.
• the Committee on Safety of Medicines (CSM) demanded that GlaxoSmithKline reinforce the warnings that should be followed by physicians and that physicians prescribe Zyban to their at-risk patients with the utmost caution and only if necessary. Finally, the CSM suggested increasing the initial dose from 150 mg to 300 mg after 6 days of treatment rather than after just 3 days.

Australia (August 2001)

• About 150,000 users.
• 1,215 adverse reaction reports, including 18 deaths.
• the Adverse Drug Reactions Advisory Committee pointed out that many of those who died were already suffering from illnesses such as alcohol abuse, diabetes and cardiomyopathy.

New Zealand (August 2001)

• 23,000 prescriptions.
• 218 adverse reaction reports.
• the Medicines Adverse Reaction Committee said last September that Zyban should be considered a second-line remedy for smoking and therefore should only be used after other treatments have been tried. The Ministry of Health nevertheless pointed out that, despite the side effects of Zyban, the advantages of this drug outnumber its disadvantages, when used correctly.

United States

• 5 million users.
• 549 reports of adverse reactions including 19 deaths (from November 1997 to May 1999).
• US data is more difficult to obtain directly than data for the countries mentioned above. We found these in a site dedicated to information on side effects of bupropion.⁴.

Françoise Ruby – PasseportSanté.net

Sources

Medical news, October 17, 2001
Protect yourself, May 2000, March 2001
Pharma.frost.com, July 2001
The Gazette, March 2, 2001
CBS Health Watch, May 2001
The British United Provident Association. Zyban – the facts. http://www.bupa.co.uk/healthy_living/lifestyle/smoking/zyban/
Zyban® / Wellbutrin® Forum. Related articles. http://www.geocities.com/borg_aw/articles/indxart.htm

1. Medwatch. FDA Medical Products Reporting Program. Summary of safety-related drug labeling changes approved by FDA, November 2000. (Posted: February 22, 2001).
2. Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, Muramoto ML, Daughton DM, Doan K, Fiore MC, Baker TB. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.N Engl J Med 1999 Mar 4; 340 (9): 685-91.
3. Gonzales DH, Nides MA, Ferry LH, Kustra RP, Jamerson BD, Segall N, Herrero LA, Krishen A, Sweeney A, Buaron K, Metz A. Bupropion SR as an aid to smoking cessation in smokers treated previously with bupropion: a randomized placebo-controlled study. Clin Pharmacol Ther. 2001 Jun; 69 (6): 438-44.
4. Zyban® / Wellbutrin® Forum. FDA Medwatch Summaries. http://www.geocities.com/borg_aw/fdarepor/indxfdar.htm