In Denmark, you can get smoking cessation medicine both over the counter and on prescription. In total, the Danish Medicines Agency has received reports on possible side effects from 480 persons who used Zyban® or Champix® in the period 2001-2011. Eight of these reports concern deaths.
The Danish Medicines Agency assesses that it is highly unlikely or improbable that any of the eight deaths are due to the medicine.
Stop smoking products
Stop smoking medicines containing nicotine (e.g. nicotine patches and chewing gums) are available over the counter at both pharmacies and a number of other shops. The side effects are few and predominantly related to local irritation caused by nicotine. Despite the easy access to these smoking cessation products, many patients ask their general practitioner for further help to stop smoking.
There are two prescription-only smoking cessation products on the Danish market. They have two different mechanisms of action, which means that the possible side effects and special circumstances to be considered before use also differ from each other.
Zyban contains bupropion, whose mechanism of action is the same as several antidepressants, whereas Champix contains the partial nicotine receptor antagonist varenicline. Both medicines affect the brain's craving for or reaction to nicotine from tobacco.
Both products are approved for smoking cessation treatment for adults - apart from pregnant women. Zyban has been approved in several European countries including Denmark since fall 2000, while Champix has been approved in all EU countries since November 2006.
Reports of suspected side effects
In the period 2001-2011, the Danish Medicines Agency received reports from 480 users who all experienced side effects that may be due to the use of Zyban or Champix.
Eight reports of suspected side effects have a fatal outcome, four from use of Zyban and four from Champix. The Danish Medicines Agency assesses that it is highly unlikely or improbable that any of the eight deaths are due to the medicine.
The reported side effects with deaths related to Zyban are from 2001, 2002, 2003 and 2007.
They are associated with the following concrete situations: Sudden death after two months of treatment during concomitant treatment for hypertension and heart failure, suicide from taking a very large number of tablets, death after 12 days of treatment where the subsequent autopsy showed signs of severe heart disease, and an induced abortion in the fifth month of pregnancy due to signs of severe malformations of the foetus, where the father had used Zyban from just before the pregnancy was determined.
The Danish Medicines Agency has also received four reports of side effects with a fatal outcome for Champix. They are from 2007, 2008, 2010 and 2011.
These deaths are associated with the following situations: Three of the deaths are related to arrhythmia of the heart, possibly following a heart attack causing cardiac arrest. In the first of the three cases, an autopsy showed narrowing of and haemorrhaging in one of the heart's coronary arteries. In the second of the three cases, the patient had an elevated cholesterol level in the blood and received treatment for it. In the third case, the death occurred after seven weeks of treatment in a woman who also used contraceptive pills. In the last case, the cause of death is less certain, and it may be related to psychiatric symptoms and alcoholic liver disease.
Repeated reassessment
Since their approval, cardiovascular side effects and especially psychiatric side effects have caused repeated reassessment of risks and benefits of each of the two smoking cessation products. The assessments have several times resulted in revisions of both summary of product characteristics and package leaflet and the addition of new information on side effects, their frequency and relevant warnings concerning use of the products.
Twice during fall 2011, the Danish Medicines Agency published information about the possible increased risk of cardiovascular side effects from Champix. We did so in our newsletter Danish Pharmacovigilance Update from 18 August 2011 and 20 October 2011. The latter issue also mentions the latest adverse reaction report on deaths with possible links to Champix.
In both 2010 and 2011, approximately 5,000 Danes bought Zyban and approximately 25,000 Danes bought Champix.
Smoking vs. use of stop smoking products
Smoking is the cause of many and comprehensive health problems, and the Danish Cancer Society estimates that it is the cause of nearly 14,000 deaths a year in Denmark - 4,500 of these are death from cancer and 3,500 of them are death from COPD (chronic obstructive pulmonary disease). The health benefits from smoking cessation should be weighed against the potential side effects from medicines intended to help people stop smoking.
The Danish Medicines Agency finds that the benefits of smoking cessation continues to far exceed the potential side effects from using Zyban and Champix, respectively.
Most of the above reports of deaths after use of Zyban and Champix contain information on known risk factors for cardiovascular disease and/or the autopsy reports document heart disease. These facts are very important to consider when assessing the balance between benefits and risks of smoking cessation products.
The summary of product characteristics and package leaflet contain a number of important recommendations intended to make smoking cessation with Zyban or Champix as efficient and safe as possible based on our current knowledge. More specifically, the documents include a number of warnings and information on side effects and their frequency. The information is updated regularly.
Both doctors and patients should read these documents and together weigh the benefits and risks in the individual before treatment is begun.
Both doctors and patients are encouraged to report side effects at meldenbivirkning.dk.
