Varenicline (Champix®, Pfizer), a partial nicotinic acetylcholine receptor agonist, is licensed as an aid to smoking cessation treatment and was registered in Singapore in August 2007.
Post-marketing neuropsychiatric adverse events
Since the drug was approved in May 2006 in the United States, the US Food and Drug Administration (FDA) had received post-marketing adverse event reports describing serious neuropsychiatric symptoms, which include changes in behaviour, agitation, depressed mood, suicidal ideation, and in cases of attempted and completed suicide associated with the use of varenicline. FDA's preliminary assessment of these adverse drug reaction reports (ADRs) revealed that in many of the cases, the neuropsychiatric symptoms
occurred within days to weeks after the initiation of varenicline therapy. However, the causal role of varenicline in these cases remained unclear as smoking cessation (with or without treatment) is associated with nicotine withdrawal symptoms and has been linked with the exacerbation of underlying psychiatric illness. Nevertheless, not all patients described in FDA's cases had pre-existing psychiatric illness and not all had discontinued smoking. Since the introduction of Champix® in Canada, Health Canada has received a total of 226 cases of neuropsychiatric adverse events over the period between April 2007 and April 2008. The types of reports include events of depressed mood, agitation, hostility, changes in behaviour, suicidal ideation and suicide, as well as worsening of pre-existing psychiatric illness regardless of whether it was previously diagnosed.
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International regulatory actions
The US FDA has recently included these serious post-marketing neuropsychiatric symptoms
in the warnings and precautions section of varenicline's prescribing information. Additionally, the FDA has recently approved a patient medication guide designed to highlight important safety information to patients who are prescribed varenicline. Similarly, Health Canada has recently revised the Canadian Product Monograph of varenicline to include these post-marketing neuropsychiatric adverse events.
In Europe, the European Medicines Agency has reviewed the case reports of suicidal ideation or attempted suicide while taking varenicline and have requested that the product information of Champix® to include warnings of behavioral changes noted in post-marketing reports.
HSA’s advisory
Champix® was recently launched locally in April 2008 and HSA has not received any local adverse reaction reports. In view of the nature of adverse events observed overseas, prescribers are advised to carefully assess patients' suitability (e.g. medical history, lifestyle, occupation) for treatment with Champix® before prescribing this medication to them.
As a risk management strategy to enhance the safe use of Champix®, HSA is working with Pfizer (Singapore) to develop a patient medication guide for patients taking the medication with the aim of providing information on possible adverse reactions associated its use so that patients can identify these reactions and seek medical help if they experience these effects. In line with this risk management strategy, prescribers are strongly encouraged to discuss the potential neuropsychiatric adverse effects associated with Champix® or smoking cessation with their patients.
HSA continues to monitor the overseas and local situation closely and requests that healthcare professionals report any adverse reactions suspected to be associated with Champix® to the Pharmacovigilance Unit.
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References
- JAMA 2006 Jul;296(1):56–63.
- Canadian Adverse Reaction Newsletter, Volume 18, Issue 2, April 2008.
- FDA Press Release: Early Communication About an Ongoing Safety Review: Varenicline (marketed as Chantix), 20 November 2007.
- FDA News: Early Communication About an Ongoing Safety Review
Varenicline (marketed as Chantix), 1 February 2008. http://www.fda.gov/cder/drug/early_comm/varenicline.htm - FDA Public Health Advisory: Important Information on Chantix (varenicline), 1 February 2008. http://www.fda.gov/cder/drug/advisory/varenicline.htm
- FDA Alert: Information for Healthcare Professionals
Varenicline (marketed as Chantix), 1 February 2008. http://www.fda.gov/cder/drug/infopage/varenicline/default.htm
