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BCANS Enquiries
This document is also available in PDF format
Pages: 4, Size: 20 K, Date: 2004-06-10

The Health Products and Food Branch (HPFB) posts on the Health Canada web site safety alerts, public health advisories, press releases and other notices as a service to health professionals, consumers, and other interested parties. These advisories may be prepared with Directorates in the HPFB which includes pre-market and post-market areas as well as market authorization holders and other stakeholders. Although the HPFB grants market authorizations or licenses for therapeutic products, we do not endorse either the product or the company. Any questions regarding product information should be discussed with your health professional.

This is duplicated text of a letter from Biovail Pharmaceuticals Canada (BPC).
Contact the company for a copy of any references, attachments or enclosures.

Health Canada Endorsed Important Safety Information on
WELLBUTRIN® SR and ZYBAN® (bupropion HCl)

Biovail Pharmaceuticals Canada

June 8, 2004

Subject: Stronger WARNING for SSRIs and other newer anti-depressants regarding the potential for behavioural and emotional changes, including risk of self harm.

Dear Health Care Professional,

Biovail Pharmaceuticals Canada (BPC), following discussions with Health Canada, would like to inform you of important safety information regarding the possibility that SSRIs (selective serotonin reuptake inhibitors) and other newer antidepressants, including bupropion HCl, may be associated with behavioural and emotional changes, including risk of self harm.

Bupropion is marketed in Canada as both the anti-depressant WELLBUTRIN® SR and the smoking cessation drug ZYBAN®. As findings from post-market spontaneous reports regarding agitation type events apply to ZYBAN® as well as WELLBUTRIN® SR, the following Class warning is therefore being incorporated into the labelling of both products.

This warning applies to both adults and pediatrics. Please note that neither WELLBUTRIN® SR nor ZYBAN® have been fully evaluated in pediatrics, and these products are not indicated for use in patients less than 18 years of age.


In WELLBUTRIN® SR labelling only:
Pediatrics: Placebo-Controlled Clinical Trial Data

  • Recent analyses of placebo-controlled clinical trial safety databases from SSRIs and other newer anti-depressants suggests that use of these drugs in patients under the age of 18 may be associated with behavioural and emotional changes, including an increased risk of suicidal ideation and behaviour over that of placebo.

  • The small denominators in the clinical trial database, as well as the variability in placebo rates, preclude reliable conclusions on the relative safety profiles among these drugs.

In both WELLBUTRIN® SR and ZYBAN® labelling:
Adults and Pediatrics: Additional data

  • There are clinical trial and post-marketing reports with SSRIs and other newer anti-depressants, in both pediatrics and adults, of severe agitation-type adverse events coupled with self-harm or harm to others. The agitation-type events include: akathisia, agitation, disinhibition, emotional lability, hostility, aggression, depersonalization. In some cases, the events occurred within several weeks of starting treatment. Given that bupropion may be prescribed as either an anti-depressant (WELLBUTRIN® SR) or a smoking cessation product (ZYBAN®), these findings affect the conditions of use of both products.

Rigorous clinical monitoring for suicidal ideation or other indicators of potential for suicidal behaviour is advised in patients of all ages given an anti-depressant drug. This includes monitoring for agitation-type emotional and behavioural changes. Although the smoking cessation patient population is not taking bupropion for depression, agitation-type changes are reported for ZYBAN® and monitoring is necessary for both products.

It should be noted that a causal role for anti-depressants in inducing self-harm or harm to others has not been established. The possibility of a suicide attempt is inherent in depression and other psychiatric disorders, and may persist until remission occurs. Therefore, high risk patients should be closely supervised throughout therapy with appropriate consideration to the possible need for hospitalization. The updated WARNING informs practitioners that all patients being treated with SSRIs or other newer anti-depressants should be rigorously monitored for clinical worsening, or onset/worsening of agitation-type adverse events or other indicators with a potential for suicidal behaviour.

New Information Added to the Consumer Information Section

The Consumer Information section of the product monographs has also been updated to reflect this new Class warning, and to advise patients that treatment with SSRIs and other newer anti-depressants is most safe and effective when there is good communication with the treating physician about how the patient is feeling.


In February 2004, a Scientific Advisory Panel set up by Health Canada was asked to provide the clinical practice perspective on the pediatric clinical trial safety data, and the spontaneous post-marketing reports for SSRIs, SNRIs (serotonin and norepinephrine reuptake inhibitors) and other newer antidepressants. The Panel agreed that a contraindication was not warranted for these drugs and supported Health Canada’s recommendations for stronger warnings, while providing suggestions and comments. The Record of Proceedings, and other information about the Panel, can be found on the Health Canada website at: Subsequently Health Canada, in discussion with the Advisory Panel, decided to include bupropion, a NDRI (noradrenalin and dopamine reuptake inhibitor), in the warning due to case reports of labile emotions, predominantly exemplified by agitation.

Biovail Pharmaceuticals Canada continues to work closely with Health Canada to monitor adverse event reporting and to ensure that up-to-date information regarding the use of WELLBUTRIN® SR and ZYBAN® is available.

The identification, characterization and management of drug-related adverse events are dependent on the active participation of healthcare professionals in adverse drug reaction reporting programs. HealthCare professionals are asked to report any suspected adverse reactions in patients receiving WELLBUTRIN® SR or ZYBAN® directly to Biovail Pharmaceuticals Canada or Health Canada at the following addresses:

Biovail Pharmaceuticals Canada
7150 Mississauga Rd.
Mississauga, Ontario.
L5N 8M5
Tel: 866-825-8120
Fax: 905-286-3256

Any suspected adverse reaction can also be reported to:
Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
Marketed Health Products Directorate
Address Locator: 0701C
OTTAWA, Ontario, K1A 0K9
Tel: (613) 957-0337 or Fax: (613) 957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Tel: 866 234-2345
Fax: 866 678-6789

For other inquiries: please refer to contact information.

The AR Reporting Form and the AR Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.

Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed drug use.

Any questions from healthcare professionals may be directed to Biovail Pharmaceuticals Canada Medical Information services at 1-866-825-8120.


original signed by

Kenneth Michalko, Pharm.D., MBA
Vice President, Regulatory Affairs
Biovail Pharmaceuticals Canada


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Last Updated - 2004-06-10 Top of page Important Notices