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 Organon Canada Ltd./Ltée.
Contact the company
for a copy of any references, attachments or
Health Canada Endorsed Important
Safety Information on REMERON RDTM / REMERON®
Organon Canada Ltd./Ltée
200 Consilium Place, Suite 700
ON M1H 3E4
May 26, 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,
Organon Canada Ltd./Ltée, 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 anti-depressants may be associated with behavioural and emotional
changes, including risk of self-harm.
The new Class warning incorporated in the product monograph of REMERON
RDTM/REMERON® (mirtazapine) is provided below.
POTENTIAL ASSOCIATION WITH THE
OCCURRENCE OF BEHAVIOURAL AND EMOTIONAL CHANGES, INCLUDING
Pediatrics: Placebo-Controlled Clinical Trial
- Recent analyses of placebo-controlled
clinical trial safety databases from SSRIs and other newer
anti-depressants suggest 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.
Adult and Pediatrics: Additional
- There are clinical trial and post-marketing
reports with SSRIs and other newer antidepressants, 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
Rigorous clinical monitoring for suicidal
ideation or other indicators of potential for suicidal behaviour is
advised in patients of all ages. This includes monitoring for
agitation-type emotional and behavioural changes.
Patients currently taking mirtazapine should
NOT be discontinued abruptly, due to risk of discontinuation
symptoms. At the time that a medical decision is made to discontinue
an SSRI or other newer anti-depressant drug, a gradual reduction in
the dose rather than an abrupt cessation is
It should be noted that a causal role for SSRIs and other newer
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 and other newer
anti-depressants should be rigorously monitored for clinical worsening, or
onset/worsening of agitation-type adverse events, or other indicators of
potential for suicidal behaviour.
Mirtazapine is not indicated for use in the pediatric population.
New Information Added to the Consumer Information
The Consumer Information Section of the product
monograph has 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 and other newer
antidepressants. The panel agreed that a contraindication was not
warranted for these medications, and supported Health Canada's
recommendation for stronger warnings, while providing suggestions and
comments. The record of proceedings, and other information about the
panel, can be found on Health Canada's website at http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/sap_ssri_2004-02-20_rop_e.html.
Organon Canada Ltd./Ltée continues to work closely with Health Canada
to monitor adverse event reporting and to ensure that up-to-date
information regarding the use of REMERON RDTM/REMERON®
(mirtazapine) 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 REMERON RDTM/REMERON® (mirtazapine) directly
to Organon Canada Ltd./Ltée or Health Canada at the following
Organon Canada Ltd./Ltée
200 Consilium Place, Suite
Toronto, ON M1H 3E4
Any suspected adverse incident can also be
Canadian Adverse Drug Reaction Monitoring
Marketed Health Products Directorate
Address Locator: 0701C
OTTAWA, Ontario, K1A 0K9
(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.
Reporting Form and the AR
Guidelines can be found on the Health Canada web site or in
The Canadian Compendium of Pharmaceuticals and
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 health care professionals may be directed to Medical
Information at 1-866-750-6048.
original signed by
Director, Scientific Affairs