Important drug safety information for paroxetine: warning for ssris and other newer anti-depressants regarding the potential for behavioural and emotional changes, including risk of self-harm - glaxosmithkline inc.
Health Products and Food Branch
Direction générale des produits de santé et des aliments
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This is duplicated text of a letter from GlaxoSmithKline Inc
Co ntact the co mp any for a copy of any references, attachm ents or enclosures.
Health Canada Endorsed Important Safety Information on
Subject: Stronger WARNING for SSRIs and other newer anti-depressants regarding the
potential for behavioural and emotional changes, including risk of self-harm.
For paroxetine, this replaces the previous interim contraindication.
GlaxoSmithKline Inc. (GSK), following discussions with Health Canada, would like to informyou of important safety information regarding the possibility that selective serotonin reuptakeinhibitors (SSRIs) and other newer anti-depressants may be associated with behavioural andemotional changes, including risk of self-harm.
The new Class warning incorporated in the product monograph of paroxetine is providedbelow.
Please note this warning replaces the interim contraindication for Paxil® (paroxetine) issued inJuly 2003 for patients under 18 years of age with Major Depressive Disorder.
POTENTIAL ASSOCIATION WITH THE OCCURRENCE OF BEHAVIOURAL AND
EMOTIONAL CHANGES, INCLUDING SELF-HARM.
Pediatrics: Placebo-Controlled Clinical Trial Data
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 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.
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 paroxetine 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 recommended.
It should be noted that a causal role for SSRIs and other newer anti-depressants in inducingself-harm or harm to others has not been established. The possibility of a suicide attempt isinherent in depression and other psychiatric disorders, and may persist until remission occurs. Therefore, high-risk patients should be closely supervised throughout therapy with appropriateconsideration to the possible need for hospitalization. The updated warning informspractitioners that all patients being treated with SSRIs and other newer anti-depressantsshould be rigorously monitored for clinical worsening, or onset/worsening of agitation-typeadverse events, or other indicators of potential for suicidal behaviour.
Paroxetine is not indicated for use in the pediatric population, and controlled clinical studieswith paroxetine in children and adolescents under 18 years of age with major depressivedisorder failed to demonstrate efficacy.
New Information Added to the Consumer Information Section
The Consumer Information Section of the product monograph has been updated to reflect thisnew 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 treatingphysician about how the patient is feeling.
In February 2004, a scientific advisory panel set up by Health Canada was asked to providethe clinical practice perspective on the pediatric clinical trial safety data, and the spontaneouspost-marketing reports for SSRIs and other newer anti-depressants. The panel agreed that acontraindication was not warranted for these medications, and supported Health Canada’srecommendation for stronger warnings, while providing suggestions and comments. Therecord of proceedings, and other information about the panel, can be found on HealthCanada’s website at .
GSK continues to work closely with Health Canada to monitor adverse event reporting and toensure that up-to-date information regarding the use of paroxetine is available.
The identification, characterization and management of drug-related adverse events aredependent on the active participation of health-care professionals in adverse drug reactionreporting programs. Healthcare professionals are asked to report any suspected adversereactions in patients receiving PAXIL® and PAXIL CR™ (paroxetine hydrochloride) directly toGSK or Health Canada at the following addresses:
73 33 Mississau ga R oad No rthM ississau ga, OntarioL5N 6L4Tel: 1-800-387-7374
Any suspected adverse reaction can also be reported to:
Ca nad ian A dverse Dru g R eac tion M on itoring P rog ram (CA DR M P)
M arke ted H ealth P rod uc ts Direc torate
Address Locator: 0701C
OTTAW A, Ontario, K1A 0K9
Tel: (613) 957-0337 or Fax: (613) 957-0335
To repo rt an A dverse Re action , co nsu m ers an d h ealth p rofessiona ls may ca ll toll free:
Tel: 866 234-2345
Fax: 866 678-6789
For o th er inquiries: plea se refer to contact in fo rm ation.
The can be found on the Health Canada web site or in The CanadianCompendium of Pharmaceuticals and Specialties
Your professional commitment in this regard has an important role in protecting the well-beingof your patients by contributing to early signal detection and informed drug use.
Any questions from health care professionals may be directed to Medical Information via GSKCustomer service at 1-800-387-7374.
original signed by
Anne Phillips, M.D., FRCPCVice-President, Research & Development and Chief Medical OfficerGlaxoSmithKline Inc.
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