May 26, 2004
Subject: Stronger WARNING for SSRIs and other newer antidepressants regarding the potential for behavioural and emotional changes, including risk of self- harm
Pfizer Canada Inc., 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 may be associated with behavioural and emotional changes, including risk of self-harm.
The new Class warning incorporated in the Product Monograph of ZOLOFT* (sertraline hydrochloride) capsules is provided below.
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 antidepressants 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 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 treatment.
Rigorous clinical monitoring for suicidal ideation or other indicators of potential for suicidal behavior is advised in patients of all ages. This includes monitoring for agitation-type emotional and behavioural changes.
Discontinuation Symptoms
Patients currently taking sertraline hydrochloride 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 antidepressant drug, a gradual reduction in the dose rather than an abrupt cessation is recommended.
The updated warning informs practitioners that all patients being treated with SSRIs and other newer antidepressants should be rigorously monitored for clinical worsening, or onset/ worsening of agitation-type adverse events, or other indicators of potential for suicidal behaviour.
New Information Added to the Consumer Information Section
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 antidepressants is most safe and effective when there is good communication with the treating physician about how the patient is feeling.
Background
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/dhp-mps/prodpharma/activit/sci-consult/serotonin/sapssri_rop_gcsisrs_crd_2004-02-20_e.html.
Any questions from healthcare professionals may be directed to the Pfizer Medical Information Group at Tel: 1 800 463-6001.
Bernard Prigent, M.D.
Vice President & Medical Director
Pfizer Canada Inc.
*Trademark Pfizer Inc.
Pfizer Canada Inc. Licensee
Zoloft
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.
Health Canada Endorsed Important Safety Information on
ZOLOFT (sertraline hydrochloride)
Paxil
Health Products and Food Branch (HPFB) posts on the Health Canada web site safety alerts, public healthadvisories, press releases and other notices as a service to health professionals, consumers, and other interestedparties.
May 2004 Subject: Stronger WARNING for SSRIs and other newer anti-depressants regarding thepotential for behavioural and emotional changes, including risk of self-harm.
The new Class warning incorporated in the product monograph of paroxetine is provided below.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 SSRIsand 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.
Adult and Pediatrics: Additional data•There are clinical trial and post-marketing reports with SSRIs and other neweranti-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.Discontinuation Symptoms Patients currently taking paroxetine should NOT be discontinued abruptly, due to riskof 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.
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.Paroxetine is not indicated for use in the pediatric population, and controlled clinical studies with paroxetine in children and adolescents under 18 years of age.
Background 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 spontaneous post-marketing reports for SSRIs and other newer anti-depressants. 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.
Any questions may be directed to Medical Information via GSK Customer service at 1-800-387-7374.
Luvox
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.
May 2004
Subject: Stronger WARNING for SSRIs and other newer anti-depressants regarding the potential for behavioral and emotional changes, including risk of self-harm
The new Class warning incorporated in the product monograph of LUVOX† (fluvoxamine maleate) is provided below.
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 behavioral and emotional changes, including an increased risk of suicidal ideation and behavior 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 liability, 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 behavior is advised in patients of all ages. This includes monitoring for agitation-type emotional and behavioral changes.
Discontinuation Symptoms
Patients currently taking fluvoxamine 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 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 behavior.
Fluvoxamine is not indicated for use in the pediatric population.
Background
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.
To report an Adverse Reaction, consumers and health professionals may call toll free:
Tel: 866 234-2345
Fax: 866 678-6789
cadrmp@hc-sc.gc.ca
Effexor XR
The information included in the Adverse Findings Observed in Short-Term, Placebo-Controlled Studies with Effexor XR subsection is based on data from three 8- and 12-week controlled clinical trials in major depressive disorder (includes two U.S. trials and one European trial), on data up to 8 weeks from a pool of five controlled clinical trials in GAD with Effexor XR®, on data up to 12 weeks from a pool of two controlled clinical trials in Social Anxiety Disorder, and on data up to 12 weeks from a pool of four controlled clinical trials in panic disorder.
Information on additional adverse events associated with Effexor XR in the entire development program for the formulation and with Effexor (the immediate release formulation of venlafaxine) is included in the Other Adverse Events Observed During the Premarketing Evaluation of Effexor and Effexor XR subsection.
Side Effects
Nervous system - Frequent: amnesia, confusion, depersonalization, hypesthesia, thinking abnormal, trismus, vertigo; Infrequent: akathisia, apathy, ataxia, circumoral paresthesia, CNS stimulation, emotional lability, euphoria, hallucinations, hostility, hyperesthesia, hyperkinesia, hypotonia, incoordination, manic reaction, myoclonus, neuralgia, neuropathy, psychosis, seizure, abnormal speech, stupor, suicidal ideation; Rare: abnormal/changed behavior, adjustment disorder, akinesia, alcohol abuse, aphasia, bradykinesia, buccoglossal syndrome, cerebrovascular accident, feeling drunk, loss of consciousness, delusions, dementia, dystonia, energy increased, facial paralysis, abnormal gait, Guillain-Barre Syndrome, homicidal ideation, hyperchlorhydria, hypokinesia, hysteria, impulse control difficulties, libido increased, motion sickness, neuritis, nystagmus, paranoid reaction, paresis, psychotic depression, reflexes decreased, reflexes increased, torticollis.
Adverse Events Associated with Discontinuation of Treatment
Approximately 11% of the 357 patients who received Effexor XR®(venlafaxine hydrochloride) extended-release capsules in placebo-controlled clinical trials for major depressive disorder discontinued treatment due to an adverse experience, compared with 6% of the 285 placebo-treated patients in those studies.
Approximately 18% of the 1381 patients who received Effexor XR in placebo-controlled clinical trials for GAD discontinued treatment due to an adverse experience, compared with 12% of the 555 placebo-treated patients in those studies. Approximately 17% of the 277 patients who received Effexor XR in placebo-controlled clinical trials for Social Anxiety Disorder discontinued treatment due to an adverse experience, compared with 5% of the 274 placebo-treated patients in those studies.
Approximately 7% of the 1,001 patients who received Effexor XR in placebo-controlled clinical trials for panic disorder discontinued treatment due to an adverse experience, compared with 6% of the 662 placebo-treated patients in those studies.
Xanax
" Adverse Events Observed during the
Premarketing Evaluation of
XANAX XR Tablets
following is a list of MedDRA terms that reflect treatment-emergent
adverse events reported by 531 patients with panic disorder treated with
XANAX XR.
Cardiac disorders: Frequent: palpitation; Infrequent: sinus tachycardia: Ear and Labyrinth disorders: Frequent: Vertigo; Infrequent: tinnitus,
ear pain , Eye disorders: Frequent: blurred vision; Infrequent: mydriasis, photophobia , Gastrointestinal disorders: Frequent: diarrhea, vomiting, dyspepsia,
abdominal pain; Infrequent: dysphasia, salivary hyper secretion
General disorders and administration site conditions: Frequent: malaise,weakness, chest pains; Infrequent: fall, pyrexia, thirst, feeling hot
and cold, edema, feeling jittery, sluggishness, asthenia, feeling drunk,chest tightness, increased energy, feeling of relaxation, hangover, loss
of control of legs, rigors
Musculoskeletal and connective tissue disorders:
Frequent: back pain,muscle cramps, muscle twitching,Nervous system disorders: Frequent: headache, dizziness, tremor; Infrequent: amnesia, clumsiness, syncope, hypotonia, seizures, depressed,level of consciousness, sleep apnea syndrome, sleep talking, stupor
Psychiatric system disorders: Frequent: irritability, insomnia,nervousness, derealization, libido increased, restlessness, agitation,
depersonalization, nightmare;
Infrequent: abnormal dreams, apathy,aggression, anger, bradyphrenia, euphoric mood, logorrhea, mood swings,
dysphonia, hallucination,
homicidal ideation, mania, hypomania, impulse, control, psychomotor retardation, suicidal ideation
Renal and urinary disorders: Frequent: difficulty in micturition; Infrequent: urinary frequency, urinary incontinence
Respiratory, thoracic, and mediastinal disorders: Frequent: nasal congestion, hyperventilation; Infrequent: choking sensation, epistaxis,
rhinorrhea
Skin and subcutaneous tissue disorders: Frequent: sweating increased;Infrequent: clamminess, rash, urticaria
Vascular disorders: Infrequent: hypotension ..."
<http://www.pfizer.com/pfizer/download/uspi_xanax_ xr.pdf
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