Cases of life-threatening hepatic failure have been reported in patients treated
with SERZONE. The reported rate in the United States is about 1 case of liver
failure resulting in death or transplant per 250,000- 300,000 patient-years of
SERZONE treatment. The total patient-years is a summation of each patients duration
of exposure expressed in years. For example, 1 patient-year is equal to 2 patients
each treated for 6 months, 3 patients each treated for 4 months, etc. (See WARNINGS.)
Ordinarily, treatment with SERZONE should not be initiated in individuals with active
liver disease or with elevated baseline serum transaminases. There is no evidence
that pre-existing liver disease increases the likelihood of developing liver
failure, however, baseline abnormalities can complicate patient monitoring.
Patients should be advised to be alert for signs and symptoms of liver
dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc) and to
report them to their doctor immediately if they occur.
SERZONE should be discontinued if clinical signs or symptoms suggest liver failure
(see PRECAUTIONS: Information for Patients). Patients who develop evidence
of hepatocellular injury such as increased serum AST or serum ALT levels ≥ 3 times
the upper limit of NORMAL, while on SERZONE should be withdrawn from the drug.
These patients should be presumed to be at increased risk for liver injury if SERZONE
is reintroduced. Accordingly, such patients should not be considered for re-treatment.
Suicidality in Children and Adolescents
Antidepressants increased the risk of suicidal thinking and behavior (suicidality)
in short-term studies in children and adolescents with Major Depressive Disorder (MDD)
and other psychiatric disorders. Anyone considering the use of SERZONE or any
other antidepressant in a child or adolescent must balance this risk with the
clinical need. Patients who are started on therapy should be observed closely for
clinical worsening, suicidality, or unusual changes in behavior. Families and
caregivers should be advised of the need for close observation and communication with
the prescriber. SERZONE is not approved for use in pediatric patients. (See WARNINGS
and PRECAUTIONS: Pediatric Use.)
Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of
nine antidepressant drugs (SSRIs and others) in children and adolescents with
major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other
psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed
a greater risk of adverse events representing suicidal thinking or behavior
(suicidality) during the first few months of treatment in those receiving
antidepressants. The average risk of such events in patients receiving antidepressants
was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.