PAXIL Warnings

PRECAUTIONS in Dear Doctor Letter - September 2005

Pregnancy: Teratogenic Effects: Pregnancy Category C.

There are no adequate and well controlled studies in pregnant women. A recent
retrospective epidemiological study of 3,581 pregnant women exposed to
paroxetine or other antidepressants during the 1st trimester suggested an increased
risk of overall major congenital malformations for paroxetine compared to other
antidepressants (OR 2.20; 95% confidence interval 1.34-3.63). There was also an
increased risk for cardiovascular malformations for paroxetine compared to other
antidepressants (OR 2.08; 95% confidence interval 1.03-4.23); 10 out of 14 infants
with cardiovascular malformations had ventricular septal defects. A separate study
based on the Swedish Medical Birth Registry evaluated 4,291 infants exposed to
SSRIs in early pregnancy. This study reported no increased risk for overall major
malformations in 708 infants born to women with paroxetine exposure in early
pregnancy.

Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6
mg/kg/day in rabbits administered during organogenesis. These doses are
equivalent to 9.7 (rat) and 2.2 (rabbit) times the maximum recommended human
dose (MRHD) for major depressive disorder, social anxiety disorder, GAD, and
PTSD (50 mg) and 8.1 (rat) and 1.9 (rabbit) times the MRHD for OCD, on an
mg/m2 basis. These studies have revealed no evidence of teratogenic effects.
However, in rats, there was an increase in pup deaths during the first 4 days of
lactation when dosing occurred during the last trimester of gestation and continued
throughout lactation. This effect occurred at a dose of 1 mg/kg/day or 0.19 times
(mg/m2) the MRHD for major depressive disorder, social anxiety disorder, GAD,
and PTSD; and at 0.16 times (mg/m2) the MRHD for OCD. The no-effect dose for
rat pup mortality was not determined. The cause of these deaths is not known.
Paroxetine should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.

See: Paxil CR Dear Doctor / Healthcare Professional Letter September 2005