animal studies, duloxetine had no effect on male fertility, and
effects in females were only evident at doses that caused maternal
in animals have shown reproductive toxicity at systemic exposure
levels (AUC) of duloxetine lower than the maximum clinical exposure.
large observational studies do not suggest an overall increased risk
of major congenital malformation (one from the US including 2,500
exposed to duloxetine during the first trimester and one from the EU
including 1,500 exposed to duloxetine during the first trimester).
The analysis on specific malformations such as cardiac malformations
shows inconclusive results.
the EU study, maternal exposure to duloxetine during late pregnancy
(at any time from 20 weeks gestational age to delivery) was
associated with an increased risk for preterm birth (less than
2-fold, corresponding to approximately 6 additional premature births
per 100 women treated with duloxetine late in pregnancy). The
majority occurred between 35 and 36 weeks of gestation. This
association was not seen in the US study.
US observational data have provided evidence of an increased risk
(less than 2-fold) of postpartum haemorrhage following duloxetine
exposure within the month prior to birth.
data have suggested that the use of SSRIs in pregnancy, particularly
in late pregnancy, may increase the risk of persistent pulmonary
hypertension in the newborn (PPHN). Although no studies have
investigated the association of PPHN to SNRI treatment, this
potential risk cannot be ruled out with duloxetine, taking into
account the related mechanism of action (inhibition of the re-uptake
with other serotonergic medicinal products, discontinuation symptoms
may occur in the neonate after maternal duloxetine use near term.
Discontinuation symptoms seen with duloxetine may include hypotonia,
tremor, jitteriness, feeding difficulty, respiratory distress and
seizures. The majority of cases have occurred either at birth or
within a few days of birth.
should be used in pregnancy only if the potential benefit justifies
the potential risk to the foetus. Women should be advised to notify
their physician if they become pregnant, or intend to become
pregnant, during therapy.
Duloxetine is very weakly
excreted into human milk, based on a study of 6 lactating patients
who did not breast-feed their children. The estimated daily infant
dose on a mg/kg basis is approximately 0.14% of the maternal dose. As
the safety of duloxetine in infants is not known, the use of Cymbalta
while breast-feeding is not recommended.
[Summary of Product Characteristics]. Utrecht, The Netherlands: Eli
Lilly Nederland B.V.